Xanya Sofra Weiss

Wnt signalling in stem cells and cancer. Xanya Sofra Weiss

2011-06-16T17:33:00.000-07:00

The canonical Wnt cascade has emerged as a critical regulator of stem cells. In many tissues, activation of Wnt signalling has also been associated with cancer. This has raised the possibility that the tightly regulated self-renewal mediated by Wnt signalling in stem and progenitor cells is subverted in cancer cells to allow malignant proliferation. Insights gained from understanding how the Wnt pathway is integrally involved in both stem cell and cancer cell maintenance and growth in the intestinal, epidermal and haematopoietic systems may serve as a paradigm for understanding the dual nature of self-renewal signals.

Stem cells are cells that have the unique ability to self- renew as well as to generate more differentiated progeny. The most primitive stem cell is the embryonic stem cell, which is derived from the inner cell mass of the blasto- cyst. This cell is pluripotent and can thus generate all the tissues of the body. Following the pioneering work on haemato- poietic stem cells over the last five decades, a multitude of recent studies have indicated that most other adult tissues also harbour stem cells. These adult stem cells are normally involved in homeo- static self-renewal processes but can also be rapidly recruited to repair tissues upon injury. With the study of adult stem cell biology, recurring roles of a limited set of signalling cascades are rapidly being uncovered. One of these is the canonical Wnt cascade. Notably, in many of the same tissues where the Wnt cascade controls stem cells, cancer ensues upon dysregulated activation of this pathway. Conceptually, this indicates that an efficient road to cancer involves the hijacking of physiological regulators of stem cell function in these particular tissues. Below, we first outline the canonical Wnt cascade, and then describe its mirror image roles in the biology of stem cells and cancer.

vertebrate genome encodes four highly similar Tcf/Lef proteins. In the absence of a Wnt signal, Tcf/Lef proteins repress target genes through a direct association with co-repressors such as Groucho. The interaction with b-catenin transiently converts Tcf/Lef factors into transcriptional activators. Drosophila genetics has recently identified two additional nuclear components, Pygopus and Bcl9 (also known as legless), conserved in vertebrates. Pygopus is essential for transcriptional activation of Tcf/Lef target genes, whereas Bcl9 seems to bridge Pygopus to Tcf-bound b-catenin. In sum, the canonical pathway translates a Wnt signal into the transient transcription of a Tcf/Lef target gene programme.

Xanya Sofra Weiss

THE INSIDE STORY OF CELL COMMUNICATION. Xanya Sofra Weiss

2011-06-16T17:29:00.000-07:00

Cells communicate by sending and receiving signals. Signals may come from the environment, or they may come from other cells. In order to trigger a response, these signals must be transmitted across the cell membrane. Sometimes the signal itself can cross the membrane. Other times the signal works by interacting with receptor proteins that contact both the outside and inside of the cell. In this case, only cells that have the correct receptors on their surfaces will respond to the signal.

Xanya Sofra Weiss

Collagen synthesis of articular cartilage explants in response to frequency of cyclic mechanical loading. Xanya Sofra Weiss

2011-06-16T17:26:00.000-07:00

Articular cartilage in vivo experiences the effects of both cell-regulatory proteins and mechanical forces. This study has addressed the hypothesis that the frequency of intermittently or continuously applied mechanical loads is a critical parameter in the regulation of chondrocyte collagen biosynthesis. Cyclic compressive pressure was applied intermittently to bovine articular cartilage explants by using a sinusoidal waveform of 0.1–1.0 Hz frequency with a peak stress of 0.5 MPa for a period of 5–20 s followed by a load-free period of 10–1,000 s. These loading protocols were repeated for a total duration of 6 days. In separate experiments, cyclic loading was continuously applied by using a sinusoidal waveform of 0.001–0.5 Hz frequency and a peak stress of 1.0 MPa for a period of 3 days. Unloaded cartilage discs of the same condyle were cultured in identically constructed loading chambers and served as controls. We report quantitative data showing that (1) no correlation exists between the relative rate of collagen synthesis expressed as the proportion of newly synthesized collagen among newly made proteins and either the frequency of intermittently or continuously applied loads or the overall time cartilage is actively loaded, and (2) individual protocols of intermittently applied loads can reduce the relative rate of collagen synthesis and increase the water content, whereas (3) continuously applied cyclic loads always suppress the relative rate of collagen synthesis compared with that of unloaded control specimens. The results provide further experimental evidence that collagen metabolism is difficult to manipulate by mechanical stimuli. This is physiologically important for the maintainance of the material properties of collagen in view of the heavy mechanical demands made upon it. Moreover, the unaltered or reduced collagen synthesis of cartilage explants might reflect more closely the metabolism of normal or early human osteoarthritic cartilage.

Xanya Sofra Weiss

Signaling Pathways for Glycated Human Serum Albumin-Induced IL-8 and MCP-1 Secretion in Human RPE Cells. Xanya Sofra Weiss

2011-06-16T17:20:00.000-07:00

PURPOSE.

To determine the signal mediators involved in glycated human serum albumin (GHSA) stimulation of interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1 secretion in human retinal pigment epithelium (hRPE) cells.

METHODOS:

hRPE cells were stimulated by GHSA in the presence or absence of a series of kinase inhibitors. The induced IL-8 and MCP-1 mRNA and proteins were determined by reverse transcription–polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Western blot analysis, electrophoretic mobility shift assay, and immunohistochemical staining were used to analyze activation of signaling mediators and transcription factors.

RESULT:

IncubatioSn of hRPE cells with GHSA resulted in rapid activation of Raf-1, extracellular signal-regulated protein kinases (ERK) 1/2, p38, and the transcription factor nuclear factor (NF)-κB. Coincubation of hRPE cells with the mitogen-activated protein (MAP) kinase (MEK) inhibitor U0126; NF-κB inhibitors BAY11-7085, caffeic acid phenethyl ester (CAPE), parthenolide, and curcumin; protein kinase (PK)C inhibitor Ro318220; and protein tyrosine kinase (PTK) inhibitor genistein largely eliminated most of the stimulated production of IL-8 and MCP-1. Combined inhibition of MEK by U0126, p38 by SB202190, and Janus kinase (jak) by AG490 revealed that GHSA stimulation of IL-8 production was predominately mediated by MEK and to a lesser extent by p38 pathways, whereas activation of MEK, p38, and jak was required for maximal MCP-1 induction. Moreover, GHSA-stimulated IL-8 secretion was more sensitive to U0126 (50% inhibitory concentration[ IC ] = 0.5 μM) than MCP-1 (IC = 10μ M)

CONCLUSIONS:

GHSA stimulates hRPE IL-8 and MCP-1 production through divergent and overlapping, but not identical, intracellular signaling cascades. GHSA induces activation of a series of kinases including PKC, PTK, MAPK, p38, and jak and the transcription factor NF-κB. The Raf/MAPK pathway plays an essential role in GHSA signaling.

Xanya Sofra Weiss

Selective Loss of Sertoli Cell and Germ Cell Function Leads to a Disruption in Sertoli Cell-Germ Cell Communication During Aging in the Brown Norway

2011-06-16T17:18:00.000-07:00

We investigated the effects of aging on Sertoli cell-germ cell interactions from Brown Norway rats using the induction of four specific mRNAs as markers. The testes from aging (24 mo old) Brown Norway rats can be normal size or regressed. One marker, a von Ebner's-like protein, is expressed in coculture and “in vivo” in germ cells from normal testes of 6- and 24-mo-old rats but not in germ cells from regressed testes of 24-mo-old rats. A second germ cell marker, the Huntington disease protein, is expressed in all germ cells. Two Sertoli cell markers, a serotonin receptor and a novel gene, are induced in Sertoli cells by meiotic germ cells. The serotonin receptor mRNA is expressed in Sertoli cells from 20-day, 6-mo, and 24-mo normal testes but not in those from 24-mo regressed testes. The novel gene is induced in Sertoli cells from all testes. We conclude that Sertoli cells from aged regressed testes are unable to respond to selective signals from germ cells from young rats, and germ cells from regressed testes show a similar selective loss. Such disruptions in communication between Sertoli cells and germ cells likely contribute to germ cell loss during aging.

Xanya Sofra Weiss

Abl Protein-Tyrosine Kinase Inhibitor STI571 Inhibits In Vitro Signal Transduction Mediated by c-Kit and Platelet-Derived Growth Factor Receptors.

2011-06-16T17:16:00.000-07:00

STI571 (formerly known as CGP 57148B) is a protein-tyrosine kinase inhibitor that is currently in clinical trials for the treatment of chronic myelogenous leukemia. STI571 selectively inhibits the Abl and platelet-derived growth factor (PDGF) receptor tyrosine kinases in vitro and blocks cellular proliferation and tumor growth of Bcr-abl- or v-abl-expressing cells. We have further investigated the profile of STI571 against related recep- tor tyrosine kinases. STI571 was found to potently inhibit the kinase activity of the ��- and ��-PDGF receptors and the receptor for stem cell factor, but not the closely related c-Fms, Flt-3, Kdr, Flt-1, and Tek tyrosine kinases. Additionally, no inhibition of c-Met or nonreceptor tyrosine kinases such as Src and Jak-2 has been observed. In cell-based assays, STI571 selectively inhibited PDGF and stem cell factor-mediated cellular signal- ing, including ligand-stimulated receptor autophosphorylation, inositol phosphate formation, and mitogen-activated protein kinase activation and proliferation. These results expand the profile of STI571 and suggest that in addition to chronic my- elogenous leukemia, STI571 may have clinical potential in the treatment of diseases that involve abnormal activation of c-Kit or PDGF receptor tyrosine kinases.

Xanya Sofra Weiss

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Xanya Sofra Weiss

2011-06-16T17:14:00.000-07:00

Identification of protein–protein interactions often provides insight into protein function, and many cellular processes are performed by stable protein complexes. We used tandem affinity purification to process 4,562 different tagged proteins of the yeast Saccharomyces cerevisiae. Each preparation was analysed by both matrix-assisted laser desorption/ ionization–time of flight mass spectrometry and liquid chromatography tandem mass spectrometry to increase coverage and accuracy. Machine learning was used to integrate the mass spectrometry scores and assign probabilities to the protein–protein interactions. Among 4,087 different proteins identified with high confidence by mass spectrometry from 2,357 successful purifications, our core data set (median precision of 0.69) comprises 7,123 protein–protein interactions involving 2,708 proteins. A Markov clustering algorithm organized these interactions into 547 protein complexes averaging 4.9 subunits per complex, about half of them absent from the MIPS database, as well as 429 additional interactions between pairs of complexes. The data (all of which are available online) will help future studies on individual proteins as well as functional genomics and systems biology.

Xanya Sofra Weiss

Protein turnover plays a key role in aging. Xanya Sofra Weiss

2011-06-09T14:45:00.000-07:00

Although the molecular mechanism of aging is unknown, a progressive increase with age in the concentration of damaged macromolecules, especially proteins, is likely to play a central role in senescent decline. In this paper, we discuss evidence that the progressive decrease in protein synthesis and turnover can be the primary cause of the increase in the concentration of damaged proteins with age. Conversely, protein damage itself is likely to be the cause of the decrease in protein turnover. This could establish a positive feedback loop where the increase in protein damage decreases the protein turnover rate, leading to a further increase in the concentration of damaged proteins. The establishment of such a feedback loop should result in an exponential increase in the amount of protein damage—a protein damage catastrophe—that could be the basis of the general deterioration observed in senescent organisms. © 2002 Published by Elsevier Science Ireland Ltd.

Xanya Sofra Weiss

Parasympathetic nerve-evoked protein synthesis, mitotic activity and salivary secretion in the rat parotid gland and the dependence on NO-generation.

2011-06-09T14:43:00.000-07:00

Incorporation of radiolabelled leucine and thymidine into trichloroacetic acid-insoluble material of the parotid gland was used as indices of protein synthesis and mitotic activity, respectively, following electrical stimulation of the parasympathetic auriculo-temporal nerve for 30 min in pentobarbitone-anaesthetized rats under adrenoceptor blockade (phentolamine and propranolol, 2 mg/kg intravenous of each) in the absence or presence of atropine (2 mg/kg intravenous) and without or with nitric oxide synthase inhibitors. In atropinized rats, the parasympathetic non-adrenergic, non-cholinergic (NANC) nerve-evoked mean increases in protein synthesis at a frequency of 10 Hz (142%) and 40 Hz (200%) were not affected in a statistically significant way (124 and 275%, respectively) by the neuronal type NO-synthase inhibitor Nwpropyl-L-arginine (N-PLA) (30 mg/kg intravenous). Neither were the increase (175%) in protein synthesis at 10 Hz in non-atropinized animals affected by N-PLA (180%). The increase (65%) in mitotic activity, 19 h after the end of stimulation at 40 Hz, in the presence of atropine, was not affected by N-PLA (55%). Neither were the increase (95%) in gland content of amylase at this point of observation statistically significant affected by N-PLA (144%). The secretion of fluid and output of amylase from the parotid gland upon nerve stimulation was not affected by N-PLA. When examining the non-selective NO-synthase inhibitor L-NAME (30 mg/kg intravenous) in atropinized rats subjected to stimulation at 10 Hz, neither the increase in protein synthesis nor the evoked fluid response or amylase outputs were affected. Hence, in contrast to an NO-dependent sympathetic-induced protein synthesis and mitosis in the parotid gland, involving the activity of the neuronal type NO-synthase, no support for a parasympathetic-induced protein synthesis (and gain in gland amylase) and mitosis, depending on NO-generation, was found.

Xanya Sofra Weiss

Non-neuronal cholinergic system and signal transduction pathways mediated by band 3 in red blood cells. Xanya Sofra Weiss

2011-06-09T14:40:00.000-07:00

BACKGROUND: Non-neuronal acetylcholine (ACh) and acetylcholinesterase (AChE) have been recognized in t Vascular ACh has been associated by us with the regulation of microcirculatory flow by modulating nitric oxide ( intracellular mobilization, metabolism (NOx) and release from erythrocytes, as well as the glycolytic flux. Velnacri maleate is a well-known AChE inhibitor which plays a competitive role by decreasing NO-mediated erythrocyte responses. A plausible hypothesis to explain the mechanisms underlying those events hinges on the NO translo among nitrosylated molecules and phosphorylated/dephosphorylated states of band 3 protein, processed by maj tyrosine-kinases (PTK: p72syk, p53/56lyn and p59/61hck) and phosphotyrosine-phosphatases (PTP).

METHODS: To assess this hypothesis under the influence of AChE effectors (acetylcholine/velnacrine), blood sa from healthy donors were harvested and Western blot analysis was subsequently used to determine the degree phosphorylation, in the presence and absence of PTK/PTP inhibitors. NO and nitrites/nitrates were quantified usi amperometric method and the Griess Reaction, respectively, in erythrocyte suspensions. Measurements of eryth metabolites (2,3-bisphosphoglycerate; glyceraldehyde 3-phosphate dehydrogenase; glucose-6-phosphodehydro lactate), hemoglobin and cyclic nucleotides were conducted afterwards.

RESULTS: Increased levels of phosphorylated-band 3 obtained upon p72syk inhibition suggest p59/61hck and as secondary involved kinases. As to NO/NOx quantification, in the presence of PTKi we reported higher levels velnacrine-AChE, as opposed to acetylcholine-AChE. Calpeptin, a PTP inhibitor which triggers full band 3-phosphorylation, led to the opposite NO mobilization, being reinforced by ACh. Oxy-hemoglobin, glyceraldehy 3-phosphate dehydrogenase and glucose-6-phosphodehydrogenase were found to decrease with ACh, whereas lactate and both cGMP/cAMP happened to increase.

CONCLUSION: Changes on human erythrocyte NOx mobilization and metabolic fluxes occur under influence of non-neuronal ACh/AChE, in turn dependent on the degree of band 3-phosphorylation. Since these vascular eve potentially change under pathological conditions, coadjuvant drugs could become accessible in the setting of microcirculation disease.

Xanya Sofra Weiss

SEX AND AGING. Xanya Sofra Weiss

2011-06-09T14:35:00.000-07:00

In nearly every culture on earth women outlive men — significantly so in the oldest years. But the men who do survive to become elderly are hardier than the women. A US National Institute of Aging study showed that 44% of men over age 80 are "robust and independent" compared with only 28% of women. And the percentage of surviving males increases from 15% at age 100 to 40% at age 105 in the United States.
If aging has been programmed by evolutionary forces, sex could be a very important contributor to the program. The reproductive organs of the human female exhibits a rate of aging that is among the most rapid of body systems. The complete shutdown of female fertility at menopause may be of value in preventing the birth of deformed children or death in childbirth of a mother who has several dependent children. For a species with a lengthy parenting period, it makes sense for fertility to cease long before the debilities of advancing age begin. Gonadotropin hormones from the pituitary gland are controlled by gonadotropin-releasing hormone, a 10-amino-acid peptide originating in neurons located in the arcuate nucleus of the hypothalamus. The two gonadotropin hormones (FSH & LH) are the same for females as for males, although their function is very different. Simplistically, FSH stimulates egg production in females & sperm production in males, whereas LH stimulates estrogen production in females & testosterone
production in males.
In fertile females FSH (Follicle-Stimulating Hormone) accelerates the growth of 6−12 primary follicles in the ovary each month — one of which may become a mature ovum. The follicles secrete estrogens, the most powerful of which is estradiol. A sudden increase in LH (Luteinizing Hormone) usually triggers ovulation (follicle rupture with discharge of the ovum) and the conversion of the follicle to the corpus luteum ("yellow body") — which also secretes estrogen, but primarily secretes progesterone. Progesterone stimulate the walls of the uterus to prepare it for implantation of the fertilized ovum. If pregnancy occurs, progesterone inhibits ovulation (by suppressing FSH & LH) and promotes uterine development until the placenta becomes more mature. (Progesterone is so-named because it promotes gestation, ie, the growth of offspring in the womb).
Aside from their role in the monthly cycle, estrogens are responsible for the development and maintenance of the female sexual organs, cause the deposition of fat in the breast&buttocks (which contributes to the feminine figure) and have a potent effect on bone development.
Menopause is the event in a woman's life when her ovary literally runs out of eggs. The loss of follicles to produce estradiol causes an end to menstrual cycling and production of estrogen & progesterone by the ovary. At age 30, a woman's period is normally 28−30 days, but by age 40 her period is typically closer to 25 days and her rate of egg-loss has accelerated. Further shortening (accompanied by periods when no ovulation occurs) eventually leads to menopause at an average age of 50 (plus or minus 10 years). The menopausal woman often experiences anxiety, irritability and fatigue. Beginning before menopause most women experience "hot flashes", ie, 3 minute surges of blood to the skin of the chest, shoulders & face leading to sudden hotness & sweating. Hot flashes are associated with a pulsatile release of LH from hypothalamic neurons associated with body temperature elevation. Estrogen therapy eliminates hot flashes. The rate of loss of ovarian follicles doubles around age 35, raising the suspicion that a hypothalamic mechanism may be the ultimate cause of menopause [SCIENCE 273:67-70 (1996)].
Graph of Female Hormonal Cycles
The most serious complications of menopause are osteoporosis and a decline in cardiovascular health. The Framingham Heart Study demonstrated that between ages 35 to 65 men have 10 times the incidence of heart attack as women — probably because estrogen protects against heart disease. Estrogen elevates HDL cholesterol and reduces LDL cholesterol in the bloodstream.
After menopause, nipples decrease in size and the surrounding alveolar tissue shrinks. Erection of these tissues with external stimulation is more difficult. Vaginal contractions during orgasm is reduced to 4−5 at 0.8-second intervals from 8−12 in young adults.
The testes have been regarded as the source of maleness at least since ancient Rome, where eunuchs & women were not permitted to "testify" (testis is Latin for "witness"). In the male, LH stimulates secretion of testosterone by the interstitial cells of Leydig in the testes. FSH stimulates spermatogenesis in the seminiferous tubules of the testes. Testosterone promotes development of male sexual organs in the foetus. At puberty testosterone stimulates hair growth on the face & pubis, causes enlargement of the larynx to deepen the voice, increases skin thickness, causes a 50% increase in muscle mass, promotes bone growth, increases basal metabolism up to 15% and increases red blood cell concentration.
There is no sudden "andropause" event in males that is comparable to the menopause event of females. Instead, testosterone levels tend to decline gradually with age. This decline occurs most dramatically in those with cardiovascular disease or a predisposition to adult-onset diabetes. Although sperm count declines, fatherhood has been verified for a male as old as 94. Semen production declines in the prostate as a man ages — and the smooth muscle is replaced by overgrowing connective tissue that enlarges the prostate, blocks urine and can lead to cancer. 85% of men over age 50 have symptoms arising from benign prostatic hyperplasia — a noncancerous overgrowth of prostate tissue possibly caused by excessive expression of the anti-apoptosis protein bcl−2 [HUMAN PATHOLOGY 27:668-675 (1996)]. In some tissues testosterone must be converted to dihydrotestosterone (by the enzyme 5−α reductase) in order to act. This occurs most notably in the prostate gland, which produces semen (a mixture of sugars, protein and water). Dihydrotestosterone has also been implicated in baldness. The European drug Permixon (an extract of the saw palmetto berry) inhibits 5−α reductase, and is used to prevent prostate hypertrophy and prostate cancer. The Life Extension Foundation sells saw palmetto berry extracts as a dietary supplement for this purpose.
Testosterone has been used in elderly men for "rejuvenation" — to restore virility & muscle strength. Testosterone increases the risk of cardiovascular disease — by increasing blood pressure, by lowering HDL cholesterol and by elevating LDL cholesterol. These same dangerous side effects are also seen in athletes who attempt to use androgens or other anabolic steroids to improve athletic performance. Eunuchs reportedly live longer, although there have been no controlled clinical trials to prove this
observation. Sterilization of a dog or cat (male or female) adds a couple of years to its lifespan. Any reduction in sex hormones would be expected to reduce cell proliferation and hence reduce the probability of cancer.
Male libido peaks in mid-adolescence, and does not correlate exactly with testosterone blood levels. In elderly men it may take from 10 seconds to several minutes to get an erection, in contrast to 3−5 seconds in young men. Contractions of the penile urethra during orgasm is reduced to 1−2 contractions per 0.8-seconds from 3−4 in young adults. Ejaculatory distance is reduced from 12−24 inches to 3−5 inches.

Xanya Sofra Weiss

EVOLUTION THEORY AND SPECIES-SPECIFIC AGING. Xanya Sofra Weiss

2011-06-09T14:34:00.000-07:00

Russell Wallace, who with Charles Darwin discovered natural selection, speculated that longevity much beyond the age of procreation would be a disadvantage for a species. Parents would threaten their children by competition for resources. This would imply an evolutionary advantage to genetically programmed aging. The programmed self-destruction with corticosteroids by Pacific salmon after spawning — and whose decaying bodies provide nutrient for their offspring — may be severe example indicating the possiblity of programmed senescence. But as biologist Herman Medawar noted, there is circular reasoning in claiming that senescence evolved so that non-senescent individuals could more readily survive. If there were no senescent, poorly-reproducing individuals, there would be no need for replacement.

If aging were the product of evolutionary forces, aging could reasonably be expected to result from programming. But since most animals in the wild die of accident, attack or disease it seems questionable that evolutionary forces determine aging. Robins in the wild, for example, have an

estimated 12-year maximum lifespan and a 40% chance of surviving any given year. With a (0.4)12 — or 1 in 60,000 — chance that a robin can avoid accident, attack or disease for 12 years, there would seem to be little opportunity for natural selection to play a role in the evolution of senescence. Against this argument is evidence that early stages of senescence reduce the ability of an animal to survive — thereby causing earlier selection against older animals.

An alternative to the view that senescence is the product of evolution compares genetic programming to the engineering of a fly-by satellite designed to gather data about a planet. The engineering is focused on ensuring that the satellite reaches its destination and performs its data gathering/transmission when passing the planet. Beyond the planet it is a matter of indifference to the engineers how long the satellite continues to function — random decay occurs. Applying the analogy, the satellite passing the planet is like an organism passing its reproductive period. Once the objectives of reproduction & parenting have been achieved the organism decays by random malfunction.

The vast range of maximum lifespan differences between species provides convincing evidence that longevity is genetically influenced. An elephant lives about 10−20 times longer than a mouse, yet both animals have roughly the same number of lifetime heartbeats — the elephant at 30 per minute and the mouse at 300 per minute. Both species take about 200 million breaths in a lifetime. And both species have a metabolic potential (total kilocalories used per gram of body weight per lifetime) of about 200 kcal. This figure is much the same for other mammals, but humans are exceptional with a metabolic potential of 800 kcal. Brains use more energy than any other human organ. (Basal metabolic rate for humans is about 80 watts = 70 Calories per hour.) Birds have a metabolic potential of 1,000 to 1,500 kcal.

Gerontologists who compare the longevity of species explain this discrepancy by saying that while body weight correlates well with longevity, there is a better correlation with brain weight for primates. For other species brain size may be more related to motor function than to cognitive capacity.

Flight, like brain weight, also confers a longevity advantage. Finches & robins live about 3 times as long as rodents the same size. Flying squirrels live twice as long as their close relatives the chipmunks. Parrots have a maximum lifespan in excess of 90 years. The Andean condor may be the most long-lived of any bird, but its maximum lifespan has not been confirmed.

Gross attributes of species typically associated with greater longevity are: large size, ability to yfl, brainy, a spiny or shelled encasement, and cold-blooded. All but the last attribute reduce vulnerability to predators. Porcupines are the longest-lived rodents. Naked mole rats, by living underground, are also safer from predators and live significantly longer than similarly-sized rats. All adaptations that afford protection from predators and other hazards justify greater developmental resources to build a more durable animal with a longer maximum lifespan.Opossums evolving on an island free of predators have been shown to have substantially longer lifespans and smaller litters than opossums living on the nearby mainland [JOURNAL OF ZOOLOGY; 229:695-708 (1993)]. Where competition between individuals of a species for mates & resources is more important than survival against predators and other hazards, evolution causes more investment in making a more hardy & durable animal — which includes having fewer offspring on each birthing (but more total offspring over the lifetime) — with each offspring receiving more care and resources. Gene survival can be better promoted (up to a point) by extending lifespan and reproductive period of reproductively successful adults than by creating many more offspring, a signficant number of whom will not survive to become reproductive adults.

Large size also confers protection against predators and confers an improved ability to escape dangerous environments. Metabolic rate decreases proportionally with increases in body size, which allows larger animals to survive longer when food & water are scarce. [For a sphere, surface area

S = 4πr2 and volume V = (4/3)πr3, which means that S/V varies inversely with r (radius). Because heat is generated in the volume and dissipates in the surface area, relative dissipation decreases with an increase in radius because of the decrease in S/V.] Large animals are better able to withstand extreme temperatures because of greater body mass. Large animals and birds are more easily able to travel long distances to find food or less harsh environments.

Cold-blooded animals needn't expend energy to maintain body temperature and therefore generate fewer free-radicals. Also, the rate of chemical reactions more than doubles for each 10oC increase in temperature. Cold-blooded animals may use one-tenth as much energy as warm-blooded animals of the same body weight. The alligator, Galapagose tortoise and lake sturgeon combine large size with cold-bloodedness. Turtles live longer than other reptiles because of the shell which protects against predators. With the combination of hard shell, large size and cold-bloodedness, it is not surprising that the Galagose turtle is probably the most long-lived vertebrate. Hard shell, cold-bloodedness and the ability to reduce metabolic rate allow some bivalves to live nearly four centuries [GERONTOLOGY; Philipp,EER; 56(1):55-65 (2010)].

A short-lived organism would waste metabolic energy by over-investing in anti-oxidant or DNA-repair enzymes when the energy could be spent on rapid growth and reproduction. When a species has fewer predators, evolution invests fewer resources into speedy reproduction and more genetic resources (DNA repair, etc.) into a longer reproductive period (longer life). In the case of birds, the mitochondrial membranes contain more unsaturated fat making them less vulnerable to lipid peroxidation. And the protein complexes of the respiratory chain of mitochondria generate fewer free radicals in birds than in mammals. It is conceivable that an animal with well-engineered cells could live many centuries. Human germ cells have arguably lived for millions of years through an investment in DNA-repair enzymes, antioxidant enzymes and telomerase.

Evolutionary biologists are able to use artificial selection in the laboratory experimentally (rather than passively studying natural selection in the wild) to seek the evolutionary determinates of longevity. Michael Rose at the University of California has shown that Drosophila(fruit-flies) bred for 15 generations by disposing of eggs laid early in life and only using eggs that were laid toward the end of reproductive life achieved maximum lifespans 30% greater than that of controls. The long-lived strains had increased levels of SOD, CAT and xanthine dehydrogenase as well as increased levels of heat shock proteins conferring stress resistance [JOURNALS OF GERONTOLOGY

55A(11):B552-B559 (2000)]. Hsp22 heat shock protein expression was 2−10 times greater in the long-lived strains as compared to controls. Transgenic Drosophila (ie, fruit flies with artificially altered genes) with extra copies of hsp70 genes live nearly 8% longer than controls following heat treatment [NATURE; Tatar,M; 390:30 (1997)].

Dr. Rose has also observed the experimental increase in mortality associated with aging ceases late in life [PHYSIOLOGICAL AND BIOCHEMICAL ZOOLOGY; Rose;MR; 78(6):869-878 (2005)]. Although mortality rates remain very high in late-life, they plateau. Studies of inbred Drosophila indicate that the plateauing cannot be due to genetic variation. From his evolutionary biology perspective Dr. Rose associates this phenomenon with a late-life end of the force of natural selection. This would imply that senescence is genetically programmed and that studying the genetics of the plateau could be the key to understanding the genetics of longevity.

Xanya Sofra Weiss

AN OVERVIEW OF AGING AND OF AGING THEORIES. Xanya Sofra Weiss

2011-06-09T14:32:00.000-07:00

Many scientists have wondered whether a single cause (probably cellular or hormonal) lies behind all aging phenomena — or whether aging is inherently multi-faceted. Differences in lifespan between species raise critical questions, in this regard. Why is a rodent old at 3 years, a horse old at 35 years and a human old at 80 years? Aren't the cells much the same? Why is it that at age 3 about 30% of rodents have had cancer, whereas at age 85, about 30% of humans have had cancer? Some species (such as lobsters, alligators and sharks) show few signs of aging. Cancer cells, stem cells and human germ cells seem "immortal" when compared to other cells.

When discussing aging it is important to distinguish two points on survival curves. Mean lifespan (average lifespan) corresponds to the age at which the horizontal line for 50% survival intersects the survival curve. Maximum lifespan corresponds to the age at which the survival curves touch the age-axis (0% survival) — and this represents the age at which the oldest known member of the species has died. (In animal studies, maximum lifespan is typically taken to be the mean lifespan of the most long-lived 10%.) Curve A as shown is a pure exponential decay curve. Curve B corresponds to the survival of small animals, such as mice or squirrels in a natural environment. Human survival was still close to curve B in ancient Rome when average lifespan was 22 years, but by the mid−1800s the typical North American lived to be 40 — more like curve C. Today, people in the most developed countries have an average lifespan of about 80 — resembling curve D. Reduction of infant mortality has accounted for most of the increased longevity, but since the 1960s mortality rates among those over 80 years has been decreasing by about 1.5% per year. Maximum lifespan for humans, however, has remained about 115−120 all through known history. The longest documented human lifespan has been for Frenchwoman Jean Calment who lived 122.3 years.

Curing specific diseases such as heart disease or cancer can do no more than further "square" the survival curve (toward curve E), with no effect on maximum lifespan. Curing cancer would add about 2 years to human life, whereas eliminating heart disease would add 3 or 4 years. Mean lifespan varies with susceptibility to disease, accident & homicide/suicide, whereas maximum lifespan is determined by "rate of aging". In aging research, maximum lifespan is regarded as a proxy for aging. Chemicals, calorie restriction with adequate nutrition, or other interventions which increase maximum lifespan are said to have slowed the aging process.

If human beings were free of disease & senescence the only causes of death would be accident, suicide & homicide. Under such conditions it is estimated that from a population of one billion, a 12-year-old would have a median lifespan of 1,200 years and a maximum lifespan of 25,000 years.In 1825 an English actuary named Benjamin Gompertz discovered that likelihood of dying increases exponentially with age after maturity — an empirical observation that has stood the test of time. A 35-year-old is twice as likely to die as a 25-year-old and a 25-year-old is twice as likely to die as a 15-year-old. The exponential increase does not continue past age 80 and death rate may even decline after age 110 [SCIENCE 280:855-860 (1998)]. (Medflies — Mediterranean fruit flies — show a plateau of linear rather than exponential death rate when 20-25% of the population remains). Similarly, the risk of getting Alzheimer's Disease doubles every 5 years past the age of 60 — probably plateauing after age 90 (when over half the population is already demented). Cancer rate increases exponentially with age, but also seems to plateau in the very elderly. One explanation might be that subsets of the population that are considerably more hardy due to genetics or behavior may remain after the more heterogenous majority have died. Another explanation suggests the complete elimination of the forces of natural selection at the oldest ages — which causes subsequent survival to be completely the result of genetic "random drift" [PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA) 93:15249-15253 (1996)]. Causes of death in middle-age tend to be due to diseases affecting high-risk individuals (cancer, diabetes, hypertension, etc.), whereas the elderly are more vulnerable to multiple pathologies due to vulnerability of aging organs &

tissues [JOURNALS OF GERONTOLOGY 58A(6):B495-B507 (2003)].

Attempts to classify theories of aging have led to the two major classifications programmed aging and wear&tear aging. Programmed aging would be aging due to something inside an organism's control mechanisms that forces elderliness & deterioration — similar to the way genes program other life-stages such as cell differentiation during embryological development or sexual maturation at adolescence. By contrast aging due to wear&tear is not the result of any specific controlling program, but is the effect of the sum effect of many kinds of environmental assaults — ie, damage due to radiation, chemical toxins, metal ions, free-radicals, hydrolysis, glycation, disulfide-bond cross- linking, etc. Such damage can affect genes, proteins, cell membranes, enzyme function, blood vessels, etc.

When Pacific salmon have lived in the ocean for 2 or 3 years, they make an arduous upstream journey against a raging riverswim until they find a place suitable for spawning. After spawning, the adrenal gland releases massive amounts of corticosteroids — leading to rapid deterioration. It would be costly for the species to have salmon that could live another year and repeat the journey — or compete with the offspring for food. Although this process is obviously "programmed", it is inaccurate to describe it as "aging". Programmed death, rather than programmed aging, is a common phenomenon among animals that reproduce only once.

Grazing animals show wear-and-tear to their teeth to the point where they can no longer eat, and they die of starvation. Again, it stretches the point to say the teeth are aging. The teeth of rabbits (like human fingernails) continue to grow as wearing occurs — and in this sense are "programmed" to compensate for "wear&tear". Why don't grazing animals have teeth that continue to grow? Human beings can replace tissue, capillaries and bone in wound-healing, yet cannot regrow a severed limb the way a salamander can. Why isn't human DNA "programmed" to re-grow kidney or liver tissue as it ages? Planarians (flatworms) have a pool of stem cells which can replace any of their fully differentiated cells. Programming that compensates for wear & tear should be distinguished from programming that causes deterioration.

Xanya Sofra Weiss

SYMPTOMS OF AGING. Xanya Sofra Weiss

2011-06-09T14:30:00.000-07:00

One can catalog changes that typically occur with age. For people of developed countries age changes include: A loss of hearing ability, particularly for higher frequencies. There is a decline in the ability to taste salt&bitter (sweet&sour are much less affected). There is a reduction of the thymus gland to 5−10% of its original mass by age 50. Levels of antibodies increase with aging. One third of men and half of women over 65 report some form of arthritis. About half of those aged 65 have lost all teeth. The elderly require twice as much insulin to achieve the glucose uptake of the young. There is reduced sensitivity to growth factors & hormones due to fewer receptors and dysfunctional post-receptor pathways. The temperature needed to separate DNA strands increases with age. Weight declines after age 55 due to loss of lean tissue, water and bone (cell mass at age 70 is 36% of what it is at age 25). Body fat increases to age 60. Muscle strength for men declines 30−40% from age 30 to age 80. Reaction time declines 20% from age 20 to 60. Elderly people tend to sleep more lightly, more frequently and for shorter periods — with a reduction in rapid eye-movement (REM) sleep. Neurogenesis in the hippocampus declines with age. Degree of saturation of fats drops by 26% in the brains of old animals. Presbyopia (reduced ability to focus on close-up objects) occurs in 42% of people aged 52−64, 73% of those 65−74 and 92% of those over age 75. Most people over age 75 have cataracts. About half of those over 85 are disabled (defined as the inability to use public transportation). Over 75% of people over 85 have 3−9 pathological conditions, and the cause of death for these people is frequently unknown.
Aging changes are frequently associated with an increase in likelihood of mortality, but this is not necessarily the case. For example, graying of hair is a symptom of aging, but graying does not increase likelihood of mortality. Aging changes which are not associated with a specific disease, but which are associated with a generalized increase in mortality would qualify as biomarkers of aging — and would distinguish biological age from chronological age. Biomarkers would be better predictors of the increased likelihood of mortality (independent of specific disease) than the passage of time (chronological age). Cross-linking of collagen, insulin resistance and lung expiration capacity have been proposed as candidates but, as yet, no biomarkers of aging have been validated and universally accepted.

Xanya Sofra Weiss

Mechanisms of Aging DEFINITION OF AGING. Xanya Sofra Weiss

2011-06-09T14:28:00.000-07:00

DEFINITION OF AGING
Aging is a syndrome of changes that are deleterious, progressive, universal and thus far irreversible. Aging damage occurs to molecules (DNA, proteins, lipids), to cells and to organs. Diseases of old age (diseases which increase in frequency with age, such as arthritis, osteoporosis, heart disease, cancer, Alzheimer's Disease, etc.) are often distinguished from aging per se. But even if the aging process is distinct from the diseases of aging, it is nonetheless true that the damage associated with the aging process increases the probability that diseases of old age will occur.
Some gerontologists prefer to use the word senescence because "aging" implies that the passage of time necessarily results in deterioration (biological entropy) — which is certainly not true during the early, developmental, time of life (before the age of 10 or 12 in humans). I will retain the word "aging" because I believe the association between aging & deterioration is universal as adult years progress and because the distinction between aging & development is very strongly established in conventional language. Also, shorter words make for slightly faster reading.

Xanya Sofra Weiss

Cell communication secrets revealed at SBC. Xanya Sofra Weiss

2011-06-09T14:26:00.000-07:00

A method that cells use to communicate and coordinate activities has been confirmed by researchers from Cornell University, Monsanto Co. and Argonne.

This work could lead to new drugs to fight such diseases as cystic fibrosis and the bubonic plague, or to new technologies that perform useful environmental tasks, such as filtering water.

Biologists have theorized that bacteria communicate by releasing and sensing chemical pheromones to detect their population densities. This activity is termed "quorum sensing."

Using Argonne's

Structural Biology Center (SBC), the researchers confirmed this theory. They determined the molecular structure of a key protein - TraR - in this interbacterial communication

and witnessed how TraR acts as a relay to sense pheromones and then activate genes to create biofilms. A common example of a biofilm is the scum found on ponds.

More than 70 types of organisms are believed to use this molecular "census-taking" process including Yersinia pestis - the bubonic plague bacterium.

"We believe the quorum-sensing process signals bacteria to create biofilms - mats of bacterial cells over a solid surface," said Argonne biophysicist Rong-guang Zhang.

Zhang is lead author of an article describing their results in the June 27 issue of Nature.

"To see how these cells communicate, we crystallized and studied the structure of the TraR protein complexed with pheromone and DNA of the well-known Agrobacterium tumefaciens,

an agricultural pathogen that causes tumors in plants," said Zhang.

Researchers got a microsecond snapshot of quorum sensing in progress.

Knowing the structure of this important quorum-sensing protein may permit researchers to treat bacterial biofilm-related diseases, such as cystic fibrosis, by creating drugs to block the chemical signals that form biofilms.

Conversely, scientists could stimulate the formation of useful biofilms to filter water or perform other useful environmental tasks.

The structural information comes from shining X-rays from the Advanced Photon Source – the nation's most brilliant source of X-rays – onto tiny, frozen protein crystals.

The X-ray images are captured by a quick, electronic camera. Advanced software converts the data into 3-D images biologists use to infer how these proteins work and interact with other molecules.

"The structure," Zhang said, "is the most asymmetrical we have seen for a protein-DNA complex. It is shaped liked a butterfly with its wings bent back."

Pheromones lie fully embedded within the protein. To activate the pheromones, several amino acid residues critical to RNA polymerase activation, or gene copying, make contact with the "butterfly body" of TraR. – Evelyn Brown

Xanya Sofra Weiss

Intercellular Communication. Xanya Sofra Weiss

2011-06-09T14:23:00.000-07:00

Cell-to-cell Communication (Cell Signaling)

“Almost without exception, whenever two or more living cells interact in a specific way, cell surface carbohydrates will be involved.“

- Dr. John Hodgson[1]

Cellular communication is a hot topic in the science industry as there are many links to cell signaling

errors and degenerative and autoimmune diseases.[2] Cell communication (cell signaling) is a new field of study which is supported by very little information. This is rapidly changing, however.

There are different ways in which a cell communicates:

Cell to Cell Contact Proteins Hormones Electrical and Chemical Signals Others...

Cell to Cell Contact

Cells respond to cell-to-cell or extracellular-matrix-cell contact.[3] These interactions are mostly done

through glycoproteins[4] (a protein coated with glyconutrients[5]). Through contact, cells can receive structural and functional signals. Through contact, a skin cell, for example, “knows” that it’s on the surface of your body and not inside, like a heart cell. Through contact, cells can even instruct cells to

undergo apoptosis.[3]

Proteins

Proteins are secreted from a cell, travel a short distance to a a neighboring cell where they are recognized and interpreted. These signals can tell one cell to become a skin cell and a nearby cell to

become a hair cell.[6]Hormones

Hormones are considered long range signals. These are created by the endocrine system, put in the

blood stream and distributed to the necessary organs.[6][7] Hormones are responsible for development, sexual development in puberty, sexual appetite, sleep, and just about every major function in your body. There exist long range proteins that are sometimes thought of as hormones, insulin is a good

example.[8]

Electrical and Chemical Signals

Electrical and chemical signals are responsible for communicating very complex messages between neurons or between neurons and muscles cells.[9] The point of contact between two cells, called synapses,[10] is where electrical signals are converted into a chemical signal and then back into an electrical signal in the other cell.[11] These signals are very interesting and may be responsible for learning, memory[12] and ultimately consciousness.

Xanya Sofra Weiss

Elaine Fuchs Honored with Albany Medical Center Prize. Xanya Sofra Weiss

2011-06-09T14:21:00.000-07:00

Howard Hughes Medical Institute investigator Elaine Fuchs is one of three scientists who have been awarded the 2011 Albany Medical Center Prize in Medicine and Biomedical Research. Fuchs, James A.

Thomson of the University of Wisconsin-Madison, and Shinya Yamanaka of Kyoto University, were honored for pioneering work in isolating human stem cells.

The Albany Prize, which is awarded annually, recognizes extraordinary and sustained contributions to improving health care and promoting biomedical research with translational benefits applied to improved patient care. Fuchs,

Thomson, and Yamanaka are being recognized for work that has moved scientists closer to realizing the regenerative and potentially healing properties of stem cells, as well as helping illuminate how human tissues develop and function.

The scientists will receive the prize on May 13 during a celebration in Albany, New York. The $500,000 prize is the largest award in medicine and science in the United States.

The science of stem cell research focuses on the earliest stage of cellular development. These remarkable cells have the ability to become any tissue in the body and to reproduce indefinitely.

Researchers hope to harness the power of these cells to one day repair or replace damaged tissue in patients, possibly building new spinal cords or growing new limbs.

Fuchs, whose lab is at Rockefeller University, studies skin and hair—two distinct structures that develop from the same skin stem cell. To use stem cells therapeutically, she says,

it is essential to first understand how the cells function on the molecular level. By unraveling the biology of skin stem cells, she hopes to answer a question that has intrigued her for more than two decades:

How does a skin stem cell decide to become skin or hair?

Understanding skin stem cells' normal behavior is also helping Fuchs learn what happens when their growth goes awry. Her studies have already uncovered the genetic basis of blistering skin diseases and clues to the way skin cancers and inflammatory skin disorders develop.

Her research may also hold clues for deciphering the extraordinary characteristics that enable stem cells to develop into distinct tissues and organs. "While there is much promise for stem cells in revolutionizing medicine, we must first learn more about stem cells before we can know whether this might be possible," she contends.

Unlike most other adult stem cells, skin stem cells can be easily grown in the laboratory. Fuchs's research has shown that multiple signaling pathways, including the Wnt and BMP pathways,

influence how stem cells are coaxed to develop into hair follicles. Together, positive Wnt signals and antagonistic BMP signals lead to activation of transcription factors, which induce the formation of a hair follicle bud.

In the absence of these signals, stem cells develop into skin epidermis. This line of research may eventually lead to new ways to restore or inhibit hair growth.

By exploring how the stem cell reservoir (niche) forms and how stem cells are activated to proliferate and differentiate, Fuchs's work is having an impact on understanding how defective stem cells can cause cancers.

Fuchs is the recipient of numerous prizes and awards, including the National Medal of Science (2009), the FASEB Excellence in Science Award (2006), the Dickson Prize in Medicine (2004) from the University of Pittsburgh,

and the Lounsbery Award (2001) from the National Academy of Sciences. She is a member of the Institute of Medicine, the National Academy of Sciences, the American Philosophical Society, and the American Academy of Arts and Sciences.

Xanya Sofra Weiss

G Protein Coupling and Signaling Pathway Activation by M1 Muscarinic Acetylcholine Receptor Orthosteric and Allosteric Agonists. Xanya Sofra Weiss

2011-06-09T14:19:00.000-07:00

Rachel L. Thomas, Rajendra Mistry, Christopher J. Langmead, Martyn D. Wood, and R. A. John Challiss

The M1 muscarinic acetylcholine (mACh) receptor is among a growing number of G protein-coupled receptors that are able to activate multiple signaling cascades.

AC-42 (4-n-butyl-1-[4-(2- methylphenyl)-4-oxo-1-butyl] piperidine) is an allosteric agonist that can selectively activate the M1 mACh receptor in the ab- sence of an orthosteric ligand.

Allosteric agonists have the potential to stabilize unique receptor conformations, which may in turn cause differential activation of signal transduction path- ways. In the present study,

we have investigated the signaling pathways activated by AC-42, its analog 77-LH-28-1 (1-[3-(4- butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone),

and a range of orthosteric muscarinic agonists [oxotremorine-M (oxo-M), arecoline, and pilocarpine] in Chinese hamster ovary cells recombinantly expressing the human M1 mACh receptor.

Each agonist was able to activate G��q/11-dependent signaling, as demonstrated by an increase in guanosine 5��-O-(3-thio-triphosphate) ([35S]GTP��S) binding to G��q/11 proteins and total [3H]inositol phosphate accumulation assays in intact cells.

All three orthosteric agonists caused significant enhancements in [35S]GTP��S binding to G��i1/2 subunits over basal; however, neither allosteric ligand produced a significant response.

In contrast, both orthosteric and allosteric agonists are able to couple to the G��s/cAMP pathway, enhancing forskolin-stimu- lated cAMP accumulation.

These data provide support for the concept that allosteric and orthosteric mACh receptor agonists both stabilize receptor conformations associated with G��q/11- and G��s-dependent signaling; however,

AC-42 and 77-LH- 28-1, unlike oxo-M, arecoline, and pilocarpine, do not seem to promote M1 mACh receptor-G��i1/2 coupling, suggesting that allosteric agonists have the potential to activate distinct sub- sets of downstream effectors.

Xanya Sofra Weiss

Electrical cues regulate the orientation and frequency of cell division and the rate of wound healing in vivo. Xanya Sofra Weiss

2011-06-06T14:47:00.000-07:00

Controlling cell division is fundamental. One environmental cue that exerts profound control over both the orientation and fre- quency of cell division in vivo is a naturally occurring, wound- induced electric field (EF). Wounds in rat corneas generate endog- enous EFs in the plane of the epithelial sheet because the transcorneal potential difference (TCPD; ��40 mV internally posi- tive) collapses at the wound edge, but is maintained at normal levels at 0.5 mm back from the wound. We manipulated the endogenous EF this creates by using drugs with differing actions. The wound-induced EF controlled the orientation of cell division; most epithelial cells divided with a cleavage plane parallel to the wound edge and perpendicular to the EF vector. Increasing or decreasing the EF pharmacologically, respectively increased or decreased the extent of oriented cell division. In addition, cells closest to the wound edge, where the EF was highest, were oriented most strongly by the EF. Remarkably, an endogenous EF also enhanced the frequency of cell division. This also was regu- lated by enhancing or suppressing the EF pharmacologically. Be- cause the endogenous EF also regulated the wound healing rate, it may act as one control of the interplay between cell migration and cell division during healing.

Xanya Sofra Weiss

Music of the Spheres. Xanya Sofra Weiss

2011-06-06T14:43:00.000-07:00

Notes in music are related to each other by specific ratios.
These ratios determine the 'space' between each tone, and in turn define the notes.
Although to the human ear the notes sound as if they are equally spaced,
the following chart shows that in fact the ratios are more complex.
Several years ago, astronomer Gerald S. Hawkins, former Chairman of the astronomy department at Boston University, noticed that some of the most visually striking of the crop-circle patterns embodied geometric theorems that express specific numerical relationships among the areas of various circles, triangles, and other shapes making up the patterns (Science News: 2/1/92, p. 76). In one case, for example, an equilateral triangle fitted snugly between an outer and an inner circle. It turns out that the area of the outer circle is precisely four times that of the inner circle.
Three other patterns also displayed exact numerical relationships, all of them involving a diatonic ratio, the simple whole-number ratios that determine a scale of musical notes. "These designs demonstrate the remarkable mathematical ability of their creators," Hawkins comments.
Hawkins found that he could use the principles of Euclidean geometry to prove four theorems derived from the relationships among the areas depicted in crop circles. He also discovered a fifth, more general theorem, from which he could derive the other four (see recent work, here). "This theorem involves concentric circles which touch the sides of a triangle, and as the [triangle] changes shape, it generates the special crop-circle geometries," he says.
Hawkins' fifth crop-circle theorem involves a triangle and various concentric circles touching the triangle's sides and corners. Different triangles give different sets of circles. An equilateral triangle produces one of the observed crop-circle patterns; three isoceles triangles generate the other crop- circle geometries.
What is most surprising is that all geometries give diatonic (musical) ratios. Never before (to my knowledge) have geometric theorems been linked with music.
Curiously, Hawkins could find no reference to such a theorem in the works of Euclid or in any other book that he consulted. When he challenged readers of Science News and The Mathematics Teacher to come up with his unpublished theorem, given only the four variations, no one reported success.
In July 1995, however, "the crop-circle makers . . . showed knowledge of this fifth theorem," Hawkins reports. Among the dozens of circles surreptitiously laid down in the wheat fields of England, one pattern fit Hawkins' theorem based on the stringent definitions, on the rules established by the circles over the period 1980 to the present.

Xanya Sofra Weiss

The evolution of cell communication: The Road not Taken. Xanya Sofra Weiss

2011-06-06T14:32:00.000-07:00

In the post-genomic era the complex problem of evolutionary biology can be tackled from the top-down, the bottom-up, or from the middle-out. Given the emergent and contingent nature of this process, we have chosen to take the latter approach, both as a mechanistic link to developmental biology and as a rational means of identifying signaling mechanisms based on their functional genomic significance. Using this approach, we have been able to configure a working model for lung evolution by reverse-engineering lung surfactant from the mammalian lung to the swim bladder of fish. Based on this archetypal cell-molecular model, we have reduced evolutionary biology to cell communication, starting with unicellular organisms communicating with the environment, followed by cell-cell communication to generate metazoa, culminating in the communication of genetic information between generations, i.e. reproduction. This model predicts the evolution of physiologic systems-including development, homeostasis, disease, regeneration/ repair, and aging- as a logical consequence of biology reducing entropy. This approach provides a novel and robust way of formulating refutable, testable hypotheses to determine the ultimate origins and first principles of physiology, providing candidate genes for phenotypes hypothesized to have mediated evolutionary changes in structure and/or function. Ultimately, it will form the basis for predictive medicine and molecular bioethics, rather than merely showing associations between genes and pathology, which is an unequivocal Just So Story. In this new age of genomics, our reach must exceed our grasp.

Xanya Sofra Weiss

Effects of extremely-low-frequency pulsed electromagnetic fields on collagen synthesis in rat skin. Xanya Sofra Weiss

2011-06-06T14:30:00.000-07:00

To investigate the effects of extremely-low-frequency PEMFs (pulsed electromagnetic fields) on the synthesis of epidermal collagen, six groups of animals each consisting of eight mature male rats were selected randomly: one group for the control and five for the test. Using a parallel set of Helmholtz coils, a uniform field intensity of 2 mT at different frequencies of 25, 50 and 100 Hz yielded the most effective frequency to be 25 Hz. Then, at this frequency, two different field intensities of 1 and 4 mT were applied. The treatment time of 2.5 h/day lasted for 8 days, keeping the same procedure for the control group, except with the field turned off. On the ninth day, the rats were killed and skin samples from the dorsal region were taken for collagen assessment by measuring hydroxyproline content using the Stegemann–Stalder [(1967) Clin. Chim. Acta 8, 267–273] method. The results indicated that a PEMF of 2 mT at 25 Hz increased the collagen synthesis (P<0.05). The other intensities and frequency setting did not have any noticeable effect; however, at a frequency of 25 Hz at 4 mT, collagen increase was also noticed. It was concluded that at 25 Hz under a field setting of 2 mT for the duration of 8 days, stimulation of skin at 2.5 h/day would cause increase in collagen synthesis in rat skin.

Xanya Sofra Weiss

Effects of extremely-low-frequency pulsed electromagnetic fields on collagen synthesis in rat skin. Xanya Sofra Weiss

2011-06-06T14:28:00.000-07:00

To investigate the effects of extremely-low-frequency PEMFs (pulsed electromagnetic fields) on the synthesis of epidermal collagen, six groups of animals each consisting of eight mature male rats were selected randomly: one group for the control and five for the test. Using a parallel set of Helmholtz coils, a uniform field intensity of 2 mT at different frequencies of 25, 50 and 100 Hz yielded the most effective frequency to be 25 Hz. Then, at this frequency, two different field intensities of 1 and 4 mT were applied. The treatment time of 2.5 h/day lasted for 8 days, keeping the same procedure for the control group, except with the field turned off. On the ninth day, the rats were killed and skin samples from the dorsal region were taken for collagen assessment by measuring hydroxyproline content using the Stegemann- Stalder [(1967) Clin. Chim. Acta 8, 267-273] method. The results indicated that a PEMF of 2 mT at 25 Hz increased the collagen synthesis (P < 0.05). The other intensities and frequency setting did not have any noticeable effect; however, at a frequency of 25 Hz at 4 mT, collagen increase was also noticed. It was concluded that at 25 Hz under a field setting of 2 mT for the duration of 8 days, stimulation of skin at 2.5 h/day would cause increase in collagen synthesis in rat skin.

Xanya Sofra Weiss

DNA-Protein Complex Crucial To Spread Of Antibiotic Resistance Among Bacteria Solved. Xanya Sofra Weiss

2011-06-06T14:25:00.000-07:00

Researchers have solved the structure of a DNA-protein complex that is crucial in the spread of antibiotic resistance among bacteria. Knowing this structure also provides fundamental insight into how cells successfully divide into two new cells with intact DNA.

Xanya Sofra Weiss

Cytological effects of 60 Hz magnetic fields on human lymphocytes in vitro: sister-chromatid exchanges, cell kin and mitotic rate. Xanya Sofra Weiss

2011-06-06T14:23:00.000-07:00

Incubation for 72 h of human peripheral blood cultures in the presence of 60 Hz sinusoidal magnetic fields (MF) magnetic flux densities of 1.0, 1.5, and 2.0 mT led to stimulation of lymphocyte proliferation but had no influence frequency of sister-chromatid exchanges (SCE). The cytotoxic potential of MF combined with the mutagen Mito also was analyzed. An opposite effect between MF exposure and Mitomycin-C treatment in terms of cell kinetics mitotic rate was found, whereas no variation in SCE frequency was observed for this coexposure condition.

Xanya Sofra Weiss

Cell Signalling Pathways. Xanya Sofra Weiss

2011-06-06T14:19:00.000-07:00

Cells use a large number of clearly defined signalling pathways to regulate their activity. In this module, attention is focused on the ON mechanisms responsible for transmitting information into the cell. These signalling pathways fall into two main groups depending on how they are activated. Most of them are activated by external stimuli and function to transfer information from the cell surface to internal effector systems. However, some of the signalling systems respond to information generated from within the cell, usually in the form of metabolic messengers. For all of these signalling pathways, information is conveyed either through protein–protein interactions or it is transmitted by diffusible elements usually referred to as second messengers. Cells often employ a number of these signalling pathways, and cross-talk between them is an important feature. In this section, attention is focused on the
properties of the major intracellular signalling pathways operating in cells to regulate their cellular activity.
During the processes of development, specific cell types select out those signalling systems that are suitable to control their particular functions. One of the aims of this website is to understand how these unique cell-specific signalsomes function to regulate different mammalian cell types.

Xanya Sofra Weiss

Phosphorylation meets nuclear import: a review. Xanya Sofra Weiss

2011-06-06T14:18:00.000-07:00

Phosphorylation is the most common and pleiotropic modification in biology, which plays a vital role in regulating and finely tuning a multitude of biological pathways. Transport across the nuclear envelope is also an essential cellular function and is intimately linked to many degeneration processes that lead to disease. It is therefore not surprising that phosphorylation of cargos trafficking between the cytoplasm and nucleus is emerging as an important step to regulate nuclear availability, which directly affects gene expression, cell growth and proliferation. However, the literature on phosphorylation of nucleocytoplasmic trafficking cargos is often confusing. Phosphorylation, and its mirror process dephosphorylation, has been shown to have opposite and often contradictory effects on the ability of cargos to be transported across the nuclear envelope. Without a clear connection between attachment of a phosphate moiety and biological response, it is difficult to fully understand and predict how phosphorylation regulates nucleocytoplasmic trafficking. In this review, we will recapitulate clue findings in the field and provide some general rules on how reversible phosphorylation can affect the nuclear-cytoplasmic localization of substrates. This is only now beginning to emerge as a key regulatory step in biology.

Xanya Sofra Weiss

Nuclear Shp-2 keeps telomerase reverse transcriptase in the nucleus – new potential anti-aging target

2011-06-06T14:15:00.000-07:00

Vascular diseases are associated with cellular aging, which is accompanied by telomere shortening counteracted in the nucleus by telomerase reverse transcriptase (TERT). Under conditions of oxidative stress TERT is exported from the nucleus and this export is mediated by Src-kinases via tyrosine phosphorylation of TERT. Nuclear export of TERT resulted in accelerated aging of endothelial cells. Therefore, the aim of this study was to determine a counterplayer for nuclear export of TERT.
In embryonic fibroblasts deficient in Src, Fyn and Yes, TERT nuclear export induced by oxidative stress is abolished. Fyn does not seem to play a role, because unlike Src and Yes it is not found in the nucleus. A putative regulator of this export is the tyrosine phosphatase Shp-2, which can regulate the activity of the Src-kinase family. We demonstrated that Shp-2 is localized in the nucleus and associated with TERT in endothelial cells. Overexpression of Shp-2 inhibited oxidative stress induced nuclear export of TERT and ablation of Shp-2 by siRNA reduced nuclear telomerase activity. This inhibition was dependent on the enzymatic activity of Shp-2 and on tyrosine 707 in TERT because overexpression of the dominant negative Shp-2 mutant (C459S) led to a reduction of TERT protein and telomerase activity, whereas telomerase activity in TERTY707F overexpressing cells was not altered by Shp-2. Thus, tyrosine 707 seems to be a critical target for regulation of TERT localization by Shp-2 mediated dephosphorylation. To establish a causal link between Shp-2, nuclear TERT and oxidative stress, we determined reactive oxygen species (ROS) formation in endothelial cells. Overexpression of Shp-2(C459S) (2.45 fold +/- 0.34 of Shp-2 wt) or ablation of Shp-2 by siRNA increased ROS levels (2.23 fold +/- 0.54 of scrambled siRNA). In contrast, keeping TERT in the nucleus by mutating tyrosine 707 or overexpressing Shp-2 wt reduced ROS formation (0.73 and 0.75 fold, respectively).
In summary, these data indicate that TERT is associated with nuclear Shp-2, Shp-2 acts as a negative regulator for nuclear export of TERT probably via regulating tyrosine 707 dephosphorylation of TERT and reducing ROS formation.
Thus, increasing nuclear Shp-2 activity could be a useful tool to delay vascular aging processes.

Xanya Sofra Weiss

Causal Protein-Signaling Networks Derived from Multiparame Single-Cell Data. Xanya Sofra Weiss

2011-06-06T14:13:00.000-07:00

Machine learning was applied for the automated derivation of causal influences in cellular networks. This derivation relied on the simultaneous measurement of multiple phosphoryl protein and phospholipid components in thousands of individual primary human immune cells. Perturbing these cells with molecular interventions drove the ordering of connection between pathway components, wherein Bayesian network computational methods automat elucidated most of the traditionally reported signaling relationships and predicted novel interpathway network causalities, which we verified experimentally. Reconstruction of netw models from physiologically relevant primary single cells might be applied to understandi native-state tissue signaling biology, complex drug actions, and dysfunctional signaling in diseased cells.

Xanya Sofra Weiss

Attenuation of age-related declines in glucagon-mediated signal transduction in rat liver by exercise training. Xanya Sofra Weiss

2011-06-06T14:11:00.000-07:00

This study investigated alterations in glucagon receptor-mediated signal transduction in rat livers from 7- to 25-mo-old animals and examined the effects of exercise training on ameliorating these changes. Sixty-six young (4 mo), middle-aged (12 mo), and old (22 mo) male Fischer 344 rats were divided into sedentary and trained (treadmill running) groups. Isolated hepatic membranes were combined with [ I-Tyr ]monoiodoglucagon and nine concentrations of glucagon to determine maximal binding capacity (B ) and dissociation constant (K d). No alterations were found in B among groups; however, middle-aged trained animals had significantly higher glucagon affinity (lowerK d; 21.1 ± 1.8 nM) than did their untrained counterparts (50.2 ± 7.1 nM). Second messenger studies were performed by measuring adenylyl cyclase (AC) specific activity under basal conditions and with four pharmacological stimulations to assess changes in receptor-dependent, G protein- dependent, and AC catalyst-dependent cAMP production. Age-related declines were observed in the old animals under all five conditions. Training resulted in increased cAMP production in the old animals when AC was directly stimulated by forskolin. Stimulatory G protein (Gs) content was reduced with age in the sedentary group; however, training offset this decline. We conclude that age-related declines in glucagon signaling capacity and responsiveness may be attributed, in part, to declines in intrinsic AC activity and changes in G protein [inhibitory G protein (Gi)/Gs] ratios. These age-related changes occur in the absence of alterations in glucagon receptor content and appear to involve both G protein- and AC-related changes. Endurance training was able to significantly offset these declines through restoration of the Gi/Gs ratio and AC activity.

Xanya Sofra Weiss

Synthesis and anti-bacterial, anti-fungal activity of some novel chalcone derivatives. Xanya Sofra Weiss

2011-06-06T14:07:00.000-07:00

S.S.Turkar, A.H. Rodge, G.D.Hatnapure, A.P.Keche, G.S.Gaikwad

Department of Chemistry, J.L.Charturvedi College of Engineering, Nagpur- India

Chalcone have displayed an impressive array of biological importance.
A new series of chalcone have been synthesized by reacting 1-(4-isobutylphenyl) ethanone with different substituted aldehyde in turn clasien-schimidt condensation.
All synthesized compounds have been evaluated for anti-bacterial and anti-fungal studies.
Compound 11 showed promising anti-bacterial activities against staphylococcus aureus having MIC50 value of 2.10ug/ml and compound 2 also showed good anti-fungal activity against Candida krusei having MIC50 value of 2.12ug/ml.

Xanya Sofra Weiss

Age-related enhancement of a protein synthesis-depende induced by low frequency paired-pulse stimulation. Xanya Sofra Weiss

2011-06-06T14:06:00.001-07:00

Protein synthesis-dependent late phase of LTP (L-LTP) is typically induced by repeated high-frequency stimulation (H and is positively correlated with age-related memory loss.Here we report a novel form of protein synthesis-dependen induced by a brief 1-Hz paired-pulse stimulation (PP-1 Hz, 1 min). In contrast to L-LTP induced by HFS, the late animals. Rather, it emerges and becomes enhanced in an age-related way. Thus, in 1.5- to 2-mo-old mice, a brief decaying to baseline in about 90 min. By contrast, PP-1 Hz stimulation induces an enduring and protein synthesis Hz-induced L-LTP is dependent on NMDA receptor activation, requires voltage-dependent calcium channels, and i memory ability declines with aging, the age-related enhancement of L-LTP induced by PP-1 Hz stimulation indic correlated with memory ability.

Xanya Sofra Weiss

Bioimpedance Neuronal Microstimulation. Xanya Sofra Weis

2011-03-27T01:49:00.000-07:00

Bioimpendance Neuronal Micro-stimulation (BNM) was engineered to treat sports injury and muscle atrophy, as well as promote lipolysis and muscle hypertrophy. A clinical study with individuals presenting abnormally clumped RBCs was completed in February 2009 with the Ion Magnum. Results indicate that this technology rapidly and efficiently leads to normalized erythrocytes’ separation at the microscopic level. Red Blood Cells’(RBCs) separation is crucial for the timely transport of hormones,antibodies, oxygen and nutrients to the cells and waste products to the kidneys. Therefore, blood separation is crucial in a number of biological processes including cellular cleansing, nourishment and oxygenation, endocrine and immune functioning. Ion Magnum’s (IM) dynamic, multi-sine, analogue waveform was originally tested at the cellular level by Dr. Donald Gilbert (1992), a molecular biologist, and was electronically composed by the Co-Inventor of the first Pacemaker (2008) to resonate at the motor nerve the signal of strenuous exercise normally emitted by the brain. Due to its resonance with the biological signal, the Ion Magnum signal spreads throughout the CNS ultimately triggering hormonal secretion such as Growth Hormone (GF), Thyroxine (T4) and Triiodothyronine (T3) for lipolysis and Insulin Growth Factor (IGF-1) for muscle hypertrophy. Power detox is an additional benefit of Ion Magnum’s induced effortless and painless isometric and isotonic muscle contractions. Sever al devices stimulate the muscles such asTENS Muscle Stimulators. However, TENS devices deplete ATP. Besides, muscle stimulation does not automatically release hormones. Neuronal synapses activated out of sync with the other inputs to the neuron stands out as odd and are eliminated. Neuronal synapses that are activated in sync with other inputs to the neuron are strengthened. The signal of a device must be in sync with the biological choreography in order to spread via the spinal cord and reach the brain. In sync, or resonance, has been touted by a number of approximate hit-ormiss techniques involving magnetic and electrical fields with dubious inconsistent results. But no technology has ever achieved nerve signaling that is biologically comparable to physical exercise. What the Co-Inventor of the first Pacemaker has accomplished, first in London University and then in the EU funded Research Center for Innovations Science, UK, is a full force, high-speed workout without actual movement, side effects or pain, that enhances hormonal secretion. Lipolysis and muscle hypertrophy following IM treatments has been reported by a number single subject design clinical studies.

Healthy Blood Vessels May Prevent Fat Growth. Xanya Sofra Weiss

2011-03-27T01:47:00.000-07:00

ScienceDaily (Sep. 23, 2008) — The cells lining blood vessels are known to be important for maintaining health, but researchers at the Indiana University School of Medicine believe these cells may perform an unsuspected task – controlling the development of fat cells.

Their findings are reported in the September issue of the journal Stem Cells.

The researchers found that precursor or stem cells have a markedly reduced tendency to develop into fat cells when placed in direct contact with healthy endothelial cells, which are the cells that line blood vessels.

"The key to this discovery was our recent observation that these cells, also known as adipose stromal cells, in fat tissue are in very close contact with endothelial cells in small blood vessels and capillaries," said Keith L. March, M.D., Ph.D., co-principal investigator of the study and director of the Indiana Center for Vascular Biology and Medicine (ICVBM).

"Once we had recognized this link between endothelial and stromal cells, it was a logical step to ask how these cells can influence each other," said Dr. March, who also is a professor of medicine, physiology and biomedical engineering at the IU School of Medicine and Krannert Institute of Cardiology.

Dr. March and his colleagues are researching uses for one of nature's building blocks, adipose stem cells, which they harvest from fat tissues. Their research looks at ways to treat vascular disease, including the use of adipose stem cells to grow new vessels as a treatment for peripheral artery disease.

When the adipose stem cells were mixed with endothelial cells, they were less likely to develop into fat cells, said Gangaraju Rajashekhar, Ph.D., lead author of the journal article and a research associate at the Indiana Center for Vascular Biology and Medicine.

What we discovered was that endothelial cells released proteins – including Wnt proteins to be precise – that play a significant role in blocking fat cell development. Wnt proteins regulate development and differentiation in many tissues and may even play a role in aging," said Dr. Rajashekhar.

The researchers cautioned that more studies are needed to determine whether repair of unhealthy endothelial cells also can help to control fat growth.

"We know now that endothelial cells in blood vessels cells help tell adipose stem cells what to do," said Matthias Clauss, Ph.D., an ICVBM co-principal investigator of the study and an associate professor for cellular and integrative physiology at the IU School of Medicine.

"What we don't know yet is how the formation of fat cells influences the blood vessel lining cells. Our current hypothesis is that endothelial dysfunction promotes fat cell development, accompanied by new blood vessel growth. We hope to soon be able to interrupt this cycle," said Dr. Clauss.

This research may result in new options for treatment of cardiovascular diseases and also could provide physicians with another weapon in the war on obesity.

Xanya Sofra Weiss

Using Quantum Medicine to Unravel Stressors That Provoke Carcinogenesis. Xanya Sofra Weiss

2011-03-27T01:46:00.001-07:00

Quantum physics when applied to the study of biological processes is known as biophysics. Biophysics studies the living cell as a whole system with electrical fields that interrelate and penetrate the entire organism.1 Carcinogenesis occurs when healthy bioelectrical fields are transformed. Quantum Medicine applies quantum physics theories to unravel the stressors that cause disruptions within bioelectrical fields.

Xanya Sofra Weiss

Human Adipose Tissue Blood Flow and Micromanipulation of Human Subcutaneous Blood Flow. Xanya Sofra Weiss

2011-03-27T01:45:00.001-07:00

Regulation of blood flow in tissues such as skeletal muscle, liver, and adipose tissue is needed to meet the changing local metabolic and physiological demands under varying conditions. In healthy individuals, adipose tissue blood flow (ATBF) is remarkably responsive to meal ingestion, but changes in ATBF in response to other physiological stimuli, such as stress and physical exercise, have also been noted. The ATBF response to nutrient intake may be of particular importance in the regulation of metabolism by facilitating transport of nutrients as well as signaling between adipose tissue and other metabolically active tissues. A reduction in both fasting and postprandial ATBF has been observed in obesity; this impairment is associated with insulin resistance. A better understanding of the physiological basis for (nutritional) regulation of ATBF may therefore give insight to the relationship between disturbances in ATBF and the metabolic disturbances observed in response to insulin resistance. In this chapter, we describe some different approaches to quantify human ATBF, with a particular emphasis on the ¹³³xenon wash-out technique and a method by which regulatory properties of subcutaneous ATBF can be studied by pharmacological micromanipulation (microinfusion).

Xanya Sofra Weiss

Xanya Sofra Weiss

Diabetic Peripheral Neuropathy. Xanya Sofra Weiss

2011-03-27T01:43:00.001-07:00

O B J E C T I V E— To evaluate the efficacy of combining electrotherapy with amitriptyline for the management of chronic painful peripheral neuropathy in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS— Patients (n = 26) with peripheral neuro p athy were treated with amitriptyline. After 4 weeks, those patients (n = 23) who failed to re s p o n d to amitriptyline or who only had partial relief were randomized between a sham tre a t m e n t g roup (control) or an electrotherapy group. Transcutaneous electrotherapy was given for 12 weeks by a portable unit (H-wave machine) that generated a biphasic exponentially decaying w a v e f o rm (pulse width 4 ms, 25–35 V, 2 Hz). The degree of pain and discomfort was graded on a scale of 0–5. An analog scale was used to re c o rd the overall change in symptoms.
R E S U LT S— Amitriptyline produced some degree of symptomatic relief in 15 (60%) of the 26 patients by the 4th week; pain scores decreased from 3.8 ± 0.1 to 2.9 ± 0.2 (P 0.1) and the overall reduction in pain was 26 ± 5% on an analog scale. In the amitriptyline plus sham treatment group (n = 9), pain scores declined from 2.8 ± 0.3 to 1.9 ± 0.5 (P 0.03) and the overall reduction in pain was 55 ± 12%, suggesting a pro c e d u re - related placebo effect. In the group receiving combined electrotherapy and amitriptyline (n = 14), symptomatic impro v ement occurred in 12 (85%) patients. Five (36%) of the patients in this group became asymptomatic. Pain scores declined from 3.2 ± 0.2 to 1.4 ± 0.4 (P 0.01) and the overall re d u c t i o n in pain was 66 ± 10%. The degree of reduction in pain scores and the incremental relief (above the amitriptyline effect) were significantly greater (P 0.03) with electrotherapy as compare d with sham treatment. The outcomes indicate a substantial beneficial effect of electro t h e r a p y over and above any placebo influ e n c e . C O N C L U S I O N S— Our clinical observations suggest that transcutaneous electrotherapy is effective in reducing the pain associated with peripheral neuro p a t h y. This form of therapy may be a useful adjunctive modality when it is combined with a pharmacological agent, such as amitriptyline, to augment symptomatic re l i e f .

Xanya Sofra Weiss

Changes in Skeletal Muscle Size and Glucose Tolerance With Electrically Stimulated Resistance Training in Subjects With Chronic Spinal Cord Injury

2011-03-27T01:41:00.001-07:00

Abstract: Mahoney ET, Bickel CS, Elder C, Black C, Slade JM, Apple Jr D, Dudley GA.
Changes in skeletal muscle size and glucose tolerance with electrically stimulated
resistance training in subjects with chronic spinal cord injury.
Objective: To determine the effect of residence-based, resistance exercise training (RET) on affected skeletal muscle size and glucose tolerance after long-standing, complete spinal cord injury (SCI).
Design: Before-after trial.
Setting: University laboratory trial.
Participants: Five men with chronic, complete SCI (C5-T9).
Intervention: Magnetic resonance images of the thighs and an oral glucose tolerance test were performed before and after RET. Subjects performed RET with both thighs, 2d/wk Abstract Article Figures/Tables References Calorie restriction initiated at middle age improved gl... Experimental Gerontology MECHANISMS OF THROMBOSIS IN SPINAL CORD INJURY Hematology/Oncology Clinics of North America Index Exercise Physiology in Special Populations Cardiovascular Health and Fitness in Persons with Spina... Physical Medicine and Rehabilitation Clinics of North A... Poster 26 assessment of plantarflexor muscle size using... Archives of Physical Medicine and Rehabilitation
Home Browse Search My Settings Alerts Help About ScienceDirect | Contact Us | Information for Advertisers | Terms & Conditions | Privacy Policy Copyright © 2010 Elsevier B.V. All rights reserved. ScienceDirect® is a registered trademark of Elsevier B.V. for 4 sets of 10 unilateral, dynamic knee extensions for 12 weeks. Neuromuscular electric stimulation induced RET by activating the knee extensors.
Main Outcome Measures: Quadriceps femoris muscle cross-sectional area (CSA), plasma glucose, and insulin concentrations were measured before and after RET.
Results: Skeletal muscle CSA increased by 35% in the right quadriceps femoris (from
32.6cm2 to 44.0cm2) and by 39% in the left quadriceps femoris (from 34.6cm2 to
47.9cm2) as a result of training (P<.05). There were no significant changes in blood glucose or insulin after training. However, a trend for a reduction in plasma glucose levels was observed (P=.074).

Xanya Sofra Weiss

A STUDY TO DETECT THE EFFICACY OF MICRO-CURRENT THERAPY ON PESSURE ULCERS. Xanya Sofra Weiss

2011-03-27T01:39:00.000-07:00

M. O. Ullah; 2007

Pressure ulcers (PU) are common international afflictions that occur in many different
healthcare settings. The aim of this prospective, randomized, multi-center study was to determine the
effectiveness of micro-current (MCT) therapy on patients with four chronic stages under The National
Pressure Ulcer Advisory Panel (NPUAP). PU on 60 male and female patients enrolled from 6 hospitals.
The analysis reveals that MCT has a significant effect on wound healing. Data analysis also reveals that
wounds of female patients are healed significantly faster than those of male patients and that age
significantly influenced wound healing.

Xanya Sofra Weiss

Live Blood Analysis. Xanya Sofra Weiss

2011-03-15T06:56:00.000-07:00

Through a live blood analysis, you can see the life gifting element of your body come alive - your blood. After your health practioner takes one small drop of blood and places it on the slide, you observe as your blood reveals nutritional deficiencies, hormonal imbalances, yeast overgrowths, digestive problems, metal toxicity, liver stress, bacteria and parasite levels. The mysteries of your health become revealed and through the 45 minute assessment provided from your practitioner, you learn how to clean your blood and become an active participant in correcting any areas of concern. In partnership with your practitioner, you establish a proactive nutritional plan that will put you back in control of your own health

Xanya Sofra Weiss

Carpal Tunnel Supplements. Xanya Sofra Weiss

2011-03-15T06:50:00.000-07:00

Just inside your wrist is a narrow, bony passage called the carpal
tunnel. Anything but empty, this tunnel contains nine tendons as well
as a nerve called the median nerve, all of which are encased,
sausage-like, in a slippery sheath called the synovium. When the
synovium and tendons become inflamed and swollen, they squeeze the
median nerve, which runs to the fingers.

Ever watch a live
electrical wire rub metal? The pinched median nerve can send angry
sparks of pain, numbness and tingling from your fingertips to your
shoulder. More often the pain is in the thumb and the index and middle
fingers. Sometimes the ring finger is also involved. Many people who
suffer from CTS say it feels like their hands have fallen asleep;
others complain of weak grips and stiff fingers.

Women seem to
suffer from CTS more often than men. Changes in female hormones caused
by pregnancy, taking birth control pills and menopause somehow make the
synovium swell. And because women generally have small wrists, just a
little swelling is enough to cause carpal tunnel pain, experts say.

Surgeons agree that CTS should not be treated with surgery during pregnancy. Studies by Dr. Ellis found that vitamin B₆
helped relieve CTS in 11 percent of the pregnant women with severe CTS
signs and symptoms during their pregnancies. These women were treated
with 50 to 300 milligrams of B₆ daily for at least 60 to 90
days before giving birth. And there was no harm to either the mother or
the child. If you'd like to try this therapy, you should discuss it
with your doctor.

Obesity creates a similar situation. "There
is about a fivefold increase in CTS in people who are obese and couch
potatoes. So we encourage them to be in better shape and lose weight,"
says Morton Kasdan, M.D., clinical professor of plastic surgery at the
University of Louisville in Kentucky and clinical professor of
preventive medicine and environmental health

at the University of Kentucky in Lexington.

CTS has also become the unofficial health complaint of the modern age,
the result of an increase in cases among people in manufacturing jobs.

Officials at the U.S. Bureau of Labor Statistics don't keep records of
the number of CTS cases reported each year. Between 1986 and 1992,
cases of "repetitive trauma disorders" (a category that includes CTS
and similar conditions) zoomed from 50,000 to 282,000.

Another
common culprit is working on a computer, which doesn't require you to
take frequent breaks, as changing paper in a typewriter would. "The
repetitive activity produces inflammation, and this leads to swelling,"
explains Dr. Tunell. "That's a major contributor for the patients I
see."

Food Factors

The
pain hits your wrist, your hand and sometimes even your shoulder. But
carpal tunnel syndrome can start in your stomach. Here are some things
to consider.

Hold the reins on cocktails.
Alcohol is known to deplete the body of nutrients, especially the B
vitamins, which are vital for preventing carpal tunnel syndrome.

Drop those pounds.
Many doctors have noted that people who lose weight sometimes also lose
their symptoms of carpal tunnel syndrome. If you're on a
weight-reducing diet, be sure to eat foods that contain vitamin B₆, such as bananas and avocados.

Prescriptions for Healing

Many doctors recommend B vitamins for carpal tunnel syndrome. Because even the foods richest in vitamin B₆, such as bananas, avocados, brewer's yeast and beef, provide barely a single milligram of B₆, you'll probably need to take a supplement. B-complex capsules often include all of the recommended vitamins.

Nutrient Daily Amount

Biotin 300 micrograms

Riboflavin 25 milligrams

Vitamin B₆ 50-200 milligrams

MEDICAL ALERT: Take vitamin B₆ in amounts above 100 milligrams only under the supervision of your doctor.

The Benefits of B₆

Doctors are divided on why vitamin B₆ seems to provide relief from CTS.

The author of five published studies that demonstrate the benefits of vitamin B₆ for CTS, Dr. Ellis contends that synovium swelling and inelasticity are caused by a B₆ deficiency.

Dr. Ellis and Karl Folkers, D.Sc., Ph.D., professor and director of the
Institute for Biomedical Research at the University of Texas at Austin,
once healed 22 of 23 people with CTS just by giving them 50 to 300
milligrams of vitamin B₆ daily for at least 12 weeks. And a number of them had already undergone surgery without experiencing relief. "Vitamin B₆ is as important to your body as oxygen and water, only it takes a little longer to show the benefits," says Dr. Ellis.

The average diet, Dr. Ellis says, provides only about 1.4 milligrams of vitamin B₆
a day, in part because the nutrient is lost in processing, so many
people are just not getting enough. "Raw foods are the best sources,
because heat destroys it," he says. Foods containing B₆ include potatoes, bananas, chicken breast, top round of beef, fish, brown rice and avocados.

Other doctors believe vitamin B₆
acts as a diuretic, helping the body to eliminate excess fluid. "During
pregnancy, your feet swell, your hands swell, rings don't fit anymore.
You're retaining fluid, especially in the wrists," says Dr. Tunell. For
some women, the problem worsens when they lie down, as fluid that makes
the ankles swell during the day is redistributed throughout the body,
including to the wrists, he says. "B₆ helps you get rid of the extra water gain that's causing carpal tunnel," he says.

Another theory, backed up by two European studies, suggests that vitamin B₆ somehow short-circuits an angry nerve's ability to transmit pain signals. "We don't know the mechanism, but we do know B₆
reduces the amount of pain that animals feel, and that may be what's
happening here," says Allan L. Bernstein, M.D., chief of neurology at
Kaiser Permanente Medical Center in Hayward, California.

Medical experts do agree on one thing: No matter how vitamin B₆
gets the job done, you have to be careful not to take too much. In
studies using laboratory animals, researchers found that excess B₆ can harm your central nervous system.

Researchers at the U.S. Department of Agriculture Western Human Nutrition

Research Center in San Francisco fed 12 experimental animals 1, 10, 100, 200 or 300 times their requirement of vitamin B₆ for seven weeks. At the three highest levels of B₆ intake, the animals' reaction time to a loud noise was reduced. Signs of a B₆ overdose also include an oversensitivity to sunlight, which produces a skin rash and numbness.

"Vitamin B₆ toxicity symptoms are rarely seen in healthy individuals. Moderate supplementation of B₆ will not cause that kind of thing," says Robert A. Jacob, Ph.D., research chemist in micronutrients at the Western Human Nutrition

Research Center. "You'd have to megadose on it. So I don't think that
would happen if you take just a multivitamin/mineral supplement with B₆ or even a 50- or 100-milligram B₆ supplement. It appears only when you chronically take massive amounts."

Doctors recommend 50 to 200 milligrams of vitamin B₆ daily to treat carpal tunnel.

Some Recommend Riboflavin and Biotin

There's some evidence that vitamin B₆
won't work properly unless you're getting adequate amounts of
riboflavin and biotin, other B vitamins. "Each one of these vitamins is
synergistic; each works in concert with the other," says Flora Pettit,
Ph.D., a research scientist at the Biochemical Institute at the
University of Texas at Austin. Doctors suggest aiming for 300
micrograms of biotin and 25 milligrams of riboflavin daily.

By
law, most cereals, flours and other grain products are fortified with
riboflavin; milk, yogurt and cheeses are good sources, too. Biotin is
found in brewer's yeast, soy flour, cereals, egg yolks, milk, nuts and
vegetables.

Older adults, alcoholics and those with nutritionally poor diets
are at particular risk for deficiencies in these vitamins, says Dr.
Tunell. "Generally, the elderly have poor diets, and they have trouble
absorbing B vitamins anyway," says Dr. Tunell. "So they couldn't go
wrong with a B-complex supplement unless they have Parkinson's disease.
In that case, vitamin B₆ may interfere with the absorption of their levodopa medication."

"My patients are getting between 50 and 100 milligrams of vitamin B₆ and riboflavin a day, using a B-complex supplement," says Dr. Kasdan. "And 60 percent of them have gotten better."

Most doctors agree that catching CTS early is a key to successful treatment. "If you have severe carpal tunnel, the vitamin B₆
isn't really going to reverse it," says Dr. Bernstein. "But if you
catch it early, when you're just starting to have pain and tingling,
and if there's no weakness and it bothers you at night but not during
the day, you'll do extremely well."

http://xanya-sofra-weiss.palaweb.com/info-xanya_sofra_weiss-nanotechnology

Xanya Sofra Weiss

Spatial-Temporal Structures of Human Alpha Rh ythms: Theory, Microcurrent Sources, Multiscale Measurements, and Global Binding of Local Networks.

2011-03-15T06:48:00.000-07:00

Paul L. Nunez, Brett M. Wingeier, and Richard B. Silberstein; 2001

Abstract: A theoretical framework supporting experimental measures of dynamic properties of human
EEG is proposed with emphasis on distinct alpha rhythms. Robust relationships between measured
dynamics and cognitive or behavioral conditions are reviewed, and proposed physiological bases for EEG
at cellular levels are considered. Classical EEG data are interpreted in the context of a conceptual
framework that distinguishes between locally and globally dominated dynamic processes, as estimated
with coherence or other measures of phase synchronization. Macroscopic (scalp) potentials generated by
cortical current sources are described at three spatial scales, taking advantage of the columnar structure
of neocortex. NewEEG data demonstrate that both globally coherent and locally dominated behavior can
occur within the alpha band, depending on narrowband frequency, spatial measurement scale, and brain
state. Quasi-stable alpha phase structures consistent with global standing waves are observed. At the
same time, alpha and theta phase locking between cortical regions during mental calculations is demonstrated,consistent with neural network formation. The brain-binding problemis considered in the context of EEG dynamic behavior that generally exhibits both of these local and global aspects. But specific
experimental designs and data analysis methods may severely bias physiological interpretations in either
local or global directions.

Xanya Sofra Weiss

Nanocurrent for Aesthetics and Anti -Aging. Xanya Sofra Weiss

2011-03-15T06:36:00.001-07:00

Xanya Sofra-Weiss

Aging is not just the sum total of individually deteriorating cells, shortened telomeres, denatured proteins and DNA molecules, or oxidative damage in the mitochondria. Aging is the dynamic process of increasing imbalances caused by: (1) cellular energy shortage, (2) incomplete cellular differentiation, (3) immune deficiency, (4) decreased systemic intelligence reflected in a/ defects in repair mechanisms, b/ inadequate spatial orientation and c/ poor network communication. International research has repeatedly shown that: (1)Electrons stabilize free radicals (2) Electron transport within DNA deflects oxidative damage; (3)Electrons provide a) direction information b) embryonic development c) cellular differentiation d) healing.(4) Electron transport chain results in Protons spinning the ATP-synthase in the mitochondria to produce ATP. Additionally, Proteins, the central intelligence mechanism of the cell are synthesized by aminoacids that are bound by virtue of their electric charge. A number of studies have shown that Protein synthesis occurs at specific frequencies below 1 Hz. Modern electronics and molecular biology research are combined to deduce the specifications for a technology that promotes Healthy Anti-aging. Resonating the firings, spatial organization and rhythms of electrically excitable cells leads to healing and rejuvenation in a completely safe, noninvasive method. However, to date, few devices pay attention to waveform formation that reflects the essence of cellular communications. There is a lot to be gained by developing a device that can emit signals capable of intertwining with those of signal transduction receptors (including G proteins, gene transcription and the activation of T cells). Such a device will not only become the protagonist in Anti-aging but it will have sufficient sophistication to heal disease and enhance overall immune efficiency.

Xanya Sofra Weiss

Ultra-Low Microcurrent Therapy: A Novel Approach for Treatment of Chronic Resistant Wounds. Xanya Sofra Weiss

2011-03-06T06:04:00.001-08:00

Bok Y. Lee, Keith Wendell, Noori Al-Waili, Glenn Butler ; 2007

This study was undertaken to investigate the efficacy of ultra-low microcurrent delivered by the Electro Pressure Regeneration Therapy (EPRT) device for the man- agement of chronic wounds. In this study, 23 patients with chronic skin ulcers and 2 with abdominal dehiscence that was present for an average of 16.5 mo, who were not responsive to standard conservative treatment in a hospital setting, were treated with the EPRT device. Wounds were treated with direct current (maximum
of 3 mA) of 1 polarity for 11.5 min and then with a current of the opposite polar- ity for another 11.5 min. Treatment was applied through ultra-low microcurrents (in the mA to nA range) conducted through special wraps applied above and below the wound. The results revealed that 34.8% of cases achieved complete wound healing after an average of 45.6 h of treatment, and 39.1% achieved ≥50% healing after an average of 39.7 h of treatment. Several patients achieved signifi- cant results after 1 to 2 treatments. The EPRT device not only accelerated healing
but also appeared to negate the effect of a person’s age on wound healing.

Xanya Sofra Weiss

Comparison of Apoptosis and Terminal Differentiation: The Mammalian Aging Process. Xanya Sofra Weiss

2011-03-06T06:02:00.000-08:00

C.E. Gagna, H.-R. Kuo, E. Florea, W. Shami, R. Taormina, N. Vaswani, M. Gupta, R.Vijh, and W.C. Lambert; 2001

Apoptosis is the ordered chain of events that lead to cell destruction. Terminal differentiation (denucleation) is the process in which cells lose their nuclei but remain functional. Our group examined cell death in three tissues using two different fixatives and a postfixation procedure, involving young (5 months) and old (2 years) guinea pigs. The data reveal that B-DNA and Z-DNA content decreases, whereas single-stranded (ss-) DNA increases, in older tissues undergoing apoptosis (skin and cornea) and terminal differentiation (ocular lens). We speculate that some of the factors that contribute to the aging process might also be responsible for the enhanced amount of damaged DNA in older tissues undergoing cell death. (J Histochem 49:929–930, 2001)

Xanya Sofra Weiss

Ionic Anti-aging Solutions for Rejuvenation and Obesity. Xanya Sofra Weiss

2011-03-06T06:00:00.001-08:00

Xanya Sofra-Weiss, Ph.D

Abstract:

The aging process cannot be conceptualized by examining a single gene or a single pathway, but can best be addressed at the systems level. Aging is not only the sum total of shortened telomeres, denatured proteins and DNA molecules, or oxidative damage in the mitochondria. Aging attacks key regulatory nodes crucial for the biological network stability. It is the dynamic process of increasing imbalances in the systemic organization of degenerating biological processes. DNA and stem cells engineering have successfully reversed certain individual components of time attrition resulting in rejuvenation and aging delay. So far, research has merely followed a sequential process that goes from the part to the whole, identifying aging genes and engineering stem cells, etc. However, discovering pieces of the puzzle still requires identification of the interconnections between matching pieces before the solution emerges. The old, the ill, and the injured all suffer from misarranged patterns of atoms. A single substitution an A for a G in a DNA molecule can cause a significant change in the conductance of the molecule leading to cancer. Such research findings demonstrate how the sequence and interrelations of amino acids in a protein, or the sequence of base pairs in a DNA molecule can become determining factors between health and disease, aging and youth. The DNA sequence alone doesn't determine everything. The importance of the spatial organization or nuclear architecture in regulating gene expression begs for scientific observation that does not merely focus on the study of atoms and molecules, (the basic components of a Gestalt); but on the interrelations, sequence, orientation and spatial organization of these atoms and molecules (the dynamic whole or Gestalt). Recent research has shown that DNA, proteins, cells, including stem cells, appear to be electrical in that they demonstrate conductivity or the presence of ionic currents. Since electricity is a dynamic entity emerging out of the interactions of atoms and molecules, we propose that perhaps the simplest way of focusing on the entire system is by decoding the complex electrical signals that map biological interactions with respect to spatial organization. Biological signals must be analyzed in terms of their amperage, frequency, voltage, interactions, orientation, spatial organization. Next will be their translation into electronic signals that comply with the specifications of amperage, frequency, voltage or biological signals. Electronic signals will then be intertwined to orchestrate a Gestalt waveform built on the basis of information attained from observations of biological interactions and architecture – a process similar to that done in Pollock’s lab (1990-2004). This Gestalt waveform will act as an electronic diplomat to awaken biological processes that have diminished with aging or disease by signaling the recuperation and activation of biological reparative mechanisms leading to extended longevity.

A clinical study with individuals presenting abnormally clumped Red Blood Cells’ (RBCs) was completed in February 2009 with a device representing the Pacemaker Technology for the Skeletal muscle. Results indicate that this technology rapidly and efficiently leads to normalized erythrocytes’ separation at the microscopic level. RBCs separation is crucial for the overall blood flow and timely transport of hormones, antibodies, oxygen and nutrients to the cells, and waste products to the kidneys. Transport of Hormones is a crucial process lipolysis (T3 and Growth Hormone -- GF) and muscle hypertrophy (Insulin Growth Factor - IGF-1). Additionally, erythro cyte separation resulting from treatment with the Pacemaker Technology appears to have a negative correlation with the number of fungal forms, poikilocytosis, thrombocyte aggregation and bac teria present in the blood prior to treatments. In summary, the erythrocyte separation resulting from treatments with the Pacemaker Thechology enhances hormonal transport including T3 and GH leading to lipolysis and muscle hypertrophy; 2) RBC;s separation enhances overall level of health by a significant reduction of free radicals. bacteria, fungal forms. etc.; 3) Obesity is characterized by reduced blood flow. The Pacemaker Thechology increases RBC’s separation resulting in normalized blood flow. In conclusion, re-establishing normal levels of blood flow will not only help reduce obesity but it will help reduce the risk of heart attack as well as all other disorders associated with obesity. Due to its resonance with the biological signal and following the rule of reinforced synapses when signals are in synch with the CNS, the signal of the Pacemaker Technology spreads throughout the CNS inducing effortless and painless isometric and isotonic muscle contractions. The Pacemaker Technology signal to the nerve ultimately triggers hormonal secretion such as Growth Hormone (GF), Thyroxine (T4) and Triiodothyronine (T3) for lipolysis and Insulin Growth Factor (IGF-1) for muscle hypertrophy.

Xanya Sofra Weiss

THYROID HORMONES IN NON-INSULIN-DEPENDENT DIABETES BEFORE AND AFTER DIETARY TREATMENT. Xanya Sofra Weiss

2011-03-06T05:58:00.000-08:00

M. C. SHEPPARD, D. B. RAMSDEN ; 1983

In a group of 8 moderately obese non-insulin-dependent diabetics, both serum total T3 and T4 concentrations and serum free T3 and T4 concentrations were significantly lower than control values. Serum TBG levels did not differ. Five patients demonstrated an apparently successful response to dietary treatment with loss of symptoms and glycosuria and fall in post-prandial blood glucose and HbAl. Serum concentrations of thyroid hormones and TBG, however, were not significantly altered. These abnormalities may be unrelated to hyperglycaemia and may reflect the nutritional status of the patients. (Clinical Endocrinology 18 (6)1365-2265)

Xanya Sofra Weiss

A Review of the Biophysical Basis for the Clinical Application of Electric Fields in Soft-Tissue Repair. Xanya Sofra Weiss

2011-03-06T05:54:00.000-08:00

Interest in the role of electrical interactions as epigenetic regulators of wound healing had its beginnings nearly 40 years ago, Because the mechanisms of action are not understood (which obviates rational therapy), the empiric application of fields to wounds has produced mixed results. However, taken collectively, clinical trials have demonstrated some beneficial effects. Tests on soft tissues of animals have shown that
electric stimulation can influence the rate of wound healing and scar strength. Natural epithelial-derived sodium currents have been discovered in the wounds of invertebrates and mammals. It is theorized that these currents may be a normal controlling factor in wound healing. Therefore, perturbation of these signals is important to understand. The purpose of this review is to put into proper perspective the biophysical, physiological, and clinical data pertaining to use of electricity to control wound healing, with the goal of minimizing much of the prevailing confusion.

Xanya Sofra Weiss

Can Electrons Act as Antioxidants? A Review and Commentary. Xanya Sofra Weiss

2011-03-04T07:21:00.001-08:00

James L. OschmanPh.D; 2007

A previous study demonstrated that connecting the human body to the earth during sleep (earthing) normalizes the daily cortisol rhythm and improves sleep. A variety of other benefits were reported, including reductions in pain and inflammation. Subsequent studies have confirmed these earlier findings and documented virtually immediate physiologic and clinical effects of grounding or earthing the body. It is well established, though not widely known, that the surface of the earth possesses a limitless and continuously renewed supply of free or mobile electrons as a consequence of a global atmospheric electron circuit. Wearing shoes with insulating soles and/or sleeping in beds that are isolated from the electrical ground plane of the earth have disconnected most people from the earth's electrical rhythms and free electrons. The most reasonable hypothesis to explain the beneficial effects of earthing is that a direct earth connection enables both diurnal electrical rhythms and free electrons to flow from the earth to the body. It is proposed that the earth's diurnal electrical rhythms set the biological clocks for hormones that regulate sleep and activity. It is also suggested that free electrons from the earth neutralize the positively charged free radicals that are the hallmark of chronic inflammation. A relationship between cortisol and inflammation was established in the pioneering work of H. Selye published in the 1950s. Current biomedical research has led to an inflammation hypothesis that is establishing chronic inflammation as the culprit behind almost every modern chronic illness. The research summarized here and in subsequent reports provides a basis for a number of earthing technologies that restore and maintain natural electrical contact between the human body and the earth throughout the day and night in situations where going barefoot on the earth is impractical. It is proposed that free or mobile electrons from the earth can resolve chronic inflammation by serving as natural antioxidants.

Xanya Sofra Weiss

The Basis for Micro Current Electrical Therapy in Conventional Medical Practice. Xanya Sofra Weiss

2011-03-04T07:19:00.001-08:00

Joseph M. Mercola, Daniel L Kirsch; 1995

The use of electricity in medicine is not new. Clinicians used it over 150 years ago to treat nonunion bone fractures. Electomedicine and nutrition, abandoned early in this century, have been recently revived. Most physicians are unaware of their therapeutic benefits. Electrotherapy, especially micro current electrical therapy (MET) is useful for a variety of clinical conditions. Indeed, it may be the best treatment for many pain-related disorders, providing fast relief of symptoms and quickly promoting healing. It has significantly less side effects than drugs in chronic conditions. The more advanced MET devices can often demonstrate effectiveness with a simple two minute office procedure, allowing validity to be quickly assessed.

Xanya Sofra Weiss

A Novel Collagen. Xanya Sofra Weiss

2011-03-04T07:17:00.001-08:00

A novel collagen-binding peptide promotes osteogenic differentiation via Ca2+/calmodulin-dependent protein kinase II/ERK/AP-1 signaling pathway in human bone marrowderived mesenchymal stem cells. Xanya Sofra Weiss

Shin MK, Kim MK, Bae YS, Jo I, Lee SJ, Chung CP, Park YJ, Min do S.

The intracellular signaling events controlling human mesenchymal stem cell (hMSC) differentiation into osteoblasts are poorly understood. Collagen-binding domain is considered an essential component of bone mineralization. In the present study, we investigated the regulatory mechanism of osteoblastic differentiation of hMSC by the peptide with a novel collagen-binding motif derived from osteopontin. The peptide induced influx of extracellular Ca2+ via calcium channels and increased intracellular Ca2+ concentration ([Ca2+]i) independent of both pertussis toxin and phospholipase C, and activated ERK, which was inhibited by Ca2+/calmodulin-dependent protein kinase (CaMKII) antagonist, KN93. The peptide-induced increase of [Ca2+]i is correlated with ERK activation in a various cell types. The peptide stimulated the migration of hMSC but suppressed cell proliferation. Furthermore, the peptide increased the phosphorylation of cAMP-response element-binding protein, leading to a significant increase in the transactivation of cAMP-response element and serum response element. Ultimately, the peptide increased AP-1 transactivation, c-jun expression, and bone mineralization, which are suppressed by KN93. Taken together, these results indicate that the novel collagen-binding peptide promotes osteogenic differentiation via Ca2+/CaMKII/ERK/AP-1 signaling pathway in hMSC, suggesting the potential application in cell therapy for bone regeneration.

Xanya Sofra Weiss

ENERGY MEDICINE AND ANTI-AGING: FROM FUNDAMENTALS TO NEW BREAKTHROUGHS. Xanya Sofra Weiss

2011-03-04T07:15:00.001-08:00

After much skepticism, energy medicine and the science behind it are emerging as rich and fascinating topics with major implications for anti-aging medicine. Those who follow this emerging field are being introduced to new vistas about how the human body works in health and disease, and anti-aging specialists are acquiring valuable new tools. The symposium will summarize the fundamentals of energetics and some of the significant breakthroughs. The fundamentals demystify energetics, answer the logical questions raised by skeptics and provide appropriate answers to patient questions. The breakthroughs are revealing how energetic methods are having a dramatic impact on health and longevity, and helping us solve one of the biggest unsolved problems in biology referenced above. We begin by discussing theories of aging to lay a foundation for new concepts based on discoveries in the fields of cell biology and biophysics.

Xanya Sofra Weiss

Nanocurrent for Aesthetics and Anti -Aging. Xanya Sofra Weiss

2011-03-04T07:13:00.001-08:00

Xanya Sofra-Weiss

Xanya Sofra Weiss

Synthesis of Nitric Oxide in Human Osteoblasts in Response to Physiologic Stimulation of Electrotherapy. Xanya Sofra Weiss

2011-03-02T09:11:00.001-08:00

Electrotherapy for bone healing, remodeling and wound healing may be mediated by modulation of nitric oxide (NO). Using NO-specific fluorophore (DAF-2), we report here that application of non-invasive, physiologic electrical stimulation induces NO synthesis in human osteoblasts, and that such NO generation is comparable to that induced by estrogen treatment. For example, application of a sinusoidal 1 Hz, 2 V/cm (peak to peak) electrical stimulation (ES) increases NO-bound DAF-2 fluorescence intensity by a 2-fold within 60 min exposure by activating nitric oxide synthase (NOS). Increase in the NO level is found to depend critically on the frequency and strength of ES. While the frequency of 1 Hz ES seems optimal, the ES strength >0.5 V/cm is required to induce significant NO increase, however. Nitric oxide synthesis in response to ES is completely prevented by blocking estrogen receptors using a competitive inhibitor, suggesting that NO generation is likely initiated by activation of estrogen receptors at the cell surface. Based on these findings, physiologic stimulation of electrotherapy appears to represent a potential non-invasive, non-genomic, and novel physical technique that could be used to regulate NO-mediated bone density and facilitate bone remodeling without adverse effects associated with hormone therapy.

Xanya Sofra Weiss

Investigation of human mitochondrial myopathies by phosphorus magnetic resonance spectroscopy. Xanya Sofra Weiss

2011-03-02T09:08:00.001-08:00

Dr. D. L. Arnold, MD, D. J. Taylor, DPhil, G. K. Radda, DPhil, FRS; 1984

Abnormal mitochondria are an increasingly recognized cause of neuromuscular disease. We have used phosphorus magnetic resonance spectroscopy to monitor noninvasively the metabolism of high-energy phosphates and the intracellular pH of human skeletal muscle in vivo in 12 patients with mitochondrial myopathy. At rest, an abnormality could be demonstrated in 11 of 12 patients. Ten patients had evidence of a reduced muscle energy state with at least one of the following abnormalities: low phosphorylation potential, low phosphocreatine concentration, high adenosine diphosphate concentration, or high inorganic phosphate concentration. Two patients had abnormal resting muscle intracellular pH. In some patients phosphocreatine concentration decreased to low values during exercise despite limited work output. This was not accompanied by particularly severe intracellular acidosis. Evidence of impaired rephosphorylation of adenosine diphosphate to adenosine triphosphate during recovery from exercise was found in approately half the patients. Phosphorus magnetic resonance spectroscopy is useful in the noninvasive diagnosis of mitochondrial myopathies and in defining the pathophysiological basis of these disorders.

Xanya Sofra Weiss

Counterregulation of beta(2)-adrenoceptor function in human mast cells by stem cell factor. Xanya Sofra Weiss

2011-03-02T09:04:00.001-08:00

Mast cells contribute to the pathophysiology of asthma with the sustained release of both preformed and
newly generated mediators in response to allergens and other diverse stimuli. Stem cell factor (SCF) is the key human mast cell growth factor, but also primes mast cells for mediator release. SCF expression is markedly increased in asthmatic airways. Short-acting beta(2)-adrenoceptor drugs such as albuterol inhibit human lung mast cell (HLMC) degranulation in vitro in the absence of SCF, but their effect in the presence of SCF is not known. OBJECTIVE: The aim of this study was to elucidate the effects of albuterol on HLMC function in the presence of SCF. METHODS: Mediator release and K(Ca)3.1 ion channel activity were analyzed in purified HLMC. Intracellular signalling and beta(2)-adrenoceptor phosphorylation and internalization were analyzed in the HMC-1 human mast cell line. RESULTS: beta(2)-Adrenoceptor agonist-dependent inhibition of K(Ca)3.1 ion channels and HLMC mediator release was markedly attenuated in the
presence of SCF. Remarkably, albuterol actually potentiated IgE-induced histamine release in a dose-dependent manner when both SCF and IgE were present. These effects were related to the SCF-dependent phosphorylation of Tyr350 on the beta(2)-adrenoceptor with immediate uncoupling of the receptor followed by receptor internalization. CONCLUSION: The potentially beneficial effects of beta(2)-adrenoceptor agonists in asthmatic airways may be blunted as a result of the high concentrations of SCF present.

Xanya Sofra Weiss

Is Melatonin the Hormonal Missing Link Between Magnetic Field Effects and Human Diseases? Xanya Sofra Weiss

2011-03-02T08:59:00.000-08:00

The disruption of melatonin secretion has been largely
studied since it could provide the missing link between the
exposure to 50/60-Hz electric and magnetic fields (EMF) and the
occurrence of possible health effects as the “melatonin
hypothesis”. We analysed the current experimental data from
animal (rodents) where contradictory results have been observed,
and from human studies conducted with volunteers or with
workers in various conditions of exposure, biological endpoints
and metrics. In humans, even in long lasting exposures, the
overall results of these studies do not support the “melatonin
hypothesis”. It is unlikely that malignancies or mood disorders
reported by people exposed to 50/60-Hz EMF could be related to
the disruption of the melatonin levels.

Xanya Sofra Weiss

Live Blood Analysis. Xanya Sofra Weiss

2011-03-02T08:57:00.001-08:00

Xanya Sofra Weiss

Diabetic Peripheral Neuropathy. Xanya Sofra Weiss

2011-02-28T05:06:00.000-08:00

Xanya Sofra Weiss

ELECTRIC CHARGE. Xanya Sofra Weiss

2011-02-28T05:04:00.001-08:00

A Closer Look Electric charge is a basic property of elementary particles of matter. The protons in an atom, for example, have a positive charge, the electrons have a negative charge, and the neutrons have zero charge. In an ordinary atom, the number of protons equals the number of electrons, so the atom normally has no net electric charge. An atom becomes negatively charged if it gains extra electrons, and it becomes positively charged if it loses electrons; atoms with net charge are called ions. Every charged particle is surrounded by an electric field, the area in which the charge exerts a force. Particles with nonzero electric charge interact with each other by exchanging photons, the carriers of the electromagnetic force. The strength and direction of the force charged particles exert on each other depends on the product of their charges: they attract each other if the product of their charges is negative and repel each other if the product is positive. Thus two electrons, each with charge -1, will repel each other, since -1 × -1 = +1, a positive number. Static electricity consists of charged particles at rest, while electric current consists of moving charged particles, especially electrons or ions.

Xanya Sofra Weiss

2011-02-28T05:02:00.001-08:00

Arasys Inch Loss Arasys Perfector Xanya Xanya Sofra Weiss Xanya Weiss Xanya Sorfa-Weiss Xanyasofraweiss xanyaweiss perfector arasys perfectorarasys arasysperfector inch loss inch-loss body shaping Ion Magnum Pacemaker Technology pacemaker Statins Heart Disease Heart attack Diabetes obesity cellulite cellulite loss nanotechnology nanocurrent pico amperes picoamperes picocurrent marren micro current microcurrents microcurrent face lift non surgical face lift Bio-identical Hormone Therapy Bio-identical Hormones Growth Hormone Free T3 Thyroid Hormones Muscle Building Acne Reduces acne Melasma Reduces Melasma Pigmentations Reduce Pigmentation Reduce Acne

Xanya Sofra Weiss

Clinical Experience of an Iontophoresis Based Glucose Measuring System. Xanya Sofra Weiss

2011-02-28T04:56:00.000-08:00

Sang Youl Rhee, Suk Chon, Gwanpyo Koh, Jeong Ryung Paeng, Seungjoon Oh, Jeong-taek Woo, Sung Woon Kim, Jin-Woo Kim, and Young Seol Kim

Currently finger pricking is the common method of blood glucose measurement in patients with diabetes mellitus. However, diabetes patients have proven to be reluctant to check their glucose profiles regularly because of the discomfort associated with this technique. Recently, a non-invasive and continuous Reverse
Iontophoresis based Glucose Monitoring Device (RIGMD) was developed in Korea. The study was conducted during the period November 2003-January 2004 on 19 in-patients. Glucose measurements were performed using RIGMD between 10 a.m. and 4 p.m. Concurrent plasma glucose levels were checked hourly and subsequently compared with RIGMD data. The mean error of RIGMD measurements was -3.45±52.99 mg/dL with a mean absolute relative error of 20±15.16%. Measurements obtained by RIGMD were correlated with plasma glucose levels (correlation coefficient; 0.784 (p<0.05))>

Xanya Sofra Weiss

Microcurrent therapy: anovel treatment method for chronic low back my of ascial pain. Xanya Sofra Weiss

2011-02-28T04:55:00.001-08:00

Carolyn R. McMakin, M.A.,D.C.; 2004

Chronic low back pain associated with myofascial trigger point activity has been historically refractory to conventional treatment (Pain Research and Manage- ment7 (2002) 81) . In this case series study,an analysis of 22 patients with chronic low back pain, of 8.8 years average duration, is presented. Following treatment with frequency-specific microcurrent, astatistically significant 3.8-fold reduction in pain intensity was observed using a visual analog scale.This outcome was achieved over an average treatment period of 5.6 weeks and a visit frequency of one treatment per week. When pain chronicity exceeded 5 years, there was a trendtoward increasing frequency of treatment required to achieve the same magnitude of pain relief. In 90%of these patients, other treatment modalities including drug therapy, chiropractic manipulation, physical therapy, naturopathic treatment and acupuncture had failed to produce equivalent benefits.The microcurrent treatment was the single factor contributing the most consistent difference in patient-reported pain relief. These results support the observation that rigorously designed clinical investigations are warranted.

Xanya Sofra Weiss

FREQUENCY SPECIFIC EFFECTS OF DOPAMINE IN THE NUCLEUS ACCUMBENS

2011-02-27T05:38:00.000-08:00

The action of dopamine was evaluated in the nucleus accumbens of acutely prepared rabbits. It was found that the effect of iontophoretically applied dopamine depended upon the frequency of stimulation of an afferent pathway; in this case the ipsilateral fimbria. Dopamine had a marked suppressive effect on field responses evoked by fimbria stimulation at 0.5 Hz, but not those responses evoked at 6.0 Hz. Dopamine was also effective in activating adenylate cyclase. Both the physiological and the biochemical effects of dopamine could be blocked by appropriate antagonists, suggesting that the phenomena observed were receptor mediated. It is suggested that dopamine serves to enhance information arriving from the hippocampal formation within the theta range by the suppression of competing non-theta activity.

Xanya Sofra Weiss

Multiple Sclerosis: Low-Frequency Temporal Blood Oxygen Level– Dependent Fluctuations Indicate Reduced Functional Connectivity —Initial Results

2011-02-27T05:35:00.000-08:00

PURPOSE: To study the correlation of low-frequency blood oxygenation level– dependent (BOLD) fluctuations on magnetic resonance (MR) images obtained of the left- and right-hemisphere primary motor regions in healthy control subjects and patients with multiple sclerosis (MS). MATERIALS AND METHODS: Sixteen healthy volunteers and 20 patients with MS underwent MR imaging with a 1.5-T imager by using a protocol designed to monitor low-frequency BOLD fluctuations. Data for low-frequency BOLD fluctuations were
acquired with subjects at rest and during continuous performance of a bilateral fingertapping task. These data were low-pass filtered (<0.08 Hz), and cross correlations of all acquired pixels to a region of interest in the left precentral gyrus were calculated. Confidence levels were calculated from the cross correlations. The fraction of pixels in the right precentral gyrus above a confidence level of 95% for correlation with the
precentral gyrus was calculated for each subject. RESULTS: A plot of the fraction of the right precentral gyrus with high correlation with the left precentral gyrus for the finger-tapping state versus the resting state showed a clear discrimination between patients with MS and control subjects. Compared with control subjects, patients with MS generally had a smaller fraction of the pixels in the right precentral gyrus above the confidence level. This finding indicates that our method results in greater than 60% sensitivity and 100% specificity for discriminating patients with MS from control subjects. No significant correlation was found between clinical measures of MS disease and correlations of low-frequency BOLD fluctuations between left and right precentral gyri. CONCLUSION: On the basis of the connectivity measure of low-frequency BOLD fluctuations, patients with MS exhibited lower functional connectivity between rightand left-hemisphere primary motor cortices when compared with that in control subjects.

Xanya Sofra Weiss

Pulsed short-wave diathermy effects on human fibroblast proliferation.

2011-02-27T05:32:00.001-08:00

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Hill J, Lewis M, Mills P, Kielty C. Pulsed short-wave diathermy effects on human fibroblast proliferation. Arch Phys Med Rehabil 2002;83:832-6. Objectives: To investigate the influence of pulsed short-wave diathermy (PSWD) on fibroblast and chondrocyte cell proliferation rates and to establish the influences of different dosages applied. Design: Four single-blind trials. Setting: Laboratory, in vitro study. Specimens: Human adult dermal fibroblast and chondrocyte cells were plated at known concentrations and incubated for 5 days. Intervention: Exposure to PSWD, twice daily, on days 2, 3, and 4. Main Outcome Measure: After crystal violet staining (day 5), optical density (cell number) was determined spectrophotometrically. Results: PSWD, given at mean power of 48W for 10 minutes, increased fibroblast proliferation compared with control groups (P[lt ].001). There was a relationship between cell proliferation and the amount of energy given (P[lt ]0.001). The optimal mean power for proliferation was estimated to be 13.8W. While keeping mean power constant at 6W, altering pulse duration and pulse repetition rate dosage parameters did not have a significant effect on proliferation (P=.519). Chondrocyte proliferation also increased with PSWD exposure of 6W at 10 minutes duration (P=.015). In addition, treatment time was significantly associated with chondrocyte proliferation (P[lt ].001). Conclusion: PSWD is associated with increased rates of fibroblast and chondrocyte proliferation in vitro, which is dose dependent. These results contribute to an understanding of the physiologic mechanisms underlying the therapeutic effects of PSWD.

Xanya Sofra Weiss

Pulsed short-wave diathermy effects on human fibroblast proliferation.

2011-02-27T05:32:00.000-08:00

Xanya Sofra Weiss

Growth hormone: uses and abuses. Xanya Sofra Weiss

2011-02-27T05:30:00.000-08:00

Raymond L Hintz; 2004

Unconvincing and therefore called for raising the price and limiting availability.1 The prime minister’s strategy unit, with access to the same evidence, concluded that controlling average consumption through the mechanism of raising the price and limiting access would have unwanted side effects and was not a viable option. They therefore called for education, more policing, improved treatment, and the alcohol industr y entering into voluntar y agreements to behave reasonably.7 The academy working group would agree that all of these actions were necessar y. But they took the view, based on evidence, that such actions should complement measures to control overall level of consumption. Two reports, same evidence, and yet such different conclusions. As scientists, steeped in alcohol (as it were), we who prepared the academy’s report no doubt came to the issue with our own set of prejudices. The prime minister’s strategy unit had a different set. It is reasonable to surmise that they found the prospect of raising the tax on alcohol unattractive, as they did reversing the trend of making it ever easier to buy alco- hol. The policy implications of the science may well have influenced their view of the evidence. This leads me, naively perhaps, to want to separate two issues: what the science shows and its policy implications. It is perfectly reasonable for governments to balance a number of interests in forming policies. Scientific evidence on dose response relations between exposure and risk is only one consideration. Others include analysis of costs and benefits, risk analysis, and appreciation of the degree to which policies fit with public values.8 It is helpful, however, to keep these distinct. Public values are important. There is much discus- sion now of individual responsibility for behaviour. This informs the government’s call for consultation as it develops a white paper on public health. A healthy tension exists in a democratic society between individual responsibility and the role of government. Smoking is a matter of individual responsibility but successive British governments have taken beneficial action by raising the price for health reasons, restricting advertising and promotion, and restricting smoking in public places. Unlike smoking, the healthi- est amount of alcohol is not zero. Nevertheless, the 50% rise in alcohol consumption in Britain means that as a population we are drinking well above the optimal level for health. As it develops its white paper on public health the government has another opportunity to look at the evidence linking harm with average alcohol consumption and consider that government has a responsibility alongside that of individual citizens.

Xanya Sofra Weiss

Endothelin. Xanya Sofra Weiss

2011-02-27T05:28:00.001-08:00

endothelin (ET): any of a group of vasoconstrictive peptides produced by endothelial cells. Three known endothelins, designated ET-1, ET-2, and ET-3, are chemically related to asp venom. ET-1 is the most potent vasoconstrictor yet discovered, being 10 times stronger than the second-most potent vasoconstrictor known, angiotensin II.

Xanya Sofra Weiss

Effects of the application of Aloe vera (L.) and microcurrent on the healing of wounds surgically induced in Wistar rats. Xanya Sofra Weiss

2011-02-27T05:26:00.001-08:00

PURPOSE: To investigate the effects of topical application of an Aloe vera gel combined or not with microcurrent application on the healing of skin wounds surgically induced in Wistar rats.

METHODS: The animals were randomly divided into the following groups: control group, animals topically treated with Aloe vera, animals treated with a microcurrent, and animals receiving topical application of Aloe vera combined with microcurrent application.

RESULTS: The results indicated differences in wound healing between the various treatments when compared to the control group. Tissue hyperplasia was lower in the control group compared to the other treated groups. Accelerated wound healing was observed in the group treated with Aloe vera compared to control. Animals submitted to microcurrent application only and the group treated with microcurrent plus Aloe vera presented an earlier onset of the proliferative phase compared to the control group and animals treated with Aloe vera gel alone. Morphometric data confirmed the structural findings.

CONCLUSION: Simultaneous application of Aloe vera gel and microcurrent is an excellent choice for the treatment of open wounds thus indicating a synergistic action of these two applications.

Xanya Sofra Weiss

Bioimpedance Neuronal Microstimulation. Xanya Sofra Weiss

2011-02-26T00:03:00.000-08:00

Electrotherapy and Tissue Repair. Xanya Sofra Weiss

2011-02-26T00:00:00.000-08:00

Electrotherapy is one form of intervention that has the capacity to influence the processes associated with tissue repair. Some modalities are more effective at achieving this than others, and there are differences in they type of tissue that respond to the different modalities. Numerous electrotherapy modalities have significant clinical effects, but not primarily on tissue repair, and they are excluded from this review for this reason.Evidence for the relationship between electrotherapy and tissue repair is continuously updated and thus, this is the story is it is at the moment – the current state of the art. It is fully expected that this will change – maybe next month, maybe next year – and therefore the latter section of this paper considers some of the emerging issues.
Xanya Sofra Weiss
Xanya Sofra Weiss

Multipotent mesenchymal stem cells from amniotic fluid originate neural precursors with functional voltage-gated sodium channels. Xanya Sofra Weiss

2011-02-25T23:57:00.000-08:00

Katia Mareschi , Deborah Rustichelli, Valentina Comunanza, Roberta De Fazio, Cristina Cravero, Giulia Morterra,Barbara Martinoglio, Enzo Medico, Emilio Carbone, Chiara Benedetto and Franca Fagioli
Background aimsAmniotic fluid (AF) contains stem cells with high proliferative and differentiative potential that might be an attractive source of multipotent stem cells. We investigated whether human AF contains mesenchymal stem cells (MSC) and evaluated their phenotypic characteristics and differentiation potential in vitro.Methods:AF was harvested during routine pre-natal amniocentesis at 14–16 weeks of pregnancy. AF sample pellets were plated in α-minimum essential medium (MEM) with 10% fetal bovine serum (FBS). We evaluated cellular growth, immunophenotype, stemness markers and differentiative potential during in vitro expansion.Neural progenitor maintenance medium (NPMM), a medium normally used for the growth and maintenance of neural stem cells, containing hFGF, hEGF and NSF-1, was used for neural induction.Results:Twenty-seven AF samples were collected and primary cells, obtained from samples containing more than 6 mL AF, had MSC characteristics. AF MSC showed high proliferative potential, were positive for CD90, CD105, CD29, CD44, CD73 and CD166, showed Oct-4 and Nanog molecular and protein expression, and differentiated into osteoblasts, adypocytes and chondrocytes. The NPMM-cultured cells expressed neural markers and increased Na+ channel density and channel inactivation rate, making the tetrodotoxin (TTX)-sensitive channels more kinetically similar to native neuronal voltage-gated Na+ channels.Conclusions:These data suggest that AF is an important multipotent stem cell source with a high proliferative potential able to originate potential precursors of functional neurons.
Xanya Sofra Weiss
Xanya Sofra Weiss

Anti-inflammatory Effects of Electronic Signal Treatment. Xanya Sofra Weiss

2011-02-25T23:51:00.000-08:00

Robert H. Odell, Jr., MD, PhD, Richard E. Sorgnard, PhD; 2008
Inflammation often plays a key role in the perpetuation of pain. Chronic inflammatory conditions (e.g. osteoarthritis, immune system dysfunction, micro-circulatory disease, painful neuritis, and even heart disease) have increased as baby boomers age. Medicine’s current antiinflammatory choices are NSAIDs and steroids; the value in promoting cure and side effect risks of these medications are unclear and controversial, especially considering individual patient variations. Electricity has continuously been a powerful tool in medicine for thousands of years. All medical professionals are, to some degree, aware of electrotherapy; those who directly use electricity for treatment know of its anti-inflammatory effects. Electronic signal treatment (EST), as an extension of presently available technology, may reasonably have even more anti-inflammatory effects. EST is a digitally produced alternating current sinusoidal electronic signal with associated harmonics to produce theoretically reasonable and/or scientifically documented physiological effects when applied to the human body. These signals are produced by advanced electronics not possible even 10 to 15 years ago. The potential long-lasting anti-inflammatory effects of some electrical currents are based on basic physical and biochemical facts listed in the text below, namely that of stimulating and signaling effective and long-lasting anti-inflammatory effects in nerve and muscle cells. The safety of electrotherapeutic treatments in general and EST in particular has been established through extensive clinical use. The principles of physics have been largely de-emphasized in modern medicine in favor of chemistry. These electrical treatments, a familiar application of physics, thus represent powerful and appropriate elements of physicians’ pain care armamentaria in the clinic and possibly for prescription for use at home to improve overall patient care and maintenance of quality of life via low-risk and potentially curative treatments.
Xanya Sofra Weiss
Xanya Sofra Weiss

Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase. Xanya Sofra Weiss

2011-02-14T02:21:00.000-08:00

The demonstration of in vivo arachidonic acid epoxidation and v-hydroxylation established the cytochrome P450 epoxygenase and v/ v–1 hydroxylase as formal metabolic pathways and as members of the arachidonate metabolic cascade. The characterization of the potent biological activities associated with several of the cytochrome P450-derived eicosanoids suggested new and important functional roles
for these enzymes in cellular, organ, and body physiology, including the control of vascular reactivity and systemic blood pressures. Past and current advances in cytochrome P450 biochemistry and molecular biology facilitate the characterization
of cytochrome P450 isoforms responsible for tissue/organ specific arachidonic acid epoxidation and v/ v–1 hydroxylation, and thus, the analysis of cDNA and/or gene specific functional phenotypes. The combined application of physiological, biochemical, molecular, and genetic approaches is beginning to provide new insights into the physiological and/or pathophysiological significance of these enzymes, their endogenous substrates, and products.—Capdevila, J. H., J. R. Falck, and R. C. Harris. Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase.

Xanya Sofra Weiss

How Do Low-Energy Electrons Cause DNA-Strand Breaks? Xanya Sofra Weiss

2011-02-14T02:18:00.000-08:00

JACK SIMONS; 2006

We overview our recent theoretical predictions and the innovative experimental findings that inspired us concerning the mechanisms by which very low-energy (0.1-2 eV) free electrons attach to DNA and cause strong (ca. 4 eV) covalent bonds to break causing so-called single-strand breaks. Our primary conclusions are that (i) attachment of electrons in the above energy range to base π orbitals is more likely than attachment elsewhere and (ii) attachment to base π* orbitals most likely results in cleavage of sugar-phosphate C-O σ bonds. Later experimental findings that confirmed our predictions about the nature of the electron attachment event and about which bonds break when strand breaks form are also discussed. The proposed mechanism of strand break formation by low-energy electrons involves an interesting through-bond electron-transfer process.

Xanya Sofra Weiss

Behaviour of skeletal muscle cells and cardiomyoctes on extracellular matrix components. Xanya Sofra Weiss

2011-02-14T02:16:00.000-08:00

K. Macfelda, B. Kapeller, U. M. Losert; 2005Background: Myocardial cell transplantation in patients with heart failure is emerging as a potential therapeutic option to augment the function of remaining myocytes. Nevertheless further investigations on the basic issues such as ideal cell type continues to be evaluated. Therefore, the aim of our study was to compare the performance of skeletal muscle cells and cardiomyocytes in respect of their proliferation rate and viability on different extracellular matrix components (EMC).
Methods: Rat cardiomyocytes (RCM) and rat skeletal muscle cells (RSMC) were cultured on EMC such as collagen type I, IV, laminin, fibronectin, and gelatine. The components were used as “double coating”. Proliferation rates were determined by proliferation assays on day 1, 2, 4, and 8 after inoculation of the cells.
Results: The most essential result is that collagen type I enhances the proliferation rate of RSMC but decreases the proliferation of RCM significantly. This effect is independent of the second EMC used for the double-coating studies. Other EMCs also influence the cellular behaviour, whereas the sequence of the EMCs is essential.
Conclusions: Results obtained with our studies reveal the significantly different proliferation behaviour of RCM and RSMC under identical conditions. As skeletal muscle cells are also used in heart tissue engineering models, these results are essential and should be investigated in further studies to prove the applicability of skeletal muscle cells for heart tissue engineering purposes.

Xanya Sofra Weiss

Basic Molecular Biology. Xanya Sofra Weiss

2011-02-14T02:09:00.000-08:00

Science

Neural Pathways and Action Potentials

Neural pathways
The simplest type of neural pathway is a monosynaptic (single connection) reflex pathway, like in the knee-jerk reflex. When the doctor taps a certain spot on your knee with a rubber hammer, receptors send a signal into the spinal cord through a sensory neuron. The sensory neuron passes the message to a motor neuron that controls your leg muscles. Nerve impulses travel down the motor neuron and stimulate the appropriate leg muscle to contract. Nerve impulses also travel to the opposing leg muscle to inhibit contraction so that it relaxes (this pathway involves interneurons). The response is a quick muscular jerk that does not involve your brain. Humans have lots of hardwired reflexes like this, but as tasks become more complex, the pathway “circuitry” gets more complicated and the brain gets involved.

nerve cross section

Action potentials
We have talked about nerve signals and mentioned that they are electrochemical in nature, but what does that mean?

To understand how neurons transmit signals, we must first look at the structure of the cell membrane. The cell membrane is made of fats or lipids called phospholipids. Each phospholipid has an electrically charged head that sticks near water and two polar tails that avoid water. The phospholipids arrange themselves in a two-layer lipid sandwich with the polar heads sticking into water and the polar tails sticking near each other. In this configuration, they form a barrier that separates the inside of the cell from the outside and that does not permit water-soluble or charged particles (like ions) from moving through it.

So how do charged particles get into cells? We’ll find out on the next page.

Concentration gradients and active transport

When you cut an onion at one end of a room, you will eventually smell it at the other end. This is because the onion juice molecules move through the air. Although their motion is random, they generally tend to move from an area of high concentration (the onion) to an area of low concentration (the other end of the room). You also see this behavior when you add a drop of food dye to water — eventually, the dye spreads out through the water. This phenomenon is called diffusion. The driving force for diffusion is a difference in concentration, or concentration gradient. Now, for ions and molecules to move across a membrane, two conditions must be met:

* There must be a concentration gradient across the membrane.
* The membrane must be permeable to that particular molecule or ion.

The ion or molecule will move “down” its concentration gradient (from high concentration to low concentration). It is possible to get an ion or molecule to move against its concentration gradient (”uphill”), but this requires energy and is called active transport. The energy for this active transport can come from ATP (the cell’s energy currency) or by coupling the “uphill” transport of this ion or molecule to the “downhill” transport of another ion or molecule on the same carrier (counter-transport or exchange).

Ion Channels

Because ions are charged and water-soluble, they must move through small tunnels or channels (specialized proteins) that span the cell membrane’s lipid bilayer. Each channel is specific for only one type of ion. There are specific channels for sodium ions, potassium ions, calcium ions and chloride ions. These channels make the cell membrane selectively permeable to various ions and other substances (like glucose). The selective permeability of the cell membrane allows the inside to have a different composition than the outside.

For the purposes of nerve signals, we are interested in the following characteristics:

* The outside fluid is rich in sodium, a concentration about 10 times higher than the inside fluid
* The inside fluid is rich in potassium, a concentration about 20 times higher inside the cell than outside.
* There are large negatively charged proteins inside the cell that are too big to move across the membrane. They give the inside of the cell a negative electrical charge compared to the outside. The charge is about 70 to 80 millivolts (mV) — 1 mV is 1/1000th of a volt. For comparison, the charge in your house is about 120 V, about 1.2 million times more.
* The cell membrane is slightly “leaky” to sodium and potassium ions, so a sodium-potassium pump is located in the membrane. This pump uses energy (ATP) to pump sodium ions from the inside to the outside and potassium ions from the outside to the inside.
* Because sodium and potassium ions are positively charged, they carry tiny electrical currents when they move across the membrane. If sufficient numbers move across the membrane, you can measure the electrical currents.

Nerve Growth and Regeneration
When nerves grow, they secrete a substance called nerve growth factor (NGF). NGF attracts other nerves nearby to grow and establish connections. When peripheral nerves become severed, surgeons can place the severed ends near each other and hold them in place. The injured nerve ends will stimulate the growth of axons within the nerves and establish appropriate connections. Scientists don’t entirely understand this process.
For unknown reasons, nerve regeneration appears most often in the peripheral and autonomic nervous systems but seems limited within the central nervous system. However, some regeneration must be able to occur in the central nervous system because some spinal cord and head trauma injuries show some degree of recovery.

Nerve Signals

The nerve signal, or action potential, is a coordinated movement of sodium and potassium ions across the nerve cell membrane. Here’s how it works:

1. As we discussed, the inside of the cell is slightly negatively charged (resting membrane potential of -70 to -80 mV).
2. A disturbance (mechanical, electrical, or sometimes chemical) causes a few sodium channels in a small portion of the membrane to open.
3. Sodium ions enter the cell through the open sodium channels. The positive charge that they carry makes the inside of the cell slightly less negative (depolarizes the cell).
4. When the depolarization reaches a certain threshold value, many more sodium channels in that area open. More sodium flows in and triggers an action potential. The inflow of sodium ions reverses the membrane potential in that area (making it positive inside and negative outside — the electrical potential goes to about +40 mV inside)
5. When the electrical potential reaches +40 mV inside (about 1 millisecond later), the sodium channels shut down and let no more sodium ions inside (sodium inactivation).
6. The developing positive membrane potential causes potassium channels to open.
7. Potassium ions leave the cell through the open potassium channels. The outward movement of positive potassium ions makes the inside of the membrane more negative and returns the membrane toward the resting membrane potential (repolarizes the cell).
8. When the membrane potential returns to the resting value, the potassium channels shut down and potassium ions can no longer leave the cell.
9. The membrane potential slightly overshoots the resting potential, which is corrected by the sodium-potassium pump, which restores the normal ion balance across the membrane and returns the membrane potential to its resting level.
10. Now, this sequence of events occurs in a local area of the membrane. But these changes get passed on to the next area of membrane, then to the next area, and so on down the entire length of the axon. Thus, the action potential (nerve impulse or nerve signal) gets transmitted (propagated) down the nerve cell.

action potential graphs

There are a few things to note about the propagation of the action potential.

When an area has been depolarized and repolarized and the action potential has moved on to the next area, there is a short period of time before that first area can be depolarized again (refractory period). This refractory period prevents the action potential from moving backward and keeps everything moving in one direction.
# The action potential is an “all-or-none” response. Once the membrane reaches a threshold, it will depolarize to +40 mV. In other words, once the ionic events are set in motion, they will continue until the end.
# These ionic events occur in many excitable cells besides neurons (like muscle cells).
# Action potentials are propagated rapidly. Typical neurons conduct at 10 to 100 meters per second. Conduction speed varies with the diameter of the axon (larger = faster) and the presence of myelin (myelinated = faster). The rapid nerve conductions throughout the neural circuitry enable you to respond to stimuli in fractions of a second.
# The channels can be poisoned and prevented from opening. Various toxins (puffer fish toxin, snake venom, scorpion venom) can prevent specific channels from opening and distort the action potential or prevent it from happening altogether. Similarly, many local anesthetics (e.g. lidocaine, novocaine, benzocaine) can prevent action potentials from being propagated in the nerve cells in an area and temporarily prevent you from feeling pain.
# The propagation of the action potential is also sensitive to temperature in experimental settings. Colder temperatures slow down the action potential, but this usually doesn’t happen in an individual. However, you can use cold-block techniques to temporarily anesthetize an area (like putting ice on an injured finger).

So, if the size of the action potential does not vary, how does an action potential code information? Information is encoded by the frequency of action potentials, much like FM radio. A small stimulus will initiate a low frequency train of a few action potentials. As the intensity of the stimulus increases, so does the frequency of action potentials.
Synaptic TransmissionLike wires in your home’s electrical system, nerve cells make connections with one another in circuits called neural pathways. Unlike wires in your home, nerve cells do not touch, but come close together at synapses. At the synapse, the two nerve cells are separated by a tiny gap, or synaptic cleft. The sending neuron is called the presynaptic cell, while the receiving one is called the postsynaptic cell. Nerve cells send chemical messages with neurotransmitters in a one-way direction across the synapse from presynaptic cell to postsynaptic cell. serotonin reuptake

Let’s look at this process in a neuron that uses the neurotransmitter serotonin:

1. The presynaptic cell (sending cell) makes serotonin (5-hydroxytryptamine, 5HT) from the amino acid tryptophan and packages it in vesicles in its end terminals.
2. An action potential passes down the presynaptic cell into its end terminals.
3. The action potential stimulates the vesicles containing serotonin to fuse with the cell membrane and dump serotonin into the synaptic cleft.
4. Serotonin passes across the synaptic cleft, binds with special proteins called receptors on the membrane of the postsynaptic cell (receiving cell) and sets up a depolarization in the postsynaptic cell. If the depolarizations reach a threshold level, a new action potential will be propagated in that cell. Some neurotransmitters cause the postsynaptic cell to hyperpolarize (the membrane potential becomes more negative, which would inhibit the formation of action potentials in the postsynaptic cell). Serotonin fits with its receptor like a lock and key.
5. The remaining serotonin molecules in the cleft and those released by the receptors after use get destroyed by enzymes in the cleft (monoamine oxidase (MAO), catechol-o-methyl transferase (COMT)). Some get taken up by specific transporters on the presynaptic cell (reuptake). In the presynaptic cell, MAO and COMT destroy the absorbed serotonin molecules. This enables the nerve signal to be turned “off” and readies the synapse to receive another action potential.
6. There are several types of neurotransmitters besides serotonin, including acetylcholine, norepinephrine, dopamine and gamma-amino butyric acid (GABA). Any given neuron produces only one type of neurotransmitter. Any one nerve cell may have synapses on it from excitatory presynaptic neurons and from inhibitory presynaptic neurons. In this way, the nervous system can turn various cells (and subsequent neural pathways) “on” and “off.” Finally, nerve cells synapse on effector cells (muscles, glands, etc.) to evoke or inhibit responses.

XXanya Sofra Weiss

Xanya Sofra Weiss

Effects of Exposure to a 50 Hz Electric Field on Plasma Levels of Lactate, Glucose, Free Fatty Acids, Triglycerides and Creatine Phosphokinase Activit

2011-02-14T02:02:00.000-08:00

We previously reported that extremely low frequency electric fields (ELF-EFs) affect energy metabolism in stressed conditions. To further confirm this, the effect of exposure to ELF-EFs on the experimental ischemic rat was examined. The test was based on a comparison of rats treated with EF alone, ischemic surgery alone, the combination of EF with ischemic surgery, or no treatment (double sham). The EF condition used in this study was an alternating current of 50 Hz EF at 17 500 Vim intensity for 15 min per day. The exposure to EF in ischemic rats significantly decreased plasma levels of free fatty acids and triglycerides, compared to those of the no treatment or EF alone group. The plasma lactate levels of two ischemic groups peaked on experimental day-4 and gradually decreased until the end of the study. The changes in the lactate levels induced by ischemia did not show any difference between rats treated with ischemia alone or a combination of ischemia with an EF. Any changes in plasma levels of glucose and creatine phosphokinase activity were not influenced by EF treatment. These results indicate that the EF effect on glycolysis parameters, plasma lactate or glucose levels, does not appear in a highly stressed condition and that EF effects varied dependent on the condition of organism but ELF-EF used in
this study have impact on lipid metabolism parameter in a hind-limb ischemic rat. However, further studies are needed to elucidate the association of ELF-EF with the lipid metabolism system.

XXanya Sofra Weiss

Xanya Sofra Weiss

A Low Power Digital IC Design Inside the Wireless Endoscopy Capsule. Xanya Sofra Weiss

2011-01-25T09:02:00.000-08:00

Xiang Xie, GuoLin Li, XinKai Chen, Lu Liu, Chun Zhang and ZhiHua Wang

This paper proposes an analog-digital mix-mode low power IC architecture inside the wireless endoscopic capsule, which assures that the capsule can implement the diagnoses of whole human digestive tract and provides real time endoscopic image monitoring. A new low complexity and low power digital IC design inside the wireless endoscopic capsule is discussed in detail. To decrease the power consumption, a novel architecture of three-stage clock management is applied for such a system. A new image compression algorithm based on Bayer image format and its corresponding hardware architecture are both presented for low power and low communication data rate application. The digital circuits were verified on FPGAs and have been implemented in 0.18μm CMOS process.

Xanya Sofra Weiss

Xanya Sofra Weiss

Microcurrent therapeutic technique for treatment of radiation toxicity. Xanya Sofra Weiss

2011-01-25T08:59:00.001-08:00

Arlene Lennox, Sandra Funder; 2000

The present technique provides a method of remediating the toxicities associated with radiation therapy. A conductive gel is applied to the affected bodily area. A sinusoidally pulsed biphasic DC current is then applied to the affected bodily area using at least one electrode. The electrode is manipulated using active tactile manipulation by for a predetermined time and the frequency of the sinusoidally pulsed biphasic DC current is decreased during the course of the treatment. The method also includes applying a spiked pulsed biphasic DC current to the affected bodily area using at least one electrode. This electrode is also manipulated using active tactile manipulation by for a predetermined time and the frequency of the spiked pulsed biphasic DC current is also decreased during the course of the treatment.

Xanya Sofra Weiss

Xanya Sofra Weiss

Studies of principle and method to depress the air-gap effect to the clamp-on micro-current transducer. Xanya Sofra Weiss

2011-01-25T05:05:00.001-08:00

Kai Zhou Pan Chen Buxin You Hao Yang Yang Li
Jiangbei Power Supply Bur. of Chongqing Electr. Power Corp., Chongqing; 2008

The amplitude-phase characteristic of the transducer and the effect of the gap to the magnetic resistance, inductance and mutual inductance of the transducer are analyzed by the equivalent model of passing through clamp-on micro-current transducer. Because of the gap, the lower limiting frequency of the transducer increase and the bandwidth turn narrow, as well as the voltage induced by the coil of the transducer is so feebleness and easy to be interfered that it is difficult to be measured accurately, which is a well-known difficult problem in the portable type measurement of the low-frequency feeble current signal. In this paper, a new method with design principle and the simulation result by Saber to reduce the effect of the gap in the transducer is introduced. The academic lower limiting frequency of the transducer is nearly zero and the upper limiting frequency is infinity. The test of the current transducer shows that the low limiting frequency of the transducer is improved, which can be use in most systems to reduce the effect of gap with broad pass-bandwidth, high linearity and high sensitivity.

Xanya Sofra Weiss

Xanya Sofra Weiss

A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. Xanya Sofra Weiss

2011-01-25T04:58:00.001-08:00

Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Manson JE, Li J ,Harris TG, Rohan TE, Xue X, Ho GY, Einstein MH, Kaplan RC, Burk RD,Wylie-Rosett J, Pollak MN, Anderson G, Howard BV, Strickler HD; 2008

Obesity is a major risk factor for endometrial cancer, a relationship thought to be largely explained by the prevalence of high estrogen levels in obese women. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed whether insulin and/or insulin-like growth factor-I (IGF-I), a related hormone, are associated with endometrial cancer while accounting for estrogen levels. We therefore conducted a case-cohort study of incident endometrial cancer in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. The study involved all 250 incident cases and a random subcohort of 465 subjects for comparison. Insulin, total IGF-I, free IGF-I, IGF-binding protein-3, glucose, and estradiol levels were measured in fasting baseline serum specimens. Cox models were used to estimate associations with endometrial cancer, particularly endometrioid adenocarcinomas, the main histologic type (n = 205). Our data showed that insulin levels were positively associated with endometrioid adenocarcinoma [hazard ratio contrasting highest versus lowest quartile (HR(q4-q1)), 2.33; 95% confidence interval (95% CI), 1.13-4.82] among women not using hormone therapy after adjustment for age and estradiol. Free IGF-I was inversely associated with endometrioid adenocarcinoma (HR(q4-q1), 0.53; 95% CI, 0.31-0.90) after adjustment for age, hormone therapy use, and estradiol. Both of these associations were stronger among overweight/obese women, especially the association between insulin and endometrioid adenocarcinoma (HR(q4-q1), 4.30; 95% CI, 1.62-11.43). These data indicate that hyperinsulinemia may represent a risk factor for endometrioid adenocarcinoma that is independent of estradiol. Free IGF-I levels were inversely associated with endometrioid adenocarcinoma, consistent with prior cross-sectional data.

Xanya Sofra Weiss

Xanya Sofra Weiss

Effect of microcurrent electrical tissue stimulation on equine tenocytes in culture. Xanya Sofra Weiss

2011-01-24T08:03:00.000-08:00

Yi-lo Lin, DVM, MSc Hugo Moolenaar, PhD P. René van Weeren, DVM, PhD Chris H. A. van de Lest, PhD; 2006

Objective—To determine effects of microcurrent electrical tissue stimulation (METS) on equine tenocytes cultured from the superficial digital flexor tendon (SDFT).

Sample Population—SDFTs were collected from 20 horses at slaughter.

Procedure—Tenocytes were isolated following outgrowth from explants and grown in 48-well plates. Four methods of delivering current to the tenocytes with a METS device were tested. Once the optimal method was selected, current consisting of 0 (negative control), 0.05, 0.1, 0.5, 1.0, or 1.5 mA was applied to cells (8 wells/current intensity) once daily for 8 minutes. Cells were treated for 1, 2, or 3 days. Cell proliferation, DNA content, protein content, and apoptosis rate were determined.

Results—Application of microcurrent of moderate intensity increased cell proliferation and DNA content, with greater increases with multiple versus single application. Application of microcurrent of moderate intensity once or twice increased protein content, but application 3 times decreased protein content. Application of current a single time did not significantly alter apoptosis rate; however, application twice or 3 times resulted in significant increases in apoptosis rate, and there were significant linear (second order) correlations between current intensity and apoptosis rate when current was applied twice or 3 times.

Conclusions and Clinical Relevance—Results of the present study indicate that microcurrent affects the behavior of equine tenocytes in culture, but that effects may be negative or positive depending on current intensity and number of applications. Therefore, results are far from conclusive with respect to the suitability of using METS to promote tendon healing in horses.

Xanya Sofra Weiss

Xanya Sofra Weiss

Exercise and arthritis. The hematology of inactivity.Xanya Sofra Weiss

2011-01-24T07:57:00.000-08:00

Arthritis tends to promote inactivity, and inactivity tends to promote an unhealthful constellation of blood abnormalities that increases the risk of heart attack and stroke. The hematology of inactivity comprises the following: low plasma volume, high hematocrit, high plasma fibrinogen, elevated blood viscosity, increased platelet aggregability, and diminished fibrinolysis. Regular exercise reverses all these adverse blood changes and, thereby, helps prevent heart attack and stroke. Simply put, exercise "improves" the blood, making it flow more easily and clot less readily. This "healthy hematology of exercisers" is one more reason why prudent exercise is as vital for patients with arthritis as it is for the rest of us.

Xanya Sofra Weiss

Xanya Sofra Weiss

nduction of microcurrents in critically ill patients in magnetic resonance systems. Xanya Sofra Weiss Xanya Sofra Weiss

2011-01-24T07:46:00.000-08:00

Measurements and Main Results: Voltage generated by saline 0.9% flowing through a magnetic field and distribution of current from a catheter tip within a sheep heart model were measured in a 0.15 Tesla MRI system. Resistance of loops formed by pacing wires, a pacing electrode, and a thermistor wire were measured in saline 0.9%. Effects of rapidly changing magnetic fields and the movement of the beating heart on epicardial pacing wires were calculated theoretically. A flow of 200 mL/min of saline 0.9% induced a current of 0.1 microampere (uA) (at 0.15 Tesla). From magnetic resonance images we derived a current density of -0.004 [mu]A/mm2 (at 0.15 Tesla). Internal resistance of pacing catheters and thermistor wires was >1 megaohm (M[OMEGA]). The maximum currents calculated (for a higher field strength of 1.5 Tesla) in a circuit formed by epicardial pacing wires were 80 [mu]A, induced by the beating heart moving the wires through the magnetic field and 46 [mu]A, induced by the rapidly changing magnetic fields.

Conclusions: Current generated by flow of conducting fluid should be safe. Pacing catheters and thermistor wires should be safe if well insulated and disconnected from external electric connections. However, current induced in epicardial pacing wires may be a hazard, and precautions should be taken. External wire tips must be separated, insulated, and coiled to lie along the axis of the magnetic field. Electrocar-diography is required, and defibrillation equipment should be available.

Xanya Sofra Weiss

Xanya Sofra Weiss

APPARATUS FOR PERFORMING MICROCURRENT ELECTROTHERAPY. Xanya Sofra Weiss

2011-01-24T07:34:00.001-08:00

An electrotherapy method and apparatus for healing injuries and tissue diseases to the human or animal body is disclosed. Particularly, the electrotherapy method disclosed herein comprises delivering a current under various conditions, such as, applying microcurrents ranging from 4 miliamperes to 1 femtoamperes, applying an laternating current with a frequency in the range of .00065 Hz to .00085 Hz, utilizing large surface area electrodes to achieve to low current densities of less than 5 microamperes per square inch. The apparatus of the present invention includes a plurality of electrode wraps for applying said electrotherapy method to a body. Each electrode wrap includes a first layer wrap of water absorptive material and a second layer wrap of moderately conductive material. Each electrode wrap is placed on a portion of the body, including, without limitation, arms, legs, hands, feet and torso. The method and apparatus of the present invention are useful in treating wounds, ulcerations, spinal cord injuries, amyotrophic lateral sclerosis, multiple sclerosis, nervous system abnormalities, scar tissue and age lines.

Xanya Sofra Weiss

Xanya Sofra Weiss

A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance. Xanya Sofra Weiss

2011-01-24T07:25:00.000-08:00

Oxidative damage caused by reactive oxygen species (ROS) is implicated in many diseases and in aging. Removal of ROS by antioxidant enzymes plays an important part in limiting this damage. For instance, peroxiredoxins (Prx) are conserved, abundant, thioredoxin peroxidase enzymes that function as tumor suppressors. In addition to detoxifying peroxides, studies in single-cell systems have revealed that Prx act as chaperones and redox sensors. However, it is unknown in what manner the different activities of Prx influence stress resistance or longevity in the context of whole animals. Here, we reveal three distinct roles for the 2-Cys Prx, PRDX-2, in the stress resistance of the nematode worm Caenorhabditis elegans. (i) The thioredoxin peroxidase activity of PRDX-2 protects against hydrogen peroxide. (ii) Consistent with a chaperone activity for hyperoxidized PRDX-2, peroxide-induced oxidation of PRDX-2 increases resistance to heat stress. (iii) Unexpectedly, loss of PRDX-2 increases the resistance of C. elegans to some oxidative stress-causing agents, such as arsenite, apparently through a signaling mechanism that increases the levels of other antioxidants and phase II detoxification enzymes. Despite their increased resistance to some forms of oxidative stress, prdx-2 mutants are short-lived. Moreover, intestinal expression of PRDX-2 accounts for its role in detoxification of exogenous peroxide, but not its influence on either arsenite resistance or longevity, suggesting that PRDX-2 may promote longevity and protect against environmental stress through different mechanisms. Together the data reveal that in metazoans Prx act through multiple biochemical activities, and have tissue-specific functions in stress resistance and longevity.

Xanya Sofra Weiss

Xanya Sofra Weiss

Melatonin in the skin: synthesis, metabolism and functions. Xanya Sofra Weiss

2011-01-23T04:20:00.001-08:00

Andrzej Slominski, Desmond J. Tobin, Michal A. Zmijewski, Jacobo Wortsman and Ralf Paus

Melatonin, a ubiquitous methoxyindole, is produced by and metabolized in the skin. Melatonin affects skin functions and structures through actions mediated by cell-surface and putative-nuclear receptors expressed in skin cells. Melatonin has both receptor-dependent and receptor-independent effects that protect against oxidative stress and can attenuate ultraviolet radiation-induced damage. The widespread expression and pleiotropic activity of the cutaneous melatoninergic system provides for a high level of cell-specific selectivity. Moreover, intra-, auto- and para-crine mechanisms equip this system with exquisite functional selectivity. The properties of endogenous melatonin suggest that this molecule is an important effector of stress responses in the skin. In this way, melatonin
actions may counteract or buffer both environmental and endogenous stressors to maintain skin integrity.

Xanya Sofra Weiss

Xanya Sofra Weiss

Acupuncture: neuropeptide release produced by electrical stimulation of different frequencies. Xanya Sofra Weiss

2011-01-23T04:17:00.001-08:00

Brain functions are regulated by chemical messengers that include neurotransmitters and neuropeptides. Recent studies have shown that acupuncture or electrical stimulation in specific frequencies applied to certain body sites can facilitate the release of specific neuropeptides in the CNS, eliciting profound physiological effects and even activating self-healing mechanisms. Investigation of the conditions controlling this neurobiological reaction could have theoretical and clinical

Xanya Sofra Weiss

Xanya Sofra Weiss

Ionic Requirements for PCH-Jnduced Pigment Aggregation in the Freshwater Shrimp, Macrobruchium potiuna, Erythrophores. Xanya Sofra Weiss

2011-01-23T04:14:00.001-08:00

Ana Lucia M. Britto, Lars Josefsson, Eliuna Scemes,Maria Aparecida Visconti, and Ana Maria de L. Castrucci

The effects of either cation removal or ionic channel blockade were determined on the doseresponse curve (DRC) to PCH (pigment-concentrating hormone) in Macrobmchium potiuna erythrophores. In sodium-, potassium- and calcium-free salines, the pigment-aggregating responses to PCH were depressed; in the former condition, maximal aggregation was not achieved and the slope of the regression curve determined from the DRC was significantly different from control. Tetrodotoxin, verapamil or tetraethylammonium (TEA) treatments also diminished the pigment-aggregating responses to PCH, and the slopes of the regression curves were different from control in the presence of 10m6 M verapamil or 10m6 M TEA. Interestingly, the DRC determined in the absence of both sodium and calcium ions was not significantly different from control. When verapamil was applied in sodium-free conditions, maximal aggregation was prevented. The erythrophore resting membrane potential ranged from -62 mV to - 78 mV and did not vary during PCH-induced pigment aggregation as compared to the control. Our results suggest that transient modifications of potassium equilibrium potential may interfere with PCH signal transduction, revealing a more relevant role of potassium in the process, and that a sodium influx and an intracellular calcium mobilization are necessary to maintain a cytosolic balance between the ions for normality of PCH-induced responses. (COMP BIOCHEM PHYSIOL 113A;4:351-359, 1996

Xanya Sofra Weiss

Xanya Sofra Weiss

Roles of Exercise and Pharmacokinetics in Cerivastatin-Induced Skeletal Muscle Toxicity

2011-01-23T04:10:00.000-08:00

Jennifer L. Seachrist, Cho-Ming Loi, Mark G. Evans, Kay A. Criswell, and Charles E. Rothwell; 2005

Three-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are associated with adverse skeletal muscle effects, but the underlying mechanisms remain unclear. To determine whether toxicity involves the level of drug exposure in muscle tissue and to test the effect of exercise on cerivastatin (CVA)-induced skeletal muscle damage, female rats were administered vehicle or CVA at 0.1, 0.5, and 1.0 mg/kg/day by gavage for two weeks and exercised or not on treadmills for 20 min/day. Clinical chemistry and plasma and tissue pharmacokinetics were evaluated; light and transmission electron microscopy (TEM) of Type I and Type II fiber-predominant skeletal muscles were performed. Serum levels of AST, ALT, CK, and plasma lactic acid were significantly elevated dose-dependently. CVA treatment decreased psoas and quadriceps weights. At 1 mg/kg all muscles except soleus demonstrated degeneration. Exercise-exacerbated severity of CVA-induced degeneration was evident in all muscles sampled except soleus and quadriceps. Early mitochondrial involvement in toxicity is suggested by the numerous membranous whorls and degenerate mitochondria observed in muscles at 0.5 mg/kg. No significant differences in CVA concentrations between either EDL and soleus or plasma and muscle were found.We found that CVA had no effect on cleaved caspase 3. In summary, we found that treadmill exercise exacerbated the incidence and severity of CVA-induced damage in Type II fiber-predominant muscles. Tissue exposure is likely not the key factor mediating CVA-induced skeletal muscle toxicity.

Xanya Sofra Weiss

Xanya Sofra Weiss

Abdominal Obesity, Impaired Nonesterified Fatty Acid Suppression, and Insulin-Mediated Glucose Disposal Are Early Metabolic Abnormalities in Families.

2011-01-23T04:07:00.001-08:00

British Indian Asian men aged !40 years have a twofold to threefold increased risk of death from coronary heart
disease (CHD) compared with British whites. Epidemiological studies have suggested an association between glucose
intolerance and hyperinsulinemia with premature CHD in Indian Asians. We tested the association of insulin action with myocardial infarction (MI) by using the hyperinsulinemic-euglycemic clamp in 17 MI patients: 8 Punjabi Sikhs (PSMIs), 9 British whites (BWMIs), and 17 control subjects (9 PSCs and 8 BWCs). Metabolic factors associated with insulin resistance were investigated in 51 MI patients (24 PSMIs and 27 BWMIs) and 53 control subjects (28 PSCs and 25 BWCs). Familial aggregation of defective insulin action was examined by studying five pedigrees of Sikh survivors of MI. Sikh survivors of premature MI demonstrated impaired insulin-mediated glucose uptake (P!.001) by use of the clamp technique and nonesterified fatty acid (NEFA) suppression (P!.05) by using both clamp techniques and the oral glucose tolerance test, as compared with Sikh control subjects. White patients had impaired insulin-mediated glucose uptake but normal NEFA suppression. Metabolic factors usually associated with insulin resistance, including increased 2-hour post–oral glucose tolerance test triglycerides, smaller low density lipoprotein particle size, and increased plasminogen activator inhibitor-1, were present in white (all P!.05) but surprisingly absent in Sikh (all P".05) MI patients compared with respective ethnic control subjects. Fasting glucose and total cholesterol levels did not differ between patients and control subjects. Abdominal obesity, impaired NEFA suppression after oral glucose, and fasting hyperinsulinemia were present in Sikh MI patients and their nondiabetic first-degree relatives compared with Sikh control subjects. PS survivors of premature MI demonstrated impaired insulin-mediated glucose disposal and NEFA suppression compared with ethnic control subjects. BWMI patients showed abnormalities of carbohydrate, but not of NEFA, metabolism compared with white control subjects. Defects of insulin action manifested as abdominal obesity, impaired NEFA suppression, and fasting hyperinsulinemia are present in Sikh MI patients and their asymptomatic, nondiabetic, first-degree relatives.We suggest that these defects may be early metabolic markers that
predict risk of premature MI among PSs. (Arterioscler Thromb Vasc Biol. 1998;18:1021-1026.)

Xanya Sofra Weiss

Xanya Sofra Weiss

ELECTRICAL PROPERTIES OF INDIVIDUAL CELLS ISOLATED FROM ADULT RAT VENTRICULAR MYOCARDIUM. Xanya Sofra Weiss

2011-01-23T04:04:00.001-08:00

The intricate anatomy of the myocardium, coupled with distinct morphology and function of specialized component cells, often presents acute problems in the inter- pretation of experimental data obtained from the whole organ. One experimental approach to minimize some of the difficulties encountered is the use of single cardiac cells isolated enzymically from adult mammalian myocardium and a technique has been developed in this laboratory whereby tissue dissociation is achieved by in vitro organ perfusion with crude bacterial collagenase (Gould & Powell, 1972;
Powell & Twist, 1976a). Myocytes isolated in this manner from adult rat heart have ntypical superficial and subcellular morphology (Gould & Powell, 1972; Powell, Steen, Twist & Woolf, 1978a), show respiratory coupling (Powell & Twist, 1975, 1976a) and have retained responsiveness to fi-adrenergic stimulation (Powell & Twist, 1976b; Powell, Terrar & Twist, 1978c). To date, however, there has been no systematic study of the electrical activity of these isolated cells, although such data are central to both the evaluation of the preparation as a useful experimental model and also to gain an insight into the electrophysiology of cardiac cells uncoupled physically from their usual syncitial state.
Experiments are presented to show that under suitable incubation conditions membrane potentials which are comparable to those reported for multicellular preparations can be recorded from isolated cells using intracellular micro-electrodes. It is also demonstrated that these cells can generate conventional action potentials, indicating that the relevant ionic mechanisms have been preserved during the iso- lation procedures. Some of these results have appeared previously in abstract form (Powell, Terrar & Twist, 1978b, c).

Xanya Sofra Weiss

Xanya Sofra Weiss

What Live Blood Cell Analysis Can Show You. Xanya Sofra Weiss

2011-01-22T07:54:00.001-08:00

Normal Red Blood Cell (RBCs)

The circulatory system is the means by which oxygen, nutrients, antibodies, and hormones are transported to the cells to keep them alive and functioning. This is how your blood looks when you are experiencing optimum health. The Erythrocytes (cells) are round and separated and move through the capillaries very easily. The average size of
healthy RBC is 7.2 microns. The average number of red blood cells in the human body is 25 trillion. The average red blood cell lives 120 days. Your blood makes a complete circuit in your body every 30 seconds.

Protein Linkage

This condition is the first sign of cell stickiness and may progress into rouleau if not corrected. Protein linkage is a sign that excessive protein is being consumed or the protein is not being digested completely. As the cells start sticking together it becomes harder for your heart to push the blood through your veins and arteries.

Xanya Sofra Weiss

Xanya Sofra Weiss

Coupling of Calcium Homeostasis to Axonal Sodium in Axons of Mouse Optic Nerve. Xanya Sofra Weiss

2011-01-22T07:51:00.001-08:00

YAKOV VERBNY, CHUAN-LI ZHANG, AND SHING YAN CHIU; 2002

Coupling of calcium homeostasis to axonal sodium in axons of mouse optic nerve. J Neurophysiol 88: 802–816, 2002; 10.1152/jn.00856.2001. Axonal populations in neonatal and mature optic nerves were selectively stained with calcium dyes for analysis of calcium homeostasis and its possible coupling to axonal Na. Repetitive nerve stimulation causes a rise in axonal [Ca2+]i the posttetanus recovery of which is impeded by increasing the number of action potentials in the tetanus. This effect is augmented in 4-aminopyridine (4-AP; 1 mM), which dramatically increases the calcium and presumably sodium load during the tetanus. Increasing axonal [Na]i with the Na-ionophore monensin (4–50 M) and ouabain (30 M) retards posttetanus calcium decline, suggesting that efficient calcium clearance depends on a low level of axonal [Na]i. the posttetanus recovery of which is impeded by increasing the number of action potentials in the tetanus. This effect is augmented in4-aminopyridine (4-AP; 1 mM), which dramatically increases the calcium and presumably sodium load during the tetanus. Increasing axonal [Na]i with the Na-ionophore monensin (4–50 M) and ouabain (30 M) retards posttetanus calcium decline, suggesting that efficient calcium clearance depends on a low level of axonal [Na]i. Posttetanus calcium clearance is not affected by K-mediated depolarization. To further examine coupling between axonal [Na]i and [Ca2+]i the resting axonal [Ca2+]i was monitored as axonal [Na+]i was elevated with ouabain, veratridine, and monensin. In all cases, elevation of axonal [Na+]i evokes a calcium influx into axons. This influx is unrelated to activation of calcium channels but is consistent with calcium influx via reversal of the Na/Ca exchanger expected as a consequence of axonal [Na+]i elevation. In conclusion, this study demonstrates that calcium homeostasis in the axons of the optic nerve is strongly coupled to axonal [Na+]i in a manner consistent with the Na/Ca exchanger playing a major role in extruding calcium following nerve activity.

Xanya Sofra Weiss

Xanya Sofra Weiss

CoQ10 and Statin Drugs. Xanya Sofra Weiss

2011-01-22T07:49:00.001-08:00

Statin drugs have become very popular and are being widely prescribed in recent years to lower high blood cholesterol and thus reduce the risk for heart disease. These drugs block cholesterol production in the body by inhibiting the enzyme called HMG-CoA reductase in the early steps of its synthesis in the mevalonate pathway. This same biosynthetic pathway is also shared by CoQ10. Therefore, one unfortunate consequence of statin drugs is the unintentional inhibition of CoQ10 synthesis. Thus, in the long run, statin drugs could predispose the patients to heart disease by lowering their CoQ10 status, the very condition that these drugs are intended to prevent.Dr. Emile Bliznakov, an authority on CoQ10, recently published a scholarly review on the interaction between statin drugs and CoQ10 (Bliznakov and Wilkins, 1998). He wrote the best-selling book "The Miracle Nutrient Coenzyme Q10" several years ago and it is still being hailed as the best reference book on CoQ10 (Bliznakov, 1987).The reduction of CoQ10 levels might be associated with myopathy, a rare adverse effect associated with statin drugs. This metabolic myopathy is related to ubiquinone (CoQ10) deficiency in muscle cell mitochondria, disturbing normal cellular respiration and causing adverse effects such as rhabdomyolysis, exercise intolerance, and recurrent myoglobinuria.It is important to note that Coenzyme Q10 supplementation does not interfere with the very important cholesterol-lowering effect of statin drugs such as Lipitor and Zocor. Therefore, if you are taking a statin drug, (especially for an extended period of time), you may want to consider discussing CoQ10 supplementation with your health care professional. The bottom line is that the popular and widely prescribed cholesterol lowering drugs called "Statins" can block the synthesis of Coenzyme Q10 in the body which may lead to sub-optimal CoQ10 levels. Supplementation with Q-Gel CoQ-10 is a prudent approach when undergoing "statin" therapy.

Xanya Sofra Weiss

Xanya Sofra Weiss

AIDS-Related Dementia and Calcium Homeostasis. Xanya Sofra Weiss

2011-01-22T07:46:00.000-08:00

STUART A. LIFTON

Our laboratory has a long-standing interest in the relationship of neuronal viability and outgrowth to intracellular Ca2+ levels (reviewed in ref. 1). Glutamate, or a related excitatory amino acid (EAA), is the major excitatory neurotransmitter that controls the level of intracellular neuronal Ca"Our laboratory has a long-standing interest in the relationship of neuronal viability and outgrowth to intracellular Ca2+ levels (reviewed in ref. 1). Glutamate, or a related excitatory amino acid (EAA), is the major excitatory neurotransmitter that controls the level of intracellular neuronal Ca2+([Ca2+]i). Escalating concentrations of glutamate have been measured in vivo following focal stroke and head injury (reviewed in refs. 2 and 3). As a result, there is a rapid rise in [Ca2+]i CaZtli may not account by itself for the ensuing neuronal injury, several laboratories have now reported that prevention of the increase in [Ca2+]i Jlie ads to amelioration of anticipated neuronal cell death (reviewed in refs. 2 and 3). Excessive intracellular Ca2+ is thought to contribute to the triggering of a series of potentially neurotoxic events leading to cellular necrosis orperhaps apoptosis. Many mechanisms are involved in intracellular calcium homeostasis, and this subject is beyond the scope of this article (but see the review in ref. 4).Here we will consider only two modes of Caz+ entry into neurons during these pathological processes. These two routes of entry of Ca2+o ccur via ion channels that are permeable to Ca2+ and can be summarized as follows: (1) Glutamate or related EAAs trigger voltage-dependent calcium channels by depolarizing the cell membrane; a major voltage-dependent calcium channel subtype that is chronically activated by prolonged depolarizations is the L-type calcium channel (reviewed in ref. 5). (2) Glutamate or related EAAs activate ligand-gated ion channels directly; a predominant glutamate receptor-operated channel that is permeable to Ca2+ under these conditions is the Nmethyl-D-aspartate (NMDA) subtype, but other non-NMDA types may also contribute (reviewed in refs. 2 and 6). We have shown that activation of these channel types can control neuronal plasticity during normal development, but our laboratory and many others have shown that in excessive amounts this stimulation can lead to neuronal death, for example, after a stroke (reviewed in ref. 1). Similar mechanisms may obtain in various neurodegenerative conditions. In fact, although not involved in the primary pathophysiology of a neurologic disorder, this mechanism may represent a final common pathway of neuronal injury. Most importantly, this pathway makes the disease process amenable to pharmacotherapy. This line of reasoning led us to think that this mechanism might be involved in acquired immunodeficiency syndrome (AIDS)-related neuronal injury.

Xanya Sofra Weiss

Xanya Sofra Weiss

Inhibitory effect of green coffee bean extract on fat accumulation and body weight gain in mice. Xanya Sofra Weiss

2011-01-22T07:44:00.000-08:00

Hiroshi Shimoda, Emi Seki, and Michio Aitani; 2006

An epidemiological study conducted in Italy indicated that coffee has the greatest antioxidant capacity among the commonly consumed beverages. Green coffee bean is rich in chlorogenic acid and its related compounds. The effect of green coffee bean extract (GCBE) on fat accumulation and body weight in mice was assessed with the objective of investigating the effect of GCBE on mild obesity.
Methods: Male ddy mice were fed a standard diet containing GCBE and its principal constituents, namely, caffeine and chlorogenic acid, for 14 days. Further, hepatic triglyceride (TG) level was also investigated after consecutive administration (13 days) of GCBE and its constituents. To examine the effect of GCBE and its constituents on fat absorption, serum TG changes were evaluated in olive oil-loaded mice. In addition, to investigate the effect on hepatic TG metabolism, carnitine palmitoyltransferase (CPT) activity in mice was evaluated after consecutive ingestion (6 days) of GCBE and its constituents (caffeine, chlorogenic acid, neochlorogenic acid and feruloylquinic acid mixture) Results: It was found that 0.5% and 1% GCBE reduced visceral fat content and body weight. Caffeine and chlorogenic acid showed a tendency to reduce visceral fat and body weight. Oral administration of GCBE (100 and 200 mg/kg· day) for 13 days showed a tendency to reduce hepatic TG in mice. In the same model, chlorogenic acid (60 mg/kg· day) reduced hepatic TG level. In mice loaded with olive oil (5 mL/kg), GCBE (200 and 400 mg/kg) and caffeine (20 and 40 mg/kg) reduced serum TG level. GCBE (1%), neochlorogenic acid (0.028% and 0.055%) and feruloylquinic acid mixture (0.081%) significantly enhanced hepatic CPT activity in mice. However, neither caffeine nor chlorogenic acid alone was found to enhance CPT activity.
Conclusion: These results suggest that GCBE is possibly effective against weight gain and fat accumulation by inhibition of fat absorption and activation of fat metabolism in the liver. Caffeine was found to be a suppressor of fat absorption, while chlorogenic acid was found to be partially involved in the suppressive effect of GCBE that resulted in the reduction of hepatic TG level. Phenolic compounds such as neochlorogenic acid and feruloylquinic acid mixture, except chlorogenic acid, can enhance hepatic CPT activity.

Xanya Sofra Weiss

Xanya Sofra Weiss