Search PubMed⌕ Search

Biomedical subjects

M F McCarty

Publications and source records attributed to M F McCarty.

At least 109 records · Page 6Linked to original sources
PubMed1997

natural antimutagenic agents may prolong efficacy of human immunodeficiency virus drug therapy.

The long-term efficacy of new combination drug therapies for human immunodeficiency virus infection may be limited by the tendency of transfected human immunodeficiency virus to mutate to drug-resistant forms. This argues for the use of safe antimutagenic measures as adjuvants to such therapies. Certain nutrients and food factors-notably selenium, green-tea polyphenols, and cruciferous phytochemicals-can suppress cancer initiation and mutagenesis in animal and cell culture models; epidemiological studies suggest that ambient variations in consumption of these food factors can have an important impact on human cancer rates. Low-fat diets may reduce deoxyribonucleic acid base damage in human leukocytes, whereas increased body iron stores are likely to increase mutation rates. Thus, ample but safe intakes of selenium, green-tea polyphenols, and cruciferous vegetables, in the context of a diet low in fat and assimilable iron, can be expected to prolong the efficacy of drug therapy in subjects infected with the human immunodeficiency virus. These measures can also be recommended for cancer prevention in the general population.

Antimutagenic Agents↗
PubMed1997

Glucosamine may retard atherogenesis by promoting endothelial production of heparan sulfate proteoglycans.

Heparan sulfate proteoglycans produced by vascular endothelium may function physiologically to restrain the migration, multiplication, and phenotypic transition of vascular smooth-muscle cells, and to maintain an anticoagulant luminal surface by bonding and activating antithrombin III. Thus, ample production of heparan sulfate proteoglycans may act to prevent atherosclerosis and its thrombotic complications. The ability of exogenous heparin to stimulate synthesis of heparan sulfate proteoglycans by vascular endothelium may be largely responsible for the positive outcomes of most controlled evaluations of low-dose heparin as a long-term therapy for coronary disease. Glucosamine, a biosynthetic precursor of mucopolysaccharides, can substantially enhance mucopolysaccharide production when added to cultured fibroblasts or chondrocytes; the clinical utility of oral glucosamine in osteoarthritis may reflect increased synthesis of cartilage proteoglycans. It is reasonable to speculate that exogenous glucosamine will likewise enhance heparan sulfate proteoglycans production by vascular endothelial cells, and, when administered orally in regimens comparable to those effective in osteoarthritis, will thereby act to retard atherogenesis.

Animals↗
PubMed1996

Chromium and other insulin sensitizers may enhance glucagon secretion: implications for hypoglycemia and weight control.

Increased pancreatic beta-cell secretory activity usually is associated with decreased alpha-cell activity; stimulated beta-cells release gamma-aminobutyric acid, which hyperpolarizes alpha-cells, inhibiting glucagon release. Thus, insulin secretion and glucagon secretion are usually inversely coupled. This suggests that chromium and other insulin-sensitizing modalities, by down-regulating beta-cell activity, may increase glucagon secretion. Such an effect might play a role in the documented therapeutic activity of supplemental chromium and biguanides in reactive hypoglycemia, and might also be of benefit to dieters.

Chromium↗
PubMed1996

Complementary vascular-protective actions of magnesium and taurine: a rationale for magnesium taurate.

By a variety of mechanisms, magnesium functions both intracellularly and extracellularly to minimize the cytoplasmic free calcium level, [Ca2+]i. This may be the chief reason why correction of magnesium deficiency, or induction of hypermagnesemia by parenteral infusion, exerts antihypertensive, anti-atherosclerotic, anti-arrhythmic and antithrombotic effects. Although the amino acid taurine can increase systolic calcium transients in cardiac cells (and thus has positive inotropic activity), it has other actions which tend to reduce [Ca2+]i. Indeed, in animal or clinical studies, taurine lowers elevated blood pressure, retards cholesterol-induced atherogenesis, prevents arrhythmias and stabilizes platelets--effects parallel to those of magnesium. The complex magnesium taurate may thus have considerable potential as a vascular-protective nutritional supplement, and might also be administered parenterally, as an alternative to magnesium sulfate, in the treatment of acute myocardial infarction as well as of pre-eclampsia. The effects of magnesium taurate in diabetes deserve particular attention, since both magnesium and taurine may improve insulin sensitivity, and also may lessen risk for the micro- and macrovascular complications of diabetes.

Animals↗
PubMed1996

Fish oil may impede tumour angiogenesis and invasiveness by down-regulating protein kinase C and modulating eicosanoid production.

Inhibition of angiogenesis shows considerable promise as a strategy for treating solid malignancies. Induction of collagenase by protein kinase C plays an important role in the angiogenic process as well as in metastasis. Lipoxygenase products are required for endothelial cell mitosis, and also promote collagenase production. By down-regulating hormonal activation of protein kinase C and modulating eicosanoid metabolism, ingestion of omega-3-rich fish oils may impede angiogenesis and reduce tumor invasiveness-thus rationalizing the growth-retardant and anti-metastatic effects of fish oil feeding almost invariably seen in animal tumour models. Certain other anti-inflammatory agents-including cromolyn (an inhibitor of protein kinase C activation) and gamma-linolenic acid (which indirectly inhibits lipoxygenase) may have analogous tumour-retardant activity. Clinical application of supplemental fish oil in cancer therapy is long overdue.

Animals↗
PubMed1996

Magnesium taurate for the prevention and treatment of pre-eclampsia/eclampsia.

The use of parenteral magnesium sulfate for the management of pre-eclampsia/eclampsia is well established. In striking analogy to the effects of hypermagnesemia, taurine has antivasospastic, antihypertensive, platelet-stabilizing, anticonvulsant and hypoxia-protective properties. Thus parenteral magnesium taurate can reasonably be proposed as a superior alternative to magnesium sulfate in the treatment of pre-eclampsia; administered orally as a component of prenatal supplementation, magnesium taurate might well have both preventive and therapeutic value in this syndrome. In the light of the hypoxia-protective actions of both magnesium and taurine, such supplementation might also protect fetuses experiencing temporary perinatal asphyxia, lessening the risk of cerebral palsy.

Eclampsia↗
PubMed1996

Glucosamine for wound healing.

The rapid production of hyaluronic acid by fibroblasts in the early stages of wound healing may be of crucial importance as hyaluronic acid stimulates the migration and mitosis of mesenchymal and epithelial cells. Increased levels of hyaluronic acid, as observed during fetal wound healing or as achieved by the topical application of hyaluronic acid during wound dressing, are associated with brisker healing and reduced scarring. Glucosamine availability appears to be rate-limiting for hyaluronic acid synthesis. Thus the administration of adequate amounts of glucosamine by mouth during the first few days after surgery or trauma can be expected to enhance hyaluronic acid production in the wound, promoting swifter healing and possibly diminishing complications related to scarring.

Administration, Oral↗
PubMed1996

Magnesium taurate and fish oil for prevention of migraine.

Although the pathogenesis of migraine is still poorly understood, various clinical investigations, as well as consideration of the characteristic activities of the wide range of drugs known to reduce migraine incidence, suggest that such phenomena as neuronal hyperexcitation, cortical spreading depression, vasospasm, platelet activation and sympathetic hyperactivity often play a part in this syndrome. Increased tissue levels of taurine, as well as increased extracellular magnesium, could be expected to dampen neuronal hyperexcitation, counteract vasospasm, increase tolerance to focal hypoxia and stabilize platelets; taurine may also lessen sympathetic outflow. Thus it is reasonable to speculate that supplemental magnesium taurate will have preventive value in the treatment of migraine. Fish oil, owing to its platelet-stabilizing and antivasospastic actions, may also be useful in this regard, as suggested by a few clinical reports. Although many drugs have value for migraine prophylaxis, the two nutritional measures suggested here may have particular merit owing to the versatility of their actions, their safety and lack of side-effects and their long-term favorable impact on vascular health.

Cortical Spreading Depression↗
PubMed1996

Fish oil may be an antidote for the cardiovascular risk of smoking.

The fact that the cardiovascular risk of ex-smokers approximates that of non-smokers after two years of abstinence, implies that accelerated atherogenesis is not the chief mechanism of smoking-related heart disease. Indeed, smoking or nicotine have adverse effects on blood rheology, thrombotic risk, coronary blood flow, and risk for arrhythmias. Omega-3-rich fish oils can be expected to correct or compensate for a remarkable number of the adverse impacts of smoking/nicotine: increased plasma fibrinogen, decreased erythrocyte distensibility, increased plasma and blood viscosity, increased platelet aggregability, increased plasminogen activator inhibitor levels, vasoconstriction of the coronary bed, reduced fibrillation threshold, increased triglycerides, reduced high-density lipoprotein cholesterol, and increased production of superoxide by phagocytes. Smokers who cannot overcome their addiction should be encouraged to substitute nicotine aerosols/gum for tobacco and advised to use supplementary fish oil and other cardioprotective nutrients.

Antidotes↗
PubMed1996

Fish oil and other nutritional adjuvants for treatment of congestive heart failure.

Published clinical research, as well as various theoretical considerations, suggest that supplemental intakes of the 'metavitamins' taurine, coenzyme Q10, and L-carnitine, as well as of the minerals magnesium, potassium, and chromium, may be of therapeutic benefit in congestive heart failure. High intakes of fish oil may likewise be beneficial in this syndrome. Fish oil may decrease cardiac afterload by an antivasopressor action and by reducing blood viscosity, may reduce arrhythmic risk despite supporting the heart's beta-adrenergic responsiveness, may decrease fibrotic cardiac remodeling by impeding the action of angiotensin II and, in patients with coronary disease, may reduce the risk of atherothrombotic ischemic complications. Since the measures recommended here are nutritional and carry little if any toxic risk, there is no reason why their joint application should not be studied as a comprehensive nutritional therapy for congestive heart failure.

Carnitine↗
PubMed1996

Up-regulation of intracellular signalling pathways may play a central pathogenic role in hypertension, atherogenesis, insulin resistance, and cancer promotion--the 'PKC syndrome'.

The modern diet is greatly different from that of our paleolithic forebears' in a number of respects. There is reason to believe that many of these dietary shifts can up-regulate intracellular signalling pathways mediated by free intracellular calcium and protein kinase C, particularly in vascular smooth muscle cells; this disorder of intracellular regulation is given the name 'PKC syndrome'. PKC syndrome may entail either a constitutive activation of these pathways, or a sensitization to activation by various agonists. The modern dietary perturbations which tend to induce PKC syndrome may include increased dietary fat and sodium, and decreased intakes of omega-3 fats, potassium, calcium, magnesium and chromium. Insulin resistance may be both a cause and effect of PKC syndrome, and weight reduction and aerobic training should act to combat this disorder. PKC syndrome sensitizes vascular smooth muscle cells to both vasoconstrictors and growth factors, and thus promotes both hypertension and atherogenesis. In platelets, it induces hyperaggregability, while in the microvasculature it may be a mediator of diabetic microangiopathy. In vascular endothelium, intimal macrophages, and hepatocytes, increased protein kinase C activity can be expected to increase cardiovascular risk. Up-regulation of protein kinase C in stem cells may also play a role in the promotion of 'Western' fat-related cancers. Practical guidelines for combatting PKC syndrome are suggested.

Arteriosclerosis↗
PubMed1995

Central insulin may up-regulate thyroid activity by suppressing neuropeptide Y release in the paraventricular nucleus.

Down-regulation of thyroid activity during underfeeding or diabetes - and upregulation during overfeeding - have not been adequately explained. Experimental findings suggest that hypothalamic secretion of thyrotropin releasing hormone (TRH) is modulated by feeding status; neuropeptide Y may be a key mediator of this modulation. I propose that insulin, acting centrally as a signal of carbohydrate availability, promotes TRH secretion by inhibiting release of neuropeptide Y in the paraventricular nucleus. This mechanism may contribute to the weight loss reported during administration of certain insulin-sensitizing agents, and observed during low-fat diets.

Animals↗
PubMed1995

Anabolic effects of insulin on bone suggest a role for chromium picolinate in preservation of bone density.

Activation of osteoclasts by parathyroid hormone (PTH) is mediated by PTH stimulation of osteoblasts, and is dependent on a PTH-induced rise in protein kinase C activity. Physiological levels of insulin reduce the ability of PTH to activate protein kinase C in osteoblasts, suggesting that insulin may be a physiological antagonist of bone resorption. In addition, insulin is known to promote collagen production by osteoblasts. These findings imply that efficient insulin activity may exert an anabolic effect on bone, and rationalize the many clinical studies demonstrating reduced bone density in Type I diabetes. Recently, the insulin-sensitizing nutrient chromium picolinate has been found to reduce urinary excretion of hydroxyproline and calcium in postmenopausal women, presumably indicative of a reduced rate of bone resorption. This nutrient also raised serum levels of dehydroepiandrosterone-sulfate, which may play a physiological role in the preservation of postmenopausal bone density. The impact of chromium picolinate (alone or in conjunction with calcium and other micronutrients) on bone metabolism and bone density, merits further evaluation in controlled studies.

Animals↗
PubMed1995

Inhibition of citrate lyase may aid aerobic endurance.

Owing to a substantial increase in glucose uptake by working muscle, glucose homeostasis during sustained aerobic exercise requires a severalfold increase in hepatic glucose output. As exercise continues and liver glycogen declines, an increasing proportion of this elevated glucose output must be provided by gluconeogenesis. Increased gluconeogenic efficiency in trained individuals is a key adaptation promoting increased endurance, since failure of hepatic glucose output to keep pace with muscle uptake rapidly leads to hypoglycaemia and exhaustion. Pre-administration of (-)-hydroxycitrate, a potent inhibitor of citrate lyase found in fruits of the genus Garcinia, may aid endurance during post-absorptive aerobic exercise by promoting gluconeogenesis. Carnitine and bioactive chromium may potentiate this benefit. The utility of this technique may be greatest in exercise regimens designed to promote weight loss.

Aerobiosis↗
PubMed1995

Hemostatic concomitants of syndrome X.

The elevated risk factors classically associated with Syndrome X do not adequately explain the increased cardiovascular risk linked to insulin resistance. Considerable indirect evidence and more limited direct evidence suggests that increases in certain prognostically significant hemostatic variables--notably plasma fibrinogen, factor VII coagulant activity, and plasminogen activator inhibitor-1 levels--may be concomitants of Syndrome X. Increased platelet aggregability, and a reduced capacity of vascular endothelium for prostacyclin generation, may also be associated with insulin resistance. Large clinical studies, involving quantification of insulin sensitivity and measurement of hemostatic variables, are required to test this hypothesis. It is unlikely that hyperinsulinemia mediates the connections between insulin resistance and hemostatic variables (or indeed other risk factors in Syndrome X). In light of the remarkably broad impact of insulin resistance on cardiovascular risk factors, promotion of optimal insulin sensitivity should assume a central role in preventive cardiology.

Animals↗
PubMed1995

Reduction of free fatty acids may ameliorate risk factors associated with abdominal obesity.

Experimental data as well as logical considerations suggest that the increased cardiovascular risk associated with abdominal obesity is mediated primarily by increased levels and flux of free fatty acids. Practical strategies for decreasing free fatty acid levels and/or flux may include: a very-low-fat, low-glycemic-index diet; promotion of insulin sensitivity (via exercise training, chromium, soluble fiber or drugs); anti-lipolytic agents; and stimulation of hepatic lipid oxidation with hydroxycitrate, carnitine and possibly fish omega-3s. Fortunately, many of these measures should also promote a leaner physique. Thus, even when abdominal obesity cannot be corrected, it may prove feasible to mitigate its dangers.

Abdomen↗