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Biomedical subjects

R Bressler

Publications and source records attributed to R Bressler.

At least 37 records · Page 2Linked to original sources
PubMed1985

Carnitine in the streptozotocin-diabetic rat.

Rats made moderately diabetic by streptozotocin (decreased growth without decreased body mass, blood glucose, 588-840 mg/dl) and nondiabetic rats were either fed a purified diet with no measurable carnitine (diet 1), the same diet supplemented with carnitine (44.5 nmol/g food, diet 2), or a closed formula, nonpurified diet (3.3 nmol/g food, diet 3). Levels of total carnitine (free + acyl) were lower (P less than 0.05) in plasma, heart, soleus, extensor digitorum longus and kidney of rats fed diet 1 compared to those fed diet 2. Liver carnitine in diabetic animals was 2.6- to 4.4-fold higher than in nondiabetic animals with urinary carnitine of rats fed diet 1 being four times greater in diabetic than in nondiabetic rats. Other changes in tissue total carnitine were less pronounced. Compared to diabetic rats, insulin-treated diabetics had lower urinary excretion of carnitine and blood glucose levels (P less than 0.05), and tissue carnitine approximating nondiabetic levels. Significant catabolism of carnitine was not found. Apparent carnitine biosynthesis (diet 1) showed no difference between nondiabetic and diabetics (31.5 +/- 1.6 and 31.2 +/- 2.2 nmol/g of body weight per day, respectively) suggesting elevated liver levels resulted from redistribution.

Animals↗
PubMed1985

Cancer in the elderly: basic science and clinical aspects.

The incidence of cancer increases progressively with age. Rearrangements of genomes have been found to accompany cellular aging. These factors, in concert with age-dependent alterations in immune function and host defense, may help to explain the increased risk of malignant disease in aged persons. The clinical presentation and natural history of neoplasia are also affected by aging. This conference reviews recent developments in these areas, examines the effects of drug use in the elderly and implications for management, and discusses current information on how age may influence the response of cancer to therapy.

Aged↗
PubMed1984

In vitro osmoregulation of taurine in fetal mouse hearts.

Regulation of taurine transport and accumulation in explanted fetal mouse hearts is shown to be under osmotic control. All osmotic agents studied, both ionic (NaCl, LiCl, choline Cl) and nonionic (sucrose, glucose) stimulated [3H]-taurine transport during an incubation of 19 h. Hyperosmotic stimulation of transport achieved statistical significance by 3 h in the presence of sucrose (P less than 0.05). After 1 h, 40 mM NaCl engendered a 56% increase in [3H]-taurine transport (P less than 0.01). The NaCl stimulation at 1 h may relate more to the transport system's absolute sodium ion requirement than hyperosmotic stimulation. Incremental addition of NaCl or sucrose linearly stimulates [3H]-taurine transport in an incubation of 19 h. Total taurine, measured by HPLC, increased 25% with addition of either 40 mM NaCl or 80 mM sucrose. Hyperosmotic stimulation of transport was not blocked with propranolol but was additive to beta-adrenergic stimulation of transport. Osmotic stimulation occurred with a large increase in Vmax (0.41----0.81 nmol/mg tissue/h) but only a small change in Km (0.51----0.43 mM). After 1 h preincubation with a hyperosmotic addition phenylalanine transport was measured, but was not different from control. Phenylalanine accumulation measured during 19 h incubation similarly was not altered. Streptozotocin induced diabetic rats had elevated plasma osmolarities (295 +/- 2.1----322 +/- 1.3 mosmol) and cardiac taurine (24.3 +/- 1.2----36 +/- 1.0 mumol/g wet wt.). The data presented demonstrates that mammalian cardiac taurine is regulated by the osmotic environment of the heart, suggesting an osmoregulatory function for intracellular taurine and physiological relevance in disease states such as diabetes.

Animals↗
PubMed1983

The effects of cyclopropane carboxylic acid on hepatic pyruvate metabolism.

The effects of the hypoglycemic agent, cyclopropane carboxylate, on the metabolism of various substrates that enter the mitochondrion via the mitochondrial monocarboxylate transporter were investigated in perfused rat livers. Metabolism of pyruvate, branched-chain alpha-keto acids, acetoacetate and, to a lesser extent beta-hydroxybutyrate, were all inhibited by cyclopropane carboxylate. In addition, the stimulation of pyruvate decarboxylation by beta-hydroxybutyrate at low pyruvate concentrations because of exchange of extramitochondrial pyruvate with intramitochondrially generated acetoacetate, was abolished by cyclopropane carboxylate. Gluconeogenesis from alanine, which is not transported via the monocarboxylate translocator, was not inhibited by low concentrations of cyclopropane carboxylate. Cyclopropane carboxylate also inhibited fatty acid oxidation, as measured by ketone body production. These results support previous findings that the hypoglycemic agent, cyclopropane carboxylate, exerts at least some of its metabolic effects at the level of the mitochondrial monocarboxylate transporter.

Animals↗
PubMed1982

Metabolic control of prevention of nephropathy by 2-tetradecylglycidate in the diabetic mouse (db/db).

The genetically diabetic mouse (db/db) exhibits hyperphagia, progressive weight gain, hyperglycemia, and hyperinsulinemia during the first few months of life during which time characteristic pathologic changes occur in several organ systems including the kidney. The extent to which long chain fatty acid oxidation (LCFAO) contributes to excessive gluconeogenesis and hyperglycemia in these animals in unknown. Therefore, the synthetic fatty acid analogue 2-tetradeclyglycidate (TDHA), a potent inhibitor of LCFAO, was given orally to db/db mice to evaluate its capacity to control the blood glucose and prevent their diabetic nephropathy. Five groups of diabetic mice (N = 6) were assigned to receive TDGA in a dose of 5, 10, and 25 mg/kg/day, vehicle (tragacanth), or nothing (control). TDGA had no observable effects on food intake or growth patterns. Drug-treated animals had significant lowering of fasting glucose at 0 and 4 h after dosing during the midportion of the study (2-6 wk). In the latter part of the study (wk 8-11), blood glucose 4 h after dosing was lowered in mice given 10 and 25 free fatty acids. Animals receiving TDGA 25 mg/kg/day exhibited significant inhibition of immunopathologic changes in the kidney. Heart weight was significantly increased in mice receiving TDGA 25 mg/kg/day, and the total amount of myocardial carnitine content was increased in all three drug-treated groups. Increased tissue deposition of lipid was not apparent on histologic examination of liver in drug-treated animals. Inhibition of long chain fat oxidation in the db/db mouse results in significant lowering of blood glucose, and decreased the renal immunopathologic features of diabetic nephropathy in this animal model.

Animals↗
PubMed1981

Carnitine transport in isolated adult rat heart myocytes and the effect of 7,8-diOH chlorpromazine.

We studied the carnitine transport system in isolated adult rat heart myocytes able to tolerate physiological concentrations of calcium. Carnitine uptake occurred against a concentration gradient and was inhibited by 2,4-dinitrophenol (2,4-DNP). The transport system had a Km of 60 microM and a Vmax of 110 pmol/mg protein per hour. The carnitine precursor deoxycarnitine, acetylcarnitine, and both the D and L isomers were effective inhibitors of uptake. The transport of carnitine was not dependent on sodium ions, but was stimulated by decreasing concentrations of calcium ions. Decreased uptake was observed in the presence of beta-adrenergic agonists and antagonists, dibutyrl cyclic AMP, local anesthetics, and ouabain. No significant alteration of uptake was effected by atropine, carbachol or a variety of tricyclic agents. The auto-oxidation product of 7,8-dihydroxychlorpromazine (7,8-diOH CPZ) decreased carnitine efflux from myocytes, which were highly permeable to low molecular weight compounds. We found that this effect was not substrate specific, and is discussed as possibly resulting from a change in the arrangement or state of polymerization of subcellular structural components.

Animals↗
PubMed1981

Clinical pharmacology of sulphonylurea hypoglycaemic agents: part 1.

The sulphonylureas are drugs of limited efficacy with fairly frequent, although usually reversible, adverse effects. Being highly protein bound, these drugs are subject to potential displacement interactions, which when combined with inhibition of their elimination, may result in profound hypoglycaemia. Due to hepatic metabolism and renal excretion of the parent drug and/or active metabolites, these agents are contraindicated in patients with liver or kidney disease. Oral hypoglycaemic agents are frequently used in elderly patients with limited vision and no dependable relatives, who cannot give themselves insulin. It is these patients--elderly, living alone in poor circumstances, often on several other medications, and possibly malnourished--who are at greatest risk for catastrophic hypoglycaemia with these drugs. Long acting agents like chlorpropamide and glibenclamide should be avoided in the elderly and in patients with irregular eating habits. Diet and exercise remain the primary modes of therapy of non-insulin-dependent diabetes mellitus. With careful patient selection and attention to drug and disease interactions, the sulphonylureas may be a useful adjunct to diet in treating a small proportion of insulin-resistant (so-called adult onset) diabetics. Patients most likely to respond to sulphonylureas are over 40 years old, mildly to moderately obese, have had diabetes for less than 5 years, and have never exhibited ketosis. There is no indication for simultaneous use of sulphonylureas and insulin. With both insulin and the oral hypoglycaemics alcohol is the agent most commonly implicated in lethal interactions.

Diabetes Mellitus↗
PubMed1981

Prevention of diabetic nephropathy by diet control in the db/db mouse.

Diabetes in the C57BL/KsJ(db/db) mouse is initially expressed as hyperinsulinemia, followed by hyperphagia, progressive obesity, and widespread pathologic abnormalities. This study was designed to evaluate the effects of metabolic control on the natural history of the diabetic nephropathy. Beginning at 1 mo of age and continuing for 12 wk, diabetic mice were subjected to controlled dietary restriction, such that their weight was maintained similar to that of age-matched, nondiabetic heterozygotes. Diet-restricted diabetics were compared with diabetics fed ad libitum and heterozygote nondiabetics. Significant lowering of fasting blood glucose, water intake, and plasma insulin was achieved by diet restriction. The diet-restricted diabetes demonstrated enhanced metabolic efficiency, consuming approximately half as much food as the nondiabetics, while maintaining a similar weight. Diabetics fed ad libitum evidenced well-defined renal lesions that included 3 + to 4 + immunoglobulin deposition in the glomerular mesangium, and generalized mesangial matrix expansion. These lesions were completely prevented in diet-restricted diabetes whose glomeruli were normal light microscopy, and demonstrated trace to 1 + mesangial immunoglobulin deposition, features identical in all respects to the nondiabetics. These results indicate that diabetic control achieved by preventing of obesity in the db/db mouse prevents the development of diabetic nephropathy.

Animals↗
PubMed1980

Liver function tests and low-dose estrogen oral contraceptives.

Twenty healthy female volunteers were treated with 35 microgram ethinyl estradiol and 0.4 mg norethindrone for a two-month period of time. Liver function tests (serum SGOT, SGPT, LDH, alkaline phosphatase, total bilirubin, total protein, albumin and prothrombin times) were measured at baseline and control prior to treatment, and at one and two months of therapy. There was a 1.25% incidence of abnormalities in the 320 tests conducted during therapy. During the first month of therapy, there was a 1.9% incidence of abnormal tests. 0.625% incidence of abnormal tests was seen in the second month of treatment. A 5% incidence of abnormalities (single episodes in each parameter) was seen in SGPT, LDH, total bilirubin and prothrombin time levels during the two-month period. This was well below the 10-30% incidence of abnormalities reported with 50-100 microgram of estrogen-containing birth control pills in previous studies. There seems to be little effect on liver function tests with use of estrogen preparations containing 35 microgram ethinyl estradiol.

Adult↗
PubMed1979

Efficacy of estradiol vaginal cream in postmenopausal women.

In a double-blind parallel study daily intravaginal administration of conjugated estrogen cream and estradiol cream for 14 days relieved vasomotor and vaginal postmenopausal symptoms in 29 postmenopausal women. By day 14, therapy with the estradiol vaginal cream resulted in plasma estrone and estradiol levels closer to those in premenopausal women than therapy with the conjugated estrogen cream. The extent of improvement and final estradiol plasma levels in the estradiol vaginal-cream group correlated. There was no correlation with severity of symptoms or estradiol plasma level at baseline. The metabolism of the conjugated estrogen cream might account for absence of correlation between improvement and final estradiol plasma levels in the conjugated vaginal-cream group.

Administration, Topical↗