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Biomedical subjects

R Bressler

Publications and source records attributed to R Bressler.

At least 19 recordsLinked to original sources

New pharmacological approaches to therapy of NIDDM.

Currently available pharmacological agents have not been completely successful in restoring euglycemia in the non-insulin-dependent diabetes mellitus (NIDDM) patient. Several new approaches to the therapy of NIDDM have been formulated in recent years and are in various stages of laboratory or pharmaceutical development. Several of these agents are discussed in this article under categories relating to their mechanisms of lowering blood glucose: 1) inhibition of the release or action of counterregulatory hormones; 2) inhibition of postprandial glucose rise; 3) sensitization of tissues to insulin's actions; and 4) inhibition of gluconeogenesis, including inhibition of the long-chain acyl-CoA-carnitine acyltransferase I, the long-chain acylcarnitine translocase, and pyruvate carboxylase.

Animals

Induction of myocardial hypertrophy after coronary ligation in rats decreases ventricular dilatation and improves systolic function.

BACKGROUND: Previous studies have shown that hypertrophy of surviving myocytes after myocardial infarction (MI) is limited. Progressive ventricular dilatation after MI may occur when compensatory hypertrophy cannot restore left ventricular (LV) wall stress to normal. METHODS AND RESULTS: To test whether induction of additional myocyte hypertrophy might prevent pathological LV remodeling after large MI, we administered 2-tetradecylglycidic acid (TDGA) 20 mg/kg/day to sham-operated (n = 12) and MI (n = 10) rats for 10 days, beginning the third day after infarction. We have previously shown that chronic inhibition of long-chain fatty acid oxidation with TDGA in rats results in myocardial hypertrophy without any apparent impairment of LV systolic function. When compared with untreated MI rats (n = 9), we found that TDGA-treated MI rats had increases in LV weight/body wt, myocyte cross-sectional area, and peak developed LV pressure during abrupt aortic occlusion. MI rats treated with TDGA had lower LV end-diastolic pressures and smaller end-diastolic volumes, whereas stroke volume was maintained. The ex vivo passive LV pressure-volume relation was shifted toward the pressure axis compared with untreated infarct rats. In sham-operated rats, TDGA caused increases in LV weight/body wt, myocyte size, peak developed LV pressure, cardiac index, and stroke volume index, and a shift of the passive LV pressure-volume relation toward the pressure axis. CONCLUSIONS: Induction of myocardial hypertrophy with an inhibitor of long-chain fatty acid oxidation retarded the process of LV dilatation and produced beneficial effects on systolic function after large myocardial infarction. These data support the hypothesis that inadequate hypertrophy of residual myocardium after infarction may contribute to LV dilatation and the development of congestive heart failure.

Animals

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

Control of the blood glucose in diabetes mellitus is it valuable? Is it feasible.

The controversy over the whether strict blood glucose control prevents or attenuates the complications of diabetes is still unresolved, but the available data support the value of good blood glucose control. The resolution of the controversy is not feasible at present because of the complexity and financial cost of a definitive prospective study and because we may not presently possess pharmacological agents which can accomplish the goal of long term strict control of the blood glucose. Finally, whereas we regard retinopathy, nephropathy and neuropathy as valid pathological endpoints, we are not secure in assuming that blood glucose represents the critical measurement for longitudinal assessment of metabolic control. Studies evaluating control based on blood and urine glucose assessments are complicated by the failure of the data to reflect changes in minute to minute regulation. Thus, the relative insensitivity of some of these parameters of control could account for failures to demonstrate a correlation between adequacy of therapy and diabetic complications.

Basement Membrane

Dose tolerance and pharmacokinetic studies of L (+) pseudoephedrine capsules in man.

Dose tolerance and pharmacokinetic studies of pseudoephedrine sustained action capsules were performed in thirty-three adult male subjects who received either 120 mg or 150 mg capsules every twelve hours for seven consecutive days in a double-blind parallel design study. Although only one subject in the 150 mg group was discontinued prematurely from this study, a large number of side effects typical of CNS stimulation were seen. A placebo effect might account for a portion of these complaints, however symptoms evaluated as being due to drug were significantly more severe and persistent in the 150 mg group. Pulse rates showed a persistent and significant increase while systolic and diastolic blood pressure fell from the baseline values in both groups. A pharmacokinetic analysis of the pseudoephedrine plasma concentration-time data provided estimates of half-life and the volume of distribution/availability ratio. The values obtained were in good agreement with values reported by others. Half-life was not influenced by urine pH probably as a result of the narrow range of urine pHs observed in the subjects. Calculations of relative bioavailability suggest that the 120 mg capsule formulation has a 30% greater bioavailability compared to the 150 mg capsule.

Adult

Insulin treatment in diabetes.

Efficacy of and indications for the use of purer forms of insulin have now been established, and arguments showing the relation of blood glucose control to the development and progression of complications have been strengthened.

Adipose Tissue

Characterization of a carrier-mediated transport system for taurine in the fetal mouse heart in vitro.

Cardiac taurine levels are elevated in hypertension and congestive heart failure. A possible mechanism for this increase in taurine is an alteration of its uptake. We sought to identify and characterize a carrier-mediated transport system for taurine in the mammalian myocardium utilizing the fetal mouse heart in organ culture. Hearts from fetuses of 16-19 days gestational age used in these studies had an endogenous taurine content of 14.1+/-0.5 nmol/mg tissue. The uptake of [(3)H]taurine was linear for up to 8 h. Taurine was accumulated against a concentration gradient as demonstrated by a net increase in taurine concentration when hearts were incubated in 0.5 mM taurine. [(3)H]Taurine uptake was saturable, K(m) = 0.44 mM, temperature dependent, and required sodium. The close structural analogues, hypotaurine and beta-alanine, reduced [(3)H]taurine uptake by 87% when present in 100-fold excess. The alpha-amino acids alanine, alpha-aminoisobutyric acid, glycine, leucine, and threonine did not inhibit uptake. Other taurine analogues tested were guanidinotaurine, guanidinopropionic acid, gamma-aminobutyric acid, 2-aminoethane phosphonic acid, aminomethane sulfonic acid, 3-aminopropane sulfonic acid, N-acetyltaurine, and isethionic acid. We conclude that a carrier-mediated transport system for taurine exists in the fetal mouse heart based on the demonstration of (a) temperature dependence, (b) saturability, and (c) structural selectivity of the uptake process. Transport was demonstrated to be mediated by a beta-amino acid uptake system. In addition, taurine uptake was observed to be sodium dependent, energy dependent, and capable of accumulating taurine against a concentration gradient.

Animals

Carnitine prevention of adriamycin toxicity in mice.

Carnitine, a naturally occurring nontoxic compound which aids the myocardial cell in efficiently meeting energy requirements, has been evaluated as a possible protective agent against acute and chronic adriamycin induced mouse toxicity. We have shown that carnitine treatment significantly decreases both acute high dose and chronic, intermittent, low dose adriamycin associated lethality in normal mice. These protective effects are accomplished without decreasing adriamycin anti-tumor activity or increasing bone marrow toxicity.

Animals