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Biomedical subjects

F H Epstein

Publications and source records attributed to F H Epstein.

At least 199 records · Page 11Linked to original sources

Indomethacin impairs water diuresis in the DI rat: role of prostaglandins independent of ADH.

The mechanisms by which endogenous renal prostaglandins regulate water excretion were investigated in these studies. Inhibition of prostaglandin synthesis slowed water diuresis in water-loaded unanesthetized Sprague-Dawley rats and in Brattleboro rats with hereditary diabetes insipidus owing to absence of endogenous vasopressin. In both strains, treatment with indomethacin or meclofenamate increased the osmolality of the renal papilla by raising sodium and urea content, and also increased the osmolality of the urine. Endogenous creatinine clearance and solute excretion were unchanged. The data are consistent with an effect of prostaglandins on solute transport by renal tubules and demonstrate that endogenous prostaglandins influence water excretion by a mechanism independent of the presence of antidiuretic hormone.

Animals↗

A study of induced hyponatremia in the prevention and treatment of sickle-cell crisis.

Because the formation of sickle cells is dependent on the intracellular concentration of deoxyhemoglobin S, we investigated the possibility of altering or preventing sickle-cell crises by reducing serum sodium so as to cause red cells to swell. In three patients with sickle-cell anemia who had been disabled by recurrent painful crises, sustained dilutional hyponatremia was induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in combination with a high fluid intake. Mean corpuscular hemoglobin concentration fell, and the degree of sickling at low partial oxygen pressure was reduced, as determined by morphologic criteria and by increased oxygen affinity of blood. Chronic hyponatremia (serum sodium, 120 to 125 mmol per liter) reduced the frequency of painful crises, whereas acutely induced hyponatremia abbreviated the duration of crises. These results, although preliminary, are encouraging enough to warrant further study of the safety and effectiveness of induced hyponatremia in the prevention and treatment of sickle-cell crises.

Adult↗

Adrenergic modulation of extrarenal potassium disposal.

We studied the role of catecholamines in the regulation of potassium homeostasis in nine healthy subjects given intravenous potassium chloride (0.5 meq per kilogram of body weight) in the presence and absence of propranolol. Potassium infusion elevated serum potassium 0.6 +/- 0.09 meq per liter (mean +/-S.E.M.). Addition of propranolol augmented the rise (0.9 +/- 0.05 meq per liter) and prolonged the elevation in serum potassium without decreasing urinary potassium excretion. In a separate study, the same potassium load was administered with a concomitant infusion of epinephrine in five subjects. Epinephrine markedly blunted the increment in serum potassium (0.1 +/- 0.06 meq per liter) while reducing renal potassium excretion. Plasma aldosterone was not altered by the experimental procedures. Serum insulin fell minimally in the presence of propranolol but was unaffected by epinephrine. beta-Adrenergic blockade impairs and epinephrine enhances extrarenal disposal of an acute potassium load. These findings suggest that in patients with impaired potassium disposal, the risk of hyperkalemia may be increased when sympathetic blockade is induced.

Adrenergic beta-Antagonists↗

Role of Na-K-ATPase in chloride cell function.

In seawater eels the efflux of sodium (and chloride) across the gill is directly proportional to the activity of Na-K-ATPase in homogenates of gill filaments. The rate of ion movement, however, is substantially greater than at the temperature of seawater. Na-K-ATPase is localized predominantly on the basolateral surface of the chloride cell so that ouabain inhibits from the blood side rather than from the apical or mucosal surface of chloride cells. Chloride, rather than sodium, is probably the actively transported ion species, and an attractive hypothesis for active chloride transport is one that invokes the cotransport of chloride with sodium across the basolateral membrane, the energy for which is supplied indirectly by the operation of the Na-K-ATPase pump. Exposure to freshwater sharply dissociates ion movements from Na-K-ATPase activity, possibly by changing the permeability of cell membranes to chloride movements.

Adaptation, Physiological↗

Recent international changes in coronary heart disease mortality.

Monitoring secular trends in mortality as well as morbidity from coronary heart disease (CHD) is important in order to relate favourable or unfavourable habits of daily living to the risk of disease, with a view toward effective preventive measures. A marked decline in CHD mortality has been observed in the United States during the past decade. Similar, but smaller, reductions have been recorded in a few other countries but the overall international tendency is toward unchanged or increasing mortality. There is a suggestion for countries with initially higher rates to register declines while the reverse tends to occur for low-mortality countries. The favourable trends in the United States can be linked to improvements in the style of life but parallel information in other countries is largely lacking. International, collaborative efforts to monitor CHD disease rates, living habits and risk factor distributions by country, region and social groups is a major need in the search for effective prevention programmes in the community.

Coronary Disease↗

[Prevention of arteriosclerosis. Current basis].

Despite the advances in therapy, the high incidence, high mortality, and prematurity of coronary heart disease demonstrate the need for prevention. Measurement of a series of easily determined risk factors permits the early recognition of subjects at risk with remarkable reliability. However, reduction of risk factors affords protection against the illness only if they are causally connected with the disease mechanisms. The major evidence for linking atherosclerosis and its consequences with risk factors is reviewed. Particular attention is focused on serum lipids and the "lipid theory", smoking, elevated blood pressure, and physical inactivity, which are, on the basis of current knowledge, not only the most important factors but those most readily influenced by changes in daily living habits. Among the multiple risk factors mention is also made of obesity, diabetes, psychosocial stress, and hereditary predisposition. The probability of a causal relationship between risk factors and disease mechanisms justifies every effort to prevent the development of these precursors, or to treat them prophylactically if already present.

Arteriosclerosis↗

[The incidence of coronary disease in Switzerland compared to the rest of Europe].

Switzerland ranks low in ischaemic heart disease mortality amongst the European countries. Evidence from field studies, however, would suggest that mortality is underestimated. Nevertheless, in Switzerland, like in France, the disease is probably rather less common than in some other comparable countries. The difference seems unexplained by the major, known risk factors, indicating a need for further research.

Coronary Disease↗

Metabolic requirements for renal function.

Renal mass accounts for only 0.5% of body weight, yet the kidney consumes 7% of the body's total oxygen uptake. Most is used for tubular transport, but a significant portion contributes to less well-recognized aspects of renal function. Cortical gluconeogenesis capacity, for example, exceeds that of the liver per gram of tissue. Basal and transport metabolic processes are examined in terms of clinical relevance.

Adenosine Triphosphatases↗

Elasmobranch rectal gland cell: autoradiographic localization of [3H]ouabain-sensitive Na, K-ATPase in rectal gland of dogfish, Squalus acanthias.

Specific binding of radiolabeled inhibitor was employed to localize the Na-pump sites (Na,K-ATPase) in rectal gland epithelium, a NaCl-secreting osmoregulatory tissue which is particularly rich in pump sites. Slices of gland tissue from spiny dogfish were incubated in suitable [3H]ouabain-containing media and then prepared for Na,K-ATPase assay, measurement of radiolabel binding, or quantitative freeze-dry autoradiography at the light microscope level. Gross freezing or drying artifacts were excluded by comparison with additional aldehyde-fixed slices. Characterization experiments demonstrated high-affinity binding which correlated with Na,K-ATPase inhibition and half-saturated at approximately 5 microM [3H]ouabain. At this concentration, the normal half-loading time was approximately 1 h and low-affinity binding to nonspecific sites was negligible. Autoradiographs from both 1- and 4-h incubated slices showed approximately 85% of the bound [3H]ouabain to be localized within a 1-micrometer wide boundary region where the highly infolded basal-lateral cell membrane are closest to the mitochondria. These results establish that most of the enormous Na,K-ATPase activity associated with rectal gland epithelium is in the basal-lateral cell membrane facing interstitial fluid and not in the luminal membrane facing secreted fluid. Moreover, distribution along the basal-lateral membrane appears to be nonuniform with a higher density of enzyme sites close to mitochondria.

Animals↗

Hormonal regulation of active chloride transport in the dogfish rectal gland.

Active transport of chloride is modulated by cyclic AMP in the rectal gland of Squalus acanthias. Vasoactive intestinal peptide (VIP) specifically activates the production of cyclic AMP by the gland and stimulates the secretion of chloride. Somatostatin inhibits VIP-induced secretion but has no effect alone. Both these peptides are present in the dogfish shark and may play an important role in electrolyte homeostasis.

Animals↗