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F H Epstein

Publications and source records attributed to F H Epstein.

At least 109 records · Page 6Linked to original sources
PubMed1990

Relation of adenosine to medullary injury in the perfused rat kidney.

In isolated perfused rat kidneys the medullary thick ascending limb (mTAL) is uniquely vulnerable to cellular injury produced by its hypoxic milieu and exacerbated by active transport. Endogenous inhibitors of transport might therefore be expected to reduce cell injury. We studied the possible role of adenosine in altering mTAL damage in isolated rat kidneys perfused for 60 min. When adenosine deaminase was added to the recirculating perfusate in 8 experiments, severe damage to mTAL cells adjacent to the inner medulla was significantly exacerbated to involve 89.4 +/- 3% of them as compared to 74.9 +/- 4.7% in 9 controls (p less than 0.025). Similar results were obtained when 6-nitrobenzylthioinosine, which inhibits adenosine efflux from hypoxic cells, was added to the perfusion (n = 5, p less than 0.025). The addition of the adenosine analogue R(-)-phenylisopropyladenosine [R(-)-PIA] conferred protection, so that now only 12.5 +/- 2.5% of deep mTAL cells exhibited severe morphological damage (n = 7, p less than 0.005). The protective effect of R(-)-PIA was minimized by 8-phenyltheophylline, which blocks adenosine receptors. The S(+)-isomer of PIA was significantly less potent than R(-)-PIA in protecting against hypoxic injury. These results suggest that endogenous adenosine may play a role in modifying the injurious effects of anoxia on medullary cells, by inhibiting active transport.

Adenosine↗
PubMed1989

Renal medullary Na-K-ATPase and hypoxic injury in perfused rat kidneys.

We wished to see if chronic alterations in Na-K-ATPase activity in the medullary thick ascending limb would modify the susceptibility of its cells to the hypoxic injury produced by perfusion of the isolated kidney. Rats were fed a diet high (64%) or low (8%) in protein for three weeks. Renal medullary Na-K-ATPase was 75 +/- 12 U/mg protein/hr (mean +/- SE) in the high protein group and 44 +/- 3 in rats given low protein. After 90 minutes of perfusion, the kidneys of rats fed a high protein diet showed almost all mTAL cells near the inner medulla with severe damage (93 +/- 4.8%), whereas the same zone in perfused kidneys of rats on a low protein diet showed only 47 +/- 7.7% injury. In a similar fashion, damage to mTAL cells seen in perfused kidneys was greatly augmented by compensatory renal hypertrophy produced by removal of the contralateral kidney two weeks earlier, and by a diet high in potassium given for two weeks, procedures which also increased the activity of medullary Na-K-ATPase. The results suggest that the level of transport work of medullary cells mediated by Na-K-ATPase is a determinant of the vulnerability of mTAL cells to hypoxic injury.

Animals↗
PubMed1989

The relationship of lifestyle to international trends in CHD.

Three components of lifestyle--nutrition, smoking and alcohol drinking patterns--have been related to rates of decline or increase of coronary heart disease (CHD) mortality in 27 countries during the past 10 to 25 years. In almost all of the countries with major falls or rises in CHD mortality, there are, respectively, corresponding decreases or increases in animal fat consumption, with reciprocal changes in the consumption of vegetable fats. Countries with moderate or small mortality declines show variable patterns of fat consumption. The prevalence of smoking is declining among men and remains unchanged or is increasing slightly among women in most countries, suggesting that differences in the rate of decline between countries or between the sexes are not related to an appreciable degree to differences in the change of smoking habits; however, the mortality changes in any individual country are most probably influenced by smoking. The consumption of alcoholic beverages increases almost everywhere and cannot be related quantitatively to the secular CHD mortality trends. These findings support in general the presently recommended courses of action for the prevention of premature CHD.

Alcohol Drinking↗
PubMed1988

Calcium and hypoxic injury in the renal medulla of the perfused rat kidney.

To study the interaction between calcium and the medullary hypoxic lesions found in isolated perfused rat kidneys, the acute effects of high extracellular calcium upon renal function and morphology were evaluated in kidneys perfused with cell-free medium at a total calcium concentration of 8 to 9 mg/dl (controls), 13 to 14 and 19 to 20 mg/dl (high Ca++). High Ca++ increased hypoxic damage to medullary thick ascending limbs from 58.2 +/- 4.0% of tubules in controls to 80.2 +/- 4.0% (P less than 0.005) in the deepest area of the outer medulla. Morphological changes in the cortex were minimal. The increase in damage to medullary thick limbs induced by high Ca++ was prevented by the calcium channel blocker verapamil. Addition of the calcium ionophore A23187 to controls reproduced the effects of high Ca++ with an increase in the proportion of damaged thick limbs to 92.1 +/- 4.1% (P less than 0.001 vs. controls). Addition of equimolar amounts of magnesium chloride did not reproduce the effect of high calcium perfusions. When transport activity was reduced with ouabain, high calcium perfusions were no longer associated with structural damage. In kidneys perfused with a medium enriched with amino acids, the proportion of tubules with severe, irreversible damage increased from 12 +/- 3 to 43 +/- 10% (P less than 0.01) after high calcium perfusion, and to 75 +/- 12% (P less than 0.001) after perfusion with the calcium ionophore. High extracellular and intracellular calcium appear to act in concert with hypoxia to increase the susceptibility of the renal medulla to injury by mechanisms potentially operative in hypercalcemic and ischemic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1988

Neural control of shark rectal gland.

Veratrum alkaloids stimulated salt secretion by the isolated perfused rectal gland of Squalus acanthias. Stimulation by veratrine was prevented by the nerve channel blockers tetrodotoxin and procaine and was not evident in a preparation of dispersed rectal gland cells. Vasoactive intestinal peptide (VIP)-like immunoreactivity was detected by histological techniques in neuronal tissue within the rectal gland. Veratrine stimulation caused the release of immunoreactive VIP into the venous effluent of perfused glands. The stimulatory action of veratrine was inhibited by somatostatin, another neuropeptide known to be present in nerves of Squalus rectal gland. These findings suggest the likelihood of neural modulation of rectal gland function.

Adenosine↗
PubMed1988

Acute renal failure with selective medullary injury in the rat.

Since human acute renal failure (ARF) is frequently the result of multiple rather than single insults, we used a combination of treatments to induce ARF in rats. Uninephrectomized, salt-depleted rats injected with indomethacin developed ARF after administration of radiocontrast. After 24 h, the plasma creatine rose from 103 +/- 3 to 211 +/- 22 mumol/liter (mean +/- SE) and the creatinine clearance dropped from 0.7 +/- 0.1 to 0.2 +/- 0.04 ml/min (P less than 0.001). Severe injury was confined to the outer medulla and comprised necrosis of medullary thick ascending limbs (mTALs), tubular collapse, and casts. Other nephron segments were free of damage except for the proximal convoluted tubules which showed vacuole formation originating from lateral limiting membranes that resembled changes reported in human contrast nephropathy. Cell damage to mTALs included mitochondrial swelling, nuclear pyknosis, and cytoplasmic disruption with superimposed calcification; these changes were most severe in the deepest areas of the outer medulla, away from vasa recta in zones remote from oxygen supply. The fraction of mTALs with severe damage was 30 +/- 7% (range 2-68) and the extent of injury was correlated with a rise in plasma creatinine (r = 0.8, P less than 0.001). Thus, the nature of mTAL injury was similar to the selective lesions observed in isolated kidneys perfused with cell-free medium and was shown to derive from an imbalance between high oxygen demand by actively transporting mTALs and the meager oxygen supply to the renal medulla. Combined multiple renal insults in the rat produce ARF that resembles the clinical syndrome of contrast nephropathy and is characterized by selective mTAL injury conditioned by medullary hypoxia.

Acute Kidney Injury↗
PubMed1988

Risk factors and prevention of atherosclerosis: specific prevention directed to the high-risk patients.

The high-risk population strategy of coronary heart disease prevention are not alternatives but complement each other, both being parts of a comprehensive community programme. High-risk persons must be detected through screening and require more individual and intensive protection than persons at lesser risk for whom the population approach provides adequate preventive care. The relative effectiveness of the two strategies may be compared, using data from prospective epidemiological studies. The high-risk strategy alone compares well with a limited population strategy alone but the balance is shifted in favour of the population at large. In practice, it does not matter to compare the two strategies in isolation but to assess their effectiveness in combination; it can be shown that the combined effect is likely to make a major dent in the burden of disease in the population. It used to be thought and hoped that the discovery of new and more powerful risk factors would discriminate more sharply between future cases and non-cases of coronary heart disease and thus concentrate the majority of new events in a minority of the population. An attempt was made to show that new advances will add to the preventive potential inherent in risk factors but are not likely to identify future victims of the disease with such precision that the high-risk strategy would eventually supplant the population strategy. Instead, new screening strategies must be developed to detect and protect to the greatest possible extent all the risk carriers who are scattered, in terms of single and multiple risk factors, all-over the population. A major responsibility for the effectiveness of the high-risk strategy is carried by the practicing physician, to select the best treatment for individuals and their families and to encourage adherence to a new life style, as well as compliance with drug therapy, if indicated.

Arteriosclerosis↗
PubMed1988

International trends in mortality and morbidity from ischaemic heart disease.

International mortality trends for ischaemic heart disease are summarized for the period 1972 to 1984, comparing the most recent with earlier changes in total mortality. A review of data on changes in incidence, short-term and long-term prognosis indicate that major declines in coronary heart disease mortality must have been due primarily to prevention, but improvements in short-term prognosis and, according to some studies, long-term prognosis have most likely contributed to the downward trends. Based on information available to date, changes in life styles, health-promoting or detrimental as the case may be, correlate with changes in risk factors and observed trends in coronary heart disease mortality.

Australia↗
PubMed1987

Physiological and clinical implications of medullary hypoxia.

Because of countercurrent capillary flow, the renal medulla of mammalian kidneys is perpetually hypoxic, the ambient oxygen tension hovering close to the critical Po2 that limits respiration. Within this environment, the mitochondria-rich cells of the medullary thick ascending limb (mTAL) require large amounts of energy to accomplish the work of ion transport. These cells are therefore uniquely vulnerable to anoxic damage, as is demonstrated by morphological changes in isolated perfused rat kidneys. The lesions of hypoxia in mTAL cells of perfused kidneys can be greatly exaggerated by maneuvers that increase the work of transport and practically eliminated by inhibitors of active transport, like ouabain or furosemide, or by interrupting glomerular filtration. The close dependence of experimental ischemic injury on active transport suggests that endogenous inhibitors of transport may play an important physiological role in modulating the susceptibility of the medulla to anoxic injury in health and disease. Candidates for this role include adenosine and locally formed derivatives of arachidonic acid that have been shown to influence metabolism and transport.

Acute Kidney Injury↗
PubMed1987

Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP.

Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. These include: perfusion with procaine (10(-2) M), perfusion with high Mg2+ (9.5 mM) and low Ca2+ (0.5 mM) concentrations, and addition to the perfusate of the calcium channel blockers nifedipine (10(-6)M), diltiazem (5 X 10(-5)M), or verapamil (10(-4)M). Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal gland nerves, into the venous effluent or perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhance local release of neurotransmitters.

Adenosine↗
PubMed1987

Perspectives for the primary prevention of coronary heart disease.

A massive body of scientific evidence from clinical, experimental, pathological and epidemiological studies as well as from risk factor intervention trials and community studies has emerged until the 1980s; interpreted as a whole it leaves no more doubt about the major role of hyperlipidaemia, hypertension, cigarette smoking and some other modifiable factors in the aetiology of atherosclerosis and CHD, and about the great potential for primary prevention of CHD. In response to this challenge, the World Health Organization Expert Committee in its report in 1982 outlined the general principles and strategies for the primary prevention of CHD, and these principles and strategies have then been reinforced and further developed toward practical action plans by international and national experts groups. The perspectives for the primary prevention during the future decades may be envisaged to include: (1) further strengthening of preventive action in those countries with high or relatively high CHD rates in which favourable changes in life-styles and risk factor levels are already going on and CHD rates are declining; (2) development and implementation of effective plans for preventive action in those countries with high or relatively high CHD rates in which these rates are not yet declining or even increasing, and (3) development and implementation of effective plans for a real primordial prevention of CHD, i.e., preventing the appearance of unhealthy life-styles and elevated risk factor levels, in those developing countries in which CHD threatens to emerge in connection with socio-cultural changes toward urbanization and industrialization.

Chronic Disease↗
PubMed1987

Sodium-potassium pump, ion fluxes, and cellular dehydration in sickle cell anemia.

We studied the role of the sodium-potassium pump in erythrocytes of 12 patients with sickle cell anemia (SS). Ouabain-binding sites per cell and pump-mediated Rb/K uptake were significantly higher in SS patients than in white or black controls. Ouabain-resistant Rb/K influx was also greater than in normal controls or patients with sickle cell trait. Deoxygenation of SS erythrocytes increased ouabain-sensitive Rb/K influx without altering ouabain binding, presumably as the consequence of an increase in the passive influx of sodium. Deoxygenation increased mean corpuscular hemoglobin concentration (MCHC) by 5.5%, and studies of the density distribution of SS cells indicated an increase in highly dense fractions known to contain sickled erythrocytes. Ouabain prevented the rise in MCHC and reduced the percentage of dense cells. These findings indicate a magnified role for the sodium-potassium pump in the pathophysiology of SS erythrocytes and suggest that its inhibition might prove useful in therapy.

Adolescent↗
PubMed1986

Mitochondrial activity: a possible determinant of anoxic injury in renal medulla.

In brain, heart and kidney, cell work in the absence of oxygen has been thought to precipitate anoxic damage by increasing the rate of depletion of cellular energy stores. In the medullary thick ascending limb of isolated perfused rat kidneys, however, reduction of ATP synthesis by a variety of mitochondrial or metabolic inhibitors caused ATP depletion comparable to that produced by oxygen deprivation but did not reproduce the lesions of anoxia. In these cells, unrestrained mitochondrial activity may be an important source of anoxic injury.

Adenosine Triphosphate↗
PubMed1986

Inhibition of chloride secretion by BaCl2 in the rectal gland of the spiny dogfish, Squalus acanthias.

In the rectal gland of the spiny dogfish (Squalus acanthias), chloride enters the cell via a cotransport system together with sodium and potassium in a 2 Cl-: 1 Na+: 1 K+ stoichiometry. The system is energized by the electrochemical potential for sodium directed into the cell. Sodium is extruded from the cell by Na-K-ATPase located on the basolateral cell membrane. Chloride leaks into the lumen following a favorable electrical gradient. Potassium is thought to recirculate across the basolateral cell membrane. Since barium ions inhibit the efflux of potassium from cells we used barium chloride to explore the role of potassium in the process of stimulated secretion of chloride by the gland. The secretion of chloride was stimulated with theophylline 2.5 X 10(-4)M and dibutyryl cyclic AMP 5 X 10(-5)M. Ba++ inhibited the secretion of chloride in a way that was reversible and dose dependent. The reduction in secretion was associated with a parallel fall in transglandular electrical potential. Inhibition was half maximal at a concentration of Ba++ of 10(-3)M. The reduction in efflux of potassium produced by Ba++ presumably decreases the potassium diffusion potential, thus reducing the electronegativity of the cell and dissipating the driving force for chloride across the apical cell membrane. Recirculation of K+ across the basolateral border of the cell would thus be essential for the maintenance of chloride secretion by the gland.

Animals↗