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Biomedical subjects

V E Pollak

Publications and source records attributed to V E Pollak.

At least 37 records · Page 2Linked to original sources

The influence of n-6 and n-3 fatty acids on kidney phospholipid composition and on eicosanoid production in aging rats.

Changes in eicosanoid production may contribute to some of the complications of the aging process such as atherosclerosis and glomerular sclerosis. Polyunsaturated fatty acids of the n-6 and n-3 series are precursors of eicosanoids. We fed diets containing safflower oil as a source of n-6 fatty acids, fish oil as a source of n-3 fatty acids or beef tallow as a source of saturated fats to three groups of normal rats from 2-18 months of age. We demonstrated incorporation of the n-3 fatty acids, 20:5n-3 and 22:6n-3 into kidney phospholipids. Feeding of the diet containing n-3 fatty acids was associated with a markedly decreased glomerular production of PGE, 6-keto-PGF1 alpha and TXB2. It also decreased the aortic production of 6-keto-PGF1 alpha and platelet production of TXB2. No significant effect of n-6 fatty acids on dienoic eicosanoid production was observed. There were no adverse effects on kidney function as measured by urinary protein excretion and serum creatinine levels or on renal morphology by any diet. A diet enriched in n-3 fatty acids for 18 months remains effective in decreasing dienoic eicosanoids in the aging rat.

6-Ketoprostaglandin F1 alpha↗

Fish oil has beneficial effects on lipids and renal disease of nephrotic rats.

The effects of fish oil on serum lipids, eicosanoid production, fibrinolysis, and renal disease of nephrotic rats were studied. Three groups of rats were given adriamycin to induce nephrotic syndrome. They were pair-fed diets containing 14% beef fat, 3%, and 14% fish oil, and killed at 4 weeks. Marked beneficial effects of the fish oil on plasma triglycerides, total cholesterol, and LDL cholesterol were observed. Fish oil suppressed dienoic eicosanoid production. Protection of renal function and morphology was achieved in the fish oil fed groups, as evidenced by lower serum creatinine levels and lesser degrees of tubular dilatation and intraluminal protein in the kidney tubules. We conclude that fish oil, rich in n-3 fatty acids, is beneficial to the plasma lipids and may prevent progression of renal disease in this model of nephrotic syndrome. These two events may be interrelated.

Animals↗

Glomerular eicosanoid production in acute serum sickness nephritis.

To determine if the induction of immune-mediated glomerular injury influences the formation of glomerular cyclooxygenase products, we measured thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) production by isolated glomeruli of rabbits induced with acute serum sickness nephritis by the administration of bovine serum ablumin (BSA). Animals were randomly assigned to one of three experimental groups: animals injected with BSA (BSA group; n = 11); animals injected with normal saline (control group; n = 11); and animals injected with BSA which were treated with the thromboxane synthetase inhibitor, OKY-046 (BSA + OKY-046; n = 6). Animals in the BSA and BSA + OKY groups developed severe proteinuria and glomerular histologic lesions of nephritis. No differences in proteinuria, serum creatinine and severity of histologic nephritis were observed between the two groups. Examination of glomerular eicosanoid production at the end of the experiment showed a marked reduction of glomerular PGE2 and 6-keto-PGF1 alpha production with a smaller reduction of glomerular TXB2 production in the BSA group. In the BSA + OKY-046 group, the production of TXB2 was significantly less than that in the BSA group; despite this, no effect on proteinuria could be discerned.

Animals↗

Use of ancrod in acute or progressing ischemic cerebral infarction.

Ancrod has been used in Europe for over 15 years for peripheral vascular disease, deep vein thrombosis, and central retinal venous thrombosis, and in patients at risk for thromboembolism. In a double-blind, randomized, placebo-controlled study at University Hospitals in Cincinnati, 20 acute cerebral infarction patients received a series of IV infusions of ancrod (ten) or placebo (ten) for seven days. Early fibrinolysis with a small decrease in fibrinogen was observed, and d-dimers were elevated at four hours, indicating early clot lysis. At three months, patients with moderate to severe strokes (less than 40 on the Scandinavian Stroke Scale) in the ancrod group showed average improvement by a factor of 3 over the placebo group. No bleeding, abnormal laboratory results, or deaths occurred, but ancrod was discontinued in one patient who had seizures. As a result of this study, a double-blind multicenter international clinical trial to further assess the safety and effectiveness of ancrod is being planned.

Ancrod↗

A thromboxane synthetase antagonist ameliorates progressive renal disease of Dahl-S rats.

Recent studies have suggested a role for thromboxane in the progression of renal disease. The current study evaluated the role of this arachidonic acid metabolite in a model of renal disease which bears many biologic similarities to that in the kidneys of patients with chronic progressive renal failure. The model is that induced by ferritin-anti-ferritin immune complex nephritis in Dahl-salt sensitive rats rendered hypertensive by a high salt intake. Rats with this model of renal disease were chronically given a thromboxane synthetase antagonist OKY-046 or a placebo treatment from 16 to 29 weeks of age. Sequential observations of serum creatinine and 24-hour urinary protein excretion showed an ameliorating effect of OKY-046 on these renal parameters. Histologic examination of the kidneys also showed significantly less glomerular sclerosis in OKY-046 treated animals. The efficacy of OKY-046 was monitored by measurements of serum TXB2 levels and of glomerular production of TXB2 (and other prostaglandins); amounts of TXB2 were significantly reduced in the OKY-046 group. It is concluded that blockade of thromboxane generation has been successful in ameliorating the functional and structural lesions in this model of renal disease, providing further support to the thesis that thromboxane is an important mediator in events leading to eventual chronic renal failure and sclerosis.

Acrylates↗

Fibrinolysis in glomerulonephritis treated with ancrod: renal functional, immunologic and histopathologic effects.

The effects of a 14-day course of ancrod on fibrinolysis, renal function and structure, and immunologic findings are reported in 37 patients with glomerulonephritis. Patients were divided into two groups. In the first, the level of fibrin degradation products within 48 h was relatively low (less than 1 mg/ml). In these patients there was a linear relationship between changes in levels of fibrin degradation products and fibrinogen, suggesting that fibrin degradation products derived from ancrod-cleaved-fibrinogen in the circulating pool; in most, level of plasma alpha 2-antiplasmin before treatment was elevated. In the second, the level of fibrin degradation products within 48 h was high (greater than 1 mg/ml). Compared with the change in fibrinogen, a disproportionate increase in levels of fibrin degradation products suggested that a significant amount derived from sources other than plasmin digested ancrod-cleaved-fibrinogen, thus reflecting effective fibrinolysis, perhaps also in tissues; in most, the level of plasma alpha 2-antiplasmin was normal before treatment. In those with initial high levels of fibrin degradation products, higher levels persisted throughout treatment, changes in other fibrinolysis components were greater, and plasminogen activator inhibitor levels became normal. In patients with initial high but not with initial low response in fibrin degradation products renal function improved within 24 to 48 h and continued to improve thereafter; there was an immediate but temporary increase in proteinuria. Microvascular thrombosis decreased significantly, indicating effective removal of fibrin from glomeruli. The relation of early fibrinolysis to changes in immunologic and histopathologic findings was analyzed in patients with lupus nephritis. With ancrod, there was an increase toward normal of serum C3 and C4, a decrease in serum Igs, gamma globulin and anti-dsDNA antibody and in glomerular C3 and Ig deposits, suggesting that ancrod had favorable effects on immunologic factors. There were no clinical differences in patients with initial high and low responses, but the relationship of microvascular and inflammatory indexes before treatment differed. Initial renal biopsies and those after treatment were carried out on average 28 days apart. Inflammatory and microvascular indexes and glomerular thrombi decreased in patients with initial high levels of fibrin degradation products; fibrosclerosis index and glomerular sclerosis increased in patients with initial low levels of fibrin degradation products. Fibrinolysis expressed as the 48 h (fibrin degradation products/fibrinogen) ratio, correlated inversely with change in fibrosclerosis index and glomerular sclerosis in the whole group, and especially in those with initial high levels of fibrin degradation products.(ABSTRACT TRUNCATED AT 400 WORDS)

Ancrod↗

Dietary fat in experimental nephrotic syndrome: beneficial effects of fish oil on serum lipids and, indirectly, on the kidney.

Three isocaloric diets with different fat composition were fed to rats for seven weeks after the production of nephrotic syndrome by adriamycin. The effects of feeding 3% and 14% fish oil were compared with those of feeding beef fat. At the fourth week of feeding the levels of triglycerides and cholesterol were lower in both fish oil fed groups. At the seventh week these levels, and the LDL cholesterol, were lower only in the 14% fish oil group. In rats fed beef fat, but not in those fed fish oil, there was a striking positive correlation of the four-week serum triglycerides and cholesterol with the seven-week serum creatinine level and with the degree of glomerular hyalinosis and endothelial swelling. The favorable effects of fish oil feeding on serum lipids may have a protective effect on the development of glomerular damage.

Animals↗

A low protein-high linoleate diet increases glomerular PGE2 and protects renal function in rats with reduced renal mass.

Renal function deteriorates progressively in partially nephrectomized rats. This deterioration of renal function may be ameliorated by a diet either low in protein or high in linoleic acid. In the present experiment, partially nephrectomized rats were pair fed diets low in protein, high in linoleic acid or both low in protein and high in linoleic acid. Survival of renal function was most prolonged in rats fed a diet with both a low protein and high linoleic acid content; glomeruli from these animals demonstrated increased glomerular PGE2 production. This additive effect may be mediated by increased production of the vasodilatory PGE2 by glomeruli.

Animals↗

Effect of first and subsequent use of hemodialyzers on patient well-being: the rise and fall of a syndrome associated with new dialyzer use.

In a single large dialysis unit in which dialyzers are routinely subjected to multiple use, the incidence rates of intradialytic symptoms during first use and reuse were compared. Dialyses administered during two periods were analyzed: During the first (26,592 treatments), dialyzers were processed by a manual method before both first and subsequent use. During the second (12,395 treatments), dialyzers were processed by an automated machine method before first and subsequent use. During the first (manual processing) period, 12 symptoms were found to occur more frequently during first use than during reuse. The most striking findings related to chest pain (2.8 times more frequent with first use), back pain (6 times), and concurrent chest and back pain (42 times). Thus, a "first-use syndrome" characterized by chest and back pain was clearly evident. During the second (machine processing) period, the previously noted increased symptom incidence during first use was no longer present. In particular, the incidence of chest pain and back pain was no longer greater during first use than during reuse. Our results suggest that subjecting dialyzers to an automated reuse processing system before first use can markedly diminish the incidence of first-use syndrome.

Back Pain↗

Beneficial effects of polyunsaturated fatty acids in partially nephrectomized rats.

Evening primrose oil, safflower oil, and salmon oil, all with high polyunsaturated fatty acid content, were fed to partially nephrectomized rats; the effects were compared to those of feeding beef tallow. All three oils had favorable effects on progression of renal failure, salmon oil on kidney histology as well. The changes induced in platelet production of thromboxane A2, and in the renal production of various eicosanoids may explain the protective role of these oils.

Animals↗

Protective effect of polyunsaturated fatty acid supplementation in apoferritin induced murine glomerulonephritis.

The effects of increasing two dietary polyunsaturated fatty acids, eicosapentaenoic and linoleic, on the glomerulonephritis induced by repeated injections of apoferritin in the mouse were studied. Urinary protein excretion was measured serially; serum creatinine, aortic and renal production of eicosanoids and kidney histology were measured at sacrifice at 8 weeks. Both high EPA and LA feedings were associated with lesser proteinuria, normalization of renal function and profound changes in the tissue production of prostaglandin and thromboxane, which may explain their protective effect in this model of renal disease.

Animals↗

The computer in quality control of hemodialysis patient care.

A computerized, custom-designed medical information system (MIS) has been used for more than eight years in the care of patients with chronic renal failure treated by hemodialysis in a Cincinnati medical center. A comprehensive clinical data base that forms the core of the system readily serves the need for sophisticated quality control analysis. Application of the MIS in the day-to-day management of patients in one limited care dialysis clinic is detailed, with particular attention to its capacity to contribute to the quality of care of the individual patient. Data can be stored in the system periodically with relative ease; this enables physicians, nurses, and other personnel concerned with patient care to monitor the quality of procedures and treatments used in their patients. The system is shown to be cost-effective.

Blood Pressure↗

Nephrotic syndrome, progressive irreversible renal failure, and glomerular "collapse": a new clinicopathologic entity?

Six patients are reported with nephrotic syndrome and relatively rapid progression to irreversible renal failure. The renal histologic findings are unusual. The most striking changes are collapse of glomerular capillary loops, such as might occur with glomerular hypoperfusion; significant tubulointerstitial damage is also seen. These patients appear to have a clinicopathologic entity hitherto unreported. Its differentiation from other causes of progressive glomerular damage, and particularly from focal and segmental glomerulosclerosis, is discussed.

Adolescent↗

Effect of first and subsequent use of hemodialyzers on patient well-being. Analysis of the incidence of symptoms and events and description of a syndrome associated with new dialyzer use.

To determine the effect of multiple dialyzer use on intradialytic symptoms, data from 26,592 successive dialyses on 147 patients were analyzed. Over the 26-month period of study 4,933 new dialyzers were used. All symptoms, considered together, occurred 1.3 times more frequently during the initial than during the subsequent use of the dialyzer. No symptom occurred more frequently in the second or subsequent use of the dialyzer. Concurrent chest and back pain were 41 times more frequent when the dialyzer was used for the first time. A syndrome associated with the first use of the dialyzer is described.

Back Pain↗

Repeated use of dialyzers is safe: long-term observations on morbidity and mortality in patients with end-stage renal disease.

In treating patients with end-stage renal disease, the dialyzer may be used on multiple occasions rather than once. Long-term effects of this practice are unknown. We report 259 and 1,059 successive patients from facilities practicing reuse in Cincinnati and Detroit, followed, respectively, for 535 and 2,209 patient years. The morbidity was relatively low, expressed by the number of hospital admissions (1.63 and 2.19/year) and by days in hospital (14.24 and 22.71/year), respectively. In Cincinnati the unadjusted case fatality rate was 70% of that in the Ohio Valley Renal Disease Network, in Detroit it was 96% of that in the Michigan Renal Network. There were no adverse long-term effects of multiple use of dialyzers.

Adult↗

Fibrinolysis in health and disease: abnormal levels of plasminogen activator, plasminogen activator inhibitor, and protein C in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is characterized by widespread occluding and persistent microthrombotic lesions. Evidence for both endothelial damage and primary platelet aggregation as possible pathogenetic mechanisms has been produced. Persistence of microthrombi has not been explained satisfactorily. In patients with TTP we studied plasma fibrinolysis and protein C. Tissue plasminogen activator (t-PA) activity levels, measured functionally, were low or unmeasurable in 11 of 12 patients; t-PA antigen levels, measured immunochemically, were normal in all six observed. The level of potent inhibitor of plasminogen activation directed against both t-PA and urokinase was elevated significantly in all 12, whereas the alpha 2-antiplasmin level was elevated in only two. Protein C antigen levels were low in three of six patients observed. Fibrinolysis levels in patients in remission did not differ from those in patients with acute disease. Plasma exchange resulted in temporary reversal of the abnormalities, but achievement of clinical remission was not associated with permanent normalization of fibrinolysis. Inasmuch as all 12 patients had severely depressed fibrinolytic mechanisms it is possible that a defect in the fibrin-clearing system permits thrombus formation to occur and proceed in an unchallenged fashion, thereby contributing to the complex events leading to arterial ischemia in vital organs.

Adult↗

Enhancing effect of dietary supplementation with omega-3 fatty acids on plasma fibrinolysis in normal subjects.

A supplement of MaxEPA oil containing 5 g of omega-3 polyunsaturated fatty acids was given for two weeks to nine normal volunteers. The vascular plasminogen activator (VPA) level increased and there was a fall in the levels of inhibitors of vascular plasminogen activator (IPA) and of plasmin, alpha 2-antiplasmin (alpha 2-AP). No significant changes occur in serum cholesterol, triglycerides, HDL or LDL levels.

Adult↗