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Biomedical subjects

A Parbtani

Publications and source records attributed to A Parbtani.

At least 37 records · Page 2Linked to original sources
PubMed1991

Dietary lipid modification of renal disorders and ether phospholipid metabolism.

The formation of arachidonic acid derived eicosanoids, including thromboxane A2 and leukotriene B4, as well as platelet-activating factor (1-O-alkyl-2-acetyl-glycerophosphocholine), has been implicated in various renal pathophysiologies. Alteration of the fatty acid composition of membrane phospholipids in platelets, the glomerulus, and inflammatory cells, and of 1-O-alkyl-2-acyl-glycerophosphocholine (platelet-activating factor precursor) can be attained by dietary lipid modifications (e.g., consumption of fish oil containing n - 3 polyunsaturated fatty acids). These changes have been associated with an attenuation in renal disease progression and modifications in the synthesis and actions-interactions of eicosanoids, cytokines, and platelet-activating factors.

Animals↗
PubMed1991

Chronic effects of omega-3 fatty acids (fish oil) in a rat 5/6 renal ablation model.

It has been proposed that fish oil dietary supplementation in the chronic rat 5/6 renal ablation model may be either protective or toxic. These conflicting hypotheses were tested in rats who underwent renal ablation or sham surgery. Twenty rats received sham surgery, and 40 received 5/6 renal ablation. All rats were fed a regular laboratory diet up to 1 week postsurgery. At that time, one half of the renal ablation group was provided with an isocaloric diet supplemented with 24% MaxEPA (fish oil), 1% safflower oil, and antioxidants. The renal ablation rats developed hypertension, albuminuria, gammaglobulinuria, and a decline in glomerular filtration rate, which was less in the fish oil group compared with that in the regular laboratory diet group at 10 and 20 wk postsurgery. The fish oil renal ablation rats had significantly less glomerulosclerosis than did the regular laboratory diet renal ablation animals, and no more glomerular fibrin deposition than did the sham controls. The renal ablation regular laboratory diet rats had a significant dyslipidemia at 20 wk which was prevented in the fish oil renal ablation cohort. The fish oil renal ablation rats also demonstrated a significant decline in renal tissue arachidonic acid incorporation and a concomitant increase in eicosapentaenoic acid and docosahexaenoic acid incorporation. The mortality of the renal ablation group was greater than that of the sham controls but not significantly different for the fish oil or the regular laboratory diet groups. These results support the hypothesis that the fish oil diet containing specific antioxidant, vitamin E, and essential fatty acid supplementation is protective in the rat remnant nephron model and prevents the evolution of glomerulosclerosis with associated renal functional impairment, while preserving glomerular filtration.

Animals↗
PubMed1990

Survival of rabbit platelets exposed to immune complexes.

Rabbits injected with human serum albumin (HSA) formed detectable immune complexes after 5 days; complex formation was maximal between 11 and 14 days after which the complexes were cleared from the circulation. Platelets from control rabbits or HSA-injected rabbits had a reduced survival upon injection into rabbits in which complexes were forming. Platelets from HSA-animals tended to survive for a longer period upon injection into control rabbits than when they were injected into HSA-rabbits, raising the possibility that some of the immune complexes may have eluted from their surface. Platelets prepared from either control animals or from HSA-treated animals at the time when complexes were being cleared from the circulation (14-21 days) did not have a shortened life span in HSA- or control rabbits. When platelet survival was reduced, it could not be attributed to platelet accumulation at sites of vessel wall injury or to accumulation in kidneys damaged by immune complexes, since the tissues (aorta and kidney) appeared to be morphologically normal and free of thrombi. The reduction in platelet survival likely results from the interactions of immune complexes with the surface of platelets leading to the platelets being recognized as "foreign" and cleared from the circulation by the reticuloendothelial system.

Animals↗
PubMed1990

Comparative efficacy of dietary treatments on renal function in rats with sub-total nephrectomy: renal polyunsaturated fatty acid incorporation and prostaglandin excretion.

The efficacy of dietary intervention with either 6% protein restriction, fish oil or safflower oil was assessed in the remnant nephron model. Female Munich Wistar rats were prefed for one week prior to 5/6 nephrectomy and followed for the ensuing 28 days. Fish oil, safflower oil and protein restriction prevented the gammaglobulinuria but only fish oil lessened the albuminuria in this model. The remnant nephrons of the fish oil treated rats contained less arachidonic acid and greater quantities of eicosapentaenoic and docosahexaenoic acid than the safflower oil or lab chow fed control rats. The fish oil, and to a lesser extent the safflower oil, treated animals had a higher ratio of 6 keto PGF1 alpha to TX B2 metabolites in their urine. We suggest these changes may be responsible for the lessening in urine protein excretion. Fish oil feeding was more effective than severe protein restriction or safflower oil dietary supplementation in lessening both the gammaglobulinuria and albuminuria of the remnant nephron model.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Omega-3 fatty acid dietary supplementation in systemic lupus erythematosus.

The effect of dietary fish oil (Omega-3 fatty acids--eicosapentenoic acid [EPA] and docosahexaenoic acid [DHA] on several mechanisms involved in immune, inflammatory and atherosclerotic vascular disease was determined in 12 subjects with systemic lupus erythematosus (SLE) and nephritis. These out-patients supplemented their usual diet for five weeks with daily doses of 6 g of fish oil, followed by a five-week washout period, then five weeks of 18 g of fish oil daily. The platelet EPA content rose six-fold with the lower and 15-fold with the higher dose of fish oil, and similar changes occurred to the platelet DHA content. The platelet arachidonic acid incorporation was reduced by 16 and 20%, respectively. These changes were associated with a reduction in collagen-induced platelet aggregation and an increase in red cell flexibility and a decrease in whole blood viscosity. Prostacyclin (PGI2) production was unaffected by the fish oil, but PGI3 formation correlated with its administration and dosage. Neutrophil leukotriene B4 release was reduced 78 and 42%, respectively, by the low and higher doses of fish oil. The higher fish oil dose induced a 38% decrease in triglyceride and a 39% reduction in VLDL cholesterol associated with a 28% rise in HDL, cholesterol. The fish oil had no effect on immune complex or anti-DNA antibody titer, albuminuria, intraplatelet serotonin or [14C]-serotonin release from platelets. We conclude that in patients with lupus nephritis, dietary supplementation with fish oil affects the mechanisms involved in inflammatory and atherosclerotic vascular disease.

Adult↗
PubMed1987

Binding of aggregated immunoglobulins to the human platelet Fc receptors: a mechanism of platelet to platelet bridging.

Aggregated immunoglobulins react with human platelets by occupying the Fc receptors present on their surface, inducing aggregation and the release reaction. We studied the effect of heat aggregated gammaglobulins (HAGG) on ADP-induced aggregation of platelets. We used the minimum concentration of ADP required to induce a reversible aggregation of platelets without any substantial amount of serotonin (14C-5HT) release. EDTA (5 mM) added at the peak of platelet aggregation resulted in rapid deaggregation of these platelets. However, incubation of platelets with HAGG at a dose that did not by itself induce any aggregation or release reaction, followed by ADP addition resulted in an irreversible platelet aggregation of greater magnitude accompanied by a substantial release of 14C-5HT. The addition of EDTA at the peak of platelet aggregation failed to deaggregate these platelets. To determine whether the augmented aggregation response and the inhibition of deaggregation was due to HAGG or a consequence of platelet release products, we used thrombin-degranulated platelets. The augmented aggregation response and the inhibition of deaggregation due to HAGG and ADP could be demonstrated using these platelets. To confirm that the binding of HAGG to the platelet Fc receptors was responsible for these observations, we incubated platelets with an excess of Fc fragments of IgG prior to the addition of HAGG and ADP. This abolished the aggregation response observed previously. From this study we conclude that interplatelet bridging by HAGG renders the platelets hyperaggregable and appears to be a mechanism involved in maintaining platelet aggregates.

Adenosine Diphosphate↗
PubMed1987

Calcium and the Fc receptor on human platelets.

We have described the calcium dependence of the IgG Fc receptor (Fc-R) on human platelets by analyzing the direct binding of radiolabelled Fc fragments, monomers and dimers of IgG. Specific binding to platelets was undetectable at 37 degrees C in a calcium-free preparation but readily detected when calcium was restored. Scatchard analysis of the binding data for the calcium-restored platelets permitted calculation of the available Fc-R and the Ka of binding for the different IgG ligands. The mean Ka of binding for 12 normal subjects varied from 10(7) to 10(8) L/M, with an equal receptor number measured by Fc fragments and dimers of IgG, but a lesser amount for monomeric IgG. There was no apparent difference in Fc-R number for platelets from 6 normal male versus 6 normal female subjects. At 4 degrees C binding was detectable for dimers and polymers of IgG in a calcium-free preparation and this was markedly increased with recalcification. Thus, our data are consistent with an Fc receptor population on human platelets whose avidity for binding is significantly enhanced in a calcium-restored medium.

Blood Platelets↗
PubMed1987

The effects of a thromboxane synthase inhibitor, a prostacyclin analog and PGE1 on the nephritis of the NZB/W F1 mouse.

One hundred NZB/W F1 female mice were studied to compare the effects of a thromboxane synthase inhibitor (TSI), a stable prostacyclin analog (iloprost) and prostaglandin E1 (PGE1) in the evolution of the nephritis. At 10 weeks of age mice were randomly assigned to cohorts of 20 to receive either no treatment, vehicle control, PGE1, iloprost or TSI. Proteinuria, mortality, systemic blood pressure, renal immune complex deposition, urinary TX B2 and 6 keto PGF1 alpha levels were measured. Mice receiving PGE1 and iloprost had a significant delay in the onset of proteinuria and reduction in mortality at 40 weeks. The TSI treatment had no apparent effect on proteinuria or mortality. The amelioration of the nephritis was not associated with an alteration in immune complex deposition in survivors at 40 weeks. Although PGE1 and iloprost lessened the age related increase in urinary TX B2, increased the urinary 6 keto PGF1 alpha levels and the ratio of 6 keto PGF1 alpha to TX B2; so did the TSI. The PGE1 treated mice did experience a marked and persistent reduction in blood pressure but this was not observed in the iloprost- or the TSI-treated mice. All drugs tested reduced the age-related increase in thromboxane B2 but only the PGE1 and iloprost had a significant effect on the evolution of the nephritis.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Identification of non-denuding endothelial injury by scanning electron microscopy.

Endothelial injury is important in the development of arterial disease. To examine the response to endothelial injury it is necessary to recognise if endothelium has been altered and how this relates to normal function. Of the several methods available to evaluate endothelial integrity, ultrastructural examination has certain advantages. In particular, scanning electron microscopy of the endothelium will permit large areas to be examined, and changes can be related to the overall anatomy of the vessel. There is good evidence that endothelial injury does not inevitably result in endothelial cell loss and denudation of the subendothelium, but that endothelial cells can be desquamated in a process of non-denuding injury. The morphological changes described in endothelial cells stimulated by a variety of agents suggest that the response varies according to the method of investigation, that there are some common features, but that each stimulus induces certain specific changes. The endothelial response to a range of agents was therefore examined in the same animal model, using carefully controlled preparation parameters. The observations indicate that the response to stimuli which induce an inflammatory type of reaction is characterised by fibrin formation and white cell adhesion. In contrast stimuli which result in vessel collapse show protruding cells and damage at vessel orifices. Certain features are seen irrespective of the stimulus. The significance of many of the observed changes remains to be elucidated.

Animals↗
PubMed1983

In vivo platelet activation with in vitro hyperaggregability to arachidonic acid in renal allograft recipients.

Renal allograft recipients were investigated to determine the extent and possible nature of in vivo platelet activation. In 92 allografted patients stable for more than 4 months' duration, intraplatelet serotonin in circulating platelets was depleted significantly. In a further 16 patients studied serially for 12 to 16 weeks following transplantation, intraplatelet serotonin fell abruptly within 4 days from transplantation to very low levels, and remained thus for 10 weeks, rising toward normal at about 12 weeks. Although some patients showed abrupt falls in intraplatelet serotonin coincident with acute rejection episodes, there was no difference in intraplatelet serotonin in seven patients whose grafts functioned well immediately and remained stable, and seven in whom repeated rejection led to graft loss within 3 months. Thus, these tests of platelet function do not permit diagnosis of rejection or prediction of graft outcome. Plasma platelet factor 4 (PF4) concentrations, in contrast, were normal in most patients during the first 6 weeks after grafting, then rose and remained abnormal up to 13 years following the allograft in the long-term stable graft recipients. This discrepancy suggests a different mode of platelet activation in the first few weeks after grafting from subsequent months. Despite universal depletion of intraplatelet amines and alpha-granule contents only four out of 14 early allograft recipients had an abnormal bleeding time, and platelet aggregation thresholds with adenosine-5'-diphosphate and collagen were not different from controls. However, thresholds for platelet aggregation with arachidonic acid were reduced significantly (P less than 0.01) and thromboxane B2 generation was increased in vitro. There was no correlation between depletion of intraplatelet serotonin and circulating platelet-agglutinating material, but nine of 17 biopsy specimens from rejecting allografts taken during the first 3 months showed extensive glomerular localization of platelet membrane antigens and PF4.

Adenosine Diphosphate↗
PubMed1982

Intraglomerular localization of platelet related antigens, platelet factor 4 and beta-thromboglobulin in glomerulonephritis.

We examined renal biopsies from 121 patients with various forms of glomerulonephritis, using antisera against platelet membrane antigens, platelet factor 4, beta-thromboglobulin and fibrinogen using the indirect immunofluorescent technique. Eight biopsies were also studied by electron microscopy for recognizable platelets. Thirty-six of sixty-four (56%) biopsies from patients with severe forms of glomerulonephritis showed some intraglomerular platelet antigen, extensive fluorescence in seventeen (25%). Of forty-six patient with milder, usually non-progressive forms of nephritis, twenty (44%) were positive, but only four (9%) showed extensive fluorescence. Platelets were identified by electron microscopy within the capillary lumina equally in those with positive and negative results for platelet-related antigens. There was no correlation between the presence of fibrin and platelet-related material in the glomeruli, nor between the presence or extent of intraglomerular platelet antigen and simultaneous measurements of intraplatelet serotonin in circulating platelets. However, there was a strong correlation between presence, extent and distribution of platelet-related antigen and platelet factor 4 fluorescence. These studies provide further evidence for the involvement of platelets in some forms of glomerular disease.

Antigens↗
PubMed1981

Platelet-aggregating immune complexes and intraplatelet serotonin in idiopathic glomerulonephritis and systemic lupus.

Immune complex-like material was studied using the platelet-aggregation test (PAT) in 114 patients with idiopathic glomerulonephritis and 55 patients with SLE nephritis, and the results obtained compared with Raji cell and Clq-binding assays. The platelet-aggregating material was not thrombin, and eluted from Sepharose CL/6B columns with a molecular weight of greater than 500,000 daltons. Sera from 17 of 55 patients with SLE nephritis were positive in all three assays, 50/55 in at least one assay. No circulating material was detected by the Raji cell assay in idiopathic glomerulonephritis patients, but both the Clq-binding and PAT assays detected material in patients with acute post-infectious nephritis and mesangiocapillary glomerulonephritis. Patients with membranous nephropathy and Henoch-Schönlein purpura were positive in the PAT, although generally negative in the other assays of immune complexes. The amount of platelet-aggregating material (PAM) found in the sera of patients with both idiopathic glomerulonephritis and SLE nephritis correlated closely with the depletion of intraplatelet serotonin, suggesting that this material is a major mechanism of in vivo platelet activation in these patients.

Antigen-Antibody Complex↗
PubMed1980

Platelet-aggregating immune complexes in idiopathic glomerulonephritis and SLE.

Immune complex-like material with a molecular weight of greater than 500,000 Daltons was detected in the majority of sera from patients with idiopathic glomerulonephritis, as well as in systemic lupus. In the Raji cell and Clq binding assays the glomerulonephritis sera gave, in general, negative results. Patients with membranous nephropathy, minimal change disease and Henoch-Schönlein purpura also gave positive results in the platelet test, in agreement with other tests not dependent upon complement fixation by the complexes. The amount of platelet-aggregating material detected in vitro correlated closely with in vivo depletion of intraplatelet amines, judged by serotonin concentrations; which suggests that this material may play a major role in platelet activation within the circulation.

Antigen-Antibody Complex↗
PubMed1980

Platelet and plasma serotonin concentrations in glomerulonephritis, II.

We studied intraplatelet serotonin and free plasma 5-OH indole ("serotonin") concentrations in patients with glomerulonephritis. Two hundred and sixty-two samples from 183 patients with primary glomerulonephritis of various types, 269 samples from 44 patients with SLE and 58 samples from 38 normal subjects were studied. Patients with minimal change lesions, focal and mesangial proliferative glomerulonephritis showed platelet and plasma serotonin concentrations indistinguishable from normal individuals. Patients with membranous nephropathy, mesangiocapillary glomerulonephritis, focal segmental glomerulosclerosis polyarteritis and systemic lupus, in contrast, showed diminished mean concentrations of intraplatelet serotonin and raised plasma serotonin concentrations. Within each group, there was a relationship between the two: the lower the platelet serotonin, the higher the plasma serotonin. The presence of a nephrotic syndrome or mild uremia (Pcreat < 400 mumoles/l) did not affect intraplatelet serotonin, although patients with severe uremia (Pcreat > mumoles/l) showed retention of plasma 5-OH indoles, and reduction in intraplatelet serotonin. These data provide further evidence for in vivo platelet activation in patients suffering from glomerulonephritis.

Adult↗
PubMed1980

Platelet and plasma serotonin in glomerulonephritis. III: The nephritis of systemic lupus erythematosus.

Intraplatelet and plasma serotonin levels were measured in 269 samples from 44 patients with systemic lupus erythematosus (SLE) and clinical nephritis. The intraplatelet serotonin levels were depressed and the plasma serotonin levels were raised in lupus nephritis. There was a strong correlation between both lowered intraplatelet serotonin concentration and raised plasma "serotonin", and the overall clinical activity of the disease. This correlation was also observed in the majority of individual patients studied serially; the platelet serotonin levels correlated with both clinical and immunological tests. Serotonin uptake by platelets was significantly diminished, but there was no correlation between serotonin uptake and platelet serotonin levels. There was, however, a correlation between the amount of platelet-aggregating material in the serum and depression of intraplatelet serotonin. This study provides further evidence of in vivo platelet activation in SLE nephritis, and provides a measure of the activation in relation to the clinical and immunological activity of the disease.

Adolescent↗