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Biomedical subjects

M A Barradas

Publications and source records attributed to M A Barradas.

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

Intraplatelet serotonin, beta-thromboglobulin, and histamine concentrations and thromboxane A2 synthesis in renal disease.

Intraplatelet serotonin (5-HT), beta-thromboglobulin (beta-TG), and histamine content as well as platelet total thromboxane A2 (TXA2) synthesizing capacity were measured in 53 patients with chronic renal disease: nephrotic syndrome (n = 18); end-stage renal failure (ESRF; n = 13); continuous ambulatory peritoneal dialysis (CAPD; n = 9); hemodialysis (HD; n = 13). These indices of platelet function were correlated with plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) concentrations. When compared with controls, intraplatelet 5-HT was significantly reduced in all patient groups studied and beta-TG was diminished in all patient groups except CAPD. Total platelet TXA2 synthesizing capacity was increased in ESRF and HD groups. Intraplatelet histamine content was not altered in any of the patient groups studied. There was a significant inverse correlation between intraplatelet 5-HT content on the one hand and plasma TC, LDL-C, and TG on the other. The depletion of intraplatelet 5-HT and beta-TG and the increase in total TXA2 synthesizing capacity are consistent with platelet activation in chronic renal disease. The correlation between these indices of platelet activation and TC, LDL-C, HDL-C, and TG suggests that changes in the concentrations of these lipids may contribute to the activation of platelets in these conditions.

Adolescent↗
PubMed1991

Plasma histamine in patients with chronic renal failure and nephrotic syndrome.

Plasma histamine concentrations were measured using a commercially available monoclonal antibody radioimmunoassay in 38 patients with nephrotic syndrome, end stage renal failure, those receiving haemodialysis, and those receiving continuous ambulatory peritoneal dialysis to determine whether histamine may mediate damage to glomerular capillaries and arterial endothelium. Plasma histamine concentrations were significantly increased in all four patient groups when compared with those of controls and were the highest in two patients with pruritus. Raised plasma histamine concentrations in such patients are consistent with the hypothesis that histamine may contribute to the damage to glomerular capillaries and to arterial endothelium. These effects may be relevant to the pathogenesis of glomerular disease and atherosclerosis. Histamine may also contribute to the pathogenesis of pruritus in patients with chronic renal failure.

Adolescent↗
PubMed1990

ADPase activity in human maternal and cord blood: possible evidence for a placenta-specific vascular protective mechanism.

ADPase enzyme activity was assessed in maternal and cord plasma by adding radiolabelled ADP and quantitating the degradation products. Cord plasma had sufficiently greater ADPase activity than the corresponding maternal plasma obtained ante- and post-partum. Thus, residual radiolabelled ADP was 30, 32 and 17% of total radioactivity after 30 min incubation (37 degrees C) in maternal ante-partum, maternal post-partum and cord plasmas, respectively. ADPase may act as a platelet aggregation inhibitor in the placental and fetal circulation.

Apyrase↗
PubMed1990

The effect of nabumetone and its principal active metabolite on in vitro human gastric mucosal prostanoid synthesis and platelet function.

Nabumetone is a novel non-steroidal anti-inflammatory drug (NSAID) which although a weak cyclooxygenase inhibitor is converted by the liver to metabolites which are more potent inhibitors of cyclooxygenase. Nabumetone may thus avoid the occurrence of gastric erosion while maintaining its efficacy as an anti-inflammatory drug. We compared the effects of nabumetone and 6-methoxy-2-naphthylacetic acid (6MNA; the principal metabolite of nabumetone) with naproxen and indomethacin on in vitro synthesis of the gastroprotective prostaglandins I2 and E2 by human gastric mucosa. To study the effects of 6MNA on peripheral target tissues the effects of the above NSAIDs on human platelet aggregation and thromboxane A2 synthesis were also studied. Prostanoid synthesis by the human gastric mucosa was inhibited by indomethacin, naproxen and 6MNA (in this order of potency) whereas nabumetone was completely without effect. Platelet aggregation and thromboxane A2 synthesis were similarly inhibited by the NSAIDS (viz. indomethacin greater than naproxen greater than 6MNA greater than nabumetone). These results support the view that nabumetone does not inhibit gastroprotective prostanoid synthesis, whereas its active metabolite 6MNA is an effective inhibitor of prostanoid synthesis in target tissues.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Bezafibrate retard in type II diabetic patients: effects on hemostasis and glucose homeostasis.

A double-blind, placebo-controlled trial assessed the effect of a slow-release formulation of bezafibrate (Bezalip Mono, 400 mg daily for 3 months) on lipid profile, glucose homeostasis, platelet function, and plasma fibrinogen concentration in non-insulin-dependent (type II) diabetics. Twenty-four patients completed the trial. There was a significant improvement in the cholesterol (p less than 0.02), triglyceride (p less than 0.01), and nonesterified fatty acid (p less than 0.05) concentrations and in the fasting blood glucose (p less than 0.03) and glycosylated hemoglobin (p less than 0.01) levels of those (n = 11) who received the active preparation but not in those (n = 13) who received placebo. Treatment, but not placebo, also resulted in a significant (p less than 0.01) fall in plasma fibrinogen concentration and a trend towards inhibition of platelet aggregation. Bezafibrate was well tolerated; only one patient (not included in the analysis of results) withdrew from the trial possibly because of side effects of the drug. A larger study is needed to establish whether bezafibrate can reduce nonlipid risk factors (e.g., plasma fibrinogen concentration, glucose intolerance, and hyperinsulinemia) in normo- and hyperlipidemic subjects.

Adult↗
PubMed1990

The effect of a slow release formulation of bezafibrate on lipids, glucose homeostasis, platelets and fibrinogen in type II diabetics: a pilot study.

A double-blind placebo-controlled prospective trial assessed the effect of a slow release formulation of bezafibrate (Bezalip Mono) on lipids, glucose homeostasis, platelet function and plasma fibrinogen in non-insulin dependent (type II) diabetics. Twenty-four patients completed the trial. There was a significant improvement in the cholesterol and triglyceride levels and in the fasting blood glucose and glycated haemoglobin levels of those who received the active preparation but not in those who received placebo. Treatment, but not placebo, also resulted in a significant fall in plasma fibrinogen concentration and a trend towards inhibition of platelet aggregation. Bezafibrate was well tolerated and only one patient withdrew from the trial possibly because of side-effects of the drug. A larger study is needed to establish whether bezafibrate can reduce non-lipid risk factors (e.g., plasma fibrinogen concentration; glucose intolerance--hyperinsulinaemia) in normo- and hyperlipidaemic patients.

Adenosine Diphosphate↗
PubMed1989

Iron chelators inhibit human platelet aggregation, thromboxane A2 synthesis and lipoxygenase activity.

The iron chelators desferrioxamine and 1,2-dimethyl-3-hydroxypyrid-4-one (L1) inhibited human platelet aggregation in vitro as well as thromboxane A2 synthesis and conversion of arachidonate to lipoxygenase-derived products. Non-chelating compounds related to L1 were without effect on cyclooxygenase or lipoxygenase activity. Since both cyclooxygenase and lipoxygenase are iron-containing enzymes, it is suggested that the inhibition of platelet function by these iron chelators may be related to the removal or binding of iron associated with these enzymes. These iron chelators may therefore be of potential therapeutic value as platelet antiaggregatory agents and of possible use in the treatment of atherosclerotic and inflammatory joint diseases.

Adenosine Diphosphate↗
PubMed1989

86Rb(K) influx and [3H]ouabain binding by human platelets: evidence for beta-adrenergic stimulation of Na-K ATPase activity.

Although active transport of potassium into human platelets has been demonstrated previously, there is hitherto no evidence that human platelets have an ouabain-inhibitable Na-K ATPase in their membrane. The present study demonstrates active rubidium (used as an index of potassium influx), 86Rb(K), influx into platelets, inhibitable by ouabain, and also demonstrates the presence of specific [3H]ouabain binding by the human platelet. This 86Rb(K) influx was stimulated by adrenaline, isoprenaline, and salbutamol, but noradrenaline caused a mild inhibition. Active 86Rb(K) influx by platelets was inhibited markedly by timolol, mildly by atenolol, but not by phentolamine. Therefore, active 86Rb(K) influx in human platelets is enhanced by stimulation of beta adrenoceptors of the beta 2 subtype. The platelet may therefore replace the leukocyte in future studies of Na-K ATPase activity. This would be a considerable advantage in view of the ease and rapidity of preparation of platelets.

Adult↗
PubMed1989

Plasma histamine concentrations are elevated in patients with diabetes mellitus and peripheral vascular disease.

Previous work has shown that plasma and tissue concentrations of histamine are elevated in rats with experimental diabetes mellitus and that leucocytes and platelets from patients with peripheral vascular disease have a higher histamine content than those from controls. In the present study, we have measured: (a) plasma histamine concentrations; (b) leucocyte and platelet histidine decarboxylase (the enzyme responsible for the biosynthesis of histamine) in patients with diabetes mellitus (Types I and II) and peripheral vascular disease; and (c) platelet and leucocyte histamine content. Plasma histamine concentration was significantly higher in patients with diabetes and peripheral vascular disease respectively than that in age-matched controls. Leucocyte histidine decarboxylase activity in diabetic and peripheral vascular disease patients was similar to that in controls, while platelets had no histidine decarboxylase activity. The leucocyte and platelet content of histamine were greater in patients with peripheral vascular disease than those in controls, but they were not altered in diabetic patients. There was no correlation between plasma histamine concentration, leucocyte and platelet histamine content, and histidine decarboxylase activity. We conclude that plasma histamine is elevated in diabetics and in patients with peripheral vascular disease and that platelet and leucocyte histamine content is increased in the latter. This increase in platelet and leucocyte histamine content is not due to an increase in histidine decarboxylase activity of these cells. The increase in plasma and cellular histamine content may contribute to the pathogenesis of increased endothelial permeability in diabetes and to the pathogenesis of intimal damage in atherosclerosis.

Adult↗
PubMed1989

An investigation into the effects of bacterial lipopolysaccharide on human platelets.

The addition of lipopolysaccharide (LPS) from Gram-negative bacteria to whole blood induced a consistent enhancement of platelet impedance aggregation (WB-PIA) and an increase in median platelet volume (MPV). In contrast, the addition of LPS to platelet rich plasma (PRP) resulted in inconsistent changes in turbidometric platelet aggregation (TPA) and no significant change in MPV. The LPS-induced increase of MPV in whole blood was inhibited by verapamil, a calcium channel blocker. We conclude that: (a) LPS consistently activates platelets in whole blood but not in PRP; (b) LPS-induced activation of platelets is probably mediated by products released by leucocytes and/or erythrocytes; (c) the increase in MPV induced by LPS is probably dependent upon calcium influx; and (4) an increase in MPV may be a useful and sensitive model for the study of platelet activation by LPS, in vitro and in vivo.

Blood Cell Count↗
PubMed1989

A study of platelet fibronectin immunofluorescence in peripheral vascular disease and diabetes mellitus.

Platelets hyperaggregability and hypersecretion fibronectin (Fn) are known to occur in peripheral vascular disease (PVD) and diabetes mellitus (DM) with microangiopathy. To determine whether an increase in platelet membrane bound Fn constitutes to hyperaggregability of platelets, washed platelets from normal subjects and from patients with peripheral vascular disease and patients with diabetes mellitus were examined for the presence of fibronectin (Fn) by means of fluorescein linked antibody to Fn. Platelets from peripheral vascular disease and diabetes mellitus patients tended to aggregate during preparation and apparently exhibited greater fluorescence in platelet "smears" than was observed in smears from controls. In contrast, when washed platelet "smears" were prepared from platelet preparations containing iloprost, an analogue of prostacyclin, platelet aggregates did not form and the 'excess' of fluorescence disappeared from all the three groups. When platelets were stained for Fn fluorescence in suspensions, no fluorescence was observed on the surface of platelets from peripheral vascular disease and diabetes mellitus patients or controls. On stimulation with thrombin washed platelet suspension showed fluorescence for Fn. Platelet activation leads to Fn appearing on platelet surface but this effect cannot be quantified by optical fluorescence microscopy.

Adult↗
PubMed1989

Dietary fish oil supplements preserve renal function in renal transplant recipients with chronic vascular rejection.

The effect of dietary fish oil supplements on renal failure and lipid abnormalities was studied in 14 adult renal transplant recipients with chronic vascular rejection. The rate of decline of renal function (assessed by studying the slope of reciprocal plasma creatinine plots) slowed significantly during a 6-month period on fish oil supplements compared with the preceding 6-month control period (slope 1/cr during supplementation -3.6 X 10(-5) mumols/l per month compared with -13.5 X 10(-5) before, the difference in slope being -9.8 X 10(-5), 95% confidence interval (CI) -16.2 X 10(-5), -3.5 X 10(-5), P less than 0.05). Total plasma triglyceride concentrations decreased during supplementation (mean change -1.15 mmol/l, 95% CI -1.84, -0.47, P less than 0.003), but there was no change in total plasma cholesterol concentration or urinary protein excretion. Platelet function was studied in nine patients. Platelet aggregation induced by adrenaline and collagen was reduced by fish oils (median change in per cent aggregation), adrenaline 2 mumols/l, -36% (95% CI -68%, -8%, P less than 0.05), collagen 1 mg/1, -13% (95% CI -44%, -2%, P less than 0.05). Platelet thromboxane A2 release in response to these agents was also significantly reduced. These results demonstrate that fish oils preserve residual function in renal graft failure due to chronic vascular rejection.

Adult↗