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Biomedical subjects

M A Barradas

Publications and source records attributed to M A Barradas.

At least 19 recordsLinked to original sources
PubMed1996

Smoking and plasma fibrinogen, lipoprotein (a) and serotonin are markers for postoperative infrainguinal graft stenosis.

OBJECTIVES: A number of systemic variables are associated with infrainguinal graft failure and also with experimental smooth muscle hyperplasia. Stenosis is the most common cause of infrainguinal graft thrombosis but it is not known if systemic variables are associated with stenosis. DESIGN, MATERIALS, AND METHODS: In this study, clinical and serological factors were measured and correlated with stenosis development in 81 infrainguinal bypass grafts (52 vein, 29 PTFE; 28 with stenosis) in prospective (n=46) and retrospective (n=35) groups. Pre-existing stenosis was excluded by perioperative graft assessment. RESULTS: There was a significantly greater proportion of smokers in the patients who developed stenosis (11/18; 61%) compared with those who did not (6/28; 21%, p=0.006; chi 2). Patients who developed stenosis also had significantly (Mann Whitney U-tests), higher circulating levels of [median (interquartile range)] fibrinogen (412.5 (356-484.5) vs. 339 (300-397.7) mg/100ml, p=0.003), Lipoprotein (a) (0.20 (0.05-0.45) vs. 0.085 (0.05-0.23) g/l, p=0.03) and 5-hydroxytryptamine (14.1 (6.6-45) vs. 4.41 (3-8.39) nmol/l, p=0.005), than those without stenosis. By logistic regression, these associations were independent of graft material and whether grafts were studied prospectively or retrospectively. CONCLUSIONS: Smoking and plasma fibrinogen, Lp(a) and 5-hydroxytryptamine are markers for postoperative infrainguinal graft stenosis.

Blood Vessel Prosthesis↗
PubMed1996

A low molecular weight heparin, nadroparin (Fraxiparine), inhibits thrombin-induced platelet shape change and does not enhance spontaneous platelet aggregation.

Therapeutic concentrations, added in vitro, of a low molecular weight heparin (LMWH), nadroparin (Fraxiparine), inhibit thrombin-induced platelet shape change (PSC), an early stage of human platelet activation. PSC was monitored by measuring the median platelet volume (MPV) using a high resolution channelyzer. The inhibitory action of nadroparin was specific to thrombin since this LMWH did not influence PSC induced by other agonists. In whole blood, unfractionated heparin (UH) but not nadroparin, significantly enhanced spontaneous platelet aggregation and increased MPV when compared with LMWH or saline controls. In conclusion, the LMWH, nadroparin, exerts less platelet activation than UH.

Adult↗
PubMed1994

Naftidrofuryl inhibits the release of 5-hydroxytryptamine and platelet-derived growth factor from human platelets.

Angioplasty and bypass-grafting are associated with restenosis which limits their efficacy. Platelet-rich thrombus formation is the predominant cause of acute occlusion whereas platelet release products with proliferating properties, e.g. 5-hydroxytryptamine (5-HT) and platelet-derived growth factor (PDGF), may contribute to late restenosis. Naftidrofuryl (NAF), a drug for the treatment of peripheral vascular disease, was shown previously to inhibit platelet shape change and aggregation. This study establishes whether NAF inhibits the release of 5-HT and PDGF from platelets obtained from healthy subjects. Platelets stimulated with agonists aggregated less and released less 5-HT/PDGF when pre-incubated with NAF. Indomethacin (INDO), a cyclooxygenase inhibitor, alone inhibited aggregation and PDGF/5-HT release; NAF enhanced the inhibitory effects of INDO. The effect of NAF, on its own or in combination with a cyclooxygenase inhibitor, may therefore confer protection against graft occlusion.

Adenosine Diphosphate↗
PubMed1994

Diminished platelet yield and enhanced platelet aggregability in platelet-rich plasma of peripheral vascular disease patients.

Centrifugation of citrated whole blood (cit-WB) for platelet rich plasma (PRP) preparation resulted in a significantly diminished platelet yield compared to when blood was collected in citrate + aspirin (acetylsalicylic acid; ASA) or EDTA anticoagulants in both apparently healthy young subjects and peripheral vascular disease (PVD) patients. The loss in platelets was significantly greater in PVD patients than in young apparently healthy subjects when using cit-WB. Median platelet volume (MePV) of PRP preparations was not different between PVD patients and apparently healthy subjects. The MePV of EDTA-PRP preparations was significantly bigger than cit-PRP and cit + ASA-PRP in both PVD patients and apparently healthy subjects. Citrate and citrate + ASA-PRP of patients was significantly more aggregable to adrenaline. In EDTA-PRP, adrenaline-induced aggregation did not occur. These findings indicate that platelet hyperactivity occurs in PVD even in the presence of ASA. Furthermore, studies involving the use of PRP may not be representative in PVD due to the significant loss of platelets during centrifugation. The methodology described here can be used by those who do not have facilities designed specifically for platelet research.

Aged↗
PubMed1994

Platelet shape change in whole blood: differential effects of endotoxin.

The effect of endotoxic lipopolysaccharide (LPS) on platelet shape change (PSC; a preaggregation event) was investigated. PSC is accompanied by an increase in median platelet volume (MPV), which was measured using a channelyzer. In whole blood, but not in platelet rich plasma (PRP), LPS (final concentration 80 mg/l) caused an increase in MPV that could be detected for 2 h. When PRP (prepared from LPS- and saline-pretreated whole blood) was incubated for 40 min, the LPS-mediated increase in MPV could no longer be detected. Taken together, these data imply that PSC is both initiated and maintained by a labile factor(s) present in whole blood, but not in PRP. PRP was prepared from LPS-pretreated whole blood and incubated for 40 min to allow reversal of the LPS-induced PSC; further stimulation with LPS caused PSC. Platelets from LPS-pretreated whole blood also showed enhanced PSC with serotonin (5-HT), diminished PSC with platelet activating factor (PAF), and no change of response to ADP and collagen. Hence, LPS pretreatment of whole blood differentially alters responses of platelets to further stimulation with LPS and other agonists. A specific PAF antagonist completely abolished the effect of LPS on MPV. These data may contribute to an understanding of the cascading thrombotic events and thrombocytopenia associated with septicaemia.

Bacterial Infections↗
PubMed1993

Effect of milrinone in human platelet shape change, aggregation and thromboxane A2 synthesis: an in vitro study.

Milrinone (MIL; a cAMP-specific phosphodiesterase type-III inhibitor), added in vitro to achieve concentrations below the therapeutic levels, inhibited agonist-induced platelet shape change (PSC). Arachidonic acid (AA)-induced PSC was significantly more inhibited by a combination of MIL and indomethacin (INDO; a cyclooxygenase inhibitor) than by either alone. PSC induced by 5-hydroxytryptamine was inhibited by MIL but not by INDO; and this effect of MIL was not augmented by INDO. Whole blood-platelet aggregation (WB-PA) and platelet-rich plasma aggregation induced by potent stimulators of thromboxane A2 (TXA2) synthesis such as AA and calcium ionophore and by less potent agonists (e.g. ADP and U46619) were inhibited by MIL at or near therapeutic concentrations. WB-PA induced by collagen was significantly more inhibited by the MIL and INDO combination than by either of these agents alone whereas with ADP-induced WB-PA no additional effect could be shown when both MIL and INDO were co-incubated. MIL and similar types of drugs may be of benefit in conditions associated with platelet hyperactivity and some of these effects may be enhanced by cyclooxygenase inhibitors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

The use of platelets as models for neurons: possible applications to the investigation of eating disorders.

The pathogenesis of eating disorders is still unclear. However, there is evidence that neurotransmitters may be involved in the control of satiety/appetite. Investigating these disorders could be facilitated if a readily available human cell model were to reflect central nervous system (CNS) function. Platelets may satisfy, at least partially, this requirement. We discuss here the use of platelets as neuronal models with an emphasis on eating disorders.

Animals↗
PubMed1992

5-Hydroxytryptamine stimulates 45Ca2+ uptake by human umbilical vein endothelial cells in culture: mediation by 5-HT2 receptor subtypes.

In cultured human umbilical vein endothelial cells, 5-HT and alpha-methyl 5-HT stimulated [45Ca2+] uptake in concentration-dependent manner, whereas the 5-HT1 agonists, m-CPP (1-(3-chlorophenyl)piperazine and 2-MPP (1-(2-methoxyphenyl)piperazine), were without effect. In turn, 5-HT-stimulated [45Ca2+] uptake was inhibited in concentration-dependent manners by the 5-HT receptor antagonists ketanserin (5-HT2), LY 53,857 (5-HT2) and methiothepine (5-HT1/2) and to a lesser degeree by MDL 72222 (5-HT3) and BRL 43694 (5-HT3) whereas (+/-)-propranolol (5-HT1) was without effect. These data indicate that 5-HT stimulates Ca2+ uptake by endothelial cells via activation of a 5-HT2 receptor subtype. 5-HT was without effect on de novo prostacyclin (PGI2) synthesis over the concentration of 5-HT that elicited [45Ca2+] uptake. Since 5-HT did not stimulate PGI2, an event associated with an increase in levels of intracellular Ca2+, it is postulated that the uptake of 45Ca2+ reflects changes of Ca2+ at the level of the plasma membrane rather than on intracellular changes. 5-HT-stimulated Ca2+ uptake may be of relevance to endothelium-dependent relaxation, vascular permeability and endothelial repair and proliferation.

Biological Transport, Active↗
PubMed1992

Serotonin, histamine and platelets in vascular disease with special reference to peripheral vascular disease.

Cardiovascular disease is a major cause of death. There is evidence that this disease is predicted and its progression influenced by various factors (e.g. hyperlipidaemia). In this review, we consider aspects of platelet structure and function which may explain how this cell type contributes to the pathogenesis of vascular disease. The platelet also contains bioamines (serotonin, 5-HT; histamine) which are potent vasoactive substances. Studies involving patients with peripheral vascular disease (PVD) where abnormalities in platelet function (platelet aggregation and platelet shape change) and in bioamine status (vascular, platelet and plasma bioamine concentrations) are reviewed. We also discuss how platelet activation (in vitro) and plasma lipids influence intraplatelet bioamine status. Finally, we report in vitro evidence of the effect of two drugs prescribed to PVD patients: aspirin and naftidrofuryl. Aspirin is an ineffective inhibitor of 5-HT-induced whole blood platelet aggregation whereas naftidrofuryl is effective in the presence or absence of aspirin. By identifying and altering the factors which contribute to the pathogenesis of atherosclerosis we will be better equipped to prevent, reverse or retard this process.

Animals↗