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Biomedical subjects

J Y Jeremy

Publications and source records attributed to J Y Jeremy.

At least 163 records · Page 9Linked to original sources
PubMed1987

Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).

1. The effects of an intravenous injection of a conventional high molecular weight heparin (HMWH) were compared with those of a low molecular weight heparinoid (Org 10172). A bolus injection of HMWH (5000 iu) was associated with: (a) a small but significant prolongation of bleeding time (BT); (b) a significant fall in PRP platelet count; (c) significantly enhanced platelet aggregation; and (d) significantly increased platelet thromboxane A2 (TXA2) release. These changes were not observed following the intravenous injection of Org 10172 (3200 anti Xa U). 2. These experiments were repeated following the oral administration of acetylsalicylic acid (ASA). HMWH again caused some enhancement of platelet aggregation despite the ASA-mediated inhibition of platelet aggregation and TXA2 release. Administration of Org 10172 to subjects taking ASA did not alter any of the platelet function indices. 3. In additional control experiments the injection of 5000 iu of HMWH was associated with a significant fall in PRP but not whole blood platelet counts. This finding suggests that the fall in PRP platelet count is a methodological artefact. 4. The HMWH also induced a significantly greater increase in serum non-esterified fatty acid (NEFA) concentrations than Org 10172. 5. The present findings indicate that Org 10172 is a less potent stimulator of platelet aggregation and lipolysis than HMWH. 6. The minor prolongation of the BT after HMWH is not compatible with enhanced aggregation but may be a consequence of alterations in the activity of coagulation factors and vascular-platelet interactions or of ongoing platelet activation accompanied by granule depletion. 7. The different effects of the two anticoagulants assessed suggests a therapeutic advantage in favour of Org 10172, especially in patients with hyperactive platelets.

Adult↗
PubMed1987

Comparison of the platelet pro-aggregatory effect of conventional unfractionated heparins and a low molecular weight heparin fraction (CY 222).

Two unfractionated heparins (UH), a porcine intestinal mucosal heparin (PIM), a bovine lung heparin (BLH) and a low molecular weight heparin (LMWH), CY 222, were assessed for their capacity to enhance platelet aggregation in vitro. Their potential proaggregatory effect was investigated in four systems: (a) enhancement of submaximal platelet aggregation induced by conventional agonists in platelet rich plasma and (b) in whole blood; (c) reversal of inhibition of platelet aggregation induced by iloprost, a stable analogue of prostacyclin; (d) the direct aggregatory effect of these anticoagulants on hyperactive platelets prepared from patients with severe peripheral vascular disease or anorexia nervosa. Whereas BLH and PIM, at therapeutic concentrations, had a proaggregatory effect in all four systems, CY 222 had no significant effect when compared with the controls. BLH was more potent than PIM in three of the four systems studied. These observations confirm that conventional UH are more proaggregatory than LMWH, and thus the latter may be potentially safer. These observations are also consistent with the fact that BLH administration causes thrombocytopenia more frequently than PIM. The direct activation by UH of platelets from patients not previously exposed to heparin also challenges the hypothesis that heparin-induced platelet activation and thrombocytopenia is solely mediated by classical heparin-dependent immune mechanisms.

Adult↗
PubMed1987

Eicosanoid synthesis by human urinary bladder mucosa: pathological implications.

Biopsies of human urinary bladder mucosa obtained during cystoscopy were shown to release eicosanoids in the following order: prostacyclin (PGI2), prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TXA2). The total and the relative amounts of eicosanoids released were similar to those reported for the rat urinary bladder. These eicosanoids may play a role in modulating the tone and contractility of the bladder as well as affecting cytoprotection of the mucosa. In view of the abundant release of eicosanoids by the bladder, caution must be exercised when considering urinary eicosanoid excretion as reflecting production by the systemic vasculature and/or the kidneys.

Dinoprost↗
PubMed1987

Platelet function in patients admitted with a diagnosis of myocardial infarction.

Platelet function and thromboxane A2 release were measured in 71 patients admitted to a coronary care unit with a provisional diagnosis of acute myocardial infarction (AMI). All measurements were carried out within twenty-four hours of admission. Of these, 35 patients had the diagnosis of AMI confirmed. The remainder (n = 36), who did not have AMI (NMI), were divided into two groups: those (n = 18) with an unequivocal history of previous vascular disease and those without vascular disease (n = 18). Platelet aggregation and thromboxane A2 (TXA2) release were significantly increased in the AMI group when compared with those in the NMI without vascular disease group or a healthy control group with similar age and sex distribution. Aggregation and TXA2 release in the NMI patients with vascular disease were greater than those in controls and did not differ significantly from those in the AMI group. Patients in the AMI or NMI with vascular disease groups who were taking beta-blockers or calcium channel antagonists at the time of admission showed significantly less platelet aggregation than those who were not taking these drugs. Heparin, added in vitro at therapeutic concentrations, induced significantly more aggregation in patients in the AMI and NMI with vascular disease groups than in the NMI without vascular disease group. We conclude that: platelets obtained from patients with AMI are hyperaggregable and release more TXA2; platelets from patients with significant vascular disease are hyperaggregable, even in the absence of AMI, although they are not as hyperaggregable as those from AMI; treatment with nifedipine and beta-blockers protects these patients from platelet hyperaggregability; heparin induces significant aggregation of platelets from patients with AMI and NMI with vascular disease. These observations are of importance in considering the pathogenesis and treatment of AMI and ischemic heart disease.

Adrenergic beta-Antagonists↗
PubMed1987

Oocyte maturity and human follicular fluid prostanoids, gonadotropins, and prolactin after administration of clomiphene and pergonal.

Follicular fluid (FF) and oocytes were obtained from 130 follicles of 52 women in whom ovulation was induced with human menopausal gonadotropin (Pergonal) and clomiphene citrate. Follicular aspiration was performed 36 h after an ovulatory injection of hCG. The concentrations of LH, FSH, PRL, and the prostanoids prostaglandin E2 (PGE2), PGF2 alpha, PGI2 (as 6-oxo-PGF2 alpha), and thromboxane A2 (as TXB2) in the FF were measured by RIA and related to the degree of maturation of the oocyte-corona-cumulus complex mass (OCCC). FF obtained from follicles with immature OCCC contained significantly lower concentrations of all four prostanoids (median concentrations, picograms per mL: PGE2, 88; PGF2 alpha, 85; 6-oxo-PGF1 alpha, 40; TXB2, 50) than those with intermediate OCCC (PGE2, 175; PGF2 alpha, 325; 6-oxo-PGF1 alpha, 130; TXB2, 65) and mature OCCC (PGE2, 425; PGF2 alpha, 860; 6-oxo-PGF1 alpha, 235; TXB2, 78; all P less than 0.01). There were no significant differences between the maturity of the complexes and the concentrations of LH, FSH, or PRL. There were significant correlations between the FF concentrations of LH and FSH and those of all of the prostanoids, but not with PRL, concentrations. These results indicate that the synthesis of prostanoids in the human Graafian follicles may be modulated by gonadotropins and consolidates the view that prostanoids may play a role in human oocyte maturation and ovulation.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Changes in eicosanoid synthesis in the cerebrum, cerebellum and brain stem of the diabetic rat.

The effect of streptozotocin-induced diabetes mellitus (DM) on rat brain prostanoid synthesis was assessed. Prostacyclin (PGI2) synthesis was significantly reduced in the DM animals in all 3 brain regions studied (cerebrum; cerebellum; brain stem). In contrast, the synthesis of the other 3 prostanoids assessed (PGF2 alpha; PGE2; TXA2) was not significantly altered in the DM animals. Insulin treatment reverted PGI2 synthesis towards the normal pattern. Since PGI2 is a vasodilator and the other 3 prostanoids (PGF2 alpha; PGE2; TXA2) are cerebral vasoconstrictors, these changes may be relevant to the pathogenesis of the previously reported abnormalities of cerebral blood flow and the increased incidence of cerebrovascular disease in DM.

Animals↗
PubMed1987

Effect of starvation on biochemical indices of renal function in the rat.

The effect of starvation on urinary output and biochemical indices of renal function was investigated in rats. Starvation resulted in a marked fall in water intake. Urinary output paradoxically increased during the first day following starvation, but fell dramatically thereafter. Urinary creatinine excretion and creatinine clearance fell markedly, but plasma creatinine concentration did not alter. Plasma urea concentration and urinary urea excretion fell. Plasma sodium concentration increased, whilst plasma potassium concentration did not alter; urinary sodium and potassium excretion fell. Plasma bicarbonate concentration fell marginally, but the anion gap increased to a greater extent. Following re-feeding, water intake and urine output increased, as did urinary creatinine excretion and creatinine clearance. Plasma urea and urinary urea concentrations, as well as sodium and potassium excretion, increased. Plasma bicarbonate increased and the anion gap decreased. These indices improved within 2 days of re-feeding and were restored to normal in 5 days.

Animals↗
PubMed1986

Platelet function defects in chronic alcoholism.

Platelet function in alcoholic patients was assessed on admission and during abstinence in hospital. On admission platelets from these patients were significantly less responsive (percentage aggregation and thromboxane A2 release) to conventional in vitro aggregating agents (adrenaline, adenosine diphosphate, and collagen) than platelets from healthy, moderate drinkers. Initially, platelet counts in platelet rich plasma tended to be low and the Simplate II bleeding times frequently prolonged. Platelet aggregation and thromboxane A2 release, however, were inhibited even in patients with normal platelet counts on admission. Platelet aggregation and thromboxane A2 release returned to normal or became hyper-responsive during two to three weeks of abstinence. Platelet counts rose during this period, the largest responses occurring in those patients with the lowest counts on admission. Bleeding times reverted to normal during abstinence and correlated significantly with changes in platelet aggregation, thromboxane A2 release, and platelet count and with the estimated ethanol consumption during the week before admission. Chronic, heavy alcohol ingestion evidently exerts an inhibitory effect on platelet function even in the absence of alcohol in the blood, and this phenomenon is reversible on abstaining. The impaired platelet function, together with the reduced platelet count, may contribute to the bleeding diathesis associated with chronic alcoholism and to the increased incidence and recurrence of gastrointestinal haemorrhage associated with excessive alcohol intake.

Adult↗
PubMed1986

Muscarinic stimulation of prostacyclin synthesis by the rat penis.

An in vitro model for the investigation of PGI2 synthesis by the rat penis is described. Acetyl-beta-methylcholine (methacholine; MeCh) and carbamyl choline (carbachol) stimulated PGI2 synthesis in a dose-dependent manner (ED50 = 1.5 X 10(-6); 2.5 X 10(-6), respectively), whereas adrenaline, noradrenaline, histamine, serotonin, vasoactive intestinal polypeptide (VIP), nicotine, dimethyl phenylpiperazinium (DMPP) and adenosine triphosphate (ATP) were without effect. MeCh (10(-6) mol/l)- and carbachol (10(-6) mol/l)-stimulated PGI2 synthesis was inhibited by atropine in a dose-dependent manner (ID50 = 2.5 X 10(-7) mol/l; 7 X 10(-6) mol/l, respectively). The inhibition by atropine of MeCh-stimulated PGI2 synthesis was competitive. MeCh (10(-6) mol/l)-stimulated PGI2 synthesis was inhibited by verapamil (ID50 = 6 X 10(-5)) and calcium-free incubation media. It is concluded that in the rat penis PGI2 synthesis is principally under muscarinic control and is calcium transport-dependent. Since PGI2 is a vasodilator, these findings may be relevant to the increased blood flow into the penis associated with penile erection. They may also be relevant to the protection of the penile vasculature from thrombosis, since PGI2 is also a potent inhibitor of platelet aggregation.

Animals↗
PubMed1986

Prostanoid synthesis by the rat urinary bladder: evidence for stimulation through muscarine receptor-linked calcium channels.

An in vitro model for the study of muscarine receptor-mediated synthesis of prostacyclin (PGI2) and other prostanoids (PGE2 and PGF2 alpha) by the rat urinary bladder is described. PGI2 synthesis was stimulated by parasympathomimetic agents (carbachol greater than methacholine greater than arecoline; McNA 343, nicotine and dimethyl phenyl piperazinium were without effect). Methacholine (3 X 10(-6) mol X l-1)-stimulated PGI2 synthesis was inhibited by muscarinic antagonists (atropine greater than ipratroprium bromide greater than gallamine greater than pirenzepine) and was completely abolished by the presence of ethylene diamine tetraacetic acid (EDTA: 10 mmol X l-1). Verapamil also inhibited methacholine-stimulated PGI2 synthesis in a dose-dependent manner. The antagonistic action of atropine was shown to be competitive, but had no effect on calcium ionophore A23187-stimulated PGI2 synthesis. High concentrations of [K+] (up to 0.11 mol X l-1) were without effect on PGI2 synthesis. PGE2, PGF2 alpha and PGI2 synthesis were all equally stimulated with methacholine, carbachol, arecoline and A23187, and methacholine-stimulated synthesis of these prostanoids was equally inhibited by atropine, ipratroprium bromide, gallamine, verapamil and EDTA. It is concluded that in vitro prostanoid synthesis by the rat urinary bladder: is stimulated by post ganglionic muscarine receptors; involves a muscarine receptor-linked calcium influx system; and is mediated by a predominance of M2 subtype receptors.

Animals↗
PubMed1986

The effect of nifedipine, nimodipine and nisoldipine on agonist- and trauma-stimulated vascular prostacyclin synthesis in vitro.

The present study shows that nifedipine, nimodipine and nisoldipine inhibit in vitro agonist-induced prostacyclin (PGI2) release from rat aortic rings. The agonists used were: U46619 (a thromboxane A2 analogue); A23187 (a calcium ionophore) and adrenaline. In contrast, these calcium channel blockers did not inhibit in vitro trauma- or arachidonic acid (AA)-induced PGI2 release. Therefore, in vitro PGI2 release models may be calcium channel dependent (adrenaline, U46619, A23187) or independent (trauma, AA), a property which is relevant to calcium channel blocker research. It is suggested that calcium channel dependent PGI2 release is relevant to modulating the relaxation phase of muscle contraction, while calcium channel independent PGI2 release is relevant to limiting the extension of thrombi following local vascular trauma.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1986

The effect of cimetidine on platelet function: a study involving gastric fluid measurements.

Gastric fluid samples were aspirated 30 and 60 minutes after the ingestion of two 200 mg tablets of cimetidine. The concentration of cimetidine in these samples was measured and their effect on platelet aggregation assessed in vitro. Gastric fluid samples significantly inhibited adrenaline- and ADP-induced platelet aggregation in vitro. In a further series of experiments, cimetidine solutions, at concentrations found in gastric fluid, inhibited platelet aggregation and thromboxane A2 (TXA2) release, in vitro. Ranitidine, another H2-receptor antagonist, was a more potent inhibitor of platelet aggregation than cimetidine. Since ranitidine is also the more potent H2-receptor antagonist which, unlike cimetidine, does not include an imidazole group (which is known to inhibit TXA2 synthesis) in its structure, we conclude that H2 blockade mediates the observed inhibition of aggregation. This platelet anti-aggregatory effect may be relevant to haemostatic mechanisms involved in bleeding peptic ulcers or gastric erosions exposed to high local concentrations of H2-receptor antagonists.

Blood Platelets↗
PubMed1986

Prostacyclin synthesis by the corpora cavernosa of the human penis: evidence for muscarinic control and pathological implications.

The present study demonstrates that human corpus cavernosum tissue has the capacity to produce prostacyclin (PGI2), a vasodilator and potent inhibitor of platelet aggregation. The release of PGI2 was stimulated by cholinergic (muscarinic) but not adrenergic agents. Since penile erection in man is dependent upon parasympathetic stimulation, the vasodilatory action of PGI2 may contribute to the initiation and maintenance of erection.

Atropine↗
PubMed1986

Adrenaline-induced hyperaggregability of platelets and enhanced thromboxane release in anorexia nervosa.

Platelet aggregation and thromboxane A2 release in response to adrenaline and the relationship of this response to body weight was investigated in female patients with anorexia nervosa. Platelets obtained from patients with body weights below 75% of the expected average weight (Group I) showed significantly greater aggregation and TXA2 release in response to adrenaline when compared with controls matched for sex and age. Patients with body weights 75-95% of the expected average weight (Group II) did not show enhancement of platelet aggregation or TXA2 release. In Group I patients, platelet hyperaggregability and enhanced TXA2 release induced by adrenaline tended to normalise following inpatient treatment and weight gain: with 0.5 mumol/l adrenaline, the pre-weight gain median aggregation was 65%, whereas the post-weight gain value was 37% - P less than 0.01. Markedly underweight patients also had hyperaggregability following stimulation with ADP and collagen. This hyperaggregability also tended to normalise after weight gain but these changes were not statistically significant. Platelet hyperaggregability (especially in response to adrenaline) in anorexia nervosa is therefore secondary to weight loss and reverts to normal with normalisation of weight. These changes may reflect the previously documented increase in platelet alpha-adrenoceptors in thin patients with anorexia nervosa and their normalisation following weight gain. However, the hyperaggregability in response to agonists other than adrenaline suggests that an additional post-receptor mechanism may be involved.

Adenosine Diphosphate↗