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Biomedical subjects

J Y Jeremy

Publications and source records attributed to J Y Jeremy.

At least 145 records · Page 8Linked to original sources
PubMed1988

The effect of cooling on in vitro vascular prostacyclin and platelet thromboxane A2 synthesis: relevance to cold-induced pathology.

The effect of cooling (at 27 degrees C) on the synthesis of prostacyclin (PGI2) by rat aortic rings, thromboxane A2 (TXA2) synthesis by human platelets and phosphodiesterase activity in human platelets was investigated. Cooling induced a significant reduction in both PGI2 synthesis by rat aortic rings and TXA2 synthesis by human platelets, but the inhibition of the former was proportionately greater. Platelet phosphodiesterase activity decreased, with a subsequent increase in intraplatelet c-AMP content. Diminished PGI2 synthesis/release associated with the previously described diminution in the sensitivity of platelets to PGI2 after cooling probably contributes to the hyperaggregability of platelets at lower temperatures. This occurs in spite of the potential antiaggregatory effect of diminished TXA2 synthesis by platelets and the increase in intraplatelet c-AMP. These observations are relevant to the pathogenesis of hyperaggregability of platelets in Raynaud's syndrome.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Ex vivo platelet studies following oral nisoldipine in normotensive insulin-dependent diabetics and non-diabetic controls.

The effect of 24 hours and 7 days treatment with nisoldipine (10 mg, twice daily) on platelet function was studied in 12 normotensive volunteers of whom six were insulin-dependent diabetics without clinical evidence of vascular complications. Platelet aggregation was assessed by platelet rich plasma (PRP) and whole blood (WB) techniques. In addition, the effect of nisoldipine on platelet hyperaggregability following exercise was assessed. After taking nisoldipine for 24 hours, in vitro platelet hypersensitivity to adenosine diphosphate was observed in PRP (p less than 0.01) and WB (p less than 0.01), to adrenaline in WB (p less than 0.03), and to collagen in PRP (p less than 0.02). After seven days treatment, platelet sensitivities to all agonists at rest in both PRP and WB showed no differences from pre-treatment values. Exercise-induced platelet hypersensitivity in WB to all three agonists was unchanged after nisoldipine treatment. Plasma noradrenaline and adrenaline concentrations increased after 24 hours treatment, although changes in agonist EC50s at 24 hours were not related to changes in plasma catecholamine levels. No effects of nisoldipine were observed on platelet thromboxane B2 release in PRP, or on plasma beta-thromboglobulin levels. No differences in the effects of nisoldipine were observed between diabetic and non-diabetic subjects. Nisoldipine treatment for seven days is not associated with altered platelet function, but platelet hypersensitivity is observed after treatment for 24 hours in both insulin-dependent diabetics and controls.

Adenosine Diphosphate↗
PubMed1988

Treatment of hypertension with captopril: preservation of regional blood flow and reduced platelet aggregation.

The BP of 12 patients with essential hypertension was controlled with captopril over a period of three months. Cerebral blood flow, muscle blood flow (anterior tibialis muscle), platelet aggregation and platelet thromboxane A2 release were measured during a baseline drug-free period, and measurements repeated during the treatment phase on achieving BP control, after one and three months. Cerebral blood flow rose during the early phase of treatment and then dropped to baseline levels during chronic therapy. Muscle blood flow, both at rest and following maximal exercise, was unaffected by captopril therapy. Platelet aggregation was diminished during therapy, and this finding was paralleled by a reduction in platelet thromboxane A2 generation. Control of hypertension with maintenance of regional blood flow and beneficial changes in platelet function during treatment with captopril may improve the overall risk profile of hypertensive patients. Inhibition of platelet aggregation and thromboxane A2 release may contribute to the antihypertensive action of captopril and the maintenance of regional blood flow.

Aged↗
PubMed1988

The role of calcium in mediating phorbol ester- and insulin-stimulated adipocyte lipogenesis.

The roles of protein kinase C, calcium and calmodulin in mediating insulin-stimulated lipogenesis by rat adipocytes were investigated using the protein kinase C activator, phorbol myristate acetate (PMA); the protein kinase C inhibitors, H7 and polymixin B; the calcium ionophore, A23187; the calcium channel blocker, verapamil; and the calmodulin inhibitor, calmidazolium. PMA caused a concentration-dependent, parallel left shift of the insulin-lipogenesis dose response curve. Both PMA- and insulin-stimulated lipogenesis were inhibited by H7 and polymixin B. A23187 enhanced the stimulatory action of both insulin and PMA was not inhibited by H7. The stimulatory effects of insulin and PMA were inhibited by verapamil and calmidazolium. These data indicate that insulin receptor-lipogenesis coupling in rat adipocytes is mediated by protein kinase C-elicited calcium influx and activation of calmodulin.

Adipose Tissue↗
PubMed1988

Double-blind placebo-controlled trial of buflomedil in intermittent claudication.

In a double-blind placebo-controlled trial, buflomedil was shown to cause a significant increase both in median claudication provoking time from 63 sec (range: 24-136 sec) to 124 sec (range: 53-261 sec) (p less than 0.01), and in maximum walking distance (MWD) from 169m (range: 157-308 m) to 293 m (range: 107-429 m) (p less than 0.01). The MWD after three months' buflomedil treatment was also significantly (p = 0.05) prolonged when compared with the MWD in the appropriate placebo group. In contrast, treatment with the placebo caused no significant change in these indices. Subjective improvement was observed in 12 out of 14 patients on buflomedil, whilst it occurred in only 6 out of 14 patients on the placebo (p less than 0.05). The clinical improvement was not associated with an increase in the ankle pressure index or a reduction in platelet aggregation and thromboxane A2 release.

Aged↗
PubMed1988

Platelet thromboxane A2 synthesizing capacity is enhanced by fasting but diminished by diabetes mellitus in the rat.

In order to investigate whether the hyperaggregability of platelets in diabetic and starved rats was due to an increase in the inherent capability of these platelets to synthesize thromboxane A2, we assessed the total thromboxane A2 synthesizing capacity of platelets in rats with streptozotocin-induced diabetes and rats which have been semistarved (nine days) or fasted for various periods (24-72 h). Fasting for 48 h or more and semistarvation resulted in highly significant increases in thromboxane A2 synthesizing capacity. Experimental diabetes, however, resulted in a marked diminution in thromboxane A2 synthesizing capacity. This decrease in thromboxane A2 synthesizing capacity was prevented in diabetic rats treated with insulin. We conclude that while the hyperaggregability of starvation is associated with an increase in thromboxane A2 synthesizing capacity, that of diabetes is associated with a fall in this capacity. The decrease of this capacity in diabetic animals can be prevented by insulin treatment. Total thromboxane A2 synthesizing capacity is therefore not a major determinant of either platelet hyperaggregability or of agonist induced platelet thromboxane A2 release.

Animals↗
PubMed1987

The role of the diacylglycerol-protein kinase C system in mediating adrenoceptor-prostacyclin synthesis coupling in the rat aorta.

The role of the diacylglycerol-protein kinase C system in mediating adrenoceptor-stimulated prostacyclin (PGI2) synthesis in the isolated rat aorta was investigated using the diacylglycerol-mimetic phorbol 12,13-dibutyrate (PDBU) and the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperizine (H7). PDBU stimulated rat aortic PGI2 synthesis in a dose-dependent manner, an action potentiated by adrenaline and the calcium ionophore A23187. EDTA (10(-2) mol X l-1) completely inhibited PDBU-stimulated PGI2 synthesis. The calcium channel blockers, verapamil and nifedipine, inhibited PDBU-stimulated PGI2 synthesis in a dose-dependent manner, as did the protein kinase C inhibitor H7. The adrenoceptor antagonists phentolamine, prazosin and yohimbine were without effect on PDBU-stimulated PGI2 synthesis. H7 also inhibited adrenaline-stimulated, but not trauma-, A23187- or arachidonate-stimulated PGI2 synthesis. These experiments constitute evidence that adrenoceptor-PGI2 synthesis coupling is mediated by diacylglycerol-protein kinase C initiation of calcium influx in the rat aorta.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1987

Differential regional changes of prostacyclin and thromboxane A2 synthesis in the intestinal tract of the fasted and semistarved rat.

The synthesis of prostacyclin (PGI2) and thromboxane A2 (TXA2) by the mucosal and muscular portions of the duodenum, jejunum, ileum and ascending colon, as well as that by mesenteric vessels, was investigated in starved and semistarved rats. The jejunal mucosa and muscularis showed a marked increase in PGI2 synthesis after fasting for 48 h and 72 h or semistarvation for 9 days when compared with controls. Jejunal TXA2 synthesis did not alter. In contrast, PGI2 and TXA2 synthesis in ileal mucosa and muscularis was significantly reduced after fasting for 48 h, 72 h and semistarvation for 9 days. PGI2 and TXA2 synthesis by duodenal and colonic muscularis was unaffected by fasting or semistarvation. PGI2 synthesis in mesenteric vessels was significantly increased by fasting and semistarvation. No changes in PGI2 or TXA2 were detected at 24 h in fasted rats in any of the tissues studied when compared with controls. These selective changes in PGI2/TXA2 secretion may be important mediators of adaptive changes in the small intestine in response to starvation.

Animals↗
PubMed1987

Fasting and diabetes mellitus elicit opposite effects on agonist-stimulated prostacyclin synthesis by the rat aorta.

The effects of prolonged fasting and experimental nonketonuric diabetes on rat aortic prostacyclin (PGl2) synthesis were compared. Whereas fasting (for 48 hours or longer) resulted in a marked increase in trauma-, adrenaline-, and U46619-stimulated aortic PGI2 synthesis, prolonged experimental (streptozotocin-induced) nonketonuric diabetes caused a marked decrease in aortic PGI2 synthesis stimulated by the above agonists. Arachidonic acid (AA)-stimulated aortic PGI2 synthesis in fasted and diabetic rats, however, was not different from that in controls. The reduction in adrenaline- and U46619-stimulated, but not AA-induced, PGI2 synthesis in the diabetic rat suggests that the diminished production of PGI2 in diabetes may be due to diminished phospholipase A2 (or of the phospholipase C-diglyceride lipase system) activity, diminished AA stores, or both. The opposite effects of prolonged fasting and diabetes on aortic PGI2 synthesis suggest that caution should be exercised when comparing the metabolic consequences of starvation with those of diabetes.

Animals↗
PubMed1987

Fluoride but not phorbol esters stimulate rat urinary bladder prostanoid synthesis: investigations into the roles of G proteins and protein kinase C.

The role of G proteins and protein kinase C in mediating muscarine receptor-linked prostanoid synthesis by the rat urinary bladder was investigated using the G protein activator, sodium fluoride (NaF); the protein kinase C activators, phorbol myristate (PMA) and phorbol dibutyrate (PDBU); the protein kinase C inhibitor, H7, and the parasympathomimetic, carbachol. NaF stimulated in vitro rat urinary bladder prostacyclin (PGI2) synthesis (EC50 = 6 mmol.l-1), an action inhibited by the presence of EDTA (10 mmol.l-1). Carbachol potentiated the stimulatory action of NaF. NaF (10 mmol.l-1)-stimulated PGI2 synthesis was inhibited by the calcium channel blockers verapamil, nifedipine and the protein kinase C inhibitor, H7, in concentration-dependent manners. Carbachol-stimulated PGI2 synthesis was also inhibited by H7. PDBU and PMA were without effect on de novo, NaF- or carbachol-stimulated urinary bladder PGI2 synthesis. Other prostanoids (PGF2 and PGF2 alpha) were stimulated to the ame degree as PGI2 by NaF, and inhibited equally by H7 and calcium channel blockers. Dibutyryl adenosine 3':5'-cyclic monophosphate was without effect on de novo or NaF-stimulated prostanoid synthesis. Since fluoride activates G proteins, these data indicate that: (1) muscarine receptor-prostanoid synthesis coupling is mediated by G proteins in the rat urinary bladder; (2) fluoride action is mediated by protein kinase C and not adenyl cyclase, probably through activation of phospholipase C and therefore the generation of the protein kinase C activator, diacyl glycerol; (3) activated protein kinase C may initiate Ca2++ mobilisation linked to prostanoid synthesis; and (4) the lack of effect of the phorbol esters on urinary bladder PGI2 synthesis, in contrast to that on other smooth muscle, indicates that in different smooth muscle tissues there are varying forms of protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1987

Platelet hyperaggregability in cystic fibrosis.

Platelet function was investigated in 15 patients with cystic fibrosis (CF) and in ten age-matched controls. Marked hyperaggregability of platelets to adrenaline, collagen and arachidonic acid was observed in platelet rich plasma (PRP) prepared from patients with cystic fibrosis. Thromboxane A2 (TXA2) release from these platelets was also markedly enhanced. Hyperaggregability and increased TXA2 release observed in patients with CF was not due to the higher platelet counts in these patients since hyperaggregability was observed even in those patients whose platelet counts were similar to those in controls. Platelet hyperaggregability and increased thromboxane release in these patients were also independent of their body weight and occurred despite supplementation with vitamin E. Hyperaggregability of platelets in CF may be clinically relevant since it may contribute to the pathogenesis of bronchoconstriction through the release of TXA2 and other bronchoconstrictor platelet products such as serotonin.

Adolescent↗
PubMed1987

Urinary bladder prostanoids--their synthesis, function and possible role in the pathogenesis and treatment of disease.

The present review surveys the factors governing the synthesis of prostanoids by the urinary bladder, their role in the maintenance of normal bladder function, the pattern of their secretion in bladder disease and, finally, their possible use in the treatment of bladder pathology. It should be emphasized that this area of investigation is in its infancy, and therefore the pathophysiological and clinical relevance of these observations is, to some extent, speculative. However, a certain degree of awareness is necessary to stimulate further studies in this promising field of research.

Animals↗
PubMed1987

Cyclosporine A enhances platelet aggregation.

In view of the reported increase in thromboembolic episodes following cyclosporine A (CyA) therapy, the effect of this drug on platelet aggregation and thromboxane A2 release was investigated. The addition of CyA, at therapeutic concentrations to platelet rich plasma from normal subjects in vitro was found to increase aggregation in response to adrenaline, collagen and ADP. Ingestion of CyA by healthy volunteers was also associated with enhanced platelet aggregation. The CyA-mediated enhancement of aggregation was further enhanced by the addition in vitro of therapeutic concentrations of heparin. Platelets from renal allograft recipients treated with CyA also showed hyperaggregability and increased thromboxane A2 release, which were most marked at "peak" plasma CyA concentration and less so at "trough" concentrations. Platelet hyperaggregability in renal allograft patients on long-term CyA therapy tended to revert towards normal following the replacement of CyA with azathioprine. Hypertensive patients with renal allografts on nifedipine therapy had normal platelet function and thromboxane release in spite of CyA therapy. These observations suggest that CyA-mediated platelet activation may contribute to the pathogenesis of the thromboembolic phenomena associated with the use of this drug. The increased release of thromboxane A2 (a vasoconstrictor) may also play a role in mediating CyA-related nephrotoxicity.

Adult↗
PubMed1987

Effect of heparin and contrast medium on platelet function during routine cardiac catheterisation.

Platelet function was studied during coronary angiography of patients complaining of chest pain. The following changes occurred 5 min after injecting 100 IU.kg-1 body weight of a conventional high molecular weight heparin: (a) a significant fall in platelet count; (b) a significant enhancement of platelet aggregation in platelet rich plasma (turbidometric technique) and in whole blood (platelet aggregation technique); and (c) significantly enhanced release of platelet thromboxane A2, a vasoconstrictor. These changes tended to reverse towards baseline values 5 min after injecting a contrast medium (Conray 420), which was found to inhibit platelet aggregation. Thus heparinisation with a high molecular weight heparin seems to cause pronounced activation of platelets in patients undergoing coronary angiography, and this may contribute to the pathogenesis of cardiac ischaemia that may occur during this procedure. Since coronary artery bypass surgery in similar patients involves the use of heparin at much higher doses without the concomitant use of an antiaggregatory contrast medium, it is possible that platelet hyperaggregability may contribute to the well documented ischaemic brain injury associated with this form of surgery. Furthermore, the use of high molecular weight heparin after successful coronary angioplasty or thrombosis may influence the incidence of reocclusion. These findings therefore suggest that low molecular weight heparinoids should be evaluated in these situations since these anticoagulants are only weak activators of platelet aggregation.

Adult↗