Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic individuals frequently have platelet hyperaggregability and increased thromboxane (TXB2) production. To evaluate whether improvement of metabolic control or changes in fatty acid composition of serum lipids might alter thromboxane (TXB2) formation and platelet function, we followed up 25 newly diagnosed type 2 diabetics without angiopathy for about 6 months. Improvement of metabolic control (HbA1, fell from 12.0 +/- 0.3 to 9.0 +/- 0.3%; p less than 0.01) was associated with significant decrease in total cholesterol, triglycerides, and ratios of total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol. Palmitic acid of phospholipids decreased significantly, whereas eicosapentaenoic acid increased. Regardless of this, the ADP-induced platelet aggregability and sensitivity were not altered. There was no effect whatever on the TXB2 synthesis capacity of clotting whole blood (204.9 +/- 25.0 vs 222.8 +/- 32.0 ng/ml) over 6 months of treatment. Platelet aggregability and TXB2 formation were not correlated to the degree of metabolic control, nor were there any correlations to serum lipids and their fatty acid composition. Thus, we are tempted to speculate that glucose metabolism in diabetes itself does not affect platelet aggregation or TXB2 formation in type 2 diabetes mellitus.
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PMID:Thromboxane production and platelet aggregation in type 2 diabetes mellitus without vascular complications. 174 4

Acrolein, a component of tobacco smoke, potentiated platelet aggregation and increased thromboxane A2 (TXA2) formation caused by thrombin and arachidonic acid (AA). Acrolein produced these effects at concentrations in the range 50-5000 microM. Acrolein had no effect on platelet responses to ADP, epinephrine, collagen or the ionophore A23187. Acrolein increased the mobilization of [3H]arachidonic acid from prelabelled platelets in response to thrombin and arachidonic acid. The increased availability of substrate could partly explain the enhanced production of TXA2 and increased aggregation observed in the presence of acrolein. These findings could provide an explanation for the increased incidence of vascular disease in cigarette smokers.
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PMID:Effects of acrolein on human platelet aggregation. 211 26

G-proteins are transducing proteins that couple a large number of membrane-bound receptors to a variety of intracellular effector systems. Pertussis toxin ADP-ribosylates certain G-proteins causing inhibition of their function. In porcine coronary arteries, pertussis toxin inhibited the endothelium-dependent relaxations evoked by alpha-2-adrenergic or serotonergic receptor stimulation, and by aggregating platelets or thrombin. Relaxations to nitric oxide and endothelium-dependent relaxations to bradykinin, adenosine diphosphate or A23187 were unaffected by the toxin. Therefore, certain endothelium-dependent relaxations are mediated by activation of a pertussis toxin-sensitive G-protein in the endothelial cells, most likely Gi-protein. In porcine coronary arteries with regenerated endothelium (following in vivo denudation), the endothelium-dependent relaxations caused by the pertussis toxin-sensitive stimuli were reduced and were not further affected by pertussis toxin. Relaxations to the other stimuli were not altered by the regeneration process and were still not affected by the toxin. In regenerating endothelial cells there may be a selective impairment of the G-protein-dependent mechanism for releasing EDRF, which may predispose the blood vessel to vasospasm or the initiation of vascular disease.
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PMID:G-proteins and endothelial responses. 212 22

Certain arachidonic metabolites may play a pathogenic role in psoriasis. Platelets are rich sources of 12-hydroxy-eicosatetraenoic acid (12-HETE) and thromboxane A2, mediators of skin inflammation and platelet aggregation, respectively. We have studied untreated psoriatic patients without a history of diabetes mellitus and smoking. In psoriatics, platelet aggregation elicited by thrombin, ADP, and ristocetin was significantly enhanced as compared with healthy adult volunteers. Enhancement of platelet aggregation was detected in patients with both minimal and widespread disease. The formation of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), a cyclooxygenase product, and 12-HETE, a 12-lipoxygenase product, was increased in psoriatics with widespread disease but not in those with minimal disease. Formation of 12-HETE was stimulated to a higher degree (125%) than HHT (98%) in psoriasis (P less than 0.05). Addition of platelet-derived 12-HETE to cultured human epidermal keratinocytes resulted in a stimulation of the DNA synthesis (68% at 10(-7) M). These data suggest that platelet activation occurs in psoriasis, and that release of inflammatory and mitogenic compounds by activated platelets may play a role in the pathophysiology of psoriasis. Whether enhanced platelet aggregation in psoriasis is associated with occlusive vascular disease needs further investigation.
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PMID:Increased aggregation and arachidonic acid transformation by psoriatic platelets: evidence that platelet-derived 12-hydroxy-eicosatetraenoic acid increases keratinocyte DNA synthesis in vitro. 243 57

We examined platelet aggregability during nocturnal sleep and daytime wakefulness in patients with a history of sleep-related stroke onset (SOS) and compared it to that of matched awake-onset stroke (AOS) patients and controls without evidence of vascular disease. Aggregability was evaluated in-vitro at least seven weeks following stroke onset. Platelets were more aggregable to ADP, collagen and arachidonic acid (AA) during both sleep and wakefulness in patients with AOS (p less than 0.01). No significant difference in the mean aggregation thresholds during sleeping or waking periods were found between SOS and control groups. However, platelets were significantly more responsive to AA during sleep than during wakefulness in the SOS patients (p less than 0.01). This difference was confined to the subgroup of SOS patients who had experienced nocturnal as opposed to daytime sleep-related stroke onset, suggesting that the observed difference in platelet responsiveness to AA may be related to a circadian fluctuation in platelet aggregability rather than to a sleep-related fluctuation. Significant sleep-related changes in platelet aggregability were not identified in the other two groups.
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PMID:Platelet aggregability in sleep-related stroke. 249 75

Abnormal activation of blood platelets may be a contributory factor in the accelerated vascular disease which occurs in hypertension. We investigated the effects of lowering blood pressure in 12 patients with mild hypertension on several aspects of platelet function, initially in a placebo-controlled, double-blind, cross-over study with nisoldipine, and subsequently in the same patients comparing nisoldipine with the patients' usual anti-hypertensive therapy. Values were compared with those from an age, sex-matched control population. Seven hypertensive patients with renal failure were also studied. Administration of nisoldipine reduced ex vivo "spontaneous" aggregation of blood platelets significantly, and a similar significant effect was seen when blood pressure was lowered by the patients usual anti-hypertensive therapy. "Spontaneous" aggregation occurring in the control population was similar to that in the treated hypertensives. Blood platelet count, and aggregation in response to ADP and adrenalin were unaffected by treatment. Median plasma beta thromboglobulin levels were significantly higher in the untreated hypertensive patients (43 ng ml-1) than in the controls (30 ng ml-1), and there was a trend to reduced values for beta thromboglobulin on treatment of the hypertension. These results indicate that blood platelet activity is enhanced in hypertension and that function returns towards normal when blood pressure is lowered by treatment.
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PMID:Anti-hypertensive drugs non-specifically reduce "spontaneous" activation of blood platelets. 253 78

In the present study the effects of a short term intensive glycaemic control obtained with subcutaneous insulin therapy on lipids and apoprotein levels, platelet aggregation, platelet sensitivity to prostacyclin and platelet thromboxane production were investigated in 20 patients with type 2 diabetes and vascular disease. In 11 out of the 20 patients there was a significant improvement of glycaemic control (fructosamine reduction). Only with tight improvement of glycaemic control there was significant change in the concentration of ADP and collagen required to produce 50% of the maximum aggregation wave response, in the responsiveness of platelet to PGI2 and in the TxB2 synthesis. Lower Apo B levels were also shown in the tight control group suggesting that Apo B changes may have influenced platelet aggregation and thromboxane synthesis.
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PMID:Platelet function in patients with type 2 diabetes mellitus: the effect of glycaemic control. 266 42

Despite efficient revascularisation procedures for vascular disease, the limb can occasionally be lost following reperfusion. One contributing factor might be the formation of oxygen free radicals. This study attempts to describe the conditions necessary for oxy-radical formation from adenine nucleotide breakdown products and the role of plasma creatine content as a marker of cellular injury. Twelve patients undergoing aortic reconstructive surgery were studied. Only partial ischaemia of the lower limbs was induced by the aortic clamping, since varying degrees of collateral circulation existed. Radial arterial and external iliac venous blood was obtained simultaneously before, during and after cross-clamping of the aorta, and plasma levels of ATP, ADP, hypoxanthine, phosphocreatine, creatine, creatinine and lactate measured using luminescence and spectrophotometry. Venous creatine content increased during ischaemia and was doubled 30 min after recirculation. This increase was possibly due to leakage following cellular injury agreeing with a previously observed decrease in muscle tissue creatine content. The iliac arterio-venous difference of hypoxanthine and lactate markedly increased immediately post-ischaemia, while the phosphocreatine difference decreased. Plasma hypoxanthine was abundant in the leg on reoxygenation. The existence of a xanthine oxidase system in skeletal muscle could produce favourable conditions for oxy-radical formation through hypoxanthine degradation, which may contribute to the known muscle tissue injury.
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PMID:Plasma metabolic disturbances and reperfusion injury following partial limb ischaemia in man. 271 61

The safety, pharmacological action and pharmacokinetics of the thromboxane (TX) synthetase inhibitor Y-20811, a prospective medication for ischemic vascular disorder, were investigated in Phase I clinical trials in which single and repeated doses were administered orally to 32 healthy adult male volunteers. In the single-dose study, subjects were given single doses of 2.5, 5, 10, 25, 50, and 100 mg; in the repeated-dose study, a single dose of 50 mg was administered daily for 5 days. In the repeated-dose study, slight elevation of liver function test parameters in 1 subject was observed, but throughout the trials, no abnormality attributable to the test drug was found in other routine laboratory tests, subjective and objective findings, vital signs (blood pressure, pulse rate, body temperature, respiration rate), ECG, or bleeding time; nor did any finding indicate a problem concerning the safety of Y-20811. In both single- and repeated-dose studies, inhibition of the serum TXB2 production and an increase in the 6-keto-prostaglandin F1 alpha production during whole-blood coagulation, and inhibition of arachidonic acid-induced platelet aggregation were observed from 1 hour after administration of Y-20811. The duration of these actions was long, the former two lasting 168 hours (1 week) and the latter 48-72 hours or more. Slight inhibition of adenosine diphosphate-induced secondary platelet aggregation was also observed. The maximum plasma concentration time (tmax) of Y-20811 was 0.5-1.1 hours. The initial-phase half-life (t1/2 alpha) was 0.8-1.1 hours and the final-phase half-life (t1/2 beta) was 4.7-9.2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of Y-20811, a new long-acting thromboxane synthetase inhibitor by oral administration. 275 25

1. Aggregation of diluted whole blood (impedance method) and thromboxane B2 production during aggregation were measured in cigarette smokers and non-smokers, aged 41-68 years, with (n = 14) and without (n = 15) major symptomatic peripheral vascular disease. The plasma level of the lyso derivative of platelet activating factor (lyso-PAF) was also measured using a bioassay with 14C-serotonin labelled rabbit platelets, after extraction and acetylation to active PAF. 2. Aggregation to ADP and collagen was significantly less in non-smokers without vascular disease (n = 8) than in the other three groups (P less than 0.01; ANOVA). Thromboxane B2 production was not significantly different between the groups. There was no significant difference in plasma lyso-PAF between groups. No change was found in any variable after smokers smoked two cigarettes. 3. In these older age subjects, both vascular disease and the smoking habit were associated with greater whole blood aggregation. However, current smoking and the smoking of two cigarettes did not affect aggregation in subjects with vascular disease and plasma lyso-PAF levels were not consistently related to either smoking or vascular disease.
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PMID:Whole blood aggregation and plasma lyso-PAF related to smoking and atherosclerosis. 280 33


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