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Biomedical subjects

P Mehta

Publications and source records attributed to P Mehta.

At least 163 records · Page 9Linked to original sources
PubMed1988

Alterations in platelet alpha 2-adrenoceptors by aspirin.

Epinephrine-induced platelet aggregation (mediated through interaction with alpha 2-adrenoceptors) is inhibited by aspirin. To determine if aspirin modulates alpha 2-adrenoceptors, we quantitated dissociation constant (KD) and maximum number of binding sites (Bmax) on isolated platelet membranes using alpha 2-antagonist 3H-yohimbine in normal subjects given 650 mg of aspirin orally. Alpha 2-receptor KD increased from 3.20 +/- 1.80 to 7.32 +/- 3.32 nM (p less than 0.02) and Bmax from 115 +/- 77 to 190 +/- 140 fmol/mg protein. To determine if these alterations in alpha 2-receptors by aspirin were mediated through circulatory or intracellular effects, intact platelets or isolated platelet membranes were incubated with aspirin for 30 minutes in vitro. In these in vitro experiments, alpha 2-receptor KD increased from 2.92 +/- 1.76 to 9.83 +/- 8.55 nM and Bmax from 140 +/- 81 to 191 +/- 129 fmol/mg protein (p less than 0.05). Oral ingestion of aspirin or incubation of aspirin with intact platelets or lysates increased (3 to 10 fold) the concentration of 1-epinephrine required for inhibition of 3H-yohimbine binding by 50% (p less than 0.05). Basal platelet cyclic AMP as well as its elevation with PGE1 or PGI2 and decrease with catecholamines were not influenced by aspirin treatment of platelets. These data indicate that aspirin decreases platelet alpha 2-receptor affinity for agonist as well as antagonist. These effects of aspirin are independent of circulatory or dynamic intraplatelet changes.

Aspirin↗
PubMed1988

Activity of calcium/phospholipid dependent protein kinase during rat kidney development.

The activity of the calcium sensitive phospholipid dependent protein kinase C (PKC) was studied in cytosol and in the proximal tubular luminal membrane of rats during growth. Cytosolic activity was elevated at 14 and 21 days of age and fell to adult levels by day 60. Luminal brush border membrane activity on the other hand was low on day 14 but reached adult levels by day 21. Changes in brush border membrane PKC activity may have important consequences for the development of electrolyte transport in proximal tubular cells.

Alkaline Phosphatase↗
PubMed1988

Modulation of human neutrophil superoxide production by selective thromboxane synthetase inhibitor U63,557A.

Prostaglandin I2 and prostaglandins of E series have been known to inhibit human neutrophil superoxide production. To examine the effects of selective thromboxane synthetase inhibition on human neutrophil superoxide production (with or without platelets), neutrophils were incubated with U63,557A and stimulated with f-MLP, serum-activated zymosan or calcium ionophore A23187. U63,557A had no significant direct inhibitory effect on neutrophil superoxide production. On the other hand, in the presence of platelets in neutrophil suspension, U63,557A significantly reduced neutrophil superoxide production and increased prostaglandin I2 release. These data suggest that selective thromboxane synthetase inhibition may reduce neutrophil superoxide generation, most likely via increase in prostaglandin I2.

Benzofurans↗
PubMed1988

Neutrophils as potential participants in acute myocardial ischemia: relevance to reperfusion.

An interaction among leukocytes, platelets and endothelial cells is important in atherogenesis and in maintenance of blood flow and vascular tone. These complex cell-cell interactions are mediated by release of such metabolic substances as arachidonic acid metabolites, growth factors, oxygen free radicals and endothelium-derived relaxing factor. These substances participate in the regulation of blood flow in health and disease, and perturbation in the delicate equilibrium among various cellular elements may lead to evolution and propagation of myocardial ischemia. During reperfusion of ischemic myocardium, neutrophils together with platelets cause capillary plugging in the coronary microcirculation and exert detrimental effects on endothelial function resulting in the "no reflow" phenomenon, ventricular arrythmias, loss of coronary vascular reserve and, perhaps, extension of cellular injury. This review addresses the mechanisms of cell-cell interactions with special reference to myocardial ischemia and the potential for development of improved therapy to protect and preserve ischemic myocardium.

Arachidonic Acids↗
PubMed1988

Increased prostacyclin and thromboxane A2 biosynthesis in atherosclerosis.

It has been proposed that atherosclerotic arteries produce less prostacyclin (PGI2) than nonatherosclerotic arteries do, thereby predisposing arteries to vasospasm and thrombosis in vivo. We reexamined this concept by measuring spontaneous as well as arachidonate-induced PGI2 biosynthesis in aortic segments from nonatherosclerotic and cholesterol-fed atherosclerotic New Zealand White rabbits. Thromboxane A2 (TXA2) generation was also measured. Formation of PGI2, as well as TXA2, as measured by radioimmunoassay (RIA) of their metabolites, was increased in atherosclerotic aortic segments relative to nonatherosclerotic segments (P less than or equal to 0.05) at 0, 5, 10, 15, and 30 min of incubation with arachidonate. Pretreatment of arterial segments with indomethacin inhibited PGI2 as well as TXA2 formation, whereas pretreatment with the selective TXA2 inhibitor OKY-046 inhibited only TXA2 release, thus confirming the identity of icosanoids. To confirm the RIA data, aortic segments were incubated with [14C]arachidonate prior to stimulation with unlabeled arachidonate. The uptake of arachidonate was similar, but the release of incorporated [14C]arachidonate was significantly (P less than or equal to 0.05) greater in atherosclerotic segments than in nonatherosclerotic ones. Conversions of released [14C]arachidonate to 6-keto[14C]prostaglandin F1 alpha and [14C]thromboxane B2 were similar in the two types of aortic segments. Thus, synthesis of PGI2 as well as TXA2 is increased in atherosclerosis, and this alteration in arachidonate metabolism is related to increased release of arachidonate.

Animals↗
PubMed1988

Diluting power of thick limbs of Henle. II. Bumetanide-sensitive 22Na+ influx in medullary vesicles.

We evaluated the effects of osmotic gradients on 22Na+ influx in vesicles prepared from rat outer renal medulla. 22Na+ influx driven in a coflow mode by an inwardly directed 100 mM KCl gradient was measured at 20 and 60 s; 1 mM bumetanide inhibited approximately 30% of 22Na+ influx. The bumetanide-sensitive 22Na+ influx was reduced by approximately 65% when either K+ or Cl- was omitted from the aqueous phases. We found that an osmotic gradient for vesicle shrinkage, that is, 600 mM urea in the extravesicular medium, enhanced the bumetanide-sensitive 22Na+ influx twofold. Conversely, an osmotic gradient for vesicle swelling, that is, with vesicles but not extravesicular media loaded with 600 mM urea, produced a 50% suppression of bumetanide-sensitive 22Na+ influx. Moreover, 600 mM extravesicular urea, an osmotic gradient for vesicle shrinkage, also reduced uptake of the nonspecific marker [14C]mannitol. These effects of osmotic gradients were not due to alterations in ionic driving forces, since bumetanide-sensitive 22Na+ influx driven in a counterflow mode by loading the vesicles with 100 mM NaCl also was activated or suppressed by osmotic gradients for vesicle shrinkage or swelling, respectively. We conclude that osmotic gradients, and/or vesicle volume changes, modulate bumetanide-sensitive Na+:K+:2Cl- activity.

Alkaline Phosphatase↗
PubMed1988

Leukotriene D4 potentiates the contractile effects of epinephrine and norepinephrine on rat aortic rings.

Previous studies have demonstrated a cooperative interaction between peptido-leukotrienes (LTs) and epinephrine (EPI) relative to induction of platelet aggregation and thromboxane formation. To examine if a similar interaction occurs in arteries, we studied the effects of LTD4 and EPI as well as norepinephrine (NOREPI) on isolated rat aortic rings. LTD4 alone (mean concentration 2 x 10(-7) M) induced contraction in 10 of 15 rings examined (mean peak tension 0.31 +/- 0.27 g/mg of tissue). However, pretreatment of aortic rings with LTD4 (10(-7) M) consistently and significantly enhanced the contractile effects of EPI and NOREPI and lowered the threshold concentration of these agonists required to evoke contraction from 4 x 10(-9) to 3 x 10(-10) M (P less than .05). This enhancement of the sensitivity of aortic rings by LTD4 was not observed when KCl or 5-hydroxytryptamine was used as agonists. Furthermore, the LTD4-induced potentiation of effects of EPI or NOREPI on aortic contraction was blocked by the LT-receptor antagonist FPL-55712, but not by indomethacin. These data suggest a specific cooperative contractile effect of LTD4 and alpha adrenergic agonists on rat aortic rings. This LTD4 potentiation of vascular contraction is mediated through LT-receptor stimulation and not through release of cyclooxygenase metabolites.

Animals↗
PubMed1988

The battered woman.

The possibility of physical abuse is seldom raised when battered women seek medical treatment. Physicians are often reluctant to broach the subject, and many of these women do not want to reveal their situations. Apart from the injuries incurred in a battering incident, subtle manifestations of an abusive relationship include psychosomatic complaints, stress, anxiety, fear and depression. Suicide may be contemplated or attempted. The children are always affected.

Attitude of Health Personnel↗
PubMed1987

Ethanol stimulates prostacyclin biosynthesis by human neutrophils and potentiates anti-platelet aggregatory effects of prostacyclin.

Previous reports on the direct effects of ethanol on human platelet aggregation function have been inconsistent. Ethanol ingestion produces vasodilation and raises intracellular cyclic AMP concentrations, effects similar to those of prostacyclin. We, therefore, hypothesized that ethanol may influence biosynthesis and/or bioactivity of prostacyclin. In our experiments, ethanol in concentrations up to 400 mg% had no consistent inhibitory effect on platelet aggregation in response to epinephrine, ADP, or combination of subthreshold concentrations of epinephrine plus ADP. However, ethanol in concentrations as low as 10 mg% potentiated the platelet aggregation inhibitory effects of prostacyclin. In addition, ethanol (20 mg%) decreased formation of thromboxane A2 in whole blood by 41% and stimulated formation of prostacyclin by 160% (both P less than 0.01). Additional studies using isolated human cells demonstrated synthesis of prostacyclin by neutrophils in the presence of platelets, and this neutrophil prostacyclin formation was enhanced in the presence of ethanol. These effects of alcohol in concentrations achieved after moderate intake may relate to the hemodynamic, biochemical, and cardioprotective effects of ethanol.

Drug Synergism↗
PubMed1987

Effect of human tumor cells on platelet aggregation: potential relevance to pattern of metastasis.

Tumor metastasis may be facilitated by interaction of tumor cells with platelets. It is not known, however, whether solid tumors which have predisposition to pulmonary metastasis affect platelets differently than lymphoid tumors, which rarely spread to lungs. We therefore examined the effects of cultured osteogenic sarcoma (MG-63, U2-OS), as well as leukemia (NALM-16, LAZ-221, K-562) and lymphoma (RAJI, MOlt 4) cells, on human platelet aggregation. Human osteogenic sarcoma (MG-63) cells alone induced platelet aggregation, whereas U2-OS cells induced platelet aggregation only after preincubation of platelets with subthreshold concentrations of epinephrine. In contrast, neither leukemia nor lymphoma cells affected platelet aggregation. These observations suggest that the platelet proaggregatory potential of tumor cells is variable and that the platelet stimulatory effects of osteogenic sarcoma cells may relate to their high risk of pulmonary metastasis.

Adenosine Diphosphate↗
PubMed1987

Spontaneous platelet aggregation: observations on potential mechanisms.

We identified SPA in three young apparently healthy women. SPA was associated with release of TXA2 and was only partially inhibited by ADP-inhibitor apyrase and alpha 2-adrenoceptor blocker yohimbine. In vitro incubation of aspirin (90 micrograms/ml) or selective TXA2 synthetase inhibitor OKY-046 (0.1 uM) with platelet rich plasma (PRP) did not abolish SPA, although platelet generation of TXA2 was markedly inhibited. In contrast, oral administration of large amounts of aspirin in one subject or in vitro incubation of PRP with TXA2 -endoperoxide receptor blocker SQ 29,548 (20-100 nM) significantly inhibited SPA. These studies suggest that SPA is associated with TXA2 release. Since TXA2 -endoperoxide receptor blocker completely abolishes the secondary wave, agents like this may be of therapeutic value in individuals with SPA and evidence of tissue ischemia.

Adult↗
PubMed1987

Inhibition of human platelet and neutrophil function by piriprost (U-60,257).

Platelets and neutrophils are important in determining the extent of myocardial injury following coronary occlusion. The detrimental effects of these blood elements are mediated in part via release of arachidonate metabolites and oxidative species. A new selective inhibitor of leukotriene formation, piriprost (U-60,257), has been observed to decrease both neutrophil accumulation in the myocardium and infarct size following coronary ligation in experimental animals. Since piriprost may have clinical use, we examined its effects on human platelet and neutrophil functions. This compound was found to exert potent inhibitory effects on epinephrine-induced human platelet aggregation and TXA2 biosynthesis (IC50 0.04 microM). Piriprost also inhibited human neutrophil chemotaxis, oxidative species release, aggregation, and LTB4 synthesis with IC50 of 0.1, 0.04, 10 and 14 microM, respectively. Thus, piriprost inhibits a variety of human platelet and neutrophil functions. Because of its suppressive effects on human platelet and neutrophil functions and protective effects in experimental myocardial infarction, this agent may have clinical applications.

Blood Platelets↗
PubMed1987

Plasma tissue plasminogen activator inhibitor levels in coronary artery disease: correlation with age and serum triglyceride concentrations.

Increased levels of an endogenous inhibitor of tissue-plasminogen activator (t-PA) have been thought to relate to the genesis of acute myocardial ischemia. To examine the role of the rapid inhibitor of t-PA, plasma samples were analyzed from 75 patients with chest pain syndrome undergoing coronary angiography (mean age 57 years), 24 patients with clinically documented coronary artery disease (unstable angina, positive exercise stress test or previous history of myocardial infarction; mean age 58 years) and 15 young normal subjects (mean age 26 years). Plasma t-PA inhibitor levels were similar in age-matched patients regardless of the absence or presence (and degree) of coronary artery disease. Plasma t-PA inhibitor levels correlated significantly with age (r - 0.46, p less than 0.005), suggesting an age-dependent decrease in fibrinolytic activity. Plasma t-PA inhibitor levels also correlated significantly with serum triglyceride levels (r - 0.60, p less than 0.001), but not with coronary risk factors such as serum cholesterol, diabetes, hypertension, serum uric acid levels or body weight. Association of high levels of inhibitor of t-PA with hypertriglyceridemia may be of importance in the development of coronary thrombosis, especially in elderly patients. Nonetheless, this study does not suggest a pathogenic role of t-PA inhibitor in coronary atherosclerosis.

Adult↗
PubMed1987

Substrate regulation of elymoclavine formation by some saccharides.

Regulation of the production of clavine alkaloids, especially elymoclavine, by sucrose, maltose, and mixtures of these saccharides was studied in submerged cultures of strains Claviceps purpurea 129/35 and Claviceps sp. SD-58. The data were statistically processed on an EC 1040 computer. Fermentation medium containing sucrose (80 g/l) in combination with glucose (20 g/l) was the best for elymoclavine formation. Retarded release of glucose from maltose increased the formation of elymoclavine and suppressed the synthesis of undesirable extracellular glucans. Carbon source can affect both the total amount of produced alkaloids and the relative proportion of individual clavines in the alkaloid mixture.

Carbohydrate Metabolism↗
PubMed1986

Leukotrienes potentiate the effects of epinephrine and thrombin on human platelet aggregation.

A cooperation between leukocytes and platelets relative to metabolism of arachidonic acid has been observed in animal studies. To determine potential stimulatory effects of leukotrienes (LTs) on human platelets, LTs were incubated with platelet rich plasma followed by addition of subthreshold concentration of aggregatory stimulus. LTs (LTE4 LTD4 LTC4) alone had no direct effect on platelet aggregation, but potentiated the effects of subthreshold concentrations of epinephrine and thrombin and caused complete platelet aggregation. This potentiation was similar in citrated or heparinized blood and was unaffected by exogenous CaCl2. LTs did not induce secondary wave of aggregation in aspirin or selective TXA2-synthetase blocker OKY-046-treated platelets. In addition, LTs stimulated TXA2 biosynthesis by platelets in the presence of subaggregatory concentrations of epinephrine, but not when platelets had been pretreated with OKY-046. These data indicate that LTs potentiate epinephrine-induced platelet aggregation by modulating TXA2 synthetase activity.

Aspirin↗