PubMed Health⌕ Search

Biomedical subjects

S Nigam

Publications and source records attributed to S Nigam.

At least 91 records · Page 5Linked to original sources
PubMed1987

Atropine is an inhibitor of the chemiluminescence induced by platelet-activating factor in human neutrophils.

Chemiluminescence provoked by platelet-activating factor can be dose-dependently inhibited by atropine. This effect of atropine is rather due to its ion channel blocking capability (at the higher doses than 10(-5) M) than to its action on the acethylcholine receptors. The differences in the roles of platelet-activating factor and acethylcholine in the activation of phagocytes are discussed.

Atropine↗
PubMed1986

Alteration of prostanoid metabolism in rats with magnesium deficiency.

Plasma and tissue concentrations of prostanoids PGE2, PGF2 alpha. 6-keto-PGF1 alpha (a stable metabolite of prostacyclin) and TXB2 (a stable metabolite of thromboxane A2) were measured in normal and magnesium-deficient rats. The mean values for prostanoids in plasma were significantly higher in magnesium-deficient rats than in normals (515 +/- 43 vs 296 +/- 31 pg/ml for 6-keto-PGF1 alpha, p less than 0.01, 3700 +/- 322 vs 346 +/- 33 pg/ml for TXB2, p less than 0.001 and 1234 +/- 132 vs 434 +/- 51 pg/ml for PGE2, p less than 0.001). Tissue levels of prostanoids were also significantly higher in magnesium-deficient rats as compared to normals. The increased synthesis of prostanoids is apparently linked to enhanced influx and translocation of Ca++ into the cells. If the adenylate cyclase is inhibited in magnesium deficiency, the lowered c-AMP will permit a high cyclooxygenase activity and a drastic increase in TXB2. It is possible that the changes in prostaglandin synthesis in magnesium deficiency are linked to the development of different diseases.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Follow-up of prostaglandin plasma levels after acute myocardial infarction.

Prostaglandin plasma levels are elevated in patients with transient myocardial ischemia. We measured 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane (B2(TXB2) in venous blood of 32 patients with myocardial infarction on the first, third, and seventh days. TXB2 and 6-keto-PGF1 alpha levels in these patients (up to 117 +/- 237 pg/ml and 96 +/- 105 pg/ml mean +/- SD, respectively) differed significantly from levels in normal control subjects (10 +/- 12 pg/ml and 4 +/- 7 pg/ml mean +/- SD, respectively) (p less than 0.01). Prostaglandin values remained elevated from day 1 through day 7. In most patients, 6-keto-PGF1 alpha levels prevailed over those of TXB2. In a subgroup suffering from cardiac arrhythmias, the ratio of 6-keto-PGF1 alpha/TXB2 was inverse. It is concluded that prostaglandin generation is increased for at least 7 days after myocardial infarction. A disturbed ratio of 6-keto-PGF1 alpha/TXB2 in favor of the latter might be associated with cardiac arrhythmias in myocardial infarction.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

The concentrations of 6-keto-PGF1 alpha and TXB2 in plasma samples from patients with benign and malignant tumours of the breast.

Peripheral plasma concentrations of 6-keto-PGF1 alpha and TXB2 were measured in patients with benign and malignant tumours of the breast, in patients with non-gynecological diseases, and in healthy female controls. The values were significantly higher in female patients with malignant tumours of the breast than in healthy controls (146 +/- 28 vs 13 +/- 2.5 pg/ml for 6-keto-PGF1 alpha p less than 0.01 and 78 +/- 17 vs 11 +/- 2 pg/ml for TXB2, p less than 0.01). Benign tumours of the breast were also associated with significantly raised plasma levels of 6-keto-PGF1 alpha and TXB2 compared to normal controls (52 +/- 5 vs 13 +/- 2.5 pg/ml for 6-keto-PGF1 alpha, p less than 0.01 and 26 +/- 5 vs 11 +/- 2 pg/ml for TXB2, p less than 0.05). The high levels of 6-keto-PGF1 alpha and TXB2 were not found to be correlated with clinical and histopathological data. The surgical removal of the primary tumour has apparently no effect on the plasma concentrations of 6-keto-PGF1 alpha and TXB2 over a follow-up period of 9 days after operation. The lack of alterations in the ratio of TXB2:6-keto-PGF1 alpha in the cancer patients and other subjects studied before and after surgery is indicative of the regulatory power of metabolic systems to preserve the homeostatic balance.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Platelet sensitivity to prostacyclin in normal subjects, and in patients with benign and malignant tumours of the breast.

Platelet sensitivity to prostacyclin (PG12) was determined in normal male and female subjects, and in patients with benign and malignant tumours of the breast. The IC50 overall mean values for PG12 on ADP-induced platelet aggregation were similar for normal men and women, being 0.97 +/- 0.05 ng ml-1 and 0.83 +/- 0.07 ng ml-1 respectively. However, there were significant differences in the IC50 values for women in the 1st (0.81 +/- 0.06 ng ml-1) vs. 2nd (1.37 +/- 0.13 ng ml-1) phase of the menstrual cycle; post-menopausal women gave similar values to normal males and to pre-menopausal women in the 1st phase of the cycle. No significant differences were found between normal subjects and patients with benign or malignant tumours of the breast when account was taken of the status of the patient in relation to the phase of the menstrual cycle and the menopause. The importance of the hormonal status in evaluating changes in platelet sensitivity in patients with breast cancer is strongly emphasised.

Adenosine Diphosphate↗
PubMed1984

Pressure effects and uptake of platelet-activating factor in isolated rat lung.

The aim of this study was, first, to examine pressure effects of platelet-activating factor (PAF) on pulmonary vasculature and bronchi in isolated perfused and ventilated rat lungs and, second, to investigate pulmonary uptake of tritium-labeled PAF injected into the pulmonary artery. Four different perfusates were used: Krebs-Ringer solution (KRS) and KRS with 0.2, 2.0, and 4% albumin. In the KRS, perfusion and inflation pressure increased by 100 and 47%, respectively, after 100 micrograms PAF. By increasing the albumin concentration, the pressure effects were reduced significantly (P less than 0.01). These changes were paralleled by increasing tritium outflow rates (15.9 +/- 3.6, 49.7 +/- 12.5, 78.3 +/- 8.7, 87.8 +/- 2.6%, respectively). Comparable changes in tritium outflow rates (19.2 +/- 3.9, 38.2 +/- 7.2%) occurred when tracer amounts of labeled PAF were injected, but, in KRS with 2.0 and 4.0% albumin, tritium outflow was significantly lower (52.8 +/- 8.0 and 60.8 +/- 11.8%, respectively). Pressure effects are related to extraction rates. Both pressure effects and extraction rates depend on binding to the albumin in the perfusion medium used. PAF might act on smooth muscle tissue of the pulmonary vasculature. Inflation pressure increases are probably due to concomitant occurrence of edema.

Animals↗
PubMed1984

Prostaglandin E2 promotes hypotension on low-sodium hemodialysis.

The influence of low-sodium dialysate (126 mmol/l) on plasma levels of prostaglandin E2 (PGE2) and PGF2 alpha, plasma renin activity (PRA) and arterial blood pressure was investigated in 16 patients on maintenance hemodialysis. PGE2 rose more than tenfold and there was a significant increase in PGF2 alpha and PRA. Mean arterial pressure dropped by 30 mm Hg causing discomfort in several patients. By contrast, conventional hemodialysis against 140 mmol/l of sodium was followed by less pronounced changes in plasma prostaglandins, and reduction of blood pressure was moderate (13 mm Hg). It is suggested that vasodilating prostaglandins may contribute to dialysis hypotension. Their origin may not be confined to the kidneys but rather extend to the lungs and circulating blood cells. The in vitro generation of prostaglandins was demonstrated when donor blood was circulated in an extracorporeal dialysis system.

Dinoprost↗
PubMed1984

Prostaglandin production in patients with pulmonary embolism.

Release of prostaglandins (PG's) after experimental pulmonary embolism has been reported. Therefore, prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were determined in venous plasma of 21 patients with acute pulmonary embolism. Venous plasma levels were followed up for one week after admission. Arterial and mixed-venous PG levels were additionally determined in 6 patients with acute pulmonary embolism prior to pulmonary angiography. Venous levels were substantially elevated (PGE2 16-1300, PGF2 alpha 48-592, TXB2 1-247, 6-ketoPGF1 alpha 1-248 pg/ml), differing significantly from normal controls (p less than 0.001). PG's remained elevated throughout the 7-day postadmission study period. No significant arterial-venous PG differences were detected, though 6-keto-PGF1 alpha and TXB2 levels were somewhat higher in arterial blood. There was no correlation between clinical data (blood pressure, mean pulmonary artery pressure, etc.) and PG levels. These data suggest that elevated prostaglandin levels are probably not, or only in part, responsible for the cardiopulmonary changes that occur in patients with acute pulmonary embolism.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Increased urinary excretion of free 20 alpha- and 20 beta-dihydrocortisol in a hypercortisolemic but hypocortisoluric patient with Cushing's disease.

We identified non-metabolized, non-conjugated 20 alpha- and 20 beta-dihydrocortisol (20 alpha- and 20 beta-DHF) in urine from a patient with Cushing's disease, by use of three different liquid-chromatographic systems and by gas chromatography-mass spectrometry. We document that these 20-isomers of dihydrocortisol may strongly contribute to unspecific interferences with the immunological assessment of urinary free cortisol (F). The urinary excretion rates of 20 alpha- and 20 beta-DHF were quantified radioimmunologically with use of a cross-reacting cortisol antiserum after effective purification by liquid chromatography. The patient with Cushing's disease had mean peripheral cortisol concentrations of 1018 nmol/L. The urinary excretion rates (nmol/24 h) were 1455 for 20 alpha-DHF, 330 for 20 beta-DHF, and 18 for F. The corresponding reference values (median in nmol/24 h) were 174 for 20 alpha-DHF, 111 for 20 beta-DHF, and 68 for F (n = 22). We conclude that (a) specific estimation of urinary free F is not as highly sensitive for diagnosis of chronic hypercortisolemic states as is generally assumed; and (b) measurement of urinary free 20 alpha- and 20 beta-DHF or of the corresponding 20-DHF:F ratios may be more sensitive.

Adult↗
PubMed1980

Hybrid information provided by the 14C-aminopyrine breath test. Studies with 14C-monomethylaminoantipyrine in the guinea pig.

N-Demethylation of 14C-aminopyrine (14C-AP), labelled at the methyl groups of the tertiary amino group, yields H14 CHO and 14C-monomethylaminoantipyrine (14C-MMAAP) which also undergoes N-demethylation, however, at a slower rate as measured in hepatic microsomes. As after intraperitoneal application to male guinea pigs of 14C-AP (75 mg/kg; 50 muCi/kg), exhalation rate of 14CO2 declines in a biphasic manner, the hypothesis was tested whether the terminal part might reflect N-demethylation of MMAAP. The application of 14C-MMAAP (70 mg/kg; 10 muCi/kg), resulted in monophasic curves of 14CO2 exhalation rate. Their half lives were, however, longer than terminal half lives obtained after 14CAP. Obviously, this terminal phase does not represent 14CO2 formation from the metabolite MMAAP only, but 14C-AP might still contribute to 14CO2 production. Confirmation was obtained by HPLC determination of AP and MMAAP in serum after injection of AP. Shortly after injection, high concentrations of AP and low ones of MMAAP were found in blood from the portal vein and systemic circulation. Thus, initial parts of 14CO2-exhalation rate curves reflect predominantly AP metabolism whereas later phases provided hybrid information.

Aminopyrine↗
PubMed1980

Hexobarbital-binding, hydroxylation and hexobarbital-dependent hydrogen peroxide production in hepatic microsomes of guinea pig, rat and rabbit.

Cytochrome P-450 dependent oxygenase (3'-hydroxy-hexobarbital) and oxidase activities (hydrogen peroxide) have been measured in hepatic microsomes from guinea pigs, rats and rabbits. A sensitive gas-chromatographic assay was developed to measure the hydroxylated product 3'-hydroxy-hexobarbital. The kinetics of its formation were determined and correlated to hexobarbital type I binding and compared with oxidase activity: in the rat, Vmax for 3'-hydroxyhexobarbital formation was 5.1 and 2.6 nmoles/mg/min, resp. This was increased by phenobarbital treated rabbits, Vmax was 15.0 nmoles/mg/min for hydroxylation and 40.8 for H2O2 formation. Spectral affinity constants (Ks) in control animals were 0.12 mM (rats) and 0.14 mM (rabbits). Phenobarbital treatment decreased these affinity constants, which were similar for each activity measured. In guinea pigs, however, hydroxylation of exobarbital was low (3.1 nmoles/mg/min) and hexobarbital-dependent formation of H2O2 was higher than hydroxylation (Vmax: 7.0 nmoles/mg/min). Phenobarbital treatment led here to two affinity constnts for each activity measured, which however, were alike. The existence of low in addition to high affinity constants observed here might explain the difficulties seen hitherto in correlating hexobarbital binding and metabolism in this species. Total oxidase activity was higher than oxygenase activity in all species tested. It is suggested that oxygenase activity of cytochrome P-450 is not limited by binding but by a competition with oxidase activity for a common intermediary species. This might be peroxy-P-450 (substrate-Fe3+O2(2-), rendering either substrate-Fe3+ O for hydroxylation reaction, or oxidized cytochrome P-450-substrate and hydrogen peroxide as product of oxidase function.

Animals↗
PubMed1979

Demonstration of drug-ethanol interactions by changes in activity of hepatic microsomal oxidase/oxygenase cytochrome P-450 function.

"Uncoupling" of microsomal hepatic oxygenases is characterized by a situation in which microsomal monooxygenases exhibit more oxidase than oxygenase activity with an increased formation of hydrogen peroxide at the expense of O2, NADPH and substrate hydroxylation. The importance of such in vitro observations with respect to physiological conditions "in vivo" has been tested by investigating elimination kinetics of ethanol. If hexobarbital, a substrate of mixed function oxygenase as well as an "uncoupler", is given to guinea pigs together with ethanol, changes in the elimination of ethanol occur. It is suggested that this is the consequence of an increased formation of H2O2 which contributes via peroxidatic reaction of catalase to the elimination of ethanol. The results also show additional interactions of hexobarbital as well as of ethylmorphine with ethanol elimination. Both compounds increased the initial blood levels of ethanol which precede accelerated elimination, probably by a first pass effect. At low concentrations of ethanol, ethylmorphine inhibits ethanol elimination by inhibition of ADH.

Alcohol Oxidoreductases↗
PubMed1976

Kinetics of nitroxyl radical reactions. A pulse-radiolysis conductivity study.

Absolute rate-constants for the reaction of the nitroxyl free radicals TAN and TMPN with radiation-chemically-formed radicals and ions have been determined. k(TAN + X) (in M(-1) sec(-1)=4-0 X 10(9) (for X = OH-), 2-9 X 10(10) (eaq-), 8-0 X 10(9) (H-), 7-2 X 10(8) (-CH2OH), 4-0 X 10(8) (CH3CHOH), 4-3 X 10(8) ((CH3)2COH) 2-8 X 10(8) (-CH2(CH3)2COH), 5-9 X 10(7) (glucose radical), 4-0 X 10(8) (c-C5H9-), and k(TMPN + X)=3-4 X 10(9) (OH-), 7-8 X 10(9) (eq-), 4-9 X 10(9) (H-), 4-4 X 10(8) (-CH2OH), 4-9 X 10(8) (CH3CHOH), 3-6 X 10(8) ((CH3)2COH), 1-5 X 10(8) (-CH2(CH3)2COH), 4-9 X 10(7) (glucose radical), 4-3 X 10(8) (c-C5H9-). Direct measurements by means of a pulse-radiolysis conductivity technique were based on the formation and destruction of charged species in these reactions within certain pH ranges. It is indicated that the radiosensitizing nitroxyls undergo both redox and addition reactions.

Cyclic N-Oxides↗