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Biomedical subjects

G Levy

Publications and source records attributed to G Levy.

At least 325 records · Page 18Linked to original sources
PubMed1983

Determination of salicylamide and five metabolites in biological fluids by high-performance liquid chromatography.

Two high-performance liquid chromatographic (HPLC) assay procedures were developed for the determination of salicylamide and its metabolites in serum, urine, and saliva. One method involves reverse-phase ion-pair chromatography and UV detection, and is used to determine salicylamide, salicylamide glucuronide, and salicylamide sulfate. The other method, with a different mobile phase and without the ion-pairing reagent, is used to determine gentisamide (the hydroxylated metabolite of salicylamide), gentisamide glucuronide, and gentisamide sulfate. The assays are performed by direct injection of the sample after protein precipitation with ethanol containing the internal standard. Increased sensitivity for the determination of low concentrations of salicylamide is obtained by organic extraction of this drug from serum or saliva. Calibration curves for the conjugates of salicylamide and gentisamide were obtained, in the absence of authentic standards, by partial enzymatic hydrolysis, using the decrease of the conjugate peaks and the concomitant increase of free salicylamide or gentisamide concentrations to determine peak area ratio-concentration relationships. Application of the HPLC assay procedures to the determination of salicylamide excretion products in the urine of three normal human subjects resulted in 98.6% (range:97.1-100.1%) recovery of a 1-g oral dose of the drug. All five metabolites of salicylamide were found in urine, but only salicylamide glucuronide, salicylamide sulfate, and gentisamide glucuronide were found consistently and in appreciable quantities. Salicylamide and all of its metabolites except gentisamide sulfate were found in human and rat serum, and unconjugated salicylamide as well as gentisamide were found in human saliva.

Animals↗
PubMed1983

Pharmacokinetics of heparin V: in vivo and in vitro factors affecting the relationship between concentration and anticoagulant effect of heparin in rat plasma.

There are appreciable interindividual variations in rats of baseline activated partial thromboplastin time (APTT) and of the anticoagulant effect of heparin added to plasma (as reflected by the slope of the regression line describing the essentially linear relationship between ln APTT and heparin concentration). Determination of baseline APTT and slope value on two occasions, 7 days apart, in the same rats revealed that (unlike in humans) these characteristics were subject also to considerable intraindividual variation. To explore the possible reasons for the observed variability, the effect of citrate concentration (acid citrate solution is used as a blood anticoagulant in the collection of plasma), calcium concentration (in the recalcifying solution used to initiate coagulation), and plasma incubation time (for activating the coagulation system) was determined. All three variables had pronounced effects on the anticoagulant response to heparin. Since rat erythrocytes are almost totally impermeable to citrate, hematocrit is a determinant of plasma citrate concentration when acid citrate solution is added in constant proportion to rat blood. Accordingly, inter- and intraindividual differences in baseline APTT and slope values were measured in another experiment in which the citrate solution to plasma (rather than blood) volume ratio was held constant and blood samples were obtained 30 days apart to permit the return of hematocrit values to normal. Intraindividual variation of the coagulation characteristics was appreciably decreased under these conditions. There are important differences between rats and humans with respect to the effect of citrate concentration and plasma incubation time on baseline APTT and on the anticoagulant action of heparin, as well as with respect to the relationship between these two characteristics.

Animals↗
PubMed1983

Effect of pregnancy on the relationship between concentration and anticoagulant action of heparin.

The anticoagulant effect of heparin, as reflected by the slope of the relationship between heparin concentration and the logarithm of the activated partial thromboplastin time (APTT), was determined in citrated plasma of seven women in the third trimester of pregnancy and in 10 nonpregnant women of comparable age. Factors II, V, and VII to XII, albumin, individual globulins, antithrombin III, fibrinogen, alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-2-macroglobulin, prothrombin time, and hematocrit were also determined. Baseline APTT (i.e., APTT without heparin) was 30.2 +/- 3.0 sec (mean +/- SD) in the pregnant women and 29.6 +/- 4.7 sec in the controls (NS). The heparin slope value was 1.68 +/- 0.46 ml/U in the pregnant women and 2.33 +/- 0.49 ml/U in the controls, showing that the anticoagulant effect of heparin is decreased in pregnancy. The prothrombin time was also decreased in pregnancy (19.1 +/- 0.8 vs 23.1 +/- 0.5 sec; P less than 0.01). Pregnancy was associated with a significant increase in the activity of factors VII, VIII, IX, and X and in the concentrations of fibrinogen, alpha-1-globulin, and alpha-1-antitrypsin. The plasma albumin concentration was decreased in the pregnant group. In both the pregnant and nonpregnant women (considered separately), the heparin slope value correlated negatively with factor XI activity (r = -0.85 and -0.71; P less than 0.05). Baseline APTT, which was consistently found to correlate with heparin slope value in previous reports on men and nonpregnant women, also showed such correlation in the nonpregnant group of the present study (r = 0.85; P less than 0.05) but not in the group of pregnant women (r = -0.54; NS). The relative heparin resistance in pregnancy in this investigation is consistent with clinical reports of increased heparin requirements during pregnancy.

Adolescent↗
PubMed1983

Serum concentration and renal excretion by normal adults of inorganic sulfate after acetaminophen, ascorbic acid, or sodium sulfate.

Depletion of endogenous inorganic sulfate can have pronounced effects on the elimination kinetics and metabolic fate of phenolic drugs. Our purpose was to determine the effects of acetaminophen (which is partly metabolized to acetaminophen sulfate), ascorbic acid (subject to more limited sulfation than acetaminophen), and sodium sulfate (useful for sulfate repletion by the oral route) on the serum concentration and renal excretion of inorganic sulfate in healthy adults. Six men and two women, 26 to 35 yr old, were studied on four occasions that were at least 4 days apart. They received no medication, 1.5 gm acetaminophen, 6 gm ascorbic acid, or 9 gm sodium sulfate decahydrate orally, in aqueous solution. A blood sample was obtained 2 hr later and urine was collected from 1 to 3 hr. Serum inorganic sulfate concentrations (mean +/- SD), 0.410 +/- 0.043 mM in the control period, were decreased after acetaminophen (0.311 +/- 0.043 mM, P less than 0.001), increased after sodium sulfate (0.513 +/- 0.055 mM, P less than 0.001), and apparently unchanged after ascorbic acid (0.417 +/- 0.059 mM). The urinary excretion of inorganic sulfate was decreased after acetaminophen and increased after sodium sulfate. The renal clearance of endogenous creatinine was not affected by any of the treatments. The renal tubular reabsorption of inorganic sulfate is capacity limited, as evidenced by the decrease of the reabsorbed fraction with increasing glomerular filtration rate of the anion (r = -0.54, P less than 0.005). This saturable reabsorption facilitates sulfate homeostasis.

Acetaminophen↗
PubMed1983

Hyperphagia alters cholesterol dynamics in diabetic rats.

Rats with streptozotocin-induced diabetes stop growing and start eating more chow. These two events elicit an interacting series of changes in cholesterol dynamics. Hyperphagia increases dietary cholesterol intake and cholesterol synthesis by the small intestine. These increases are balanced by a decrease in cholesterol synthesis in the rest of the body so that total cholesterol input is normal. With growth failure, utilization of cholesterol for formation of new tissue ceases. This decrease is balanced by an increase in bile acid synthesis by the liver. The bile acid pool in the contents of the small intestine is enlarged by hyperphagia. Despite these changes, fecal sterol excretion and total utilization of cholesterol are normal. During the course of changes in growth and food intake and the attendant changes in cholesterol flux, the total tissue cholesterol pool does not change. Therefore influx equals efflux and the systems regulating cholesterol and bile acid synthesis are responding appropriately and are themselves unperturbed by insulin deficiency. However, plasma cholesterol level increases threefold. This elevation is due to increased influx of cholesterol from the small intestine and decreased synthesis in the rest of the body, so that a larger portion of total body cholesterol influx passes through the blood.

Animals↗
PubMed1983

Absorption of sulfate from orally administered magnesium sulfate in man.

The purpose of this investigation was to determine the suitability of orally administered magnesium sulfate as a source of inorganic sulfate for counteracting the systemic depletion of sulfate caused by large doses of acetaminophen and certain other drugs that are metabolized to sulfate conjugates. Oral administration of 13.9 g magnesium sulfate U.S.P., in 4 equal hourly increments, to seven healthy men resulted in the urinary excretion (corrected for baseline excretion rate) of an amount of inorganic sulfate equivalent to 30.2 +/- 17.2 percent (mean +/- SD) of the dose during the first 24 hours. Excretion during the subsequent 48 hours was negligible. Six of the subjects experienced loose stools or diarrhea. Compared to sodium sulfate, magnesium sulfate appears to be absorbed less completely and more erratically, and to produce more adverse effects.

Administration, Oral↗
PubMed1983

Effect of pregnancy on the pharmacokinetics of acetaminophen in rats.

Acetaminophen (A), in single doses of 15 mg/kg and 300 mg/kg, was administered by i.v. injection to nonpregnant (180-240 g) and 20 days pregnant Lewis rats (250-330 g). Blood samples (for plasma) and urine were collected serially and analyzed by high-performance liquid chromatography for A, A glucuronide and A sulfate. Serum inorganic sulfate concentrations were determined in a separate study. With respect to the 300-mg/kg dose, pregnant animals exhibited a significant decrease in relative (body weight normalized) total clearance and no change in absolute total clearance, no change in relative apparent volume of distribution and a significantly increased biological half-life. As a fraction of the administered dose, pregnant animals excreted more A, less A sulfate and the same fraction of A glucuronide as did nonpregnant animals. Pregnancy had no apparent effect on base-line serum inorganic sulfate concentration. Both normal and pregnant rats became inorganic sulfate-depleted after injection of A, 300 mg/kg. The relative total clearance of the 300-mg/kg dose of A decreased with increasing litter size, whereas the relative apparent volume of distribution was unaffected. The relative total clearance of a 15 mg/kg dose of A was much higher than that of the 300-mg/kg dose and approximated liver plasma flow rate; it was not changed by pregnancy. The relative renal clearances of A glucuronide, A sulfate and creatinine were decreased in pregnancy, whereas the absolute renal clearances of the two conjugates and creatinine were unaffected. Comparative assessment of the effect of pregnancy on the pharmacokinetics of A and other drugs in different species requires consideration of possible dose dependence and of the implications of normalizing clearance and volume of distribution values.

Acetaminophen↗
PubMed1982

Immediate increases in plasma prolactin and neurophysin but not other hormones after electroconvulsive therapy.

Plasma prolactin, growth hormone, cortisol, luteinising-hormone-releasing hormone (LHRH), thyrotropin-releasing hormone (TRH), and nicotine and oestrogen stimulated neurophysin (NSN and ESN) were measured before and for 6 min after electroconvulsive therapy (ECT) in eight women with severe electroconvulsive therapy (ECT) in eight women with severe depression. Plasma concentrations of NSN and ESN had increased significantly (as much as 10-fold for NSN) within 1 min of the seizure, and concentrations of prolactin had increased within 2-4 min after the seizure. Whereas plasma prolactin and ESN either continued to increase or remained raised throughout the 6 min after seizure, the concentrations of NSN fell to reach a value at 6 min that was approximately 50% of the maximum. There were no increases in any of the other hormones or peptides within the 6 min period under study. Thus ECT has selective effects on hormone release which cannot be attributed simply to a generalised release of pituitary or hypothalamic hormones in response to brain stimulation and/or stress.

Adult↗