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Biomedical subjects

J Kaplanski

Publications and source records attributed to J Kaplanski.

At least 37 records · Page 2Linked to original sources
PubMed1991

Disposition of hexobarbitone and antipyrine in DOCA-hypertensive rats.

The disposition of antipyrine and hexobarbitone, and their effects on drug metabolizing hepatic enzymes have been investigated in DOCA-hypertensive rats. Antipyrine pharmacokinetic parameters were the same in hypertensive and control animals. Hexobarbitone sleeping time was longer in hypertensive rats compared with controls, while the activity of hepatic hexobarbitone hydroxylase was the same in both groups. Hepatic aminopyrine-N-demethylase activity was elevated in hypertensive rats while aniline hydroxylase and aryl hydrocarbon hydroxylase were lower. Glucuronyl transferase was the same in both groups. The sensitivity of the central nervous system of hypertensive rats to hexobarbitone was not altered, as determined by hexobarbitone concentration in blood and in brain. The total hepatic blood flow (arterial and portal) was significantly increased. Thus it is suggested that the difference in the disposition of the two drugs is probably not due to drug metabolizing enzyme activity. It is likely that the increase in total hepatic blood flow and rapid saturation of hepatic hexobarbitone metabolizing enzymes have significant roles in the slower metabolism and increased activity of hexobarbitone in hypertensive rats as compared with control rats.

Animals↗
PubMed1989

Cardiac glycoside toxicity in small laboratory animals.

Cardiac glycosides are frequently administered to laboratory animals for research purposes. The effects achieved depend not only upon the particular glycoside and dose administered, but also upon an entire array of variables from the species of animal to the temperature of the animal housing facility. We review a number of these factors and their influence upon the effects achieved by the administration of cardiac glycosides to laboratory animals.

Age Factors↗
PubMed1989

Age-related digoxin-verapamil interactions in the adult rat.

We have previously described a method for inducing atrial ectopic tachycardia (AET) in the anesthetized adult rat using digoxin, 30 mg/kg s.c. In this study, we used this model to study digoxin-verapamil interactions in young and older male rats and have found age-related differences in their responses to digoxin alone and to digoxin-verapamil interactions as well. Overall, 90% of the animals of both groups combined that developed AET, developed a ventricular proarrhythmic response to verapamil. Thus, this model might broaden the pre-clinical evaluation of anti-arrhythmic agents and predict which drugs are most likely to have a proarrhythmic effect.

Aging↗
PubMed1988

Pregnancy outcome in heat-exposed hamsters; the involvement of the pineal.

The effect of high ambient temperature (34 degrees C) on the function of the female reproductive system, on embryonic development and on outcome of pregnancy, was investigated in heat-exposed sham-operated (Sh) and pinealectomized (Px) golden hamsters maintained under short photoperiod. Plasma prolactin levels were reduced in both heat-exposed groups (ShH and PxH) but pituitary prolactin was increased in the pinealectomized groups irrespective of ambient temperature (21 or 34 degrees C). Pituitary weights and LH contents were not affected in any test group. Heat exposure brought about a reduction in the number of corpora lutea and of pups born, the latter being more drastically reduced in absence of the pineal; the depressant effect of heat on ovarian weight was evident only in the pinealectomized animals. Progesterone levels were not affected in any test group and pregnancy was not prolonged, thus, it would seem that pregnant hamsters adapt themselves well to heat. Moreover, high ambient temperature promoted a rise in pineal. HIOMT activity and boosted cortisol levels in presence of the pineal gland only, which, together with the above findings, shows that the pineal can provide protection for pregnant hamsters against adverse effects of high ambient temperature.

Animals↗
PubMed1988

Mechanisms of digoxin-amiodarone interaction in the rat.

Amiodarone and digoxin are often used in combination and clinical experience suggests that amiodarone may increase serum digoxin levels and toxicity. We have investigated the influence of amiodarone on digoxin pharmacokinetics and tissue distribution in the rat. Forty-nine rats were injected with 10 mg/kg amiodarone sc three times a day for 7 days, while 49 others were injected with saline only. On the eighth day, all the rats received 0.5 mg/kg digoxin ip; 4, 5, 6, 7, 8, 10, and 12 hr later, groups of 7 amiodarone-pretreated and control animals were sacrificed, and plasma, heart, liver, muscle, brain, and kidney digoxin concentrations measured by radioimmunoassay. Data were analyzed by two-way ANOVA, with group comparisons using the Waller-Duncan multiple comparison procedure. Digoxin levels were significantly higher in the plasma, heart, muscle, and kidney of the amiodarone-pretreated rats at most points of measurement (P less than 0.05) whereas liver digoxin levels were elevated at 8, 10, and 12 hr. Kidney/plasma, heart/plasma, muscle/plasma, and especially liver/plasma ratios in the control groups significantly exceeded the values found in the amiodarone-pretreated group at most time points. Concentrations of digoxin in brain were not changed. This suggests that the volume of distribution is significantly altered in the amiodarone-pretreated group. Amiodarone increases plasma digoxin levels in rats as it does in humans, but the mechanism is unclear.

Algorithms↗
PubMed1987

Gonadotoxicity and kinetics of dibromochloropropane in male rats.

Adult male rats were injected with [3H]dibromochloropropane dissolved in dimethylsulfoxide containing about 10 X 10(6) dpm. Blood from the tail and 24-h urine samples were collected up to 2 days post-injection. Tissue samples were further taken from the kidneys, liver, spleen, adrenals, epididymis, seminal vesicles and testes 7 h and 7 days post-injection. The results demonstrate that there is no preference in labelling of the testes compared with other organs, and the kidney and liver may have an important role in the elimination of DBCP.

Animals↗
PubMed1986

Effect of neonatal pinealectomy on circadian periodicity of adrenocortical activity.

Newborn male and female rats aged between 24 and 48 hours were pinealectomized (Px) or sham-operated (Sh). Animals were sacrificed at 45 and 60 days of age, at the trough and peak of the adrenocortical diurnal cycle. Blood was collected for corticosterone determinations and the adrenal glands weighed. Adrenal gland weight was greater at 45 days (p less than 0.01) in Px rats than in Sh rats. This difference in adrenal gland weight disappeared in the group sacrificed 60 days post-operatively. On the other hand, the diurnal plasma rhythm of corticosterone remained intact in male and female rats with or without pineal at 45 and 60 days. Furthermore, the trough and peak plasma corticosterone levels were not different in Px 45 and 60 days post-operatively. These data do not support the assumption of the important role of the pineal in the newborn rat for the maintenance of a normal circadian rhythm of the pituitary-adrenal system.

Adrenal Cortex↗
PubMed1986

Theophylline pharmacokinetics in pregnant and lactating rats.

As a preliminary investigation to a human study, we examined the pharmacokinetics of theophylline in pregnant and lactating rats. Three groups of female rats--pregnant, lactating, and virgin controls were injected IP with theophylline solution. Pregnant rats eliminated theophylline at a slower rate than both lactating rats and virgin controls, resulting in a longer half life (t1/2) and lower clearance. The approximate volume of distribution (aVd) and extrapolated peak concentration (Cp0) in the 3 groups were not different.

Animals↗
PubMed1985

Effects of salicylate and indomethacin in nonfebrile rats at different ambient temperatures.

The effects of sodium salicylate (SS) and indomethacin (INDO) on rectal temperature (RT) and on prostaglandin (PG) concentration in the anterior hypothalamus of nonfebrile rats exposed to ambient temperatures (AT) of 4 +/- 1 degrees C, 23 +/- 2 degrees C and 34 +/- 2 degrees C were investigated. In rats treated with SS and exposed to AT of 4 degrees C and 23 degrees C, RT decreased by 1-1.5 degrees C (p less than 0.01). On the other hand at AT of 34 degrees C, SS-treated rats had an elevation of RT of 2 degrees C (p less than 0.01). However, in rats treated by INDO, RT did not change, in spite of significant decreases (p less than 0.01) in PGE2 under all three environmental conditions. In SS treated rats a significant decrease (p less than 0.01) of PGE2 was observed only at At 23 degrees C, whereas hypothalamic PGE levels were not inhibited at 4 degrees C or 34 degrees C. This data do not support the hypothesis that PG is the mediator of normal thermoregulation in the rat. The changes in deep body temperature observed in nonfebrile rats treated with salicylate may be related to a mechanism that is not associated with PG cyclooxygenase inhibition.

Animals↗
PubMed1985

Plasma and tissue levels of digoxin in the rat following pretreatment with verapamil.

Verapamil and digoxin are frequently used in combination, and clinical experience suggests that verapamil may increase digoxin toxicity. We have investigated the influence of verapamil on digoxin pharmacokinetics in the rat. Rats were injected with 10 mg/kg verapamil s.c. twice a day for 7 days while control rats were injected with saline only. On the 7th day, all the rats received 0.5 mg/kg of digoxin i.p. Two, 4, 6, 8 and 10 hours later, groups of 6 to 8 verapamil pretreated and control animals were sacrificed and plasma, heart, brain, liver, kidney and muscle digoxin concentrations were assayed. Digoxin levels were significantly higher in the plasma, heart, liver and muscle of the verapamil pretreated rats at 6, 8 and 10 hours (p less than 0.01).

Animals↗
PubMed1985

Effect of acute and chronic exposure to heat on pharmacokinetic parameters of digoxin in rats.

Digoxin pharmacokinetic parameters in acute heat-exposed male rats (AHE) maintained for 3 hours at 35 degrees C, and chronic heat-exposed rats (CHE) maintained at 35 degrees C for 4 weeks, were compared to control rats (C) maintained at 22 degrees C. Digoxin concentration in the plasma was measured by radioimmunoassay which gave values similar to thin layer chromatography method. The half life time of digoxin during the elimination phase of the drug (t 1/2 beta) was similar in all three experimental groups (2.8; 2.7; 3.0 hrs) while the values obtained by extrapolation of digoxin plasma concentration to zero time (CpO) was 40% higher in AHE rats and 375% higher in CHE rats than in C rats. The apparent distribution volume of the drug (Vapr) was 40% lower in AHE rats and 80% lower in CHE rats as compared to C rats.

Animals↗
PubMed1985

Brain, myocardium and plasma concentrations and toxicity of digoxin in newborn and adult rats.

Digoxin tissue concentrations and elimination kinetics were determined to explore possible explanations of the age-related changes in response to digoxin in the rat. Digoxin concentrations were measured in brain, myocardium, and plasma of newborn and adult rats at serial time intervals after nontoxic doses and at the time of death after toxiequivalent doses. After SC administration of a nonlethal dose of 500 micrograms/kg digoxin, brain, myocardium and plasma concentrations and areas under the curve of digoxin concentrations vs time were considerably greater (P less than 0.01) in the newborn than in the adult rats. Following toxiequivalent doses of digoxin (2.5X LD50), digoxin concentrations were several fold greater in the myocardium and plasma of adult rats than in newborn specimens; in contrast, despite the 30-fold smaller digoxin dose per kilogram body weight given to 1-day-old rats, mean digoxin concentration was 2.9 times greater in their brain than in adult brain. These findings suggest that changes in tissue distribution and in the disposition of digoxin play a role in the greater sensitivity of newborn rats to digitoxicity and in the distinct digitoxic arrhythmic effects observed in the newborn as compared to the adult rat.

Aging↗
PubMed1984

Vascular hypersensitivity to noradrenaline: a possible mechanism of hypertension in rats with chronic uraemia.

Studies were performed to evaluate the mechanism involved in the hypertension of moderate renal failure in partially (five-sixth) nephrectomized rats. Cardiac index (CI) was studied by means of the microsphere technique, and systemic vascular resistance (SVR) calculated from the mean arterial resistance MAP/CI, in four groups of experimental animals: (A) partially nephrectomized rats; (B) group A rats chronically treated with the calcium channel blocker verapamil; (C) sham-operated rats; (D) sham-operated rats treated with verapamil. The results demonstrate a significant increase in MAP in group A rats, which was due to a 72% increase in SVR as compared with groups C and D. In group B rats, MAP decreased significantly owing to a marked decrease in SVR (40%) as compared with group A. However, MAP remained higher in group B than in group C. The vascular responsiveness to noradrenaline was studied in group A, group C and group A rats after parathyroidectomy (group A1). An increased pressor responsiveness to noradrenaline was indicated by a shift of the noradrenaline dose-response curve to the left in group A rats as compared with group C rats. This change was corrected after partial nephrectomy. We conclude that hypertension in nephrectomized rats is due to an increase in SVR, and that an increased pressor responsiveness to catecholamines may play a role in this phenomenon. Furthermore, verapamil reduced the hypertension, and parathyroidectomy improved the abnormal sensitivity to noradrenaline in group A rats. These results raise the possibility that an abnormality in calcium metabolism, possibly due to secondary hyperparathyroidism, may be implicated in the hypertension of mildly uraemic rats.

Animals↗
PubMed1984

Renal clearance of urea, inulin, and p-aminohippurate in heat-acclimated rats.

Clearance values of urea, inulin, and p-aminohippurate (PAH) were measured in heat-acclimated (HA) rats exposed for 3 wk to 35 degrees C, in control rats (C) exposed to 23 degrees C, and in HA rats deacclimated (DA) for 3 wk. In HA rats, urea clearance was lower by 73%, inulin clearance by 61%, and PAH clearance by 56%, compared with C rats. The clearance values of these substances returned to the control values in DA rats. The data suggest that the low clearance values reflect both reduced renal blood flow and possible changes in the capacity of the glomeruli for filtration and the tubules for either reabsorption or secretion.

Acclimatization↗
PubMed1984

Effect of exercise and environmental heat on theophylline kinetics.

The pharmacokinetics of theophylline were studied in 6 healthy volunteers at rest, during light and moderate exercise and during exercise in a hot environment. Exercise was performed between 2 and 4 h after oral ingestion of theophylline in solution at a dose of 200 mg/m2 body surface. Significant prolongations of the half-life (t1/2) of the drug and reductions in its body clearance were observed during exercise to 30% of VO2, max both at 22 and 40 degrees C, as well as during exercise to 50% of VO2, max at 22 degrees C. t1/2 was (mean +/- SEM) 8.5 +/- 0.8, 8.0 +/- 1.0 and 7.2 +/- 1.0 h at the three exercise sessions, respectively, compared with 6.4 +/- 0.9 h at rest. Plasma clearances at the three exercise sessions were 0.70 +/- 0.09, 0.62 +/- 0.1 and 0.75 +/- 0.09 ml/min/kg, respectively, compared with 0.99 +/- 0.13 ml/min/kg at rest. The apparent volumes of drug distribution (Vd) decreased significantly at the 50% and the 30% exercise in the heat, suggestive of some dehydration. The areas under the concentration-time curves (AUC0-infinity) and the elimination rate constants (Kel) also changed significantly under the different experimental conditions. It is suggested that appropriate dose adjustments may have to be made in moderately active patients who are treated with theophylline.

Administration, Oral↗
PubMed1983

The pineal and endocrine changes in heat exposed male hamsters.

Decreased testicular weight with damaged seminiferous tubules were observed in hamsters pinealectomized and exposed continuously to high ambient temperature. In hamsters with intact pineals, exposure to heat resulted in reduced testicular weight without recognizable histological damage. In both groups, serum testosterone levels were elevated, evidently through a compensatory mechanism in the interstitial cells, which did not appear to be damaged. Concomitantly with these findings, reduced serum LH, and pituitary LH and prolactin concentrations were encountered in the heat-exposed pinealectomized hamsters, compared to those of their heat-exposed sham-operated counterparts. These results in hamsters reaffirm a previous postulation of a moderating, protective role for the pineal, against adverse effects of prolonged exposure to heat, in rodents.

Acclimatization↗
PubMed1983

Increased decidual prostaglandin E concentration in human abortion.

Prostaglandin E (PGE) concentration was measured in decidual tissue after spontaneous and missed abortion and compared with that obtained from induced abortion. Tissues were obtained by curettage from groups of 10 patients each and PGE was estimated by radioimmunoassay. After spontaneous and missed abortions decidual tissue contained significantly higher mean concentrations of PGE, (486.3 and 66.7 ng/g wet tissue respectively) than after induced abortion (18.6 ng PGE/g wet tissue). It is suggested that an increased rate of PGE biosynthesis or reduced breakdown, or both, may play a role in the mechanism of human abortion.

Abortion, Induced↗