Effect of an antiglucocorticoid (RU-38486) on hydrocortisone induction of maltase-glucosamylase,sucrase-isomaltase and trehalase in brush border membranes of suckling rats

Summary Induction of -glycosidases by hydrocortisone in suckling rats is inhibited by the daily administration of an antiglucocorticoid (RU-38486). Conversely, RU-38486 injected daily in 15-day-old rats for 7 days does not prevent the spontaneous development of -glycosidases.     

RU49953: a non-hormonal steroid derivative that potently inhibits P-glycoprotein and reverts cellular multidrug resistance

Progesterone and the antiprogestin RU38486 have been reported as non-transported modulators of P-glycoprotein-mediated drug efflux. However, their hormonal properties limit their potential for clinical trials. The present work shows that some derivatives from either progesterone/RU38486 or estradiol, displaying differential interaction with hormone receptors, bind to P-glycoprotein and chemosensitize the growth of MDR1-transfected cells to vinblastine more strongly than does RU38486. Structure comparison of the compounds indicates that the highly hydrophobic estradiol derivative RU49953, which does not interact with any hormone receptor, inhibits P-glycoprotein-mediated drug efflux very efficiently, as monitored by flow cytometry, and prevents drug site photoaffinity labeling by azidopine. It induces a much higher chemosensitization than the well-known P-glycoprotein modulator verapamil, which is itself more efficient than RU38486. RU49953 therefore constitutes a promising new lead for steroid-type modulators of multidrug resistance.     

Similarity between the effects of suprachiasmatic nuclei lesions and of pinealectomy on gonadotropin release in ovariectomized,sulpiride-treated and melatonin-replaced rats

The aim of this study was to compare the effects of pineal indole treatments on LH and FSH release in pinealectomized and suprachiasmatic lesioned and ovariectomized rats rendered hyperprolactinemic by acute sulpiride treatment. pinealectomy or suprachiasmatic nuclei lesions in female rats both decreased plasma LH and FHS at 10, but not at 20 d after surgery, whereas the daily afternoon administration of melatonin effectively restored levels of both gonadotropins to control values. In ovariectomized rats, pinealectomy or suprachiasmatic nuclei lesions were ineffective in counteracting the high plasma levels of LH and FSH. However, sulpiride treatment in both pinealectomized and suprachiasmatic nuclei lesioned and castrated female rats significantly decreased the levels of LH and FSH, an effect which was counteracted by daily afternoon melatonin administration. Other pineal indoles tested, i.e., 5-hydroxy- and 5-methoxytryptophol, were ineffective in regulating gonadotropin levels. The results suggest that the pineal gland, through its hormone melatonin, can modulate gonadotropin secretion by acting on a dopamine mechanism independent of hypothalamic suprachiasmatic areas.     

Endurance training and antioxidants of lung

Mice and rats were adjusted to daily treadmill training programs, which were heavy enough to increase the oxidative capacity of skeletal muscles. Endurance training did not affect the activities of catalase and glutathione peroxidase and the concentration of vitamin E in the lungs of mice and rats. Thus increased ventilation and oxygen utilization induced by exercise training do not modify lung antioxidants, in contrast to hyperoxia and hypoxia.     

Effect of daily parenteral injection of betamethasone on histamine concentration of gastric tissue in albino rats

Summary Gastric tissue histamine concentration was determined in albino rats following daily parenteral injection of betamethasone over a period of 12 days. The result shows a highly significant fall in gastric tissue histamine concentration in comparison with that in saline-treated albino rats over a similar period.This investigation was carried out as a part of a project supported by a research grant from Medical Research Centre, Bombay Hospital Trust, Bombay, India.     

Effect of daily parenteral injection of betamethasone on histamine concentration of gastric tissue in albino rats

Gastric tissue histamine concentration was determined in albino rats following daily parenteral injection of betamethasone over a period of 12 days. The result shows a highly significant fall in gastric tissue histamine concentration in comparison with that in saline-treated albino rats over a similar period.     

50 ppm MnBK subclinical neuropathy in rats

Summary 40 rats were subjected daily for 6 months to an atmosphere containing 50 ppm MnBK. 32 of the rats presented with demyelination of the sciatic nerve and 2 of these with axonal hypertrophy.This work was supported in part by General Support Grant RR. 5414.We thank Dr Cedric Raines, Einstein Medical Center, New York, for helpful criticisms and suggestions and Dr Saul Francis for intoxicating the rats.     

Effect of gum Arabic on aminopyrine demethylation in rats

Summary Stimulation of aminopyrine demethylation induced in rats by oral or i.p. administration of phenobarbital was partially inhibited in animals receiving daily treatments of 2×200 mg/kg gum Arabic p.o.     

50ppm MnBK subclinical neuropathy in rats.

40 rats were subjected daily for 6 months to an atmosphere containing 50ppm MnBK. 32 of the rats presented with demyelination of the sciatic nerve and 2 of these with axonal hypertrophy.     

Endurance training and antioxidants of lung

Summary Mice and rats were adjusted to daily treadmill training programs, which were heavy enough to increase the oxidative capacity of skeletal muscles. Endurance training did not affect the activities of catalase and glutathione peroxidase and the concentration of vitamin E in the lungs of mice and rats. Thus increased ventilation and oxygen utilization induced by exercise training do not modify lung antioxidants, in contrast to hyperoxia and hypoxia.This study was supported by the Academy of Finland and the Research Council for Physical Education and Sport (Ministry of Education, Finland). We thank Mr Matti Virtanen for skillful technical assistance.     

Alleviation of mortality induced by salicylate and stress

Protection from the deleterious effects of the interaction of environmental stress and salicylate by calcium supplement was investigated in 96 pigmented rats. Within a 2×2×4 factorial design, rats were assigned to groups defined by:A) ad lib access to 1) plain tap water, or 2) 50 mM calcium chloride solution;B) exposure to stressors consisting of daily 10 h periods of 1) 98 dB SPL noise, or 2) confinement precluding movements;C) daily injections of 233, 350, or 410 mg/kg of sodium salicylate or the saline vehicle. For subjects maintained on tap water, weight loss and mortality increased with salicylate levels, with all subjects dying in the group drinking water and injected with 410 mg/kg. Calcium protected all of the subjects in the noise stress group but not in the confined group.     

Effect of adrenalectomy and dexamethasone treatment on the monoamine oxidase activity in the thyroid gland of the rat

Summary Adrenalectomy increased MAO activity in the thyroid gland of rats. The administration (200 g/100 g daily for 7 days) to adrenalectomized rats decreased MAO activity below levels of intact controls.     

Preliminary evidence that a dopamine receptor antagonist blocks the prolactin-inhibitory effects of melatonin in anosmic male rats

Summary Previous studies have shown that daily afternoon injections of melatonin in anosmic male rats result in depressed accessory sex organ weights and serum prolactin levels. The present data indicate that the prolactin-inhibitory effect of melatonin may be mediated via the dopaminergic system.This work was supported by NIH Biomedical Research Support Grant No. 3150-80.     

On the mineralocorticoid and hypertensogenic properties of 16beta-hydroxy-dehydroepiandrosterone.

Dosages of either 1 or 2 mg daily of 16beta-hydroxy-dehydroepiandrosterone, given to mononephrectomized, salt-loaded female rats, had no detectable effect upon saline consumption, blood pressure, kallikrein excretion or heart and kidney weight. Its alleged mineralocorticoid properties, as judged by these criteria, were not demonstrable.     

Salivary gland enlargement as a test for a new way of permanent isoproterenol application

Summary Low doses of isoproterenol, given permanently by a new application-method, show the same effects on salivary-gland enlargement of rats throughout approx. 6 days than 10fold higher concentrations given by previous workers as single daily injections.We are very much indebted to Mrs K. Stökl and Miss E. Stangl for their valuable technical assistance.     

Effects of handling normal and bulbectomized rats at adrenal and plasma corticosterone levels

Summary Normal and bulbectomized adult rats, male and female, handled daily for 4 weeks, show plasma and adrenal corticosterone values significantly lower than the non-handled ones.     

Fluoreszenzmikroskopische Untersuchungen am Hypothalamus männlicher Ratten nach Behandlung mit einer antimaskulin wirkenden Substanz

Summary In new-born male rats daily injections of a strong antiandrogenic substance led to an increase of the catecholamine content in the parvicellular perikarya as well as in nerve fibres leading to the paraventricular and supraoptic nuclei. The same effect was observed in male rats castrated immediately after birth. A possible relationship between gonadotropic releasing factors and the catecholamin content of the hypothalamic nuclei is discussed.     

Effect of acetylsalicylate on surgical bleeding, postoperative mortality and allograft survival in rats undergoing heart transplantation.

18 rats were treated with L-ASA before heart transplantation and daily thereafter until death or rejection. 22 animals acted as controls. A significantly higher post-operative mortality rate, without any significant modification of the transplant survival time, was found in L-ASA-treated group.     

Über die antithyreotoxische Wirkung der Pantothensäure

Summary Administration of calcium pantothenate to white rats in daily doses of 50–100 mg improved the signs of experimental thyreotoxicosis and decreased the metabolic rate.     

Interaction of salicylate and noise results in mortality of rats

Summary Survival as a function of salicylate dose and the intensity of environmental noise was investigated in 150 adult female pigmented rats. Rats were assigned to groups (n=6/group) defined by combinations of salicylate levels from 0- (saline) to 300 mg/kg, injected subcutaneously, and noise levels from ambient noise to 98 dB SPL, presented daily for 10-h periods for up to 17 days. Mortality occurred in groups exposed to the higher combinations of salicylate and noise.