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Biomedical subjects

S Levine

Publications and source records attributed to S Levine.

At least 469 records · Page 26Linked to original sources

Stimulation of phrenic nerve activity by salicylate.

To assess the possibility that salicylate stimulates VE by direct excitation of phrenic motoneurons, we compared two groups of anesthetized vagotomized dogs with respect to increases in phrenic nerve activity elicited by a large dose of sodium salicylate (225 mg/kg). The sole difference between the two groups of animals was the condition of the spinal cord (SC); SC remained intact in one group of animals (i.e., intact animals) whereas the other group of animals (i.e., T1 spinal-transected animals) underwent complete transection of the SC at the first thoracic level. Both groups of animals were ventilated by a respirator and arterial PCO2 was maintained constant throughout all experiments. Following salicylate infusion, intact animals exhibited two- to threefold increases in the frequency of phrenic nerve bursts and three- to fivefold increases in moving average minute phrenic activity (i.e., the summation of peak integrated burst activity per minute). In contrast, salicylate infusion into T1 spinal-transected animals elicited no statistically significant increase in the frequency of phrenic nerve bursts while increases in minute phrenic activity were limited to 32 +/- 8%. Since T1 spinal transection markedly diminishes increases in phrenic nerve activity elicited by salicylate, we conclude that salicylate stimulates VE by a reflex mechanism whose afferent pathways originate in metameres below T1.

Action Potentials↗

Ventilatory response to muscular exercise: observations regarding a humoral pathway.

To assess the role of humoral mechanisms in eliciting the hyperpnea of muscular exercise, anesthetized dogs underwent complete spinal transection at the second lumbar level (L2). Muscular exercise of the denervated hindlimbs was then induced by electrical stimulation. Coincident with hindlimb muscle contraction, oxygen consumption (VO2) increased 173% and ventilation (VE) increased 163%; no statistically significant changes occurred in arterial carbon dioxide tension (PCO2), arterial pH, or arterial oxygen saturation. Similar results were obtained after peripheral chemodenervation and vagotomy plus spinal transection. In order to evaluate the possibility that extracranial receptors mediate the increases in VE elicited by exercise-induced humoral factors, heads of vagotomized L2 spinal-transected dogs were perfused entirely by a support dog with blood of unchanging gas composition via both carotid and both vertebral arteries. The carotid bodies lay within the region of the perfused head; the aortic bodies were denervated. These L2 spinal-transected head-perfused animals still responded to hindlimb exercise with a 156% increase in VO2 and a 122% increase in VE. We conclude that muscular exercise can stimulate VE via humoral factors other than usual chemical stimuli in arterial blood (i.e., PCO2, pH, or O2 saturation). Extracranial receptors (other than conventional peripheral arterial chemoreceptors) appear to mediate a major portion of the increase in VE elicited by exercise-induced humoral factors.

Animals↗

Role of peripheral tissue receptors in stimulation of ventilation by 2,4-dinitrophenol.

Previous workers have demonstrated that hindlimb receptors can mediate some portion of the increase in VE elicited by 2,4-dinitrophenol (DNP). Liang and Hood have recently demonstrated that these hindlimb receptors communicate with the respiratory center via afferent pathways of the lumbar spinal cord. Accordingly, to determine the quantitative contribution of these hindlimb receptors to increases in VE elicited by DNP (4 mg/kg), we compared two groups of animals with respect to ventilatory, metabolic, and thermal responses elicited by this drug. Group I animals underwent complete transection of the spinal cord at the first lumbar level, whereas the spinal cord in Group II animals remained intact. Our results indicate that Group I and Group II animals did not differ with respect to increases in VE, VO2, and rectal temperature elicited by DNP. These results suggest that hindlimb receptors do not play an obligatory role in mediating increases in VE elicited by DNP. Therefore, these observations raise the possibility that multiple afferent pathways may exist for stimulation of VE by DNP.

Animals↗

Serum-cholesterol-binding reserve in patients with the nephrotic syndrome.

Hyperlipidemia and premature atherosclerosis are known metabolic complications in patients with the nephrotic syndrome. In this study, we have measured serum levels of cholesterol, triglycerides and serum-cholesterol-binding reserve (SCBR) in 22 patients (14 men, 8 women) with the nephrotic syndrome and in 21 hyperlipidemic men who served as control subjects. Serum cholesterol levels were higher (p less than 0.005) in patients when compared to those of controls while triglyceride levels did not differ significantly between the groups. SCBR levels were lower (p less than 0.001) in the nephrotic subjects. The abnormally low SCBR values may be an important risk factor for atheroclerosis as suggested by previous studies in patients surviving premature myocardial infarction.

Adult↗

A controlled comparative trial of a new antidepressant, ciclazindol.

The author describes a controlled, double-blind, comparative trial of a new tetracyclic compound, ciclazindol (WY 23409), against amitriptyline in the treatment of thirty-five patients admitted to hospital with depressive illness. Each patient was randomly allocated to three weeks treatment with either 50 mg b.d. ciclazindol or 50 mg b.d. amitriptyline. In the event of a poor response the dose level was raised to 75 mg b.d. Separation of cases of endogenous depression and severity of depression were assessed by the Levine-Pilowsky Depression Questionnaire, a self-rating technique. Severity of depression was also assessed using the Hamilton Rating Scale. No significant difference was noted between the drugs in either the degree or the rate of response nor when the endogenous cases alone were studied. The interesting observation was made that only one-third of ciclazindol patients gained weight compared to almost three-quarters of the amitriptyline group and the mean weight gain of the latter was over double that of the ciclazindol group. The author concludes that ciclazindol offers promise and merits further study using higher dosage levels once its full safety trials have been completed.

Amitriptyline↗

Suppression of experimental allergic encephalomyelitis by EN3638: dependence on adjuvants and treatment schedules.

Oral administration of 2, 3 or 4 doses of 100 or 250 mg/kg of EN3638 during the incubation period of experimental allergic encephalomyelitis delayed the onset and reduced the incidence and severity of clinical signs and histological lesions. Five doses of 50 or 100 mg/kg effected virtually complete and permanent suppression of clinical signs even after cessation of therapy, and five doses of 250 mg/kg eliminated histological lesions as well. Optimum results required coverage of the entire incubation period regardless of dose level. These results were obtained only when carbonyl iron was used as the adjuvant for production of EAE. When complete Freund's adjuvant was used, EN3638 delayed the onset but had little or no influence on late-developing clinical signs and histologic lesions after cessation of therapy. The permanence of suppression when carbonyl iron was used is related to the absence of an oil depot. Carbonyl iron is a superior adjuvant for drug suppression studies.

Adjuvants, Immunologic↗

Pituitary-adrenal response to separation in mother and infant squirrel monkeys.

Pituitary-adrenal response in mother and infant squirrel monkeys following brief separation was assessed. Each mother and infant pair was tested under each of 3 conditions: (1) Basal; (2) Separation-Reunion; and (3) Separation. Samples were obtained from mothers and infants in the Separation and Separation-Reunion conditions 30 min following the initial disturbance. A similar paradigm was used to assess the effects of separation in surrogate-reared animals. The results indicate that mothers, infants, and surrogate-reared infants respond to 30-min separation with a substantial increase in plasma cortisol. The values obtained in the Separation-Reunion condition did not differ significantly from Basal values in any of the 3 groups, suggesting that the effect of separation on the pituitary-adrenal system is not due to the disturbance involved in the separation procedure. The response of surrogate-reared infants suggests that these infants develop similar attachments to the surrogate as normal infants to their own mothers.

Animals↗

Differential effects of handling on exploration in male and female rats.

In this study, sex differences in the exploratory behavior of handled and nonhandled animals were measured under conditions of both high and low stimulus variation. The apparatus used was a hole-board, which provided an exploratory response independent of ambulation. Significant effects of handling were found: nonhandled animals decreased head-dipping over days whereas handled animals maintained a high rate. Sex differences were also observed: patterns of head-dipping for males and females differed over days depending on whether objects was present (high stimulus variation) or absent (low stimulus variation) under the hole-board; females also head-dipped for longer durations than males when objects were present; further, males and females showed completely opposite patterns of exploration depending on handling treatment and on level of stimulus variation. We conclude that handling differentially affects males and females, particularly as level of stimulus variability changes.

Animals↗

Perinatal malnutrition and early handling: interactive effects on the development of the pituitary-adrenal system.

The preweaning development of the pituitary-adrenal system was investigated in perinatally malnourished rodents. Malnourished pups that were routinely handled displayed an earlier plasma corticosterone stress response to electric shock and an accelerated development of feedback inhibition of the stress response by exogenously elevated steroid levels. Although malnourished pups displayed elevated basal corticosterone levels compared to well-fed controls, the post-stress levels were also higher in these malnourished young. Thus, the corticosterone response to stress was not impaired in malnourished pups. The influence of the early handling of malnourished young on pituitary-adrenal activity was also studied. Whereas the accelerated development of the stress response and the elevated post-shock levels were not the result of early handling, the elevated basal corticosterone levels displayed by handled malnourished pups were not present in nonhandled malnourished pups. Thus, the early non-nutritional environment interacts with malnutrition to alter the development of the pituitary-adrenal system.

Animals↗