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Biomedical subjects

S Levine

Publications and source records attributed to S Levine.

At least 775 records · Page 43Linked to original sources

Repeated toxic injury of peritoneum: accumulation of toxicity and adaptation to injury.

In order to develop new methods for the study of pathogenesis of post-injury fibroplasia, a rat model of chemical peritonitis was explored. Sodium hypochlorite (NaOCl) of various concentrations was injected intraperitoneally one or more times using different intervals between doses. Some time later, the surface fibrosis of liver, spleen, omentum and other abdominal organs was evaluated. A dose-response relation at intermediate concentrations and an apparent threshold at low concentrations were observed. Fibroplasia was increased by repeated doses (accumulation) but it was ameliorated compared to the same total amount of chemical given as a single injection (adaptation during repeated dosing). The rapid disappearance of the chemical irritant and the large size and easy accessibility of the peritoneal cavity suggest that this model may be useful in further study of chemical toxicity and fibroplasia in relation to human fibrosing diseases and injuries (trauma, surgery, peritoneal dialysis). The model has the unique feature of evaluating the morphological effects of the toxic injury and secondary functional effects at the same time.

Adaptation, Physiological↗

Treatment of psoriatic arthritis with azaribine.

Thirty-two patients with psoriatic arthritis unresponsive to conventional therapy were treated wtih the antipyrimidine azaribine. For the group, improvement was highly significant (P less than 0.01) when average painful joint count, ring size, grip strength, pain, and morning gel were compared with baseline measurements. The spectrum of response of individual patients varied from total remission or arthritis in 5 patients to no improvement in 7. Dermatitis improved more than 50% in 26 patients. Reduction in hematocrit, gastrointestinal irritation, and occasional central nervous system toxicity were readily reversed by decreasing or discontinuing dosage. Azaribine appears to be a useful agent for trial in the treatment of refractory psoriatic arthritis.

Adult↗

Lymphocyte involvement in rheumatoid arthritis. Studies during thoracic duct drainage.

Grip strength, ring size, duration of morning stiffness, and the number of tender joints improved significantly in 9 patients with severe rheumatoid arthritis during prolonged continuous removal of thoracic duct lymphocytes through a surgical fistula. There was no improvement in 4 subjects in whom surgery failed to establish satisfactory lymph drainage. Reinfusion of unlabeled or 51Cr-labeled autologous lymphocytes resulted in transient exacerbation of disease activity in 3 subjects. Following reinfusion, some 51Cr-labeled lymphocytes could be found in the inflamed synovium and synovial fluid by autoradiography, and radioactivity was detected over the joints by surface counting of gamma radiation. Active rheumatoid arthritis recurred in all subjects at variable intervals after cessation of lymph drainage. These findings are compatible with the hypothesis that some of the lymphocytes in the thoracic duct lymph are essential for the continued activity of the inflammation associated with rheumatoid arthritis.

Adult↗

A double-blind trial of high versus conventional dosages of gold salts for rheumatoid arthritis.

In a double-blind study, patients were randomly selected for treatment using conventional doses (CD; 50 mg) or high doses (HD; 150 mg) of sodium aurothiomalate given weekly by injection. Twenty-three patients were assigned to the CD group and 24 to the HD group. Neither efficacy nor toxicity correlated with serum gold concentrations. Conventional doses were as efficacious as high doses with respect to both rapidity and degree of response. However, side effects were much more frequent and severe in the HD group. Thus there is no reason to recommend a 150 mg weekly dosage regimen.

Adult↗

Peritoneal toxicity of water: a model of chronic peritonitis caused by osmotic dysequilibrium in rats.

The purpose of this work was to determine whether the osmotic dysequilibrium created by intraperitoneal (i.p.) injection of pure water has any permanent, damaging toxic sequelae. Rats were injected i.p. with pure water on five successive days. Necropsies were performed 1 week after the last injection. Necropsies revealed fibrosis of peritoneal surfaces of liver and spleen, similar to the effects of chemical irritants but milder. The severity of the lesions depended on the dose of water and the number of injections. A few minutes of contact with pure water was sufficient to ensure subsequent development of fibrosis. Soon after the initial injury, the inoculum became less hypotonic and then isotonic. Isotonic or moderately hypotonic electrolyte solutions did not produce peritoneal fibrosis but very hypotonic solutions were toxic. Injection of the synthetic compound 48/80, which is known to cause discharge of mast cell granules, did not produce peritonitis, nor was contamination by endotoxin or by blood responsible for the lesions. Injection of water may be a useful method for investigating the role, if any, of mast cells and/or mesothelial cells in the toxic effects of osmotic dysequilibrium.

Animals↗

Inhibition of experimental allergic encephalomyelitis by lithium chloride: specific effect or nonspecific stress?

Intraperitoneal injections of lithium chloride inhibited development of experimental allergic encephalomyelitis (EAE) in rats. The degree of inhibition was inversely related to the intensity of the immunologic stimulation, which depended on the choice of adjuvant. High dosage of lithium, the intraperitoneal route, and an intermittent schedule of administration were required to achieve suppression of EAE. This suggested that the immunosuppression was a toxic effect, mediated, at least in part, through the hypothalamic-pituitary-adrenal cortex axis. This hypothesis was supported by evidence that the lithium treatment schedule, especially the intermittent schedule, had caused adrenal cortical activation with thymolysis in intact rats and that it was lethal to adrenalectomized rats. Lithium also inhibited EAE produced by adoptive immunization, thus implicating the efferent arm of the immune response. A single dose of lithium was effective in this form of EAE, even in adrenalectomized rats. Therefore lithium affects EAE by both specific immunosuppressive and nonspecific adrenocortical-dependent mechanisms.

Adrenal Glands↗

Bidirectional responsiveness of the pituitary-adrenal system in old and young male and female rats.

Bidirectional responsiveness of the pituitary-adrenal system was examined in young adult (3-5 months) and old (24-26 months) male and female rats. In Experiment 1, an approach-avoidance conflict was created by exposing food- and water-deprived subjects to a flavored solution which had previously been paired with lithium chloride-induced illness in a conditioned taste aversion paradigm. Young and old males and young females elevated plasma corticosterone in response to deprivation; males showed a further elevation when reexposed to the solution, whereas young females did not. Old females did not exhibit a corticosterone elevation to deprivation or upon reexposure. In Experiment 2, water was restricted to a fixed period in the morning when corticosterone levels are typically low. Plasma corticosterone was measured before and after watering. Young and old males and young females reentrained their circadian corticosterone rhythm so that levels were elevated just prior to watering; consumption was followed by a drop in corticosterone. Old females failed to reentrain or to suppress corticosterone secretion upon drinking. These findings indicate that the lability of the pituitary-adrenal system is more markedly affected by senescence in females than in males.

Aging↗

Tin concentration in the thymus glands of rats and mice and its relation to the involution of the gland.

Tin is an ubiquitous element and thus enters mammals through the food chain. It has never been found to be dysfunctional in either plants or animal tissue and has been regarded as an innocuous background material. Of the many organs and glands that have been analyzed for tin, only the thymus gland exhibits an above average value for tin. A complete study on the tin content in the thymus gland has never been published and this work is an attempt to investigate this subject. Three types of rodents were used in this study; inbred Lewis rats, inbred A/KI mice (a breast cancer prone mouse) and outbred COBS mice (a cancer resistant mouse). The tin analysis of the muscle, spleen, and thymus indicated constant values for the muscle and spleen tissue, but an increase in the thymic tin concentration (ppm) with age. Besides normal aging studies, the animals were administered the disodium salt of dexamethasone-21-phosphate (dexa), which causes rapid loss of lymphocytes from the spleen and thymus but has no effect upon the muscle. Tin concentration in the muscles remained constant, showed a loss from the spleen and an increase in the thymus gland. The increase indicates that the tin was probably located in the medulla of the thymus, which may be the active biochemical site for tin in rodents. When compared to the COBS mice, the A/KI mice showed a non-statistical difference in tin content in the muscle and spleen and statistically significant lower tin content in the thymus gland.

Aging↗