Incidentally discovered mass of the adrenal gland

Increasing numbers of asymptomatic masses of the adrenal gland are being discovered by high resolution computed tomography (CT) scanning. The significance of these masses and the question of further evaluation or treatment, or both, have posed a dilemma. From 1976 to 1983, an incidental finding of adrenal gland mass was identified in 88 patients undergoing abdominal CT scanning for unrelated problems. Adrenelectomy was performed upon 23 patients (26 per cent), including three adenomas (2.5, 3.0 and 6.5 centimeters), five carcinomas of the adrenal gland (6 to 20 centimeters), two hyperplasias and three adenocarcinomas of unknown origin. Thirty-eight (43 per cent) of the nonfunctioning masses were observed with repeat scans for an average of 25.1 months (three to 60 months), revealing no change in size. Twenty-seven patients (31 per cent) were lost to follow-up study. Silent primary (nonmetastatic) masses 3.5 centimeters or less manifested benign behavior without exception. Based upon these data, we conclude that all solid metabolically inactive lesions in the adrenal glands greater than 3.5 centimeters on CT abdominal scan deserve exploration. Lesions less than 3.5 centimeters may be safely followed with serial CT scans.     

Glutathione monoethyl ester protects against glutathione deficiencies due to aging and acetaminophen in mice

Our previous results indicated that glutathione (GSH) and/or cysteine (Cys) deficiency occurs in many aging tissues and also after acetaminophen (APAP) administration. The aim of this study was to investigate whether GSH monoethyl ester (GSH-OEt) can correct these deficiencies. Mice of different ages (3–31 months) through the life span were sacrificed 2 h after i.p. injection of GSH-OEt (10 mmol/kg). In separate experiments, old mice (30–31 months) received the same dose of ester 30 min before the administration of APAP (375 mg/kg) or buthionine sulfoximine (BSO, 4 mmol/kg), an inhibitor of GSH synthesis. Liver and kidney samples were analyzed for GSH and Cys by HPLC. The hepatic GSH and renal cortical GSH and Cys concentrations were about 30% lower in old mice (30–31 months) compared to mature mice (12 months). GSH-OEt corrected these aging-related decreases. APAP decreased both hepatic and renal cortical GSH and Cys concentrations in old mice, but GSH-OEt prevented these decreases. GSH-OEt also prevented the BSO-induced decreases in hepatic and renal GSH concentrations. The results demonstrated that GSH-OEt protected against GSH deficiency due to biological aging as well as APAP-induced decreases in old mice.     

Effects of calorie restriction on thymocyte growth, death and maturation

We previously reported that calorie restriction (CR) significantly delays the spontaneous development of thymic lymphomas and other neoplasms in p53-deficient mice and their wild-type littermates. The purpose of the present study was to further characterize the anti-lymphoma effects of CR by assessing thymocyte growth, death and maturation in response to acute (6 day) and chronic (28 day) CR regimens. Male C57BL/6J mice fed a CR diet (restricted to 60% of control ad libitum intake) for 6 days displayed a severe reduction in thymic size and cellularity, as well as a decrease in splenic size and cellularity; these declines were sustained through 28 days of CR. Mice maintained on a CR diet for 28 days also displayed a significant depletion in the cell numbers of all four major thymocyte subsets defined by CD4 and CD8 expression. Analysis within the immature CD4(-)8(-) thymocyte subset further revealed an alteration in normal CD44 and CD25 subset distribution. In particular, CR for 28 days resulted in a significant decrease in the percentage of the proliferative CD44(-)25(-) subset. In addition, a significant increase in the percentage of the early, pro-T cell CD44(+)25(-) population was detected, indicative of a CR-induced delay in thymocyte maturation. Taken together, these findings suggest that CR suppresses (through several putative mechanisms) lymphomagenesis by reducing the pool of immature thymocytes that constitute the lymphoma-susceptible subpopulation.     

Acetaminophen-induced depletion of glutathione and cysteine in the aging mouse kidney.

Glutathione (GSH) plays an essential role in the detoxification of acetaminophen (APAP) and the prevention of APAP-induced toxicity in the kidney. Our previous results demonstrated that a GSH deficiency is a general property of aging tissues, including the kidney, suggesting a hypothesis that senescent organisms are at greater risk to APAP-induced renal damage. To test this, C57BL/6NIA mice of different ages through the life span were injected with various doses of APAP, and the extent of GSH and cysteine (Cys) depletion and recovery were determined. At time intervals up to 24 hr, kidney cortex samples were obtained, processed and analyzed for glutathione status, namely GSH, glutathione disulfide (GSSG), Cys and cystine, using an HPLC method with dual electrochemical detection. In the uninjected controls, GSH and Cys concentrations decreased about 30% in the aging mouse, but the GSSG and cystine levels were unchanged during the life span. APAP administration depleted the kidney GSH and Cys contents in a dose- and time-dependent manner. Four hours after APAP administration, GSH levels of the young, growing (3- to 6-month) and the mature (12-month) mice decreased 34 and 58%, respectively, and recovered to near control values by 24 hr (95 and 98%). In contrast, the extent of depletion in old (31-month) mice was greater (64%) and the 24-hr recovery was less, returning only to 56%. Likewise, Cys levels of the young and mature mice decreased 49 and 65%, respectively, 4 hr following APAP, and increased to 99 and 85% by 24 hr. In contrast, in old mice, there was a 78% depletion after 4 hr followed by a recovery of only 65% by 24 hr. These results demonstrated clearly that in the aging mouse kidney, a GSH and Cys deficiency occurs that is accompanied by an impaired APAP detoxification capacity.     

Effects comparés du muscimol et du diazépam sur les inhibitions du comportement induites chez le rat par la nouveauté, la punition et le non-renforcement

Diazepam and muscimol, a direct GABA agonist, were compared on behavioral inhibition induced in rats by (1) novelty, (2) punishment, and (3) nonreward.(1) Muscimol (0.03–0.25 mg·kg^-1 i.p. 30 min before testing, or i.v. immediately before testing) failed to enhance food intake consistently in a nonfamiliar situation and (0.125–0.5 mg · kg^-1 i.p. or i.v.) to increase the ingestion of an unknown food (chocolate); (2) muscimol (0.125–0.5 mg · kg^-1 i.p. or 0.25 i.v. 10 min before testing) was ineffective in reducing the inhibition of lever presses for food elicited by the delivery of an electric shock at every eighth press; (3) muscimol (0.125–0.5 mg · kg^-1 i.p.) failed to attenuate the inhibitory effects on responding induced by the suppression of the reinforcement during extinction.Contrastingly, diazepam (2 mg · kg^-1 i.p. 30 min before testing) was found to reduce each type of behavioral inhibition.These data lend no support to the hypotheses of GABA control of behavioral inhibition and of GABA involvement in the action of benzodiazepines on inhibition induced by novelty, punishment, or nonreward.