Effect of vitamin C supplements on antioxidant defence and stress proteins in human lymphocytes and skeletal muscle.

Oxidative stress induces adaptations in the expression of protective enzymes and heat shock proteins (HSPs) in a variety of tissues. We have examined the possibility that supplementation of subjects with the nutritional antioxidant, vitamin C, influences the ability of lymphocytes to express protective enzymes and HSPs following exposure to an exogenous oxidant and the response of skeletal muscle to the physiological oxidative stress that occurs during exercise in vivo. Our hypothesis was that an elevation of tissue vitamin C content would reduce oxidant-induced expression of protective enzymes and HSP content. Lymphocytes from non-supplemented subjects responded to hydrogen peroxide with increased activity of superoxide dismutase (SOD) and catalase, and HSP60 and HSP70 content over 48 h. Vitamin C supplementation at a dose of 500 mg day-1 for 8 weeks was found to increase the serum vitamin C concentration by ~50 %. Lymphocytes from vitamin C-supplemented subjects had increased baseline SOD and catalase activities and an elevated HSP60 content. The SOD and catalase activities and the HSP60 and HSP70 content of lymphocytes from supplemented subjects did not increase significantly in response to hydrogen peroxide. In non-supplemented subjects, a single period of cycle ergometry was found to significantly increase the HSP70 content of the vastus lateralis. Following vitamin C supplementation, the HSP70 content of the muscle was increased at baseline with no further increase following exercise. We conclude that, in vitamin C-supplemented subjects, adaptive responses to oxidants are attenuated, but that this may reflect an increased baseline expression of potential protective systems against oxidative stress (SOD, catalase and HSPs).

Time course of responses of human skeletal muscle to oxidative stress induced by nondamaging exercise.

Previous studies in animals have demonstrated that a single period of aerobic exercise induces a rise in the skeletal muscle activity of the antioxidant enzymes superoxide dismutase and catalase and an increase in the muscle content of heat shock proteins (HSPs). The purpose of this study was to examine the time course of response of human skeletal muscle superoxide dismutase and catalase activities and the content of HSP60 and HSP70 after a period of exhaustive, nondamaging aerobic exercise. Seven volunteers undertook one-legged cycle ergometry at 70% maximal oxygen uptake for 45 min. Biopsies were obtained from the vastus lateralis muscle 7 days before and at 1, 2, 3, and 6 days after exercise. Muscle superoxide dismutase activity increased to a peak at 3 days postexercise, muscle catalase activities were unchanged, and muscle content of HSP60 and the inducible HSP70 increased by variable amounts to reach means of 190% and 3,100% of preexercise values, respectively, by 6 days postexercise. These data indicate that human skeletal muscle responds to a single bout of nondamaging exercise by increasing superoxide dismutase activity and provide the first evidence of an increase in HSP content of human skeletal muscle after a submaximal exercise bout.

Decision analysis in the clinical and imaging diagnosis of acute cholecystitis.

The importance of clinical, laboratory and imaging data in the diagnosis of acute cholecystitis (AC) was studied in 825 patients with right upper quadrant pain hospitalized in the Surgical Clinic of the Fundeni Hospital--Bucharest, between January 1, 1986 and June 30, 1988. A number of 21 parameters were analysed in each case. Of these 825 patients, 259 were considered after surgery as AC. These 259 cases were divided, after the microscopical examination of the surgically-obtained specimens, into two groups: 1) pathologically confirmed AC (137 cases) and 2) pathologically non-confirmed AC (122 cases). The importance of every parameter in establishing a histologically confirmed diagnosis of AC was determined by the diagnostic probability calculated according to Bayes'theorem. The hierarchy of the value of parameters in the diagnosis of AC was based on their capacity to distinguish between the cases histologically confirmed and those detected on surgery, but without microscopically demonstrated changes of AC. The same decision criterion was used in building the decision trees in the exploration of the cases of presumed AC. In the 825 cases with right upper quadrant pain, the main and most frequent cause was chronic calculous cholecystitis (31.8%), followed by AC pathologically confirmed (16.6%), AC non-confirmed (14.7%) and chronic acalculous cholecystitis (12.4%). The most useful parameters in distinguishing between pathologically confirmed AC and pathologically non-confirmed AC were: 1) sudden onset of pain; 2) mild resistance to abdominal palpation; 3) frank peritoneal irritation; 4) stone impacted in the gallbladder neck (ultrasonography); 5) fever; 6) palpable gallbladder; 7) lithiasis (ultrasonography); 8) gallbladder wall with double outline (ultrasonography). Ultrasonography supplied a diagnostic probability of 85% for the correct diagnosis of AC in cases without a clinical picture suggestive for AC. The decision tree analysis supported the same conclusion: only ultrasonography gives a good distinction between pathologically confirmed AC and pathologically non-confirmed AC.

Secretion of basal gonadotropins after LRH decapeptide and tripeptide. Stimulation in hypogonadotropic hypogonadism.

Sixteen females with pubertary delay of the isolated hypogonadotropic hypogonadism type (mean age 19 years, age range 14-25 years) were studied by radioimmunoassay of LH and FSH. The mean values +/- SE were compared to the values obtained from 10 girls in the B 5 Tanner stage and 15 normal adult women investigated on the 14th and 21st day of their ovarian cycle. Two females were given the LRH decapeptide and LRH-LA tripeptide stimulation test. In one case the daily variations of circulating serum LH and FSH were followed up. The fluctuations found suggest an ovarian rhythm which is present in the normal adult woman.

Pituitary function in 20 cases of prolactinoma in females.

Women with prolactinic pituitary tumor in the fertile period have increased (60-400 ng/ml) blood prolactin values and decreased LH and FSH as compared to healthy women of the same age. Among the mechanisms implied in prolactin hypersecretion in females with prolactinic tumor worth noting are: low receptivity to dopamine, low dopamine production, elevated serotonin and TRH production, stress factors. Suppression of prolactin secretion with bromcriptine induces a rise in LRH and consequently in LH and FSH. A drug treatment is suggested for prolactin hypersecretion in women with prolactinic pituitary tumor, consisting in association of small doses of bromcriptine, L-DOPA, metergolina and thyroxine, and avoidance of stressing circumstances.

Biochemical changes in the rat brain associated with dinitrophenol-induced brain edema.

The present paper was designed to the study of cerebral edema induced by intracarotid infusion of dinitrophenol. The determinations included variations in three lysosomal enzymes (acid phosphatase, cathepsin C and beta-glucuronidase), Na+-K+-ATP-ase, changes in cerebral RNA and protein concentrations and the synthesis of these macromolecules in vitro. In experimental brain edema a drastic drop in the activity of lysosomal enzymes took place. The acid phosphatase decreased to less than 30% of controls. Cathepsin C and beta-glucuronidase were reduced about 30% and 50% of control levels respectively. Protein concentration in the cerebral tissue also decreased by more than 50%. The concentration of RNA, RNA synthesis, and the level of Na+-K+-ATP-ase remained unchanged. Protein synthesis was stimulated by 75% (against controls). All these phenomena were suppressed when the animals subjected to the action of dinitrophenol were concomitantly treated with the antiacidotic substance, tris (hydroxymethyl) aminomethane.

Variations in LH and FSH serum gonadotropins in the hypophyseal chromophobe adenoma and acromegaly in the woman in relation to age.

Investigation of the gonadotropic function by radioimmunoassay of serum LH and FSH in 62 women with hypophyseal chromophobe adenoma and acromegaly in relation to age and by comparison with 40 normal women revealed low values for LH and FSH during the reporduction period (20--43 years) and increased values in the postmenopausal period (48--84 years) like in physiologic postmenopause. The increase of the gonadotropic function in the hypophyseal tumoral syndrome of the chromophobe adenoma and acromegaly type above the age of 48 from low values compared to the normal to high values like those in physiologic menopause (a gonadotropic turning phenomenon) demonstrate an alteration of the hypothalamic receptors in relation to age and to these diseases.

Dynamics of the h-LH and h-FSH response after the stimulation test with Gn-RH-LH/FSH in man.

A study was carried out on a number of 17 subjects concerning the dynamics of LH and FSH response after stimulation with Gn-RH-LH/FSH. The results show a stimulation 10 minutes after quick i.v. injection of synthetic RH, with a peak at 20-30 minutes and a persistence of the response of up to 180 min. The variation of the response is proportional with the dose, the response to stimulation being higher for LH than for FSH. The response in the normal adult male is of 82-858% for LH and of 157-250% for FSH. In aged subjects there is an increased response capacity showing that the hypophysis still reacts at an advanced age, with variations depending on the individual characteristics. In Sheehan's syndrome the basal values of FSH and LH are low, with a slight response after stimulation with RH, suggesting the possibility of a partial regeneration of the hypophysis if any intact areas were left after the initial necrotic process.