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Biomedical subjects

N Y Zachariah

Publications and source records attributed to N Y Zachariah.

At least 19 recordsLinked to original sources

Anabolic steroid-induced hepatotoxicity: is it overstated?

OBJECTIVE: There have been numerous reports of hepatic dysfunction secondary to anabolic steroid use based on elevated levels of serum aminotransferases. This study was conducted to distinguish between serum aminotransaminase elevations secondary to intense resistance training and anabolic steroid-induced hepatotoxicity in elite bodybuilders. DESIGN: This was a case-control study of serum chemistry profiles from bodybuilders using and not using anabolic steroids with comparisons to a cohort of medical students and patients with hepatitis. PARTICIPANTS: The participants were bodybuilders taking self-directed regimens of anabolic steroids (n = 15) and bodybuilders not taking steroids (n = 10). Blood chemistry profiles from patients with viral hepatitis (n = 49) and exercising and nonexercising medical students (592) were used as controls. MAIN OUTCOME MEASURES: The focus in blood chemistry profiles was aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (GGT), and creatine kinase (CK) levels. RESULTS: In both groups of bodybuilders, CK, AST, and ALT were elevated, whereas GGT remained in the normal range. In contrast, patients with hepatitis had elevations of all three enzymes: ALT, AST, and GGT. Creatine kinase (CK) was elevated in all exercising groups. Patients with hepatitis were the only group in which a correlation was found between aminotransferases and GGT. CONCLUSION: Prior reports of anabolic steroid-induced hepatotoxicity based on elevated aminotransferase levels may have been overstated, because no exercising subjects, including steroid users, demonstrated hepatic dysfunction based on GGT levels. Such reports may have misled the medical community to emphasize steroid-induced hepatotoxicity when interpreting elevated aminotransferase levels and disregard muscle damage. For these reasons, when evaluating hepatic function in cases of anabolic steroid therapy or abuse, CK and GGT levels should be considered in addition to ALT and AST levels as essential elements of the assessment.

Adult↗

Neuroendocrine-associated behavioral patterns in the male Asian elephant (Elephas maximus).

Steroid-responsive behaviors have been reported in various species; however, the reports thus far on the male Asian elephant (bull) during musth are few in number and most have been conducted on single captive animals for short time periods. The purpose of this investigation was to perform a longitudinal study on steroid-responsive behavior in 3 male Asian elephants from a captive herd of 11 male Asian elephants in Nepal. Male Asian elephants were 18, 25, and 43 years old. The animals had serum collected for 11 months and were observed on a daily basis for aggressive behavior according to the Species Survival Plan (SSP) collection protocol on SSP data sheets. Testosterone (T) and dihydrotestosterone (DHT) were measured in each animal by radioimmunoassay. Testosterone levels rose during musth 26-fold compared to nonmusth, and DHT was elevated 12-fold in musth. Maximal aggressive behavior episodes occurred during peak elevations of T and DHT, with correlation coefficients of 0.82 and 0.89, respectively. Therefore, we suggest that the aggressive episodes are dependent on elevated circulating androgens acting on androgen-responsive neural tissues.

Animals↗

Left ventricular size and function in elite bodybuilders using anabolic steroids.

OBJECTIVE: To investigate the relationship between resistance training, anabolic steroid use, and left ventricular function. DESIGN: Sixteen competitive bodybuilders were recruited for an echocardiography study. SETTING: University of North Texas Health Science Center (Fort Worth, TX, U.S.A.); the cardiologist and technician were blinded as to subjects' drug status. SUBJECTS: Eight competitive heavyweight drug-free (DF) bodybuilders and eight competitive heavyweight body-builders on self-directed regimens of anabolic steroids. RESULTS: Average body mass indexes (BMI; kg/m2) for the drug-user (DU) and DF groups were not significantly different (34.1 +/- 2.8 and 32.0 +/- 4.3, respectively). Increases in left ventricular posterior wall and ventricular septal thickness were apparent in the DU group (p < 0.05). The ratio of echocardiographic findings to BMI revealed a significantly smaller left ventricular end-diastolic dimension (LVDEd/BMI; p < 0.05) in the DU group. The smaller LVDEd in DUs is coupled with a significantly disproportionate septal and posterior wall thickness in DUs when indexed to body mass compared to DFs. There was no direct evidence of diastolic dysfunction detected by mitral inflow velocity patterns. CONCLUSION: Anabolic steroids may potentiate concentric left ventricular hypertrophy with decreasing ventricular compliance without affecting cardiac function.

Adult↗

Absorption of a topical steroid and evaluation of adrenal suppression in patients with erosive lichen planus.

This study was designed to investigate the absorption of a topical steroid applied to the gingiva and buccal mucosa of patients with erosive lichen planus and to healthy control patients. In addition, adrenal suppression was assessed by measurements of serum and urine cortisol levels. Ten patients with erosive lichen planus and eight control patients provided urine and blood samples at baseline, day 3, and day 21. After establishment of baseline laboratory values, patients were instructed to apply 500 mg of a 0.05% fluocinonide gel to the gingiva and buccal mucosa three times a day for 3 weeks. Measurements of cortisol levels revealed no significant changes in either the disease or the control group. Although procedures were developed to detect fluocinonide, none of the patients showed evidence of the steroid during the study. It was concluded that the topical application of a fluocinonide gel to the gingiva and buccal mucosa over a 3-week period in patients with erosive lichen planus produced no adrenal suppression.

Absorption↗

Steroid receptors in benign mastectomy tissue.

Estrogen and progesterone receptors (ERs and PRs, respectively) were measured in both cancerous and noncancerous components of 104 modified radical mastectomy specimens. In addition, ER and PR levels were determined for 14 benign breast specimens obtained by reduction mammoplasty. The receptor levels were measured by scatchard method. Each of these groups--cancerous, corresponding noncancerous, and mammoplasty specimens--were divided into subgroups according to their receptor levels. Fourteen of the 104 noncancerous specimens were found to be ER positive (ER+). Most cases of ER+ noncancerous tissue (13 of 14 cases) were associated with ER+ tumors. The reverse was not true because only 13 of 64 cases of the ER+ tumors were associated with positive ER in their noncancerous counterparts. Comparable results were obtained for PR. The average ER-PR level of the noncancerous mastectomy tissue was significantly higher than that of the mammoplasty specimens despite the similar histologic findings in both groups.

Breast Diseases↗

Regression of left ventricular hypertrophy in hypertension. Effects of prazosin therapy.

Left ventricular hypertrophy is a common consequence of chronic hypertension. Although the hypertrophic response can be considered an adaptive mechanism in the initial stages, its progression is associated with increased cardiovascular morbidity and mortality rates. Therefore, reversal of left ventricular hypertrophy may provide considerable clinical benefits to hypertensive patients. Although treatment of hypertension per se is important, blood pressure alone may not explain the course of the hypertrophic process. Not all antihypertensive drugs cause a reversal of hypertrophy, though they may produce equal effects on blood pressure. Factors other than the severity of blood pressure may play a role in the genesis of left ventricular hypertrophy. Adrenergic inhibitors cause its regression, whereas direct vasodilators may promote progression. In this study, therapy with the alpha-adrenergic inhibitor prazosin resulted in significant regression of left ventricular hypertrophy in a group of patients with moderate-to-severe hypertension. This study utilized a new technique--[123I]phenylpentadecanoic acid myocardioscintigraphy--to measure the left ventricular mass. In this study, it was shown that monotherapy with prazosin produced significant relative reductions in systolic and diastolic blood pressure, along with significant reductions in left ventricular mass.

Blood Pressure↗

Bioavailability of progesterone with different modes of administration.

The bioavailability of micronized progesterone (P) was studied by measuring sequential serum P concentrations after a single bolus of 50-200 mg P given sublingually, orally (capsule and tablet), vaginally and rectally (suppositories) during the follicular phase in a group of normally menstruating women. When compared to other modes of P administration, the area under the curve during the first eight hours was twice as high with the rectal route. With 50 and 100 mg P given sublingually and 100 and 200 mg ingested as tablets, peak levels and area under the curve were twice as high with the higher dosage. The response was more sustained with the higher dosage. All subjects exhibited a significant increase in serum P levels over baseline that persisted for at least eight hours. P levels were still increased over baseline at 24 hours in all subjects after the administration of 100-mg vaginal and rectal suppositories and 200-mg tablets. These findings are in general agreement with previous reports showing that luteal phase serum P concentrations can be reached easily with non-parenteral modes of administering micronized P and that oral P administration could become an attractive alternative to the currently used oral mode of administering synthetic progestins.

Absorption↗

A method for the determination of sex hormone binding globulin in human serum.

A simple and rapid method for serum sex hormone binding globulin (SHBG) was developed. Sera from pregnant women were pooled and the SHBG concentration was measured by Rosner's method. This pool was diluted with charcoal-treated and heated serum to give standards ranging in concentrations from 26.8-0.8 micrograms/L. Two sets of tubes containing dihydrotestosterone (DHT), assay and control tubes, were prepared. Diluted standards and unknowns were added to assay and control tubes along with tritiated DHT. Following incubation, cold saturated ammonium sulfate was added to each tube, mixed, centrifuged and the supernatant counted. Mean SHBG concentration (microgram/L +/- SEM) in normal men was 3.6 +/- 0.4, normal women 11.4 +/- 2.2, pregnant women 58 +/- 2.6, obese women 3.3 +/- 1.0, hirsute women 2.9 +/- 0.2, hypothyroid women 7.3 +/- 1.0, and hyperthyroid women 26.0 +/- 1.6. These results correlate well with previous reports. This method is fast, convenient, and up to 40 samples can be analyzed in one assay.

Buffers↗

A fast and convenient method for determining estrogen receptor using rabbit uterus as a standard.

A fast and convenient method is described for the determination of estrogen receptors (ERs). This method involves the use of rabbit uterus as a standard. ER content of the rabbit uterus powder was determined using the conventional methods, i.e., Scatchard plot and sucrose density gradient methods. The rabbit uterus cytosol was serially diluted to give a range of protein concentrations from 1 to 0.062 mg/ml. A standard curve was thus generated with the corresponding ER concentrations, and this curve was used for the determination of ERs in breast tumors. The method involved incubating the standards with 125I-estradiol and subsequent removal of the free radiolabeled estradiol using dextran-coated charcoal. A parallel sample was also incubated with diethylstilbestrol. A standard curve was obtained between the 125I-estradiol percentage of binding and the corresponding ER concentration. Tumor cytosols were also treated in a similar manner, and the receptor content was determined from the standard curve. Excellent correlation was obtained between this method and other conventional methods. This method is simpler and less time consuming, and up to ten tumors can be analyzed at one time. It is especially useful when limited amounts of tumor tissue are available, as a concentration of only 1 mg of protein per ml is required.

Animals↗

Stability of estrogen- and progesterone-receptor concentrations in human uterus tissue.

Homogeneous control specimens for estrogen receptor (ER) and progesterone receptor (PR) assays were prepared from freshly collected human uterus. After removal of the connective tissue, the specimen was washed with isotonic saline, cut into small pieces, quickly frozen in liquid nitrogen, and stored at -70 degrees C until analyzed. Cytosol prepared from this specimen was lyophilized and stored at -70 degrees C. A single step of reconstitution, with glycerol (100 mL/L) in water, is sufficient to prepare a control. Two specimens prepared this way were found to be reasonably stable for 20 months (first specimen, mean +/- SD: ER = 22.1 +/- 2.9 fmol/mg, PR = 136.5 +/- 26.9 fmol/mg; second specimen: ER = 107.2 +/- 11.7 fmol/mg, PR = 922 +/- 71.6 fmol/mg). Another specimen, prepared similarly but not frozen in liquid nitrogen soon after collection, was less stable; its ER and PR concentrations deteriorated faster.

Cytosol↗

Action of steroids on H+ and NH+4 excretion in the toad urinary bladder.

This study was done to determine if steroid compounds will stimulate the urinary bladder of the toad to increase its capacity to acidify the urine and excrete NH+4. Aldosterone, 17 beta-estradiol, dexamethasone, pregnenolone, and cholesterol were tested on the bladder. All compounds tested were found to stimulate the rate of acidification by the bladder, above that of a paired control hemibladder. In contrast, only the steroids aldosterone and 17 beta-estradiol were found to stimulate NH+4 excretion in the bladder. Cycloheximide was found to block the action of aldosterone on the NH+4 excretion, but did not have a significant effect on the stimulation of acidification by aldosterone. We conclude that steroids stimulate H+ and NH+4 excretion in the toad urinary bladder. In addition, the NH+4 excretory system seems to be more specific to this effect than is the H+ excretory system.

Aldosterone↗

A radioimmunoassay method for the rapid detection of Candida antibodies in experimental systemic candidiasis.

Rabbits were employed as experimental models to evaluate a solid-phase radioimmunoassay (RIA) method for the diagnosis of systemic candidiasis. Ten rabbits were inoculated subcutaneously to mimic superficial candidiasis and were found to produce no antibodies to Candida as determined by both immunodiffusion and RIA procedures. However, 94 per cent of 18 rabbits systemically infected by intravenous injection of Candida cells were observed to produce antibody as assessed by the RIA technique. These data encourage further tests with human sera and the continued development ofthis RIA procedure as a useful tool in the early serodiagnosis of systemic candidiasis.

Animals↗

Phospholipase A2 in experimental hypertension.

An assay method has been developed to measure phospholipase A2 (PLA2) in ratserum and to study the possible role of this enzyme in experimental hypertension. Experiments with rat serum following 48 h of bilateral nephrectomy indicated a decrease inPLA2 activity, suggesting that kidneys might be playing an important role in regulating serum PLA2 activity and that kidneys might be a source of this enzyme. Experiments with renal hypertensive rats, spontaneously hypertensive rats, and rats receiving a low-salt diet demonstrated that a decrease in PLA2 activity was found only in those conditions in which elevated plasma renin activity was accompanied by elevated blood pressure. When elevated plasma renin activity was not accompanied by elevated blood pressure, serum PLA2 activity was unchanged. These observations represent the first biochemical separation between conditions of elevated plasma renin activity without an increase in blood pressure and conditions of elevated plasma renin activity with an increasein blood pressure.

Animals↗