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Biomedical subjects

R Rittmaster

Publications and source records attributed to R Rittmaster.

5 recordsLinked to original sources

The effect of dutasteride on intraprostatic dihydrotestosterone concentrations in men with benign prostatic hyperplasia.

The dual 5alpha-reductase inhibitor, dutasteride has been shown to suppress serum dihydrotestosterone (DHT) by >90%. In the present study, the effect of dutasteride 0.5 mg/day on intraprostatic DHT levels was investigated. In this multicenter, double-blind trial, 43 men with benign prostatic hyperplasia (BPH) scheduled to undergo transurethral resection of the prostate (TURP) were randomized to receive dutasteride, 0.5 mg/day or placebo for 3 months before surgery. Intraprostatic DHT, testosterone and dutasteride levels were determined at the time of TURP. Changes in serum DHT and testosterone from baseline, and both serum and intraprostatic dutasteride levels at the time of TURP were also assessed. Dutasteride reduced intraprostatic DHT by 94% relative to placebo (P<0.001); the adjusted mean intraprostatic DHT concentration was 3.23 and 0.209 ng/g in the placebo and dutasteride groups, respectively. In the dutasteride group, serum DHT was reduced from baseline by 93% at month 3, a significantly greater reduction (P<0.001) than the 15% decrease observed in the placebo group. There was a reciprocal increase in intraprostatic testosterone but the level of intraprostatic testosterone in the dutasteride group tended to be lower than the intraprostatic DHT level in the placebo group (P=0.06). Significant intraprostatic DHT suppression was achieved in all subjects who received dutasteride, regardless of the level of intraprostatic dutasteride. There was a strong positive correlation between serum and intraprostatic dutasteride concentrations (R(2)=0.73). After 3 months of treatment, dutasteride 0.5 mg/day provided near-complete suppression of both intraprostatic and serum DHT in men with BPH.

Aged↗

The effects of the dual 5alpha-reductase inhibitor dutasteride on localized prostate cancer--results from a 4-month pre-radical prostatectomy study.

BACKGROUND: As dihydrotestosterone (DHT) is the most potent androgen in the prostate, inhibition of the 5alpha-reductase isoenzymes, which convert testosterone to DHT, could be an appropriate target for the treatment of prostate cancer. METHODS: Eighty-one men with clinically localized prostate cancer received daily dutasteride 3.5 or 0.5 mg, or no therapy for 4 months before radical prostatectomy. Histopathological assessments were conducted on prostatectomy specimens. RESULTS: Treatment with dutasteride was associated with reductions in serum and intraprostatic DHT of >or=90%, and a decrease in total prostate and tumor volumes. No effect of dutasteride was noted on Gleason grade. Histopathological effects on benign tissue were similar but less prominent than those seen with androgen ablation, whereas there was no significant difference in cancer histology among the groups. CONCLUSIONS: Dutasteride treatment results in similar but less marked changes compared with androgen ablation.

5-alpha Reductase Inhibitors↗

Abnormal hypothalamic-pituitary-adrenal function in anorexia nervosa. Pathophysiologic mechanisms in underweight and weight-corrected patients.

To study the pathophysiology of hypercortisolism in patients with anorexia nervosa, we examined plasma ACTH and cortisol responses to ovine corticotropin-releasing hormone before and after correction of weight loss. We also studied patients with bulimia whose weight was normal, since this disorder has been suspected to be a variant of anorexia nervosa. Before their weight loss was corrected, the anorexic patients had marked hypercortisolism but normal basal plasma ACTH. The hypercortisolism was associated with a marked reduction in the plasma ACTH response to corticotropin-releasing hormone. When these patients were studied three to four weeks after their body weight had been restored to normal, the hypercortisolism had resolved but the abnormal response to corticotropin-releasing hormone remained unchanged. On the other hand, at least six months after correction of weight loss their responses were normal. The bulimic patients whose weight was normal also had a normal response to corticotropin-releasing hormone. We conclude that in underweight anorexics, the pituitary responds appropriately to corticotropin-releasing hormone, being restrained in its response by the elevated levels of cortisol. This suggests that hypercortisolism in anorexics reflects a defect at or above the hypothalamus. The return to eucortisolism soon after correction of the weight loss indicates resolution of this central defect despite persistence of abnormalities in adrenal function.

Adrenocorticotropic Hormone↗

Renal sugar transport in the winter flounder. III. Two glucose transport systems.

Teased renal tubules of the winter flounder (Pseudopleuronectes americanus) were employed to investigate the structural requirements for two pathways of D-glucose transport which take place preponderantly across the basal (antiluminal) face of renal cells. 1) An inhibition analysis of the equilibrating, Na-independent and phlorizin-sensitive transport of the nonmetabolizable methyl-alpha-D-glucoside (0.1 and 0.5 mM), with 20 glucose analogs (5 mM), was employed to establish the structural requirements for the substrate-carrier interaction: a (pyranose) ring, oxygen, or F at C1, C2-OH, C3-OH, and C4-OH (all axial, 1C model). Some interaction may also occur at C6-OH. D-Glucose shares this transport system. Hydrogen bonding between the oxygens and the carrier is suggested. 2) The phloretin- and phlorizin-sensitive, ouabain-insensitive transport of D-glucose, 2-deoxy-D-glucose, and D-mannose is associated with considerable phosphorylation. The three sugars mutually compete for a shared transport site. The specificity pattern characterizing the transport system defines the following structural requirements: a (pyranose) ring, a free C1-OH, C3-OH, and C4-OH (both axial) and possibly C6-OH. Hydrogen bonding between the carrier and the oxygens at C3, C4, and C6, and covalent bonding at C1 is suggested.

Animals↗