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The effects of three kinds of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activity of human hepatic cytochrome P450 (P450 or CYP) were investigated. Metabolic activities of P450s expressed in recombinant Escherichia coli at substrate concentrations around the Michaelis constant were compared in the presence or absence of the antibiotics. Amoxicillin, ampicillin, and piperacillin at 0.5 or 1 mM concentrations neither inhibited nor stimulated CYP2C9-mediated tolbutamide methylhydroxylation, CYP2D6-mediated dopamine formation from p-tyramine, or CYP3A4- or CYP3A5-mediated testosterone 6β-hydroxylation. However, amoxicillin and piperacillin inhibited CYP2C8-mediated aminopyrine N-demethylation at 50% inhibitory concentration of 0.83 and 1.14 mM, respectively. These results suggest that piperacillin might inhibit CYP2C8 clinically, although the interactions between these three penicillin-based antibiotics and other drugs that are metabolized by P450s investigated would not be clinically significant. testosterone.

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While the influence of testosterone levels on vulnerability to affective disorders is not straightforward, research suggests this hormone may confer some degree of resiliency in men. We recently demonstrated a role for the dentate gyrus in mediating testosterone’s protective effects on depressive-like behavior in gonadectomized male rats. Here, testosterone may exert its effects through androgen receptor-mediated mechanisms or via local aromatization to estradiol. testosterone.

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The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. testosterone.

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Body mass index increased markedly with age (coefficient 0·119, SE 0·016 standard deviation scores per year), at twice the rate of the U.K. population, due to increased adiposity. Three per cent of girls had premature thelarche variant and 6% of boys had persistent undescended testes. Both fat and muscle mass were reduced in areas underlying large naevi, resulting in limb asymmetry and abnormal truncal fat distribution. Anterior pituitary hormone profiling revealed subtle and variable abnormalities. Oral glucose tolerance tests revealed moderate-severe insulin insensitivity in five of 10, and impaired glucose tolerance in one. testosterone.

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Chemical castration and the associated decrease in serum T levels reduced the frequency and intensity of sexual thoughts in 76% and 71% of group A patients and in 78% and 72% of group B patients, respectively. Reductions in masturbation frequency were observed in 74% of group A and 83% of group B patients. The median Wilson’s Sex Fantasy Questionnaire (SFQ) scores were also significantly reduced in both groups. In group A, an upsurge of serum T to the flare level was observed during the first 2 months of the off-cycle, accompanied by an intense sexual drive and fantasy. In group B, serum T gradually recovered to the baseline level and continued to upsurge beyond baseline levels during the observational period. SFQ scores of group A returned to pretreatment levels following the observational period; however, SFQ scores of group B remained suppressed. Lack of objective assessments for psychobehavioral outcomes was a limitation. testosterone.

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