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A rapid and accurate in vitro drug metabolism strategy has been proposed based on the design of a biomimetic nanoreactor composed of amino-functionalized periodic mesoporous organosilica (NH2-PMO) and microsomes. The amphiphilic nature and positive charge of NH2-PMO make it highly suited for the immobilization of hydrophobic and negatively charged microsomes to form nanoreactors, which can in turn extract substrates from solutions. Such nanoreactors provide a suitable environment to confine multiple enzymes and substrates with high local concentrations, as well as to maintain their catalytic activities for rapid and highly effective drug metabolic reactions. Coupled with high-performance liquid chromatography-mass spectrometry analysis, the metabolites of nifedipine and testosterone were quantitatively characterized, and the reaction kinetics was evaluated. Both the metabolism conversion and reaction rate were significantly improved with the NH2-PMO nanoreactors compared to bulk reactions. This strategy is simple and cost-effective for promising advances in biomimetic metabolism study. testosterone.

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Testosterone (TES), other androgens and female sex steroids induce non-genomic rapid relaxing effects in airway smooth muscle (ASM). In guinea pig ASM, basal tension was relaxed by dehydroepiandrosterone (DHEA) and TES; 17β-estradiol (E2) had a small effect. Blockers of L-type voltage dependent Ca(2+) channel (L-VDCC, D-600) and store operated Ca(2+) channel (SOC, 2-APB) also relaxed the basal tone. In tracheal myocytes, DHEA and TES diminished intracellular basal Ca(2+) concentrations (b[Ca(2+)]i) as D-600+2-APB but to a higher extend. TES after D-600+2APB or Pyr3, a blocker of canonical transient receptor potential 3 (TRPC3), further decreased b[Ca(2+)]i rendering this response equal to TES alone. With indomethacin, the b[Ca(2+)]i decrease induced by the blockade of L-VDCC and TRPC3 was not changed by the addition of TES. PGE2 or forskolin addition after D600+2-APB, decreased b[Ca(2+)]i resembling TES response. An adenylate cyclase inhibitor followed by D-600+2-APB lowered b[Ca(2+)]i, TES showed no further effect. Carbachol-induced [Ca(2+)]i increment was reduced by TES or DHEA. 17β-estradiol diminished KCl-induced contraction and, in tracheal myocytes, the voltage-dependent inward Ca(2+) current. testosterone.

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The aim of this study was to investigate the efficiency of low-level laser therapy (LLLT) to recovery testicular degeneration in rams. In the first study, rams were induced to testicular degeneration by scrotal insulation, and then, they were treated using LLLT at 28 J/cm(2) (INS28) or 56 J/cm(2) (INS56) energy densities. Sperm kinetics, morphology, and membranes integrity as well as proportion of lumen area in seminiferous tubule were assessed. In the second study, rams were submitted or not to scrotal insulation and treated or not by the best protocol of LLLT defined by experiment 1 (INS28). In this study were evaluated sperm kinetics, morphology, membranes integrity, ROS production, and DNA integrity. Testosterone serum concentration and proportion of lumen area in seminiferous tubule were also analyzed. Insulation was effective in promoting sperm injuries in both experiments. Biostimulatory effect was observed in experiment 1: INS28 presented smaller proportion of lumen area (P = 0.0001) and less degeneration degree (P = 0.0002). However, in experiment 2, there was no difference between the groups (P = 0.17). In addition, LLLT did not improve sperm quality, and there was a decreasing for total and progressive motility (P = 0.02) and integrity of sperm membranes (P = 0.01) in LLLT-treated groups. Moreover, testosterone concentration was not improved by LLLT (P = 0.37). Stimulation of aerobic phosphorylation by LLLT may have led to a deregulated increase in ROS leading to sperm damages. Thus, LLLT at energy of 28 J/cm(2) (808 nm of wavelength and 30 mW of power output) can induce sperm damages and increase the quantity of cells in seminiferous tubule in rams. testosterone.

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AF of 78 male and 94 female healthy newborns was analyzed by LC-MS/MS at 16 weeks of gestation. The levels of androstenedione, corticosterone, cortisol, cortisone, deoxycorticosterone, 11-deoxycortisol, dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), 17-hydroxyprogesterone, progesterone (17-OHP) and testosterone were measured. Steroid levels were compared to RIA and GC-MS levels of midgestation from the literature. Cross-validated logistic regression was used to obtain statistical predictions of gender at birth from testosterone and the above steroids. testosterone.

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This study was designed to investigate the impact of representative antihypertensive drugs of 5 classes on the sexual function in male spontaneously hypertensive rats (SHR) at doses that achieved similar blood pressure (BP) reduction. The experiment was performed in 6 groups of male SHR. The dose are 20 μg/kg/day for clonidine, 3 mg/kg/day for enalapril, 20 mg/kg/day for atenolol, 2 mg/kg/day for amlodipine, and 10 mg/kg/day for dihydrochlorothiazide. SHR were treated for 3 months, and then the penile erection and sexual behavior were detected. After BP recording, SHR were killed to evaluate the organ-damage, weight of accessory sex organs and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone in serum. Five drugs had the similar efficacy on BP reduction. All drugs except of enalapril, significantly prolonged the mount latency, and decreased the mount frequency (P<0.05). Clonidine also reduced the conception rate (45% vs. 80% in control group, P<0.05). Amlodipine and dihydrochlorothiazide significantly increased the testosterone level (0.79±0.30, 0.80±0.34 vs. 0.49±0.20 in control group, unit: ng/dl, P<0.05). Enalapril, atenolol and amlodipine also significantly decreased the BP variability (systolic, 8.2±2.5, 7.6±1.8, 8.9±2.0 vs. 12.2±3.8 in control group, unit: mm Hg). All these drugs significantly decreased the organ-damage (P<0.05). In conclusion, long-term treatment with 5 common antihypertensive drugs possessed obvious organ protection in SHR. Clonidine, atenolol, amlodipine and dihydrochlorothiazide, but not enalapril, impair sexual function. testosterone.

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Elevated serum E2/fT ratio is a precipitating factor for recurrent varicose veins in male patients. testosterone.

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