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Compared with hemorrhoidectomy, dearterialization with mucopexy resulted in similar postoperative pain and morbidity, and a similar long-term cure rate.

Anabolic-androgenic steroid (AAS) abuse is associated with multiple neurobehavioral disturbances. The sites of action and the neurobiological sequels of AAS abuse are unclear at present. We investigated whether two different AASs, nandrolone and methandrostenolone, could affect neuronal survival in culture. The endogenous androgenic steroid testosterone was used for comparison. Both testosterone and nandrolone were neurotoxic at micromolar concentrations, and their effects were prevented by blockade of androgen receptors (ARs) with flutamide. Neuronal toxicity developed only over a 48-hr exposure to the steroids. The cell-impermeable analogues testosterone-BSA and nandrolone-BSA, which preferentially target membrane-associated ARs, were also neurotoxic in a time-dependent and flutamide-sensitive manner. Testosterone-BSA and nandrolone-BSA were more potent than their parent compounds, suggesting that membrane-associated ARs were the relevant sites for the neurotoxic actions of the steroids. Unlike testosterone and nandrolone, toxicity by methandrostenolone and methandrostenolone-BSA was insensitive to flutamide, but it was prevented by the glucocorticoid receptor (GR) antagonist RU-486. Methandrostenolone-BSA was more potent than the parent compound, suggesting that its toxicity relied on the preferential activation of putative membrane-associated GRs. Consistently with the evidence that membrane-associated GRs can mediate rapid effects, a brief challenge with methandrostenolone-BSA was able to promote neuronal toxicity. Activation of putative membrane steroid receptors by nontoxic (nanomolar) concentrations of either nandrolone-BSA or methandrostenolone-BSA became sufficient to increase neuronal susceptibility to the apoptotic stimulus provided by β-amyloid (the main culprit of AD). We speculate that AAS abuse might facilitate the onset or progression of neurodegenerative diseases not usually linked to drug abuse.

Enantiomers of 4'-aza-2',3'-dideoxynucleosides have been prepared by two different synthetic approaches, on the basis of 1,3-dipolar cycloaddition of a chiral nitrone. Cytotoxicity and apoptotic activity have been investigated. (5'S)-5-Fluoro-1-isoxazolidin-5-yl-1H-pyrimidine-2,4-dione [(-)-AdFU], while showing low level of cytotoxicity, is a good inductor of apoptosis on lymphoid and monocytoid cells, acting as a strong potentiator of Fas-induced cell death.

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Isoxazolidinyl polycyclic aromatic hydrocarbons (isoxazolidinyl-PAHs) have been synthesized in good yields by 1,3-dipolar cycloaddition methodology promoted by microwave irradiation. The structures of the obtained cycloadducts have been determined by NOE experiments and supported by computational studies at the AM1 level. The cytotoxicity and antiviral activity of the synthesized compounds have been investigated. In particular, compounds 7c and 7e show high levels of cytotoxicity on MOLT-3 leukemia cells; 7e exerts a remarkable enhancing activity on apoptosis caused by anti-fas antibody addition. Furthermore, compounds 7b and 8b exhibit specific antiviral effects against the Punta Toro virus.

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