No abstract

Our study supports the need for caution when using intramuscularly administered, abruptly increasing, high-dose neuroleptics, particularly in mentally retarded or agitated patients, regardless of environmental temperature.

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Systemic or intratesticular release of TNF alpha and IL1 beta have been implicated in the reduced testosterone biosynthesis and impaired production of competent spermatozoa found in human patients suffering from sepsis or chronic inflammation. Although in vitro and in vivo studies have demonstrated that TNF alpha and IL1 beta intercept the hypothalamic-pituitary testis axis at different levels, the site(s) of action and relative contribution of each cytokine to the overall testicular failure associated to systemic inflammatory processes remains poorly defined. In this study we show that intratesticular delivery of TNF alpha induced a rapid (4 h) and sustained (up to 24 h) reduction in steroidogenic acute regulatory (StAR) protein expression and testosterone biosynthesis in nonstimulated or human chorionic gonadotropin-treated intact or hypophysectomized rats. Bilateral treatment with cell-permeant short-chain ceramides (C2-cer or C6-cer) reproduced the early (4 h) inhibitory action of TNFalpha on testosterone biosynthesis and testicular StAR expression. The inhibitory action of C2-cer or C6-cer was not observed in animals treated with inactive analogs (dihydroceramide), phosphorylcholine, sphingosine, or sphingosine-1P. In sharp contrast to the previously described ability of IL1 beta to prevent human chorionic gonadotropin-stimulated Leydig cell steroidogenesis in vitro, serum testosterone and testicular StAR protein expression remained unchanged in animals bilaterally injected with this cytokine. These data support the concept that TNF alpha triggers different effector mechanisms to directly inhibit Leydig cell StAR expression and steroidogenesis, which ultimately contribute to the global reproductive failure associated with chronic inflammation and sepsis.

The synthesis of chiral periodic mesoporous organosilicas (ChiMO) of MCM-41 type using a bissilylated tartramide derived from L-(+)-dimethyl tartrate (Sharpless and Kagan ligand) has been studied. The ChiMO materials were characterized by powder XRD, TEM, and nitrogen adsorption-desorption measurements, verifying their successful preparation. The evidence of the covalent bonding between the organic chiral precursor and the inorganic silica framework structure was confirmed by 13 C and 29 Si NMR solid state measurements. The synthesized chiral PMO was found to catalyze the asymmetric oxidation of thioanisole with good sulfoxide yield and moderate enantioselectivity. Reutilization of the "solid" chiral ligand led to similar optical yields to that obtained with the fresh ChiMO, revealing the true heterogeneous nature of the immobilized tartrate derivative.

One of the major challenges in medicine is the delivery and control of drug release over time. Current approaches take advantage of mesostructured silica nanoparticles (MSNs) as carriers but suffer several problems including complex synthesis that requires sequential steps for (1) removal of surfactants and (2) functionalization of MSNs to allow upload of the drugs. Here, a novel solution is presented to these restrictions: the design of drug-structure-directing agents (DSDAs) with dual inherent pharmacological activity and ability to direct the formation of solid and hollow-shell MSNs. Pharmacologically active DSDAs obtained by amidation of drugs with fatty acids are allowed to form micelles, around which the inorganic species self-assembled to form MSNs. Since the DSDAs direct the formation of MSNs, the steps to remove surfactants, functionalization, and drug upload are not required. The MSNs thus prepared provide sustained release of the drug over more than six months, as well as rapid cellular internalization by both physiological and tumoral human colon cells without affecting cell viability. Moreover, the gradual intracellular release of both, the active drug and lipid moiety with potential nutraceutical properties is proved. MSN particles designed with this approach are promising vehicles for controlled and sustained intra-or extracellular drug-delivery.

No abstract

Persistent advanced HRP was significantly improved with O3T. The addition of O3T can be useful as a complementary treatment in the long-term management of HRP and, as such, merits further evaluation.