Chronic exercise reduces hypothalamic transforming growth factor-ß1 in middle-aged obese mice.

Obesity and aging are associated with hypothalamic inflammation, hyperphagia and abnormalities in the thermogenesis control. It has been demonstrated that the association between aging and obesity induces hypothalamic inflammation and metabolic disorders, at least in part, through the atypical hypothalamic transforming growth factor-ß (TGF-ß1). Physical exercise has been used to modulate several metabolic parameters. Thus, the aim of this study was to evaluate the impact of chronic exercise on TGF-ß1 expression in the hypothalamus of Middle-Aged mice submitted to a one year of high-fat diet (HFD) treatment. We observed that long-term of HFD-feeding induced hypothalamic TGF-ß1 accumulation, potentiated the hypothalamic inflammation, body weight gain and defective thermogenesis of Middle-Aged mice when compared to Middle-Aged animals fed on chow diet. As expected, chronic exercise induced negative energy balance, reduced food consumption and increasing the energy expenditure, which promotes body weight loss. Interestingly, exercise training reduced the TGF-ß1 expression and IkB-α ser32 phosphorylation in the hypothalamus of Middle-Aged obese mice. Taken together our study demonstrated that chronic exercise suppressed the TGF-ß1/IkB-α axis in the hypothalamus and improved the energy homeostasis in an animal model of obesity-associated to aging.

Hypothalamic S1P/S1PR1 axis controls energy homeostasis in Middle-Aged Rodents: the reversal effects of physical exercise.

Recently, we demonstrated that the hypothalamic S1PR1/STAT3 axis plays a critical role in the control of food consumption and energy expenditure in rodents. Here, we found that reduction of hypothalamic S1PR1 expression occurs in an age-dependent manner, and was associated with defective thermogenic signaling and weight gain. To address the physiological relevance of these findings, we investigated the effects of chronic and acute exercise on the hypothalamic S1PR1/STAT3 axis. Chronic exercise increased S1PR1 expression and STAT3 phosphorylation in the hypothalamus, restoring the anorexigenic and thermogenic signals in middle-aged mice. Acutely, exercise increased sphingosine-1-phosphate (S1P) levels in the cerebrospinal fluid (CSF) of young rats, whereas the administration of CSF from exercised young rats into the hypothalamus of middle-aged rats at rest was sufficient to reduce the food intake. Finally, the intracerebroventricular (ICV) administration of S1PR1 activators, including the bioactive lipid molecule S1P, and pharmacological S1PR1 activator, SEW2871, induced a potent STAT3 phosphorylation and anorexigenic response in middle-aged rats. Overall, these results suggest that hypothalamic S1PR1 is important for the maintenance of energy balance and provide new insights into the mechanism by which exercise controls the anorexigenic and thermogenic signals in the central nervous system during the aging process.

Vitrification of Human Oocytes and its Contribution to In Vitro Fertilization Programs.

OBJETICVE: To study the cumulative pregnancy outcome, particularly in terms of live births, with the consecutive transfer of embryos from fresh and vitrified/warmed oocytes to infertile patients in a routine infertility program. METHODS: Patients were initially submitted to in vitro fertilization embryo transfer with fresh embryos, while surplus oocytes were vitrified with the Vitri-Ingá method. Patients who did not succeed to carry their gestation to term underwent a new cycle with embryos from their own warmed oocytes. Some of the patients participating in the first warming cycle, who still possessed surplus oocytes, underwent a second warming cycle. Clinical and pregnancy outcomes obtained with fresh and warming cycles were compared using the chi-square test at a level of significance of 5%. RESULTS: Of the 211 participating patients, 97 (46%) got pregnant with fresh embryo transfer, and 69 (32.7%) carried their pregnancies to term. Of the patients participating in the first and second warming cycles, 32/100 (32%) and 6/20 (30.0%) resulted in live births, respectively. Thus, of the 211 participating patients, 107 carried their pregnancies to term, representing a cumulative live birth rate of 50.7%. No statistically significant differences between the use fresh and vitrified oocytes were found for any of the variables studied. CONCLUSIONS: Oocyte vitrification offered the possibility of gestation in more than one attempt after just one controlled hyperstimulation. Apart from alleviating the financial burden on patients, vitrification of oocytes may result in a feasible solution for the problems generated by abandoned frozen embryos.

Characterization of stationary phases based on polysiloxanes thermally immobilized onto silica and metalized silica using supercritical fluid chromatography with the solvation parameter model.

Stationary phases (SP) prepared by immobilization of polymers on silica or metalized silica are interesting for use in reversed-phase high-performance liquid chromatography (RP-HPLC) due to better protection of residual silanols or Lewis acid sites, as well as ease of preparation. On the other hand, there are no previous reports of the use of such phases in packed column supercritical fluid chromatography (SFC). Fourteen different SPs based on polysiloxanes (phenyl, C1, C8, C14, C18) thermally immobilized onto different supports (silica, titanized silica, zirconized silica) and one chemically bonded and end-capped C18 stationary phase having a doubly zirconized silica support, were characterized with identical SFC conditions (CO2 with 10% of methanol, 25°C, 15.0 MPa backpressure). Characterization was achieved based on retention factors measured for 85 test compounds and linear solvation energy relationships (LSER), namely the solvation parameter model based on Abraham descriptors. The polysiloxane SP were compared to a commercial C18-bonded silica (Kromasil C18), and to the native silica and metalized silica supports to better unravel the effects of stationary phase chemistry on chromatographic behavior. Together, 19 stationary phases were compared. The results highlight the variety of polarities provided by the column set. The polysiloxane backbone contributes significantly to the SP polarity as evidenced by the comparison to a classical alkylsiloxane-bonded SP. Metalization also appears to modify the polar characteristics of the SP, particularly toward basic compounds. Sample applications illustrate the applicability of these SP in SFC to the analysis of compounds of interest to the pharmaceutical and cosmetic industries.

Improved chemical stabilities for end-capped high performance liquid chromatography stationary phases based on poly(methyloctadecylsiloxane) thermally immobilized onto metalized silicas.

Endcapped stationary phases were prepared after thermal immobilization of poly(methyloctadecylsiloxane) (PMODS) onto zirconized and titanized silica supports. These new stationary phases have lower densities of residual hydroxyl groups, according to infrared spectroscopy and 29Si CP-MAS NMR and as shown by the symmetrical peaks of basic compounds from the Tanaka, Engelhardt and SRM 870 test mixtures. Stability tests for the endcapped stationary phases, measured using severe alkaline conditions (70:30 (v/v) methanol:0.05 mol/L K2CO3/KHCO3, pH 10, 50 °C), revealed that the stabilities of these phases are greater than the stabilities of similar nonendcapped phases. The stationary phases showed good performance for the separation of basic pharmaceuticals.

Preparation and characterization of a poly(methyloctadecylsiloxane) thermally immobilized onto zirconized silica stationary phase for high-performance liquid chromatography.

This study describes the preparation and characterization of a HPLC stationary phase (SP) obtained by deposition of poly(methyloctadecylsiloxane) (PMODS) onto the surface of porous zirconized silica particles, followed by thermal immobilization. The SP were characterized using elemental analysis and infrared and (29)Si NMR spectroscopies, while their chromatographic behaviors were investigated by separation of selected neutral, acidic and basic compounds of different test mixtures (Engelhardt, SRM 870 and Tanaka tests). The preparation of the metalized support and the thermal immobilization of PMODS onto zirconized silica, optimized by experimental design, produced a SP based on PMODS that showed high values of efficiency (up to 85000 plates/m) and appropriate asymmetry factors. The presence of zirconium on the surface significantly decreases silica solubility in severe conditions (alkaline mobile phase at pH 10 and high temperature), increasing column lifetime.