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The function of the protein-coupled receptor 35 (GPR35) in the central nervous system (CNS) remains largely unknown. Due to its expression in the ventral striatum, a key area in the brain reward system, the function of GPR35 in reinforcing actions is questioning. To analyze if activation of GPR35 in the ventral striatum is related to reinforcing actions, male Wistar rats (250-300 g) received stereotaxic surgery to place guide cannulae in the ventral striatum. Lodoxamide (a full rat-GPR35 agonist) or vehicle (DMSO 10%) were injected (intra-ventral-striatum) in the absence and during the pretreatment with ML-194 (a selective GPR35 antagonist). Lodoxamide (100 pmol) induced a significant increment in preference for the drug-conditioning chamber (p < 0.05), but not vehicle or ML-194 per se (p > 0.05). On the other hand, the pretreatment with ML-194 did not prevent lodoxamide's reinforcing effects. Thus, the reinforcing actions of lodoxamide (intra-ventral-striatum) involve mechanisms likely independent of GPR35 which remains to be identified; and a role for GPR35 in the brain reward systems (at least in ventral striatum) seems improbable. [ABSTRACT FROM AUTHOR]

Antitumor conventional treatments including chemo/radiotherapy result in several side effects and non-specificity. Therapies including the use of oncolytic viruses, particularly the Newcastle disease virus (NDV), have emerged as an attractive alternative due to their capacity to kill cancer cells directly or through stimulation of the immune system. In the present study, a commercial vaccine composed of a recombinant attenuated NDV strain P05 (rNDV-P05) was assessed for antitumor and immunostimulatory activity. Firstly, hemagglutination activity was evaluated at different pH and temperature conditions. Then, cancer cell lines and peripheral blood mononuclear cells (PBMC) were co-cultured with or without rNDV-P05 and cytoplasmic nucleosomes were measured by enzyme-linked immunosorbent assay (ELISA) as an apoptosis indicator. Antitumor cytokines produced by PBMC in response to the virus were analyzed by ELISA and reverse transcription quantitative polymerase chain reaction. Characterization of rNDV-P05 indicates that the virus is slightly sensible to acid and basic pH, and stable at temperatures no greater than 42°C. The majority of cell lines developed apoptosis in co-culture with rNDV-P05 in a dose-time dependent manner. The highest level of HeLa, HCC1954 and HepG2 cell apoptosis was at 48 h/50 hemagglutination units (HU), and HL-60 was 24 h/50 HU. A549 cell line and PBMC did not show sensitivity to apoptosis by the virus. PBMC from healthy donors stimulated with the rNDV-P05 increased significantly the levels of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α and soluble TNF-related apoptosis-inducing ligand in culture supernatants, as well as their mRNA expression. These results demonstrate that the pro-apoptotic effect of rNDV-P05 and its magnitude is specific to particular tumor cell lines and is not induced on PBMC; and the virus stimulates the expression of several key antitumor cytokines. This study promotes the use of rNDV-P05 in an alternate application of different viral strains during virotherapy with [ABSTRACT FROM AUTHOR]

Leuprolide acetate (LA), a gonadotropin-releasing hormone (GnRH) agonist, was identified to cause changes in body weight in experimental and clinical trials; however, to date, the effect of LA on the body composition has not been properly assessed. The aim of the present study was to evaluate the long-term effect of LA administration on body composition and the mRNA expression of ghrelin and lipoprotein lipase (LPL) in rats. Ovariectomized (OVX), ovariectomized and LA-treated (OVX+LA), non-ovariectomized (CTRL) and non-ovariectomized but LA-treated (LA) rats were used. LA treatment was performed by intramuscular injection at 5 µg/kg every 72 h over 120 days. Analysis of body composition and mRNA expression of ghrelin and lipoprotein lipase were performed. The results indicated significant changes in body composition after treatment; in the OVX, LA, OVX+LA and CTRL group, the body weight was increased by 216.1, 183.7, 175.4 and 150.1%, respectively, compared with baseline. The fat mass in the LA group was 14% higher than that in the CTRL group, while that in the OVX group was 19% higher than that in the OVX+LA, and the fat-free mass was similar between the LA and CTRL as well as the OVX and OVX+LA groups. Following 120 days of treatment, the mRNA expression of ghrelin and LPL in the LA group was ~20% higher than that in the CTRL group, while that in the OVX+LA was downregulated in comparison with that in the OVX group. The results of the present study confirmed changes in body composition and mRNA expression of ghrelin and LPL caused by long-term administration of LA. LA may contribute to regulate food consumption and exert control over adipogenesis. [ABSTRACT FROM AUTHOR]

Gonadotropin-releasing hormone (GnRH) and its synthetic analog leuprolide acetate, a GnRH agonist, have neurotrophic properties. This study was designed to determine whether administration of leuprolide acetate can improve locomotor behavior, gait, micturition reflex, spinal cord morphology and the amount of microglia in the lesion epicenter after spinal cord injury in rats. Rats with spinal cord compression injury were administered leuprolide acetate or saline solution for 5 weeks. At the 5(th) week, leuprolide acetate-treated rats showed locomotor activity recovery by 38%, had improvement in kinematic gait and exhibited voiding reflex recovery by 60%, as compared with the 1(st) week. By contrast, saline solution-treated rats showed locomotor activity recovery only by 7%, but voiding reflex did not recover. More importantly, leuprolide acetate treatment reduced microglial immunological reaction and induced a trend towards greater area of white and gray matter in the spinal cord. Therefore, leuprolide acetate has great potential to repair spinal cord injury.

Syntaxin-1 and 25-kDa Synaptosome-associated Protein (SNAP-25) are present in the plasma membrane of several different secretory cell types and are involved in the exocytosis process. In this work, the free-living amoeba Difflugia corona was studied in relation to ultrastructure, structural membrane proteins, and proteins such as Syntaxin-1 and SNAP-25. Our results obtained by scanning electron microscopy in the amoeba without its theca, showed many membrane projections and several pore-like structures. Using immunocytochemistry, we found structural proteins Syntaxin-1 and SNAP-25.

Objective: The protein SNAP-25 is located in the plasma membrane and is known to participate in hormone exocytosis process. In the present work we studied the role of SNAP-25 on LH secretion in permeabilized adenohypophyseal cultured cells. The question of whether GnRH regulates SNAP-25 expression in adenohypophyseal cultured cells and in the adenohypophyses in vivo was also investigated., Methods: In digitonin-permeabilized cells incubated with anti-SNAP-25, stimulated LH secretion with Ca2+ was analysed. The presence and expression of SNAP-25 in adenohypophyseal cultured cells incubated with GnRH and in adenohypophyses of orchidectomized rats with GnRH administration was studied by immunochemistry and immunoblotting., Results: Immunochemical study revealed that SNAP-25 was present in cultured adenohypophyseal cells and in adenohypophysis of orchidectomized rats both with GnRH treatment. We found that LH secretion can be blocked by antibodies raised against SNAP-25 in permeabilized cells. Likewise, GnRH administration induced a significant decrease of SNAP-25 expression in cultured adenohypophyseal cells and in adenohypophysis of orchidectomized rats., Conclusion: Our study showed that SNAP-25 is present in adenohypophyses in vitro as well as in vivo and that is involved in LH release and that GnRH can modify its expression.