Effects of castration and of testosterone replacement on alpha(1)-adrenoceptor subtypes in the rat vas deferens

The contractions of the rat vas deferens in response to noradrenaline are mediated through alpha(1A)-adrenoceptors. We observed participation of alpha(1B)-adrenoceptors in these contractions after castration. We now investigated the time course of this plasticity and the effects of testosterone by determining the actions of competitive antagonists on noradrenaline-induced contractions after 7, 14, 21 and 30 days of castration. BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) antagonised noradrenaline-induced contractions in control and castrated rats with low pA(2) values (approximately = 6.8). In control vas deferens, WB 4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride) had a slope in the Schild plot no different from 1.0, while slopes lower than 1.0 (approximately 0.6) were observed for vas deferens from castrated rats. Chloroethylclonidine was ineffective in the control vas while it inhibited noradrenaline-induced contractions in vasa from castrated rats and converted the complex antagonism by WB 4101 into simple competitive antagonism. Treatment of castrated rats with testosterone prevented the effects of castration. The results suggest that alpha(1B)-adrenoceptors are detectable in vas deferens from at least the 7th through the 30th day after castration and that testosterone prevents this plasticity.

Use of autogenous bone and beta-tricalcium phosphate in maxillary sinus lifting: a prospective, randomized, volumetric computed tomography study

The correction of bone defects can be performed using autogenous or alloplastic materials, such as beta-tricalcium phosphate (β-TCP). This study compared the changes in bone volume (CBV) after maxillary sinus lifting using autogenous bone (n=12), autogenous bone associated with β-TCP 1:1 (ChronOS; DePuy Synthes, Paoli, CA, USA) (n=9), and β-TCP alone (n=11) as grafting material, by means of cone beam computed tomography (CBCT). CBV was evaluated by comparing CBCT scans obtained in the immediate postoperative period (5-7 days) and at 6 months postoperative in each group using OsiriX software (OsiriX Foundation, Geneva, Switzerland). The results showed an average resorption of 45.7±18.6% for the autogenous bone group, 43.8±18.4% for the autogenous bone+β-TCP group, and 38.3±16.6% for the β-TCP group. All bone substitute materials tested in this study presented satisfactory results for maxillary sinus lifting procedures regarding the maintenance of graft volume during the healing phase before the insertion of implants, as assessed by means of CBCT.

Mirabegron relaxes urethral smooth muscle by a dual mechanism involving β3-adrenoceptor activation and α1-adrenoceptor blockade

Mirabegron is the first β3-adrenoceptor (AR) agonist approved for treatment of overactive bladder syndrome (OAB). This study aimed to investigate the effects of β3-adrenoceptor (AR) agonist mirabegron in mouse urethra. The possibility that mirabegron exerts α1-AR antagonism was also tested in rat smooth muscle preparations presenting α1A- (vas deferens and prostate), α1D- (aorta) and α1B-AR (spleen). Functional assays were carried out in mouse and rat isolated tissues. Competition assays for the specific binding of [(3) H]Prazosin to membrane preparations of HEK 293 cells expressing each of the human α1-ARs, as well as β-AR mRNA expression and cyclic AMP measurements in mouse urethra were performed. Mirabegron produced concentration-dependent urethral relaxations that were right shifted by the selective β3-AR antagonist L 748,337, but unaffected by β1- and β2-AR antagonists (atenolol and ICI 118,551, respectively). Mirabegron-induced relaxations were enhanced by the phosphodiesterase-4 inhibitor rolipram, and this agonist stimulated cAMP synthesis. Mirabegron also produced rightward shifts in urethral contractions induced by the α1-AR agonist phenylephrine. Schild regression analysis revealed that mirabegron behaves as a competitive antagonist of α1-AR in urethra, vas deferens and prostate (α1A-AR, pA2  ≅ 5.6) and aorta (α1D-AR, pA2  ≅ 5.4), but not in spleen (α1B-AR). The affinities estimated for mirabegron in functional assays were consistent with those estimated in radioligand binding with human recombinant α1A- and α1D-ARs (pKi ≅ 6.0). The effects of mirabegron in urethral smooth muscle are the result of β3-AR agonism together with α1A / α1D-AR antagonism.

Immunohistochemical expression of B and T-lymphocytes and TGF-beta in experimentally transplanted canine venereal tumor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A complex structure in the (beta+gamma(0)) region of the Cu-Al alloys

The identification, characterization and stability range of the phases present in a series of Cu-Al alloys, with Al content from 11.0 to 15.0 wt.%, were studied by Differential Thermal Analysis (DTA), Optical Microscopy (OM), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Selected Area Electron Diffraction (SAED), Auger Electron Spectroscopy (AES), Energy Dispersive X-Ray Spectroscopy (EDX) and X-Ray Diffraction (XRD). In some alloys and in a temperature range from 790 degrees C to 850 degrees C the presence of black spots exhibiting regular shapes and an homogeneous distribution was noticed through metallographic microscopy. Data from TEM and AES indicate that these spots are made of two monocrystalline phases having different Al contents and a crystallographic orientation relationship. (C) 1998 Elsevier B.V. S.A. All rights reserved.

Modulation of thyroid hormone receptors, TR alpha and TR beta, by using different doses of triiodothyronine (T3) at different times

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Farmacocinética pré-clínica e avaliação toxicológica do novo composto α2-adrenérgico 3-(2-cloro-6-fluorobenzil)-imidazolidina-2,4-diona - PT-31 GIRSUPAN

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Índice de resistência múltipla aos antimicrobianos, concentração inibitória e beta-lactamases de espectro estendido em linhagens de Proteus mirabilis e Proteus vulgaris isoladas de diferentes afecções em animais domésticos

Pós-graduação em Medicina Veterinária - FMVZ

Organic light emitting diodes with europium (III) emissive layers based on beta-diketonate complexes: The influence of the central ligand

This work shows a comparative study of organic light emitting diodes based on four different europium complexes with the general formula, Eu(CLs)(3)bipyridine, where the central ligands are DBM [tris(dibenzoylmethane)], TTA [tris(1-(2-thieneyl)-4,4,4-trifluoro-1,3-butanedione)], NTA [tris(1-(2-naphthoyl)-3,3,3-trifluoroacetone)] and BTA [tris(1-(2-benzoyl)-3,3,3-trifluoroacetone)]. All devices have a driving voltage of 14-16 V, a very low electrical current at normal operation (less than 1 mA) and a good Wall Plug Efficiency (up to near 10(-3)%). The most suitable central ligand was found to be DBM, with an optical power up to 200 nW (at 612 nm). The BTA exhibits the lowest stability under high applied voltages. The other central ligands have similar results among them. The electroluminescence spectra clearly show the europium ion transitions (with a strong (5)D(0) -> (7)F(2) line) with a CIE color coordinate around (0.56, 0.34). (C) 2008 Elsevier B.V. All rights reserved.

Transforming growth factor beta and apoptosis in leprosy skin lesions: possible relationship with the control of the tissue immune response in the Mycobacterium leprae infection

The course of leprosy depends of the host immune response which ranges from the lepromatous pole (LL) to the tuberculoid pole (TT). A comparative study was conducted in 60 patients with the LL and TT The results showed a mean expression of TGF-beta of 339 +/- 99.4 cells/field for TT and of 519.2 +/- 68.2 cells/field for LL. Frequency of apoptosis was 6.3 +/- 1.8 in TT and 14.0 +/- 6.1 in LL. A correlation (p = 0.0251) between TGF-beta and caspase-3 in the LL was found. This finding indicates a role of TGF-beta and apoptosis in the immune response in leprosy. (C) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

HIV-1 induces NALP3-inflammasome expression and interleukin-1 beta secretion in dendritic cells from healthy individuals but not from HIV-positive patients

Objective: NALP3-inflammasome is an innate mechanism, alternative to type-1 interferon, which is able to recognize nucleic acids and viruses in the cytoplasm and to induce pro-inflammatory response. Here, we hypothesized the involvement of inflammasome in the early defense against HIV-1 and in the full maturation of dendritic cells: for this, we evaluated the response of dendritic cells pulsed with HIV-1 in terms of inflammasome activation in healthy donors. Moreover, inflammasome response to HIV was evaluated in HIV-infected individuals. Design and methods: Monocyte-derived dendritic cells isolated from 20 healthy individuals (HC-DC) and 20 HIV-1-infected patients (HIV-DC) were pulsed with alditrithiol-2-inactivated HIV-1. We then analyzed inflammasome genes expression and interleukin-1 beta (IL-1 beta) secretion. Results: In HC-DC, HIV-1 induced higher NLRP3/NALP3 mRNA expression compared with other inflammasome genes such as NALP1/NLRP1 or IPAF/NLRC4 (P < 0.001). This augmented expression was accompanied by CASP1-increased and IL1B-increased mRNA levels and by a significant increment of IL-1b secretion (P < 0.05). Otherwise, HIV-1 failed to activate inflammasome and cytokine production in HIV-DC. HIV-DC showed an increased NLRP3/NALP3 basal expression, suggesting a chronic inflammatory profile of patients' immune cells. Conclusion: HIV-1 was able to induce a NALP3-inflammasome response in healthy individuals, indicating that this inflammasome could play a role in the first steps of HIV-1 infection; the consequent inflammatory process may be important for directing host immune response against the virus and/or disease progression. HIV-DC seemed to be chronically activated, but unresponsive against pathogens. Our findings could be of interest considering the ongoing research about dendritic cell manipulation and therapeutic strategies for AIDS involving dendritic cell-based immune-vaccines. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Probing the properties of Be star discs with spectroastrometry and NLTE radiative transfer modelling: beta CMi

While the presence of discs around classical Be stars is well established, their origin is still uncertain. To understand what processes result in the creation of these discs and how angular momentum is transported within them, their physical properties must be constrained. This requires comparing high spatial and spectral resolution data with detailed radiative transfer modelling. We present a high spectral resolution, R similar to 80 000, sub-milliarcsecond precision, spectroastrometric study of the circumstellar disc around the Be star beta CMi. The data are confronted with 3D, non-local thermodynamic equilibrium radiative transfer calculations to directly constrain the properties of the disc. Furthermore, we compare the data to disc models featuring two velocity laws: Keplerian, the prediction of the viscous disc model, and angular momentum conserving rotation. It is shown that the observations of beta CMi can only be reproduced using Keplerian rotation. The agreement between the model and the observed spectral energy distribution, polarization and spectroastrometric signature of beta CMi confirms that the discs around Be stars are well modelled as viscous decretion discs.

Lack of beta(2)-AR improves exercise capacity and skeletal muscle oxidative phenotype in mice

beta(2)-adrenergic receptor (beta(2)-AR) agonists have been used as ergogenics by athletes involved in training for strength and power in order to increase the muscle mass. Even though anabolic effects of beta(2)-AR activation are highly recognized, less is known about the impact of beta(2)-AR in endurance capacity. We presently used mice lacking beta(2)-AR [beta(2)-knockout (beta(2) KO)] to investigate the role of beta(2)-AR on exercise capacity and skeletal muscle metabolism and phenotype. beta(2) KO mice and their wild-type controls (WT) were studied. Exercise tolerance, skeletal muscle fiber typing, capillary-to-fiber ratio, citrate synthase activity and glycogen content were evaluated. When compared with WT, beta 2KO mice displayed increased exercise capacity (61%) associated with higher percentage of oxidative fibers (21% and 129% of increase in soleus and plantaris muscles, respectively) and capillarity (31% and 20% of increase in soleus and plantaris muscles, respectively). In addition, beta 2KO mice presented increased skeletal muscle citrate synthase activity (10%) and succinate dehydrogenase staining. Likewise, glycogen content (53%) and periodic acid-Schiff staining (glycogen staining) were also increased in beta 2KO skeletal muscle. Altogether, these data provide evidence that disruption of beta(2)AR improves oxidative metabolism in skeletal muscle of beta 2KO mice and this is associated with increased exercise capacity.

Metabolic and functional effects of beta-hydroxy-beta-methylbutyrate (HMB) supplementation in skeletal muscle

Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite derived from leucine. The anti-catabolic effect of HMB is well documented but its effect upon skeletal muscle strength and fatigue is still uncertain. In the present study, male Wistar rats were supplemented with HMB (320 mg/kg per day) for 4 weeks. Placebo group received saline solution only. Muscle strength (twitch and tetanic force) and resistance to acute muscle fatigue of the gastrocnemius muscle were evaluated by direct electrical stimulation of the sciatic nerve. The content of ATP and glycogen in red and white portions of gastrocnemius muscle were also evaluated. The effect of HMB on citrate synthase (CS) activity was also investigated. Muscle tetanic force was increased by HMB supplementation. No change was observed in time to peak of contraction and relaxation time. Resistance to acute muscle fatigue during intense contractile activity was also improved after HMB supplementation. Glycogen content was increased in both white (by fivefold) and red (by fourfold) portions of gastrocnemius muscle. HMB supplementation also increased the ATP content in red (by twofold) and white (1.2-fold) portions of gastrocnemius muscle. CS activity was increased by twofold in red portion of gastrocnemius muscle. These results support the proposition that HMB supplementation have marked change in oxidative metabolism improving muscle strength generation and performance during intense contractions.

Characterization of a new beta titanium alloy, Ti-12Mo-3Nb, for biomedical applications

In recent years, different beta titanium alloys have been developed for biomedical applications with a combination of mechanical properties including a low Young's modulus, high strength, fatigue resistance and good ductility with excellent corrosion resistance. From this perspective, a new metastable beta titanium Ti-12Mo-3Nb alloy was developed with the replacement of both vanadium and aluminum from the traditional Ti-6Al-4V alloy. This paper presents the microstructure, mechanical properties and corrosion resistance of the Ti-12Mo-3Nb alloy heat-treated at 950 degrees C for 1 h. The material was characterized by X-ray diffraction and by scanning electron microscopy. Tensile tests were carried out at room temperature. Corrosion tests were performed using Ringer's solution at 25 degrees C. The results showed that this alloy could potentially be used for biomedical purposes due to its good mechanical properties and spontaneous passivation. (c) 2011 Elsevier B.V. All rights reserved.