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.

Exploring the virome of diseased horses

Metagenomics was used to characterize viral genomes in clinical specimens of horses with various organ-specific diseases of unknown aetiology. A novel parvovirus as well as a previously described hepacivirus closely related to human hepatitis C virus and equid herpesvirus 2 were identified in the cerebrospinal fluid of horses with neurological signs. Four co-infecting picobirnaviruses, including an unusual genome with fused RNA segments, and a divergent anellovirus were found in the plasma of two febrile horses. A novel cyclovirus genome was characterized from the nasal secretion of another febrile animal. Lastly, a small circular DNA genome with a Rep gene, from a virus we called kirkovirus, was identified in the liver and spleen of a horse with fatal idiopathic hepatopathy. This study expands the number of viruses found in horses, and characterizes their genomes to assist future epidemiological studies of their transmission and potential association with various equine diseases.

Uncaria tomentosa increases growth and immune activity in Oreochromis niloticus challenged with Streptococcus agalactiae

Cat's claw (Uncaria tomentosa) is an Amazon herb using in native cultures in Peru. In mammals, it has been described several effects of this herb. However, this is the first report of its use on the diet of fish. The aim of this study was to determinate the effect of this plant on the growth and immune activity in Oreochromis niloticus. Nile tilapia (81.3 ± 4.5 g) were distributed into 5 groups and supplemented with 0 (non-supplement fish), 75, 150, 300, and 450 mg of U. tomentosa.kg(-1) of diet for a period of 28 days. Fish were inoculated in the swim bladder with inactivated Streptococcus agalactiae and samples were taken at 6, 24, and 48 h post inoculation (HPI). Dose dependent increases were noted in some of the evaluated times of thrombocytes and white blood cells counts (WBC) in blood and exudate, burst respiratory activity, lysozyme activity, melanomacrophage centers count (MMCs), villi length, IgM by immunohistochemistry in splenic tissue, and unexpectedly on growth parameters. However, dietary supplementation of this herb did not affect red blood cells count (RBC), hemoglobin, and there were no observed histological lesions in gills, intestine, spleen, and liver. The current results demonstrate for the first time that U. tomentosa can stimulate fish immunity and improve growth performance in Nile tilapia.

First detection of Leishmania spp. DNA in Brazilian bats captured strictly in urban areas

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

Efeito prolilático da associaçao de MOG com vitamina D na encefalomielite autoimune experimental

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Pasteurelose em juvenis de cobias (Rachycentron canadum) criados em tanques-redes no litoral norte do estado de São Paulo - Brasil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Production of autoantibodies associated with polyclonal activation in Yersinia enterocolitica 0:8-infected mice

Polyclonal lymphocyte stimulation is one of the immunomodulatory mechanisms induced by arthritogenic pathogens. In this study we examined the polyclonal activation potential of a virulent strain of Y. enterocolitica serotype O:8 (WA 2707+) and its plasmidless isogenic pair (WA 2707-). SPF Swiss mice were infected intragastrically and spleen cells were obtained on days 7, 14, 21, 28, 35 and 42 after infection. The number of cells secreting nonspecific immunoglobulins of IgG, IgM and IgA isotypes was determined by the ELISPOT technique. The presence of serum-specific antibodies was investigated by ELISA and the presence of autoantibodies by dot-blot assay. Although the patterns of infection of the two bacterial strains were almost the same, only the animals infected with the virulent strain presented clinical anomalies. Neither arthritic nor inflammatory signs were observed in the joints of the infected animals. The greatest activation observed was that of the nonspecific IgM-secreting cells, and their peak of secretion occurred between the 28th and the 42nd day after infection, for both strains of Y. enterocolitica O:8. Only the animals infected with the virulent strain (WA 2707+) produced IgG-specific antibodies in the serum, from the 28th day after infection. The serum of animals infected with either strain showed reactivity to all the autologous constituents tested, mainly on the 28th and 42nd day after infection. It was concluded that infection of mice with either the virulent strain of Y. enterocolitica O:8 or with its plasmidless isogenic pair resulted in the polyclonal activation of the splenic B lymphocytes including some autoreactive clones.

Suplementação de unha-de-gato (Uncaria tomentosa) em dietas para tilápias-do-Nilo e acará-bandeira (Pterophyllum scalare)

Pós-graduação em Aquicultura - FCAV

Tiouréia no desenvolvimento de girinos de rã-touro e no desempenho de animais pós-metamórficos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Clinical and parasitological evaluation of dogs naturally infected by Leishmania (Leishmania) chagasi submitted to treatment with meglumine antimoniate and allopurinol

Aiming to assess the efficacy of the treatment, to verify the occurrence of possible disease relapses and to search for the presence of parasites after the treatment, seven dogs naturally infected by Leishmania sp., were submitted to a treatment with meglumine antimoniate and allopurinol. For this, lymph node and bone marrow aspiration biopsies were carried out at seven moments. After the end of the six-month observation period all dogs were submitted to euthanasia. Then, spleen and liver “imprints” and in vitro cultures were carried out to search for amastigote forms of the parasite. All animals presented remission of the symptoms and during all the observation period no dog presented relapse of the disease, although amastigote forms of the parasite were observed in two of the animals at the end of the experiment. Thus, it was possible to conclude that the treatment promotes clinical healing but it does not eliminate the parasites completely.

Spleenic Lymphoma and Hemoperitoneum in Jersey Bull: Clinical and Pathological Aspects

Lymphoma is the most prevalent neoplasia in dairy cattle. The etiology can be viral in animals affected by bovine leukemia virus (BLV) or be classified as primary. Lymphoma can affect several organs and according to the system involved, the clinical signs could manifest themselves in different ways. These tumors can be classified through macroscopic characteristics, histology and immunostaining. This classification can be used to predict prognosis and response to therapy. The aim of this case report was to immunostain and classify the tumor, for which anti-CD4, anti-CD8, anti-CD79 and anti-CD3 markers were used in addition to histopathological findings, in order to classify the tumor. The tumor was positive only for anti-CD3 marker, indicating that it is a tumor of young cells and, in association with histopathology and hematological data, it can be concluded that spleen neoplasia is lymphocytic lymphoma originated from a lymphocytic leukemia.

Elastografia acoustic radiation force impulse (ARFI), doppler e ultrassonografia contrastada do baço canino

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

Infecção experimental para avaliar a excreção do vírus da diarreia viral bovina por leitões desmamados e transmissão viral por via aerógena

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

Novas alternativas terapêuticas para o tratamento da Criptococose: análogos de Resveratrol e microRNAs

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Imunohistoquímica em órgãos de tilápias-do-Nilo imunizadas com antígeno insolúvel de Streptococcus agalactiae

Pós-graduação em Medicina Veterinária - FCAV