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.

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.

Cytotoxic and genotoxic effects of two hair dyes used in the formulation of black color

According to the International Agency for Research on Cancer (IARC), some hair dyes are considered mutagenic and carcinogenic in in vitro assays and exposed human populations. Epidemiological studies indicate that hairdressers occupationally exposed to hair dyes have a higher risk of developing bladder cancer. In Brazil, 26% of the adults use hair dye. In this study, we investigated the toxic effects of two hair dyes, Basic Red 51 (BR51) and Basic Brown 17 (BB17), which are temporary dyes of the azo group (R-N=N-R'), used in the composition of the black hair dye. To this end, MTT and trypan blue assays (cytotoxicity), comet and micronucleus assay (genotoxicity) were applied, with HepG2 cells. For cytotoxic assessment, dyes were tested in serial dilutions, being the highest concentrations those used in the commercial formula for hair dyes. For genotoxic assessment concentrations were selected according to cell viability. Results showed that both dyes induced significant cytotoxic and genotoxic effects in the cells, in concentrations much lower than those used in the commercial formula. Genotoxic effects could be related to the azo structure present in the composition of the dyes, which is known as mutagenic and carcinogenic. These results point to the hazard of the hair dye exposure to human health.

Efeitos das formulações nanoestruturadas de doxorrubicina e cisplatina em dispersão de óxido de grafeno reduzido no tratamento da progressão do câncer de bexiga Não-músculo invasivo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Eficácia e efeitos hemodinâmicos da anestesia raquidiana com ropivacaína isobárica, hipobárica ou hiperbárica seletiva em cães anestesiados com isofluorano

Pós-graduação em Ciência Animal - FMVA

Avaliação dos dados obtidos em um programa de esterilização cirúrgica de gatos em Araçatuba, SP no período de 1996 a 2010

Cats are gradually occupying a more important position as pets and this preference is a result of how easy cat maintenance in an urban environment is, even though they are very prolific and need surgical sterilization. This paper aims at evaluating obtained data within 15 years of research in a university service program that offers free cats sterilization surgery. We carried out a statistical analysis of data shown in the records of animals treated by the program. Surgical sterilization was performed on 647 animals (409 females – 63% and 238 males – 37%). Unilateral cryptorchidism was observed in 9 (3.8%) male cats. Forty (10%) female cats were pregnant at the time of the surgery and the treatment with contraceptives was observed in 67 (16.4%) female cats. One death occurred during anesthesia recovery and 2 cats were euthanized because of wound infection, totalizing an amount of 0.5% of severe complications. From 1996 to 2004, 212 female cats were spayed (122 adults and 90 prepubertal) and during that time two different approaches for ovariohysterectomy were compared: flank laparotomy and ventral midline celiotomy. The flank laparotomy approach was used in only 46 female cats (21.7%) due to some disadvantages observed – the need of an incision on each flank in prepubertal or nulliparous animals and the difficulty or impossibility of total uterus removal. In the same period, 105 male cats underwent orchiectomy via an open technique in which the spermatic cord was linked with nylon thread. From 2005 to 2010, 197 females (106 adults and 91 prepubertal) were spayed. The minilaparotomy technique was used to perform ovariohysterectomy on 139 female cats (70.6%). In this procedure, ovaries and uterus were exteriorized in a blind fashion with a hook through a small midline incision. The traditional midline ovariohysterectomy, which incision length permits direct visualization of the ovaries and uterus, had to be performed in 58 (29.4%) female cats due to advanced pregnancy, full urinary bladder during surgery or obesity. Over the past 6 years, 133 male cats (48 adults and 85 prepubertal) were castrated by means of an open technique in which the spermatic cord was tied to itself. The demand for surgeries during the project demonstrated that people are becoming aware concerning the importance of sterilization when facing cat overpopulation and abandonment.

Atividade toxicogenética de corantes usados na formulação da tintura capilar preta, individuais e em associação, por meio de diferentes ensaios biológicos

Pós-graduação em Ciências Biológicas (Biologia Celular e Molecular) - IBRC

Avaliação clínico-laboratorial e da expressão de metaloproteinases 2 e 9 de equinos com obstrução experimental do cólon menor

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ureterostomias cutânea e colônica em suínos: avaliação da exequibilidade das técnicas e complicações pós-operatórias

Pós-graduação em Medicina Veterinária - FCAV

Implantação da vigilância do câncer relacionado ao trabalho em Londrina-PR entre 2011 e 2014

Pós-graduação em Saúde Coletiva - FMB

Estudo mielográfico comparativo entre meios de contraste iopamidol e ioexol em bezerros

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Prevalência de bexiga hiperativa e avaliação do impacto desse diagnóstico em mulheres de diferentes faixas etárias

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Correlação entre a força muscular do assoalho pélvico e status hormonal da vagina em mulheres continentes

Pós-graduação em Bases Gerais da Cirurgia - FMB

Valor prognóstico da avaliação urodinâmica e da força do assoalho pélvico na incontinência urinária pós prostatectomia radical

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

Diferentes terapias na osteoartrite induzida por papaína em joelhos de ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)