Sympathetic hyperactivity, increased tyrosine hydroxylase and exaggerated corpus cavernosum relaxations associated with oxidative stress plays a major role in the penis dysfunction in townes sickle cell mouse

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOSickle cell disease patients display priapism that may progress to erectile dysfunction. However, little is known about the pathophysiological alterations of corpus cavernosum in sickle cell disease. Objective Thus, this study aimed to evaluate the functional and molecular alterations of sympathetic machinery and nitric oxide-cyclic guanosine monophosphate signaling pathway in Townes transgenic sickle cell disease mice. Methods Concentration-response curves to contractile (phenylephrine) and relaxant agents (acetylcholine and sodium nitroprusside) were obtained in corpus cavernosum strips from sickle and C57BL/6 (control) mice. Neurogenic contractions and nitrergic relaxations were obtained using electrical-field stimulation. Measurements of endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), phosphodiesterase-5 (PDE5) and a alpha(1A)-, alpha(1B)-and alpha(1D)-adrenoceptor mRNA expressions and reactive-oxygen species were performed. Tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expressions in cavernosal tissues were also measured. Results The neurogenic contractions were higher in the sickle cell disease group, in association with elevated tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expression, as well as increased tyrosine hydroxylase mRNA expression. Likewise, phenylephrine-induced contractions were greater in the sickle mice, whereas a alpha(1A)-, alpha(1B)-and alpha(1D)-adrenoceptor mRNA expression remained unchanged. Cavernosal relaxations to acetylcholine, sodium nitroprusside and EFS were higher in sickle mice, accompanied by decreased eNOS and nNOS, along with lower PDE5 mRNA expression. An increase of about 40% in reactive-oxygen species generation in corpus cavernosum from sickle mice was also detected. Conclusion Our study shows that decreased nitric oxide bioavailability in erectile tissue due to increased oxidative stress leads to both sympathetic hyperactivity and dysregulation of nitric oxide signaling in corpus cavernosum from Townes sickle mice.Sickle cell disease patients display priapism that may progress to erectile dysfunction. However, little is known about the pathophysiological alterations of corpus cavernosum in sickle cell disease. Objective Thus, this study aimed to evaluate the functional and molecular alterations of sympathetic machinery and nitric oxide-cyclic guanosine monophosphate signaling pathway in Townes transgenic sickle cell disease mice. Methods Concentration-response curves to contractile (phenylephrine) and relaxant agents (acetylcholine and sodium nitroprusside) were obtained in corpus cavernosum strips from sickle and C57BL/6 (control) mice. Neurogenic contractions and nitrergic relaxations were obtained using electrical-field stimulation. Measurements of endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), phosphodiesterase-5 (PDE5) and a alpha(1A)-, alpha(1B)-and alpha(1D)-adrenoceptor mRNA expressions and reactive-oxygen species were performed. Tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expressions in cavernosal tissues were also measured. Results The neurogenic contractions were higher in the sickle cell disease group, in association with elevated tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expression, as well as increased tyrosine hydroxylase mRNA expression. Likewise, phenylephrine-induced contractions were greater in the sickle mice, whereas a alpha(1A)-, alpha(1B)-and alpha(1D)-adrenoceptor mRNA expression remained unchanged. Cavernosal relaxations to acetylcholine, sodium nitroprusside and EFS were higher in sickle mice, accompanied by decreased eNOS and nNOS, along with lower PDE5 mRNA expression. An increase of about 40% in reactive-oxygen species generation in corpus cavernosum from sickle mice was also detected. Conclusion Our study shows that decreased nitric oxide bioavailability in erectile tissue due to increased oxidative stress leads to both sympathetic hyperactivity and dysregulation of nitric oxide signaling in corpus cavernosum from Townes sickle mice.1112FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2013/19781-2; 2014/00984-

Increased Rho-kinase-mediated prostate contractions associated with impairment of β-adrenergic-cAMP-signaling pathway by chronic nitric oxide deficiency

AbstractImpairment of nitric oxide (NO) – cyclic GMP signaling pathway is likely to contribute to human begnin prostate hyperplasia (BPH). In the present study we have used a model of chronic NO synthesis inhibition to evaluate the functional alterations of prostate smooth muscle (PSM) machinery, and involvement of Rho-kinase pathway. Wistar rats were treated with the NO inhibitor Nω-nitro-l-arginine methyl ester (L-NAME, 20mg/kg/day; 4 weeks), after which contractile responses to phenylephrine (α1-adrenoceptor agonist; 1nM to 100µM), carbachol (muscarinic agonist; 1nM to 1mM) and α,β-methylene ATP (P2X receptor agonist; 1–10µM), as well as to electrical-field stimulation (EFS; 1–32Hz) were evaluated. PSM relaxations to isoproterenol (non-selective β-adrenoceptor agonist, 0.1nM to 10µM) and sodium nitroprusside (NO donor, 1nM to 10mM) were also evaluated. The ratio prostate weight/body weight was 22% greater (P<0.05) in L-NAME compared with control group. The PSM contractions to phenylephrine, carbachol and α,β-methylene ATP were higher in L-NAME (Emax: 3.85±0.25, 3.52±0.35 and 2.03±0.2mN, respectively) compared with control group (Emax: 3.08±0.17, 2.37±0.18 and 1.57±0.18mN, respectively). The PSM contractions induced by EFS were also significantly greater in L-NAME group. Prior incubation with the Rho-kinase inhibitor Y27632 (1µM) fully reversed the enhanced contractions to phenylephrine and carbachol. Isoproterenol-induced PSM relaxations were 34% lower in L-NAME group, which was associated with reduced levels of cAMP in prostate tissue. The relaxations to sodium nitroprusside remained unaltered in L-NAME group. In summary, chronic NO deficiency leads to increased Rho-kinase-mediated PSM contractile responses accompanied by impairment of β-adrenergic-cAMP-signaling pathway

Distribuição e conservação do rato-do-bambu Kannabateomys amblyonyx (Rodentia, Echimyidae) no Estado de Minas Gerais, Brasil

This note reports data on occurrence of the echimyid Kannabateomys amblyonyx in Minas Gerais State, southeastern Brazil. Data were obtained from consult to 26 museums, bibliography search and field sampling. We found nine municipalities with species records, eight within the Atlantic Forest biome and one in the transitional area between the Atlantic Forest and Cerrado. Habitats occupied comprised bamboo groves in Montane Stational Semidecidual Forest, Submontane Stational Semidecidual Forest and bamboo patches located in middle of open area, originally covered by Submontane Stational Semidecidual Forest. Potential impacts detected were deforestation, fires, hunting and the presence of livestock and domestic dogs. Key words: bamboo rat, Atlantic Forest, threats, records.Este trabalho apresenta dados sobre a ocorrência do equimídeo Kannabateomys amblyonyx no Estado de Minas Gerais, sudeste do Brasil. Dados foram obtidos a partir de consultas a 26 museus, pesquisa bibliográfica e de amostragens de campo. Encontramos nove municípios com registros da espécie, sendo oito inseridos no bioma Mata Atlântica e um em área de transição entre Mata Atlântica e Cerrado. Os habitats ocupados compreenderam bambuzais em Floresta Estacional Semidecidual Montana, Floresta Estacional Semidecidual Submontana e manchas de bambu localizadas em meio a áreas aberta, originalmente coberta por Floresta Estacional Semidecidual Submontana. Os potenciais impactos detectados foram desmatamento, queimadas, caça e presença de gado e cães domésticos.Palavras-chave: rato-do-bambu, Mata Atlântica, ameaças, registros

Wild dogs at stake: deforestation threatens the only Amazon endemic canid, the short-eared dog (Atelocynus microtis)

The persistent high deforestation rate and fragmentation of the Amazon forests are the main threats to their biodiversity. To anticipate and mitigate these threats, it is important to understand and predict how species respond to the rapidly changing landscape. The short-eared dog Atelocynus microtis is the only Amazon-endemic canid and one of the most understudied wild dogs worldwide. We investigated short-eared dog habitat associations on two spatial scales. First, we used the largest record database ever compiled for short-eared dogs in combination with species distribution models to map species habitat suitability, estimate its distribution range and predict shifts in species distribution in response to predicted deforestation across the entire Amazon (regional scale). Second, we used systematic camera trap surveys and occupancy models to investigate how forest cover and forest fragmentation affect the space use of this species in the Southern Brazilian Amazon (local scale). Species distribution models suggested that the short-eared dog potentially occurs over an extensive and continuous area, through most of the Amazon region south of the Amazon River. However, approximately 30% of the short-eared dog's current distribution is expected to be lost or suffer sharp declines in habitat suitability by 2027 (within three generations) due to forest loss. This proportion might reach 40% of the species distribution in unprotected areas and exceed 60% in some interfluves (i.e. portions of land separated by large rivers) of the Amazon basin. Our local-scale analysis indicated that the presence of forest positively affected short-eared dog space use, while the density of forest edges had a negative effect. Beyond shedding light on the ecology of the short-eared dog and refining its distribution range, our results stress that forest loss poses a serious threat to the conservation of the species in a short time frame. Hence, we propose a re-assessment of the short-eared dog's current IUCN Red List status (Near Threatened) based on findings presented here. Our study exemplifies how data can be integrated across sources and modelling procedures to improve our knowledge of relatively understudied species

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

OS PROFESSORES QUE ENSINAM CIÊNCIAS E O LIVRO DIDÁTICO: REFLEXÕES COLETIVAS NO CONTEXTO DE UM GRUPO DE ESTUDOS

Normal 0 21 false false false PT-BR X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabela normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Resumo: A discussão acerca do papel do livro didático na escola e de modo especial na condução do currículo escolar tem sido exaustiva nas últimas décadas. Esta sensação de exaustão parece concorrer para o abandono, por parte de muitos pesquisadores, da discussão sobre essa temática. Mas, quando estamos trabalhando na formação continuada de professores e nos deparamos com as seguintes falas: “não participei da escolha ... outra pessoa escolhe”, “para ensinar ciências utilizo o livro didático”, “o livro didático é distribuído para ser utilizado, do contrário seria um gasto a menos para nós contribuintes”, a chama aparentemente apagada se reacende e nos convida  a discussão reflexiva, nos convida a repensar o contexto de produção de sentidos e significados acerca do uso do livro didático na escola básica, em especial quando se trata do seu uso no ensino de ciências. Neste ensino, além dos conhecimentos e conceitos defasados presentes nos livros (GÜLLICH, 2004), são passadas concepções de ciência, sobretudo uma visão reproducionista de ciência, que acaba reforçando uma visão simplista de docência, na qual o professor é um mero transmissor mecânico dos conteúdos cristalizados e reprodutor de práticas /experimentos estampados como receitas culinárias. A partir disso, este texto tem o intuito de discutir algumas categorias acerca do livro didático, que são: a escolha do livro didático, imagens do livro didático e a reflexão sobre o livro didático como articuladora da formação continuada, emergidas das falas e discussões ocorridas durante o processo de reflexão compartilhada entre pesquisadores/professores universitários, licenciandos e cinco professoras que ministram a disciplina de Ciências para o segundo ciclo do Ensino Fundamental (6º. ao 9º. Ano), em uma escola pública de periferia de um município do Estado de Mato Grosso do Sul. A reflexão compartilhada visava a evolução conceitual das professoras sobre o seu fazer docente em ciências, tomando como referência suas concepções e práticas pedagógicas. Palavras-chave: Formação de Professores, Ensino de Ciências, Livro Didático.</p

Treatment with metformin improves erectile dysfunction in a murine model of obesity associated with insulin resistance

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOOBJECTIVE To evaluate the effects of treatment with metformin on a murine model of obesity-associated erectile dysfunction. MATERIAL AND METHODS C57BL/6 male mice were fed for 10 weeks with standard chow or high-fat diet. Lean and obese mice were treated with the insulin sensitizer metformin (300 mg/kg/day, 2 weeks). Intracavernosal pressure (ICP) and in vitro corpus cavernosum (CC) relaxations to both acetylcholine and electrical field stimulation, as well as phenylephrine-induced contractions, were obtained. Levels of cyclic guanosine monophosphate in CC were detected by enzyme immunoassay. RESULTS High-fat-fed mice exhibited higher body weight and insulin resistance. Cavernous nerve stimulation caused frequency-dependent ICP increases, which were significantly lower in obese compared with lean mice (P < .05). Two-week therapy with metformin reversed the decreased ICP in obese group. The maximal response to acetylcholine in CC was 35% lower (P <. 05) in the obese compared to the lean group, which were restored by metformin treatment. Likewise, the impaired electrical field stimulation-induced CC relaxations in obese mice were also partly restored by metformin. Contractile responses to phenylephrine were significantly greater (P <. 05) in obese compared to lean mice, which were fully restored by metformin. Basal and stimulated cyclic guanosine monophosphate productions in the erectile tissues were significantly lower (P <. 05) in the obese group, an effect fully restored by metformin. CONCLUSION Treatment with metformin restored the erectile function in obese mice, through improvement of in vitro endothelial and nitrergic cavernosal relaxations. Therefore, use of metformin may be a good pharmacologic approach to treat insulin resistance-associated erectile dysfunction. (C) 2015 Elsevier Inc.To evaluate the effects of treatment with metformin on a murine model of obesity-associated erectile dysfunction. MATERIAL AND METHODS C57BL/6 male mice were fed for 10 weeks with standard chow or high-fat diet. Lean and obese mice were treated with the insulin sensitizer metformin (300 mg/kg/day, 2 weeks). Intracavernosal pressure (ICP) and in vitro corpus cavernosum (CC) relaxations to both acetylcholine and electrical field stimulation, as well as phenylephrine-induced contractions, were obtained. Levels of cyclic guanosine monophosphate in CC were detected by enzyme immunoassay. RESULTS High-fat-fed mice exhibited higher body weight and insulin resistance. Cavernous nerve stimulation caused frequency-dependent ICP increases, which were significantly lower in obese compared with lean mice (P < .05). Two-week therapy with metformin reversed the decreased ICP in obese group. The maximal response to acetylcholine in CC was 35% lower (P <. 05) in the obese compared to the lean group, which were restored by metformin treatment. Likewise, the impaired electrical field stimulation-induced CC relaxations in obese mice were also partly restored by metformin. Contractile responses to phenylephrine were significantly greater (P <. 05) in obese compared to lean mice, which were fully restored by metformin. Basal and stimulated cyclic guanosine monophosphate productions in the erectile tissues were significantly lower (P <. 05) in the obese group, an effect fully restored by metformin. CONCLUSION Treatment with metformin restored the erectile function in obese mice, through improvement of in vitro endothelial and nitrergic cavernosal relaxations. Therefore, use of metformin may be a good pharmacologic approach to treat insulin resistance-associated erectile dysfunction862423.e1423.e6FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçã

Distribuição e conservação do rato-do-bambu Kannabateomys amblyonyx (Rodentia, Echimyidae) no Estado de Minas Gerais, Brasil

This note reports data on occurrence of the echimyid Kannabateomys amblyonyx in Minas Gerais State, southeastern Brazil. Data were obtained from consult to 26 museums, bibliography search and field sampling. We found nine municipalities with species records, eight within the Atlantic Forest biome and one in the transitional area between the Atlantic Forest and Cerrado. Habitats occupied comprised bamboo groves in Montane Stational Semidecidual Forest, Submontane Stational Semidecidual Forest and bamboo patches located in middle of open area, originally covered by Submontane Stational Semidecidual Forest. Potential impacts detected were deforestation, fires, hunting and the presence of livestock and domestic dogs. Key words: bamboo rat, Atlantic Forest, threats, records.Este trabalho apresenta dados sobre a ocorrência do equimídeo Kannabateomys amblyonyx no Estado de Minas Gerais, sudeste do Brasil. Dados foram obtidos a partir de consultas a 26 museus, pesquisa bibliográfica e de amostragens de campo. Encontramos nove municípios com registros da espécie, sendo oito inseridos no bioma Mata Atlântica e um em área de transição entre Mata Atlântica e Cerrado. Os habitats ocupados compreenderam bambuzais em Floresta Estacional Semidecidual Montana, Floresta Estacional Semidecidual Submontana e manchas de bambu localizadas em meio a áreas aberta, originalmente coberta por Floresta Estacional Semidecidual Submontana. Os potenciais impactos detectados foram desmatamento, queimadas, caça e presença de gado e cães domésticos.Palavras-chave: rato-do-bambu, Mata Atlântica, ameaças, registros