Carbamazepine can induce kidney water absorption by increasing aquaporin 2 expression

Background. Carbamazepine (Carba) is an anticonvulsant and psychotropic drug used widely for the treatment of intellectual disability and severe pains, but the incidence of hyponatremia is a common related occurrence. This hyponatremia is frequently attributed to a SIADH induced by this drug. It is also known that Carba is used to decrease the urinary volume in Diabetes Insipidus (DI) because it has an antidiuretic effect. Lithium (Li) is one of the most important drugs used to treat bipolar mood disorders. However Li has the undesirable capacity to induce DI. Nowadays, the association of these drugs is used in the treatment of patients with psychiatric and neurological problems. Methods. In vivo and in vitro (microperfusion) experiments were developed to investigate the effect of Carba in the rat Inner Medullary Collecting Duct (IMCD). Results. The results revealed that Carba was able to stimulate the V2 vasopressin receptor-Protein G complex increasing the water permeability (Pf) and water absorption. In vivo studies showed that in rats with lithium-induced DI, Carba decreased the urinary volume and increased the urinary osmolality. AQP2 expression was increased both in normal IMCD incubated with Carba and in IMCD from lithium-induced DI after Carba addition to the diet, when compared with the control. Conclusion. These results showed that the hyponatremia observed in patients using this anticonvulsant drug, at least in part, is due to the Carba capacity to increase IMCD`s Pf and that the Lithium-Carbamazepine association is beneficial to the patient.

PPAR gamma expression is increased in systemic lupus erythematosus patients and represses CD40/CD40L signaling pathway

Systemic lupus erythematosus (SLE) is a heterogeneous disease involving several immune cell types and pro-inflammatory signals, including the one triggered by binding of CD40L to the receptor CD40. Peroxisome-proliferator activated receptor gamma (PPAR gamma) is a transcription factor with anti-inflammatory properties. Here we investigated whether CD40 and PPAR gamma could exert opposite effects in the immune response and the possible implications for SLE. Increased PPAR gamma mRNA levels were detected by real-time PCR in patients with active SLE, compared to patients with inactive SLE PPAR gamma/GAPDH mRNA = 2.21 +/- 0.49 vs. 0.57 +/- 0.14, respectively (p < 0.05) or patients with infectious diseases and healthy subjects (p < 0.05). This finding was independent of the corticosteroid therapy. We further explored these observations in human THP1 and in SLE patient-derived macrophages, where activation of CD40 by CD40L promoted augmented PPAR gamma gene transcription compared to non-stimulated cells (PPAR gamma/GAPDH mRNA = 1.14 +/- 0.38 vs. 0.14 +/- 0.01, respectively; p < 0.05). This phenomenon occurred specifically upon CD40 activation, since lipopolysaccharide treatment did not induce a similar response. In addition, increased activity of PPAR gamma was also detected after CD40 activation, since higher PPAR gamma-dependent transcription of CD36 transcription was observed. Furthermore, CD40L-stimulated transcription of CD80 gene was elevated in cells treated with PPAR gamma-specific small interfering RNA (small interfering RNA, siRNA) compared to cells treated with CD40L alone (CD80/GAPDH mRNA = 0.11 +/- 0.04 vs. 0.05 +/- 0.02, respectively; p < 0.05), suggesting a regulatory role for PPAR gamma on the CD40/CD40L pathway. Altogether, our findings outline a novel mechanism through which PPAR gamma regulates the inflammatory signal initiated by activation of CD40, with important implications for the understanding of immunological mechanisms underlying SLE and the development of new treatment strategies. Lupus (2011) 20, 575-587.

Aerobic conditioning and allergic pulmonary inflammation in mice. II. Effects on lung vascular and parenchymal inflammation and remodeling

Vieira RP, de Andrade VF, Duarte AC, dos Santos AB, Mauad T, Martins MA, Dolhnikoff M, Carvalho CR. Aerobic conditioning and allergic pulmonary inflammation in mice. II. Effects on lung vascular and parenchymal inflammation and remodeling. Am J Physiol Lung Cell Mol Physiol 295: L670-L679, 2008. First published August 29, 2008; doi: 10.1152/ajplung.00465.2007.-Recent evidence suggests that asthma leads to inflammation and remodeling not only in the airways but also in pulmonary vessels and parenchyma. In addition, some studies demonstrated that aerobic training decreases chronic allergic inflammation in the airways; however, its effects on the pulmonary vessels and parenchyma have not been previously evaluated. Our objective was to test the hypothesis that aerobic conditioning reduces inflammation and remodeling in pulmonary vessels and parenchyma in a model of chronic allergic lung inflammation. Balb/c mice were sensitized at days 0, 14, 28, and 42 and challenged with ovalbumin ( OVA) from day 21 to day 50. Aerobic training started on day 21 and continued until day 50. Pulmonary vessel and parenchyma inflammation and remodeling were evaluated by quantitative analysis of eosinophils and mononuclear cells and by collagen and elastin contents and smooth muscle thickness. Immunohistochemistry was performed to quantify the density of positive cells to interleukin (IL)-2, IL-4, IL-5, interferon-gamma, IL-10, monocyte chemotatic protein (MCP)-1, nuclear factor (NF)-kappa B p65, and insulin-like growth factor (IGF)-I. OVA exposure induced pulmonary blood vessels and parenchyma inflammation as well as increased expression of IL-4, IL-5, MCP-1, NF-kappa B p65, and IGF-I by inflammatory cells were reduced by aerobic conditioning. OVA exposure also induced an increase in smooth muscle thickness and elastic and collagen contents in pulmonary vessels, which were reduced by aerobic conditioning. Aerobic conditioning increased the expression of IL-10 in sensitized mice. We conclude that aerobic conditioning decreases pulmonary vascular and parenchymal inflammation and remodeling in this experimental model of chronic allergic lung inflammation in mice.

DNA damage and repair in leukocytes of melanoma patients exposed in vitro to cisplatin

Resistance to chemotherapeutic drugs can be an obstacle to a successful treatment of cancer patients in part associated with individual response and differences in the DNA repair system. The Comet assay is an informative test to investigate DNA damage and repair in cells in response to a variety of DNA-damaging agents, including chemotherapeutic drugs. The aim of this study was to assess leukocytes damage after in-vitro cisplatin treatment and DNA repair action using the Comet assay in 20 patients with melanoma and 20 cancer-free individuals. Leukocytes` DNA damage before and after cisplatin treatment, in three different concentrations, was analyzed. The DNA repair capability was investigated after 1-5 h of in-vitro cells growing without cisplatin. The Comet score of the patients` basal DNA damage was higher than that observed in controls, but the difference was not statistically significant (P=0.85). Although both groups had similar Comet scores to all cisplatin concentrations tested and the DNA repair times, the basal DNA damage (P < 0.001) and cisplatin damages (P < 0.005) were statistically lower than the different repair times investigated. Considering the progressive increase in the Comet score due to repair time, the negative results here observed could be associated with the reduced cell culture incubation that should be better evaluated. Considering the mutagenic action of cisplatin on tumor cells and the importance of individual DNA repair mechanisms in the chemotherapeutic melanoma treatment, the peripheral leukocytes could be particularly useful as a tool for DNA repair response identified by the Comet assay. Melanoma Res 21:99-105 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Airway epithelium mediates the anti-inflammatory effects of exercise on asthma

Airway epithelium plays an important role in the asthma physiopathology. Aerobic exercise decreases Th2 response in murine models of allergic asthma, but its effects on the structure and activation of airway epithelium in asthma are unknown. BALB/c mice were divided into control, aerobic exercise, ovalbumin-sensitized and ovalbumin-sensitized plus aerobic exercise groups. Ovalbumin sensitization occurred on days 0, 14, 28, 42, and aerosol challenge from day 21 to day 50. Aerobic exercise started on day 22 and ended on day 50. Total cells and eosinophils were reduced in ovalbumin-sensitized group submitted to aerobic exercise. Aerobic exercise also reduced the oxidative and nitrosative stress and the epithelial expression of Th2 cytokines, chemokines, adhesion molecules, growth factors and NF-kB and P2X7 receptor. Additionally, aerobic exercise increased the epithelial expression of IL-10 in non-sensitized and sensitized animals. These findings contribute to the understanding of the beneficial effects of aerobic exercise for chronic allergic airway inflammation, suggesting an immune-regulatory role of exercise on airway epithelium. (C) 2011 Elsevier B.V. All rights reserved.

Cholinergic Hyperresponsiveness of Peripheral Lung Parenchyma in Chronic Obstructive Pulmonary Disease

Background: Up to 60% of chronic obstructive pulmonary disease ( COPD) patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also shows an exaggerated response to agonists in COPD. Objectives: To investigate the in vitro mechanical behavior and the structural and inflammatory changes of peripheral lung tissue in COPD patients and compare to nonsmoking controls. Methods: We measured resistance and elastance at baseline and after acetylcholine (ACh) challenge of lung strips obtained from 10 COPD patients and 10 control subjects. We also assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, as well as the content of alpha-smooth muscle actin-positive cells and elastic and collagen fibers. We further investigated whether changes in in vitro parenchymal mechanics correlated to structural and inflammatory parameters and to in vivo pulmonary function. Results: Values of resistance after ACh treatment and the percent increase in tissue resistance (%R) were higher in the COPD group (p <= 0.03). There was a higher density of macrophages and CD8+ cells (p < 0.05) and a lower elastic content (p = 0.003) in the COPD group. We observed a positive correlation between %R and eosinophil and CD8+ cell density (r = 0.608, p = 0.002, and r = 0.581, p = 0.001, respectively) and a negative correlation between %R and the ratio of forced expiratory volume in 1 s to forced vital capacity (r = -0.451, p < 0.05). Conclusions: The cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and to the degree of airway obstruction on the pulmonary function test. Copyright (C) 2011 S. Karger AG, Basel

Pkd1 Haploinsufficiency Increases Renal Damage and Induces Microcyst Formation following Ischemia/Reperfusion

Mutations in PKD1 cause the majority of cases of autosomal dominant polycystic kidney disease (ADPKD). Because polycystin 1 modulates cell proliferation, cell differentiation, and apoptosis, its lower biologic activity observed in ADPKD might influence the degree of injury after renal ischemia/reperfusion. We induced renal ischemia/reperfusion in 10- to 12-wk-old male noncystic Pkd1(+/-) and wild-type mice. Compared with wild-type mice, heterozygous mice had higher fractional excretions of sodium and potassium and higher serum creatinine after 48 h. In addition, in heterozygous mice, also cortical damage, rates of apoptosis, and inflammatory infiltration into the interstitium at time points out to 14 d after injury all increased, as well as cell proliferation at 48 h and 7 d. The mRNA and protein expression of p21 was lower in heterozygous mice than wild-type mice at 48 h. After 6 wk, we observed dilated tubules, microcysts, and increased renal fibrosis in heterozygotes. The early mortality of heterozygotes was significantly higher than that of wild-type mice when we extended the duration of ischemia from 32 to 35 min. In conclusion, ischemia/reperfusion induces a more severe injury in kidneys of Pkd1-haploin-sufficient mice, a process that apparently depends on a relative deficiency of p2l activity, tubular dilation, and microcyst formation. These data suggest the possibility that humans with ADPKD from PKD1 mutations may be at greater risk for damage from renal ischemia/reperfusion injury.

Projeto porto sem papel

O setor portu??rio envolve uma grande diversidade de usu??rios e ??rg??os intervenientes, cada um com suas normas e processos pr??prios. Tal situa????o, associada ao fato de que todo o fluxo de informa????es e documentos solicitados pelos ??rg??os aos usu??rios era realizado em papel, n??o permitia clareza e efici??ncia na troca de informa????es. A falta de dados confi??veis e tempestivos tamb??m n??o permitia efetividade na gest??o e planejamento do setor. Nesse contexto, foi implantado, na fase inicial do Porto Sem Papel, um sistema que permitia a troca de informa????es e documentos digitais entre os usu??rios e os diversos ??rg??os intervenientes. Assim, os fluxos de informa????es e documentos, que antes eram realizados em papel, passaram a ser realizados digitalmente, dando agilidade e transpar??ncia aos processos. Cabe destacar que todas as informa????es est??o presentes agora em uma base ??nica de dados, o que permite a realiza????o de an??lises que subsidiem a gest??o e a melhoria de processos no setor portu??rio

O censo Suas como processo de aprimoramento e institucionaliza????o da pol??tica de assist??ncia social no Brasil

O Censo Suas ?? um processo de monitoramento que coleta dados por meio de um formul??rio eletr??nico preenchido pelas secretarias e conselhos de Assist??ncia Social. ?? realizado anualmente desde 2007, por meio de uma a????o integrada entre a Secretaria de Assist??ncia Social e a Secretaria de Avalia????o e Gest??o da Informa????o. Esse processo alcan??ou sua maturidade com a incorpora????o de novos question??rios para a coleta de informa????es sobre ??rg??os gestores, Conselhos e entidades privadas de Assist??ncia Social. Em 2010, 99,2% dos munic??pios preencheram 28.519 question??rios. Assim, a Assist??ncia Social aprimorou seu processo de tomada de decis??o, expandindo a rede e a cobertura dos servi??os. Com os indicadores e as metas de desenvolvimento dos Centros de Refer??ncia de Assist??ncia Social (Cras), apurados com base no Censo, foram retroalimentados a????es e projetos de assist??ncia social, institu??dos processos gradativos de adequa????o dos servi??os ??s normas e constitu??dos processos de planejamento para melhoria da gest??o e do controle social do Sistema ??nico de Assist??ncia Social (Suas)

O combate ?? viol??ncia contra a mulher: a luta entre antigos valores e novos padr??es de pol??ticas p??blicas

O caso relata uma situa????o de viol??ncia dom??stica vivenciada por uma mulher negra e os obst??culos por ela enfrentados para denunciar o agressor e fazer valer seus direitos. Mostra a contradi????o entre normas e sua efetiva aplica????o, quando o comportamento de agentes p??blicos ainda conserva padr??es e valores de um Estado autorit??rio, patriarcal e escravocrata. O caso ?? fict??cio, mas espelha situa????es reais coletadas em documentos e relat??rios da Ouvidoria da Secretaria de Pol??ticas para as Mulheres- SPM/PR. O estudo suscita discuss??es sobre a dimens??o ??tica da atividade de agentes p??blicos de um Estado democr??tico, englobando quest??es referentes aos direitos humanos, direitos e deveres do Estado e da sociedade, o papel da transpar??ncia, do controle social e da responsabiliza????o por resultados (accountability) etc. Pode ser aplicado em cursos sobre ??tica e servi??o p??blico, pol??ticas p??blicas de g??nero e ra??a e atendimento ao cidad??o

O servi??o de an??lises cl??nicas em sintonia com o meio ambiente

As atividades humanas s??o inerentemente poluidoras. Os servi??os de diagn??stico t??m alcan??ado altos n??veis de evolu????o tecnol??gica, mas os cuidados com os res??duos gerados n??o tiveram o mesmo ritmo de crescimento. O Servi??o de An??lises Cl??nicas do Hospital de Cl??nicas da Universidade Federal do Paran?? (UFPR), preocupado com esse panorama, iniciou um projeto para valoriza????o do meio ambiente, contemplando a segrega????o de res??duos, que foram classificados de acordo com as normas vigentes em 2002 (resolu????es Conama 05/93 e 283/01). A principal etapa do projeto foi o treinamento dos funcion??rios, a padroniza????o de lixeiras, a avalia????o dos res??duos, a forma????o de um grupo de teatro e a apresenta????o da pe??a ???Lixo pro lixo???. Com o adequado gerenciamento dos res??duos, houve redu????o de envio ?? coleta hospitalar e incalcul??veis ganhos ambientais

Texto para discuss??o 5: reforma administrativa e direito adquirido ao regime da fun????o p??blica

O direito adquirido tem sido argumento freq??entemente invocado pelos opositores da reforma constitucional do aparelho administrativo do Estado. Nesse debate, entretanto, este argumento ?? completamente destitu??do de validade t??cnica. Dizer que a reforma constitucional n??o pode alterar o regime jur??dico dos servidores p??blicos (o estatuto jur??dico da estabilidade, disponibilidade, remunera????o etc.) ?? incorrer em completo equ??voco. As raz??es dessa incompreens??o decorrem do desconhecimento de no m??nimo dois t??picos relevantes encartados no tema, a saber: a) a natureza do regime jur??dico que vincula o servidor p??blico civil ?? administra????o; e b) a distin????o entre efic??cia imediata e efic??cia retroativa das normas constitucionais

Projeto de racionaliza????o e moderniza????o do sistema normativo do Banco do Nordeste

Racionaliza????o e moderniza????o do sistema de normas do Banco do Nordeste, mediante a consolida????o e sistematiza????o de normas esparsas, constantes em diversos manuais, circulares e avisos-circulares, cujos conte??dos se sobrepunham e at?? se contradiziam, implementando solu????es informatizadas n??o s?? para o processo de elabora????o e divulga????o, como tamb??m para as consultas por parte dos usu??rios, resultando numa redu????o de cerca de 3.500 folhas de normas para cerca de 600, ou seja, de cerca de 612.500 folhas nas 175 ag??ncias para cerca de 105.000. Institui????o de mecanismos r??pidos e on line de consultas ??s normas, e de formula????o de consultas com respostas no mesmo dia e, na maioria das vezes, na mesma hora. Implementa????o de ferramentas para a compila????o de respostas ??s consultas mais freq??entes, ensejando a redu????o permanente das consultas, por serem dadas maiores e melhores condi????es de apreens??o dos conte??dos normativos pelos usu??rios. Redu????o de custos com pessoal (redu????o das equipes de normas de 39 pessoas para uma s?? equipe de 5 pessoas) e material (redu????o com custos de impress??o, tinta e papel), assim como com comunica????es telef??nicas

Constru????o: construindo seguran??a

O resumido n??mero de fiscais da Subdelegacia do Trabalho e Emprego de Novo Hamburgo que atende cerca de cinq??enta mil estabelecimentos industriais, comerciais e de servi??os, preocupados com o elevado n??mero de acidentes graves e fatais que ocorriam na constru????o civil, em geral pelo descumprimento das normas de seguran??a e sa??de do trabalhador. Sem condi????es humanas para fiscalizar todas as obras e ainda por sofrer press??es atrav??s de den??ncias do Sindicato dos Trabalhadores, de jornais, das Promotorias P??blicas, da Justi??a, resolveram reunir as entidades interessadas: Sindicato dos Trabalhadores na Constru????o Civil, Sinduscon e a Fiscaliza????o do Trabalho, para juntos encontrarem uma solu????o. Desta forma, foi elaborado um programa pr??-seguran??a no trabalho com a participa????o de um n??mero de empresas, onde todos fiscalizam cada item do programa de inten????es, atribuindo notas e discutindo em reuni??es posteriores. Superado os obst??culos iniciais, os resultados foram at?? inesperados, conseguindo-se redu????o dr??stica nos acidentes, n??o se verificando no ano de 1999 nenhum acidente incapacitante ou com morte nas empresas do programa, economia nos gastos para Uni??o e empresas, e a dignifica????o e valoriza????o dos empregados, com o mesmo n??mero de fiscais. Hoje a parceria j?? conta com a Prefeitura Municipal de Novo Hamburgo e o CREA (Conselho Regional de Engenharia e Arquitetura)

Negocia????o tripartite: uma nova metodologia para normaliza????o

O in??cio do processo de forma????o do arcabou??o legal de seguran??a e medicina do trabalho foi marcado por forte influ??ncia do regime ditatorial - fim da d??cada de 70. Com a consolida????o da democracia no Pa??s e visando estabelecer uma legisla????o eficiente e eficaz em contribuir para a melhoria das condi????es e ambientes de trabalho, foi concebida, no in??cio dos anos 90, uma nova metodologia para elabora????o e revis??o de normas na ??rea de seguran??a e sa??de no trabalho. Tal metodologia tem como princ??pio b??sico a ado????o do sistema tripartite e parit??rio, com a participa????o de representa????es do governo, trabalhadores e empregadores, atrav??s de ampla negocia????o em todas as etapas do processo. De acordo com o novo procedimento foram elaboradas 9 (nove) Normas Regulamentadoras e, como resultado dessa inova????o, temos assistido a um cont??nuo decl??nio do n??mero de acidentes de trabalho nos respectivos setores ou atividades, ocasionado pelo comprometimento das partes envolvidas em melhorar as condi????es e ambientes de trabalho