Renal redox-sensitive signaling, but not blood pressure, is attenuated by Nox1 knockout in angiotensin II-dependent chronic hypertension

We demonstrated previously that, in mice with chronic angiotensin II-dependent hypertension, gp91phoxcontaining NADPH oxidase is not involved in the development of high blood pressure, despite being important in redox signaling. Here we sought to determine whether a gp91phox homologue, Nox1, may be important in blood pressure elevation and activation of redox-sensitive pathways in a model in which the renin-angiotensin system is chronically upregulated. Nox1-deficient mice and transgenic mice expressing human renin (TTRhRen) were crossed, and 4 genotypes were generated: control, TTRhRen, Nox1-deficient, and TTRhRen Nox1-deficient. Blood pressure and oxidative stress (systemic and renal) were increased in TTRhRen mice (P < 0.05). This was associated with increased NADPH oxidase activation. Nox1 deficiency had no effect on the development of hypertension in TTRhRen mice. Phosphorylation of c-Src, mitogen-activated protein kinases, and focal adhesion kinase was significantly increased 2-to 3-fold in kidneys from TTRhRen mice. Activation of c-Src, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and focal adhesion kinase but not of extracellular signal regulated kinase 1/2 or extracellular signal regulated kinase 5, was reduced in TTRhRen/Nox1-deficient mice (P < 0.05). Expression of procollagen III was increased in TTRhRen and TTRhRen/Nox1-deficient mice versus control mice, whereas vascular cell adhesion molecule-1 was only increased in TTRhRen mice. Our findings demonstrate that, in Nox1-deficient TTRhRen mice, blood pressure is elevated despite reduced NADPH oxidase activation, decreased oxidative stress, and attenuated redox signaling. Our results suggest that Nox1-containing NADPH oxidase plays a key role in the modulation of systemic and renal oxidative stress and redox-dependent signaling but not in the elevation of blood pressure in a model of chronic angiotensin II-dependent hypertension.

Substance P regulates the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in cultured human gingival fibroblasts

Background and Objective: Substance P may play a role in the pathogenesis of periodontal disease; however, its mechanisms of modulation are not clear. This study evaluated the effect of two concentrations of Substance P on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human gingival fibroblasts. Materials and Methods: Fibroblasts were stimulated for 48 h with 10(-4) or 10(-9) m Substance P; untreated fibroblasts served as controls. The expression of MMP-1, -2, -3, -7 and -11 and of TIMP-1 and -2 was evaluated using real-time polymerase chain reaction and western blotting. Resulsts: There was a significant, concentration-dependent stimulatory effect of Substance P on MMP-1, -2, -3 and -7 and TIMP-2 gene expression (p < 0.05), and a probable effect on MMP-11 (p = 0.06). At the higher concentration (10(-4) m Substance P), MMP-1, -2, -3, -7 and -11 and TIMP-2 showed the greatest up-regulation; at the lower concentration (10(-9) (M) Substance P), MMP-1, -3 and -7 and TIMP-2 exhibited diminished up-regulation, with MMP-2 and -11 showing down-regulation (p < 0.05). Expression of TIMP-1 was not affected by Substance P (p > 0.05). Western blotting confirmed that Substance P up-regulated MMP-1, -2, -3 and -11 and TIMP-2. MMP-1, -3 and -11 and TIMP-2 showed greater up-regulation at the higher Substance P concentration and diminished up-regulation at the lower concentration. MMP-2 was up-regulated to a similar degree at both Substance P concentrations. Conclusion: In gingival fibroblast cells, Substance P at the higher concentration (10(-4) m) induced greater up-regulation of MMP-1, -3 and -11 and TIMP-2 expression, but at the lower concentration (10(-9) (M)) induced diminished up-regulation, which may represent a mechanism for modulating periodontal breakdown.

Rela????es de parceria entre poder p??blico e entes de coopera????o e colabora????o no Brasil

O primeiro volume da s??rie Inova????o na Gest??o P??blica trata dos v??nculos de coopera????o entre a administra????o p??blica e entidades civis sem fins lucrativos, apresentando texto elaborado a partir de pesquisa financiada pela AECID sobre a dissemina????o no Brasil dos institutos do Servi??o Social Aut??nomo (SSA), da Organiza????o Social (OS) e da Organiza????o da Sociedade Civil de Interesse P??blico (OSCIP), no ??mbito dos governos federal, estadual e municipal. Esta publica????o est?? organizada como segue: o Cap??tulo I cont??m uma an??lise geral das rela????es entre o Poder P??blico e o chamado Terceiro Setor, desde as origens hist??ricas da atividade assistencial, e seus impactos no modelo assistencial brasileiro. O cap??tulo discute, tamb??m, o conceito de Terceiro Setor e os atuais formatos de financiamento das entidades civis que atuam no campo da assist??ncia social. O Cap??tulo II, por sua vez, contempla os resultados do diagn??stico das formas de relacionamento da Administra????o P??blica com entes de coopera????o e colabora????o, segundo pesquisa realizada entre novembro de 2008 e fevereiro de 2009 no ??mbito da coopera????o entre a extinta Secretaria de Gest??o (SEGES) e a AECID. O Cap??tulo III trata dos principais aspectos do processo de avalia????o e fiscaliza????o dos contratos de gest??o firmados entre o Poder Executivo Federal e as OS, com ??nfase no processo de presta????o de contas dos resultados do contrato

Disciplina 1.3: sistema pol??tico brasileiro

Diagn??stico geral a respeito das institui????es pol??ticas brasileiras. Sistema eleitoral e seus impactos sobre o sistema partid??rio. Rela????es Executivo-Legislativo e a Organiza????o Congressual no Brasil. O federalismo e seus impactos sobre o processo decis??rio. Judici??rio e Pol??tica no Brasil

M??dulo 1 - contexto do planejamento estrat??gico: curso gest??o da estrat??gia com uso do BSC

Esse documento trata de: Evolu????o do Planejamento nas Organiza????es; Planejamento em um Contexto de Mudan??as

M??dulo 1 - planejamento das contrata????es de TI na APF e documento de oficializa????o da demanda: curso planejamento da contrata????o de TI (PCTI)

Esse documento trata de: Raz??es para contratar servi??os de TI; Fundamentos legais da contrata????o de Solu????es de TI; Contrata????o de servi??os de TI na APF: O estado da arte; No????es de Planejamento; Planejamento de TI; Rela????o entre planejamento e contrata????o; Modelo de Contrata????o de TI na vis??o da SLTI/MP; IN 04/2008 x IN 04/2010; Instru????o Normativa n?? 04/2010 - Vis??o Geral; Guia Pr??tico para Contrata????o de solu????es de TI; Quadro Referencial Normativo; Planejamento da Contrata????o de Tecnologia da Informa????o; O Documento de Oficializa????o da Demanda ??? DOD; Equipe de Planejamento da Contrata????o

M??dulo 1 - gest??o de contratos de TI: curso Gest??o de Contratos de Tecnologia da Informa????o (GCTI)

Esse documento trata de:gest??o de contratos; legisla????o aplicada; elementos necess??rios para uma boa gest??o contratual; modelo de contrata????o; elementos do modelo (atores); elementos do modelo (artefatos;) elementos do modelo (processos e atividades); atividades do processo de inicia????o contratual; plano de inser????o

A 5GHz/1.8V CMOS Active Balun Integrated with LNA

The development of high performance monolithic RF front-ends requires innovative RF circuit design to make the best of a good technology. A fully differential approach is usually preferred, due to its well-known properties. Although the differential approach must be preserved inside the chip, there are cases where the input signal is single-ended such as RF image filters and IF filters in a RF receiver. In these situations, a stage able to convert single-ended into differential signals (balun) is needed. The most cited topology, which is capable of providing high gain, consists on a differential stage with one of the two inputs grounded. Unfortunately, this solution has some drawbacks when implemented monolithically. This work presents the design and simulated results of an innovative high-performance monolithic single to differential converter, which overcomes the limitations of the circuits.The integration of the monolithic active balun circuit with an LNA on a 0.18μm CMOS process is also reported. The circuits presented here are aimed at 802.11a. Section 2 describes the balun circuit and section 3 presents its performance when it is connected to a conventional single-ended LNA. Section 4 shows the simulated performance results focused at phase/amplitude balance and noise figure. Finally, the last section draws conclusions and future work.

Immunoglobulins and C3 in the P. brasiliensis granuloma

The experimental model of paracoccidioidomycosis induced in mice by the intravenous injection of yeast-forms of P. brasiliensis (Bt2 strain; 1 x 10(6) viable fungi/animal) was used to evaluate sequentially 2, 4, 8, 16 and 20 weeks after inoculation: 1. The presence of immunoglobulins and C3 in the pulmonary granuloma-ta, by direct immunofluorescence; 2. The humoral (immunodiffusion test) and the cellular (footpad sweeling test) immune response; 3. The histopathology of lesions. The cell-immune response was positive since week 2, showing a transitory depression at week 16. Specific antibodies were first detected at week 4 and peaked at week 16. At histology, epithelioid granulomas with numerous fungi and polymorphonuclear agreggates were seen. The lungs showed progressive involvement up to week 16, with little decrease at week 20. From week 2 on, there were deposits of IgG and C3 around fungal walls within the granulomas and IgG stained cells among the mononuclear cell peripheral halo. Interstitital immunoglobulins and C3 deposits in the granulomas were not letected. IgG and C3 seen to play an early an important role in. the host defenses against P. brasiliensis by possibly cooperating in the killing of parasites and blocking the antigenic diffusion.

The alternative complex III from Rhodothermus marinus - a prototype of a new family of quinol: electron acceptor oxidoreductase

Dissertation presented to obtain a PhD degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Energy transduction by respiratory complex I

Dissertation presented to obtain a PhD degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Evidence of a higher prevalence of HPV infection in HTLV-1-infected women: a cross-sectional study

INTRODUCTION:HTLV-1 infection increases susceptibility to other infections. Few studies have addressed the co-infection between HPV and HTLV-1 and the immune response involved in this interaction. The aim of this study was to determine the prevalence of cervical HPV infection in HTLV-1-infected women and to establish the risk factors involved in this co-infection. METHODS: A cross-sectional study was carried out in Salvador, Brazil, between September 2005 and December 2008, involving 50 HTLV-1-infected women from the HTLV Reference Center and 40 uninfected patients from gynecological clinic, both at the Bahiana School of Medicine. HPV infection was assessed using hybrid capture. HTLV-1 proviral load was quantified using real-time polymerase chain reaction (PCR). RESULTS: The mean age of HTLV-1-infected women (38 ± 10 years) was similar to that of the control group (36 ± 13 years). The prevalence of HPV infection was 44% in the HTLV-1-infected group and 22.5% in uninfected women (p = 0.03). HTLV-1-infected women had lower mean age at onset of sexual life (17 ± 3 years versus 19 ± 3 years; p = 0.03) and greater number of lifetime partners compared with the control group (4 ± 3 versus 2 ± 1; p < 0.01). In the group of HTLV-1-infected patients, there was neither difference in HTLV-1 proviral load between HPV-infected women and the uninfected. CONCLUSIONS: The prevalence of HPV infection was higher in HTLV-1-infected women. Further studies should be performed to evaluate the progression of this co-infection.

Interleucina 1β correlaciona-se com MIBG e parâmetros do exercício, na insuficiência cardíaca?

FUNDAMENTO: Na insuficiência cardíaca, níveis de interleucina 1β (IL 1β) se associam a prognóstico. A atividade adrenérgica cardíaca avaliada através da cintilografia com metiodobenzilguanidina (I123 MIBG) e parâmetros do exercício são importantes preditores de prognóstico. A relação entre essas variáveis não está bem definida. OBJETIVO: Avaliar associação entre níveis de IL 1β com parâmetros do exercício e do I123 MIBG. MÉTODOS: Estudo observacional transversal, com avaliação de 25 pacientes consecutivos com insuficiência cardíaca e fração de ejeção menor que 45%, através de: dosagem de IL 1β; parâmetros do I123 MIBG [relação coração/mediastino precoce e tardia, taxa de washout (WO)]; e teste ergométrico em esteira pelo protocolo de Rampa. RESULTADOS: Separados em dois grupos pelos níveis de IL 1β (normal vs. elevado), o grupo com níveis aumentados apresentava menor reserva de duplo produto (RDP), menor capacidade funcional (CF) e recuperação mais lenta da frequência cardíaca no 1º (RFC 1º) e 2º minuto (RFC 2º), e maior WO. Na análise univariada, todas as variáveis se correlacionaram com a IL 1β; RDP: r = 0,203, p = 0,024; CF: r = 0,181, p = 0,034; RFC 1º: r = 0,182, p = 0,034; RFC 2º: r = 0,204, p = 0,023; WO: r = 0,263, p = 0,009. Na multivariada, apenas a WO permaneceu com correlação significativa (r2 = 0,263, p = 0,009). CONCLUSÃO: A hipertonia adrenérgica foi o principal determinante dos níveis de IL 1β, demonstrando que a atividade simpática excessiva influencia a atividade inflamatória sistêmica. As variáveis do teste ergométrico não foram capazes de identificar pacientes com níveis elevados de IL 1β.

Ezrin-Radixin-Moesin-binding Sequence of PSGL-1 Glycoprotein Regulates Leukocyte Rolling on Selectins and Activation of Extracellular Signal-regulated Kinases.

P-selectin glycoprotein ligand-1 (PSGL-1) mediates the capture (tethering) of free-flowing leukocytes and subsequent rolling on selectins. PSGL-1 interactions with endothelial selectins activate Src kinases and spleen tyrosine kinase (Syk), leading to α(L)β(2) integrin-dependent leukocyte slow rolling, which promotes leukocyte recruitment into tissues. In addition, but through a distinct pathway, PSGL-1 engagement activates ERK. Because ezrin, radixin and moesin proteins (ERMs) link PSGL-1 to actin cytoskeleton and because they serve as adaptor molecules between PSGL-1 and Syk, we examined the role of PSGL-1 ERM-binding sequence (EBS) on cell capture, rolling, and signaling through Syk and MAPK pathways. We carried out mutational analysis and observed that deletion of EBS severely reduced 32D leukocyte tethering and rolling on L-, P-, and E-selectin and slightly increased rolling velocity. Alanine substitution of Arg-337 and Lys-338 showed that these residues play a key role in supporting leukocyte tethering and rolling on selectins. Importantly, EBS deletion or Arg-337 and Lys-338 mutations abrogated PSGL-1-induced ERK activation, whereas they did not prevent Syk phosphorylation or E-selectin-induced leukocyte slow rolling. These studies demonstrate that PSGL-1 EBS plays a critical role in recruiting leukocytes on selectins and in activating the MAPK pathway, whereas it is dispensable to phosphorylate Syk and to lead to α(L)β(2)-dependent leukocyte slow rolling.

The Thioredoxin TRX-1 Modulates the Function of the Insulin-Like Neuropeptide DAF-28 during Dauer Formation in Caenorhabditis elegans

Thioredoxins comprise a conserved family of redox regulators involved in many biological processes, including stress resistance and aging. We report that the C. elegans thioredoxin TRX-1 acts in ASJ head sensory neurons as a novel modulator of the insulin-like neuropeptide DAF-28 during dauer formation. We show that increased formation of stress-resistant, long-lived dauer larvae in mutants for the gene encoding the insulin-like neuropeptide DAF-28 requires TRX-1 acting in ASJ neurons, upstream of the insulin-like receptor DAF-2. Genetic rescue experiments demonstrate that redox-independent functions of TRX-1 specifically in ASJ neurons are needed for the dauer formation constitutive (Daf-c) phenotype of daf-28 mutants. GFP reporters of trx-1 and daf-28 show opposing expression patterns in dauers (i.e. trx-1 is up-regulated and daf-28 is down-regulated), an effect that is not observed in growing L2/L3 larvae. In addition, functional TRX-1 is required for the down-regulation of a GFP reporter of daf-28 during dauer formation, a process that is likely subject to DAF-28-mediated feedback regulation. Our findings demonstrate that TRX-1 modulates DAF-28 signaling by contributing to the down-regulation of daf-28 expression during dauer formation. We propose that TRX-1 acts as a fluctuating neuronal signaling modulator within ASJ neurons to monitor the adjustment of neuropeptide expression, including insulin-like proteins, during dauer formation in response to adverse environmental conditions.