Expressao genica associada ao estresse oxidativo no coracao de camundongo apos isquemia intestinal

FUNDAMENTO: O fenômeno da isquemia e reperfusão intestinal é um evento frequente na clínica e está associado a repercussões deletérias em órgãos a distância, em especial ao coração. OBJETIVO: Investigar a expressão gênica do estresse oxidativo e defesa antioxidante no coração de camundongos isogênicos, submetidos a isquemia e reperfusão intestinal (IR). MÉTODOS: Doze camundongos (C57BL/6) foram distribuídos em dois grupos: Grupo IR (GIR) com 60 min de oclusão da artéria mesentérica superior, seguidos de 60 min de reperfusão. Grupo Controle (GC) submetidos a anestesia e a laparotomia sem o procedimento de IR observados por 120 min. As amostras de intestino e coração foram processadas pelo método (RT-qPCR / Reverse transcriptase - quantitative Polymerase Chain Reaction) para determinar a expressão gênica de 84 genes relacionados ao estresse oxidativo ("t" de Student, p < 0,05). RESULTADOS: Observou-se no tecido intestinal (GIR) uma expressão significantemente aumentada em 65 (74,71%) genes em relação ao tecido normal (GC), e 37 (44,04%) genes estiveram hiperexpressos (maior que três vezes o limiar permitido pelo algoritmo). No tocante aos efeitos da I/R intestinal a distância no tecido cardíaco verificou-se a expressão significantemente aumentada de 28 genes (33,33%), mas somente oito genes (9,52%) se hiperexpressaram três vezes acima do limiar. Quatro (7,14%) desses oito genes se expressaram simultaneamente nos tecidos intestinal e cardíaco. No GIR notaram-se cardiomiócitos com núcleos de menor tamanho, picnóticos, ricos em heterocromatina e raros nucléolos, indicando sofrimento cardíaco. CONCLUSÃO: A I/R intestinal promoveu a hiperexpressão estatisticamente significante de oito genes associados ao estresse oxidativo a distância no tecido miocárdico.

Estudos anatômicos e histológicos do ducto intestinal de Embolyntha batesi MacLachlan, 1877 (Embiidina)

É descrito antômica e histològicamente o ducto digestivo do Embiídeo Embolyntha batesi. Consta de: Cavidade bucal com as partes bucais e hipofaringe; faringe com musculatura circular de 5 pares de dilatadores; esôfago com a inglúvia que é pouco acentuada; proventrículo com válvulas funcionando como esfincter controlando a entrada e saída dos alimento. Essas expansões cuticulares entram em contato com a válvula cardíaca; ênteron (intestino mediano) começando no mesotórax e estendendo-se até o quinto segmento abdominal; piloro com 25 tubos de Malpithi em grupos de 2 a 5; íleo (intestino delgado) dilatável com numerosas dobras longitudinais e forte musculatura; colon (intestino grosso) também dilatável, constituindo a parte que liga o íleo ao reto; reto com seis papilas retais e cujas paredes possuem listras longitudinais cuticulares ligadas por tonofibrilas à musculatura circular, talvez podendo ser esvaziada pela contração circular e ânus com forte musculatura formando um esfíncter. As glândulas salivares formam um par de sacos com lóbulos, no protórax. São descritas aqui cinco fases secretoriais e um estado de reabsorção. É provável que êste siga ao últimoestado de secreção.

Estudos anatômicos e histológicos sôbre a subfamília Triatominae (Heteroptera, Reduviidae): VII. Estudo anatômico do ducto intestinal do Triatoma infestans

Devido à imprtãncia que certos Triatomíneos hematófagos representam na vida humana, continuarmos a série de estudos já iniciados em nosso laboratório sôbre seus organismos. É feito, no presente trabalho, a anatomia e microanatomai do aparelho digestivo de Triatoma infestans. Das três distintas regiões do duto intestinal estomodeo, mesêntero e proctodeo, a primeira e a terceira são de origem ectodérmica. A região do estomodeo é constituída pela faringe e esôfago; a do proctodeo pelo piloro, íleo e reto. A segunda, de origem endodérmica, consta promesêntero, postmesêntero e da zona de transição. A anatomia e a microanatomia do faringe já foi estudada minuciosamente por BARTH (1952). O esôfago possui numerosas dobras no seu interior revestida de fina cutícula. A musculatura longitudinal e circular acham-se representadas por feixes que, provàvelmente, trabalham, preistàlticamente, transportando o alimento. Não encontramos um proventrículo, de maneira que o esôfago está ligado diretamente à primeira parte endodérmica, isto é, ao promesêntero. No início do promesêntero existe a válvula cardíaca, que, juntamente com as dobras do fim do esôfago, impedem que haja um refluxo do alimento. Durante a alimentação, a parede do preomesêntero, que apresenta numerosas dobras, sofre uma dilatação, a fim de reter u'a maior quantidade de sangue. Entre promesêntero e postmesêntero há um pequeno esfíncter formado pelo aumento da musculatura e das dobras do epitélio. O postmesêntero alcança cinco vêzes mais que o tamanho total do corpo do inseto, e dispõe no abdome em curvas completas, que, muitas vêzes, se superpõem. O seu epitélio possue célula altas e estreitas, e forma muitas dobras para dentro do seu lume. Na parte apical as células possuem um rabdório. O postmesêntero termina após a válvula cardíaca situada atrás do desembocamento das quatro ampolas dos tubos de Malpighi. Entre postmesêntero e proctodeo está situada a zona de transição, que é constituída pelas ampolas dos tubos de Malpighi, válcula pilórica e zona clara de células cubóides. Os quatro tubos de Malpighi são longos, finos e simples formando emaranhados. As ampolas são dilatações das bases dos tubos de Malpighi. Apresentam sempre células características. A formação da válvula pilórica pode ser acompanhada na série de cortes de 27-44. O piloro é revestido, internamente, por fina cutícula, e sua hipoderme é sinsicial. No íleo temos dobras mais elevadas e maior quantidade de musculatura. O reto acha-se deslocado para a região dorsal do corpo devido ao aumento exagerado do aparelho copulador. As células de sua hipoderme são bem limitadas.

Taxorchis caviae sp. n. (Trematoda, Paramphistomidae), parasito intestinal de Cavia aperea Erxleben, 1777 (Rodentia, Caviidae)

Descreve-se uma nova espécie de trematóide paranfistomídeo, encontrado no intestino grosso de preá, Cavia aperea aperea Erxleben, 1777, roedor silvestre muito freqüente no Estado de São Paulo de outras regiões do país. Para o trematóide em apreço é proposto o nome de Taxorchis caviae sp. n. São discutidas as diferenças entre T. caviae e as espécies próximas,dos gêneros Chiorchis, Taxorchis e Stichorchis. São propostas alterações na diagnose clássica do gênero Taxorchis, de modo a nele ser incluído T. caviae.

Lymph node cell responsiveness in BALB/C mice infected with Leishmania mexicana

In the present study we measured the blastogenic response of lymph node cells from BALB/c mice infected with Leishmania mexicana throughout the course of infection. Results showed that infected mice displayed normal blastogenic responses in the lymph nodes until twenty weeks of infection. Thereafter, there was a gradual suppression. Comparison of the immunoresponsiveness in the spleen and lymph nodes, revealed normal responses in the lymph nodes several weeks after suppression in the spleen had occurred. Suppression of blastogenic responses in the lymph nodes was related to an adherent macrophage-like cell which actively suppressed normal proliferative responses to mitogens.

Differential effect of culture epimastigotes and blood-form Trypamastigotes on normal mouse splenocyte responsiveness to mitogens

Blood form trypomastigotes of the Y strain of T. cruzi, produced a strong inhibition of the blastogenic response to T and B cell mitogens, of the C3H/He, C57BLand BALB/cJ strains of mice, while culture epimastigotes of the Y strain kept in a medium that allows parasite growth at 26°. 30° and 37°C produced a strong stimulatory effect that was even higher than the effect of the mitogens alone. Both the inhibitory or the stimulatory effects were dose-dependent. The stimulatory effect of epimastigotes was also temperature-dependent producing increasedstimulation indexes as the temperature of parasite cultures was raised. Metabolically active,living parasites seemed to be necessary for an improved lymphocyte stimulation suggesting a potential role of secreted metabolites as polyclonal activators of mouse lymphocytes.

Validity, reliability and responsiveness of the French language translation of the Western Ontario Shoulder Instability Index (WOSI).

BACKGROUND: The WOSI (Western Ontario Shoulder Instability Index) is a self-administered quality of life questionnaire designed to be used as a primary outcome measure in clinical trials on shoulder instability, as well as to measure the effect of an intervention on any particular patient. It is validated and is reliable and sensitive. As it is designed to measure subjective outcome, it is important that translation should be methodologically rigorous, as it is subject to both linguistic and cultural interpretation. OBJECTIVE: To produce a French language version of the WOSI that is culturally adapted to both European and North American French-speaking populations. MATERIALS AND METHODS: A validated protocol was used to create a French language WOSI questionnaire (WOSI-Fr) that would be culturally acceptable for both European and North American French-speaking populations. Reliability and responsiveness analyses were carried out, and the WOSI-Fr was compared to the F-QuickDASH-D/S (Disability of the Arm, Shoulder and Hand-French translation), and Walch-Duplay scores. RESULTS: A French language version of the WOSI (WOSI-Fr) was accepted by a multinational committee. The WOSI-Fr was then validated using a total of 144 native French-speaking subjects from Canada and Switzerland. Comparison of results on two WOSI-Fr questionnaires completed at a mean interval of 16 days showed that the WOSI-Fr had strong reliability, with a Pearson and interclass correlation of r=0.85 (P=0.01) and ICC=0.84 [95% CI=0.78-0.88]. Responsiveness, at a mean 378.9 days after surgical intervention, showed strong correlation with that of the F-QuickDASH-D/S, with r=0.67 (P<0.01). Moreover, a standardized response means analysis to calculate effect size for both the WOSI-Fr and the F-QuickDASH-D/S showed that the WOSI-Fr had a significantly greater ability to detect change (SRM 1.55 versus 0.87 for the WOSI-Fr and F-QuickDASH-D/S respectively, P<0.01). The WOSI-Fr showed fair correlation with the Walch-Duplay. DISCUSSION: A French-language translation of the WOSI questionnaire was created and validated for use in both Canadian and Swiss French-speaking populations. This questionnaire will facilitate outcome assessment in French-speaking settings, collaboration in multinational studies and comparison between studies performed in different countries. TYPE OF STUDY: Multicenter cohort study. LEVEL OF EVIDENCE: II.

Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response.

RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). METHODS: Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e., decrease in HAM-D21 total score). The model demonstrated that the interaction of CSF S-CIT concentrations and clinical improvement was the most powerful predictor of AUC cortisol responsiveness. CONCLUSION: The present study shows that decreased AUC cortisol was highly associated with S-CIT concentrations in plasma and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations rather than the R/S-CIT dose should be considered as an indicator of the selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis responsiveness as measured by AUC cortisol response.

Endogenous and exogenously-induced immunomodulation of tumour-host responsiveness

In spite of the availability of multiple effector mechanisms of the immune system to combat tumour growth and metastases, their impairment frequently accompanies the appearance of cancer. Factors contributing to this impairment may be related to properties of the host and/or the tumour itself and may be with respect to their origin -endogenous or exogenour. Based on the unique biological behavior of prostate cancer (PCa), and its apparent escape from immune surveillance in the presence of tumour immuno genicity, continuing investigation of endogenous and exogenous factors thought to be relevant to its pathogenesis have been made. For this purpose further studies of the suggested role of human seminal plasma (SePl) and the synthetic oestrogen, diethylstiboestrol (DES), as representative endogenous and exogenous immunomodulatory factors (IMF) of tumour-host responsiveness, together with evaluation of human prostatic tissue extracts and leuprolide (the luteinizing-hormone-releasing-hormone proposed as an alternate to DES therapy) have been made by evaluating their effect on the lytic activity of natural killer (NK) cells. SePl and prostate extracts significantly suppressed NK cell lysis. Physicochemical studies suggest SePl and prostate IMF to be associated with high and low molecular weight macromolecules; and implicate the participation of transglutaminase and prostaglandins. Comparative study of therapeutic levels of DES vs. leuprolide on NK cell lysis demonstrated significant suppression by DES vs. a negligible effect of leuprolide. Metastases are highly prevalent in PCa, and contribute significantly to its morbidity and mortality. Further knowledge of the range of effects of endogenous and exogenous IMF on effector mechanisms of tumour-host responsiveness, to include suppression of NK cells, and elucidation of their nature, may contribute toward our understanding of the unique biological behavior of tumours of the prostate, in addition to improvement in their clinical management.

Targeting of secretory IgA to Peyer's patch dendritic and T cells after transport by intestinal M cells.

In addition to being instrumental to the protection of mucosal epithelia, secretory IgA (SIgA) adheres to and is transported by intestinal Peyer's patch (PP) M cells. The possible functional reason for this transport is unknown. We have thus examined in mice the outcome of SIgA delivered from the intestinal lumen to the cells present in the underlying organized mucosa-associated lymphoreticular tissue. We show selective association of SIgA with dendritic cells and CD4(+) T and B lymphocytes recovered from PP in vitro. In vivo, exogenously delivered SIgA is able to enter into multiple PP lining the intestine. In PP, SIgA associates with and is internalized by dendritic cells in the subepithelial dome region, whereas the interaction with CD4(+) T cells is limited to surface binding. Interaction between cells and SIgA is mediated by the IgA moiety and occurs for polymeric and monomeric molecular forms. Thus, although immune exclusion represents the main function of SIgA, transport of the Ab by M cells might promote Ag sampling under neutralizing conditions essential to the homeostasis of mucosal surfaces.

Age, smoking and overweight contribute to the development of intestinal metaplasia of the cardia.

AIM: To assess the role of Helicobacter pylori (H. pylori), gastroesophageal reflux disease (GERD), age, smoking and body weight on the development of intestinal metaplasia of the gastric cardia (IMC).¦METHODS: Two hundred and seventeen patients scheduled for esophagogastroduodenoscopy were enrolled in this study. Endoscopic biopsies from the esophagus, gastroesophageal junction and stomach were evaluated for inflammation, the presence of H. pylori and intestinal metaplasia. The correlation of these factors with the presence of IMC was assessed using logistic regression.¦RESULTS: IMC was observed in 42% of the patients. Patient age, smoking habit and body mass index (BMI) were found as potential contributors to IMC. The risk of developing IMC can be predicted in theory by combining these factors according to the following formula: Risk of IMC = a + s - 2B where a = 2,...6 decade of age, s = 0 for non-smokers or ex-smokers, 1 for < 10 cigarettes/d, 2 for > 10 cigarettes/d and B = 0 for BMI < 25 kg/m² (BMI < 27 kg/m² in females), 1 for BMI > 25 kg/m² (BMI > 27 kg/m² in females). Among potential factors associated with IMC, H. pylori had borderline significance (P = 0.07), while GERD showed no significance.¦CONCLUSION: Age, smoking and BMI are potential factors associated with IMC, while H. pylori and GERD show no significant association. IMC can be predicted in theory by logistic regression analysis.

Multinational Firms’ Heterogeneity in Tax Responsiveness: the Role of Transfer Pricing

In this paper we show that the ability of multinational firms to manipulate transfer prices affects the tax sensitivity of foreign direct investment (FDI). We offer a model of international capital allocation where firms are heterogeneous in their ability to manipulate transfer prices. Perhaps paradoxically, we show that the ability to shift profits can make parent companies' investment more sensitive to host-country tax rates, as long as investors expect fisscal authorities to use price and profit detection methods. We then offer a comprehensive empirical study to test our predictions in the case of Japanese FDI. We exploit the finding that the unobservable ability to manipulate transfer prices is correlated with whole ownership of a±liates and R&D expenditure. Based on country, parent firm and sector characteristics, we estimate an investment equation on a sample of 3614 Japanese affiliates in 49 emerging countries. We obtain a greater semi-elasticity of investment to the statutory tax rate in a±liates that are wholly-owned and that have R&D intensive parents. We interpret these results as indirect evidence that abusive transfer pricing is one of the determinants of FDI activity.