Expressão de iNOS, COX-2, GLUT1, e Nitrotirosina como biomarcadores preditivos da evolução do adenocarcinoma prostático em pacientes com margens positivas pós-prostatectomia radical / Expression of iNOS, COX-2, GLUT1, and nitrotirosina as predictive biomarkers from progression of prostatic adenocarcinoma in patients with positive surgical margins post-radical prostatectomy

Apesar dos bem estabelecidos parâmetros clínicos, cirúrgicos e anatomopatológicos utilizados na atualidade para podermos predizer a evolução para recidiva bioquímica do adenocarcinoma da próstata, após seu tratamento cirúrgico, sobretudo quando da presença de margens cirúrgicas positivas, análises imunoistoquímicas tem se revelado importantes ferramentas para apoiar a indicação de tratamentos adjuvantes precocemente ou não com base na expressão de determinados marcadores que sinalizam a agressividade do tumor. O iNOS (sintase do óxido nítrico induzível) sintetiza óxido nítrico (NO) que tem importante papel no crescimento tumoral e na angiogênese, como também influencia a citotoxicidade de macrófagos e a imunosupressão induzida pelo tumor, sendo um marcador muito encontrado em células do adenocarcinoma da próstata diferenciando este de tecido benigno. A COX-2 que tem produção estimulada pelo NO, também tem sido associada a diversas neoplasias por sua ação angiogênica e no processo da inflamação, sendo estudada como via alvo terapêutico. O GLUT1 é um ativo transportador de glicose expressado em tecidos normais e expresso em altos níveis em numerosos tumores, sendo um marcador intrínseco e mediador de hipóxia reduzindo a fosforilação oxidativa e agindo na via de sinalização oxigênio-dependente através do fator de hipóxia induzida (HIF-1). A Nitrotirosina é um produto da nitração da tirosina mediado por espécies reativas do nitrogênio, tais como o ânion peroxinitrito e o dióxido de nitrogênio, sendo detectado em condições patológicas como em neoplasias sendo considerado marcador de estresse oxidativo dependente de NO. Os objetivos deste trabalho foram avaliar as expressões desses marcadores em espécimes cirúrgicos de próstatas com adenocarcinoma e avaliar suas relações com o prognóstico pós-prostatectomia radical em pacientes com margens cirúrgicas positivas, fator este considerado na literatura como significativo para recidiva bioquímica. Foram analisados...

In spite of the well-established clinical, surgical and anatomopathological parameters currently used to allow us to predict the evolution to biochemical recurrence of adenocarcinoma of the prostate, after its surgical treatment, especially when in the presence of positive surgical margins, immunohistochemical tests have become very important tools to support the indication of adjuvant therapies, either precociously or not, based on the expression of certain markers that signalize the tumor’s aggressiveness. The iNOS (inducible nitric oxide synthase) synthesizes nitric oxide (NO) which plays an important role in the tumor’s growth and in the angiogenesis, affecting as well the macrophages cytotoxicity and the tumor-induced immunosuppression, being a marker very commonly found in prostate adenocarcinoma cells, thus differentiating this from a benign hyperplasia. The COX-2, which production is stimulated by the NO, has also been associated to various neoplasias due to its angiogenic action and to its influence on the inflammation process as well, being then studied as a therapeutic target via. The GLUT1 is an active glucose transporter expressed in normal tissues and expressed at high levels in numerous tumors, playing the role as intrinsic and mediator hypoxia marker, reducing oxidative phosphorylation and acting on the oxygen-dependent signalizing via through hypoxia inducible factor (HIF-1). Nitrotyrosine is a product of tyrosine nitration mediated by reactive nitrogen species such as peroxynitrite anion and nitrogen dioxide, being detected in pathological conditions such as in neoplasias, thus being considered a marker of NO-dependent oxidative stress. The objectives of this work were to evaluate the expressions of those markers in surgical specimens of prostates with adenocarcinoma, as well as to evaluate their relation with prognosis after radical prostatectomy in patients with positive surgical margins, factor which has been considered...

Vascular, metabolic, and inflammatory abnormalities in normoglycemic offspring of patients with type 2 diabetes mellitus.

Endothelial dysfunction, insulin resistance, and elevated levels of circulating proinflammatory markers are among the earliest detectable abnormalities in people at risk for atherosclerosis. Accelerated atherosclerosis is a leading contributor to morbidity and mortality in type 2 diabetes mellitus, a complex genetic disorder. Therefore, we hypothesized that normoglycemic offspring of patients with type 2 diabetes mellitus (NOPD) may have impaired vascular and metabolic function related to an enhanced proinflammatory state. We compared NOPD (n = 51) with matched healthy control subjects without family history of diabetes (n = 35). Flow- and nitroglycerin-mediated brachial artery vasodilation were assessed by ultrasound to evaluate endothelium-dependent and -independent vascular function. Each subject also underwent an oral glucose tolerance test to evaluate metabolic function. Fasting levels of plasma adiponectin and circulating markers of inflammation (high-sensitivity C-reactive protein, CD40 ligand, interleukin 1beta, tumor necrosis factor alpha, vascular cell adhesion molecule 1, and intracellular adhesion molecule) were measured. Both NOPD and the control group had fasting glucose and insulin levels well within the reference range. However, results from oral glucose tolerance test and quantitative insulin sensitivity check index revealed that NOPD were insulin resistant with significantly impaired flow- and nitroglycerin-mediated dilation compared with the control group. Adiponectin levels were lower, whereas many circulating markers of inflammation were higher, in NOPD compared with the control group. Normoglycemic offspring of patients with type 2 diabetes mellitus have impaired vascular and metabolic function accompanied by an enhanced proinflammatory state that may contribute to their increased risk of diabetes and its vascular complications.

Multislice computed tomography in an asymptomatic high-risk population.

Approximately 50% of all acute coronary syndromes occur in previously asymptomatic patients. This study evaluated the value of multislice computed tomography for early detection of significant coronary artery disease (CAD) in high-risk asymptomatic subjects. One hundred sixty-eight asymptomatic subjects with >or=1 major risk factor (hypertension, diabetes, hypercholesterolemia, family history, or smoking) and an inconclusive or unfeasible noninvasive stress test result (stress electrocardiography, echocardiography, or nuclear scintigraphy) were evaluated in an outpatient setting. After clinical examination and laboratory risk analysis, all patients underwent multislice computed tomographic (MSCT) coronary angiography within 1 week. In all subjects, conventional coronary angiography was also carried out. Multislice computed tomography displayed single-vessel CAD in 16% of patients, 2-vessel CAD in 7%, and 3-vessel CAD in 4%. Selective coronary angiography confirmed the results of multislice computed tomography in 99% of all patients. Sensitivity and specificity of MSCT coronary angiography were 100% and 98%, respectively, with a positive predictive value of 95% and a negative predictive value of 100%. In conclusion, MSCT coronary angiography is an excellent noninvasive technique for early identification of significant CAD in high-risk asymptomatic patients with inconclusive or unfeasible noninvasive stress test results.

Association between enhanced soluble CD40 ligand and proinflammatory and prothrombotic states in major depressive disorder: pilot observations on the effects of selective serotonin reuptake inhibitor therapy.

OBJECTIVE: Major depressive disorder (MDD) is associated with low-grade inflammation, and it is considered a risk factor for coronary artery disease (CAD). CD40 ligand (CD40L) plays an important role in inflammation, platelet activation, and clotting system activation. We investigated soluble CD40L (sCD40L) expression in MDD and assessed whether it may represent a molecular mechanism that links inflammation and a prothrombotic state and whether this condition may be modified by selective serotonin reuptake inhibitor (SSRI) therapy. METHOD: Levels of sCD40L, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble P-selectin (sP-selectin), activated factor VII (FVIIa), and prothrombin fragment 1+2 (F1+2) were measured in 46 drug-naïve, first-episode MDD patients without conventional CAD risk factors and in 46 matched healthy controls. Participants were screened between March 2002 and November 2005. Twenty of the 46 MDD patients were then randomly assigned to either sertraline 100 mg/day (N = 10) or citalopram 20 mg/day (N = 10); the aforementioned variables were measured at baseline and after 6 weeks of treatment. RESULTS: Compared with control subjects, MDD patients had higher baseline levels of sCD40L, IL-1beta, IL-6, TNF-alpha, sP-selectin, FVIIa, and F1+2. In the clinical group, sCD40L levels, HAM-D total scores, and proinflammatory markers were strongly intercorrelated. In contrast, there were no significant correlations in the control group. Mood improvement achieved with SSRI therapy was associated with significant reduction in sCD40L, proinflammatory markers, and prothrombotic markers expression. (All p values < .0001.) CONCLUSIONS: This pilot study shows that CD40/ CD40L pathway up-regulation in MDD patients relates increased levels of sCD40L to a prothrombotic state and, preliminarily, indicates that SSRI therapy may significantly reduce sCD40L and CD40L levels associated with proinflammatory and prothrombotic states.

Plasma ghrelin in anorexia, bulimia, and binge-eating disorder: relations with eating patterns and circulating concentrations of cortisol and thyroid hormones.

The present study was designed to investigate the relations between plasma ghrelin concentrations, eating patterns, and circulating concentrations of cortisol and thyroid hormones in women with anorexia nervosa, bulimia nervosa, and binge-eating disorder. The patterns of disordered eating behavior were assessed using the Eating Attitudes Test (EAT-26) and the Bulimia Test-Revised (BULIT-R). In women with eating disorders, but not in healthy control women, plasma ghrelin concentrations were negatively correlated with body mass index (BMI) and plasma concentrations of thyreotropin (TSH), free T3 and free T4, and positively correlated with plasma concentrations of cortisol. The ghrelin concentrations of women with binge-eating and purging behavior were significantly lower than those of women with anorexia nervosa, restricting type, and there was a negative relation between the frequency and severity of binge-eating and purging behavior, as measured by the BULIT-R total score, and ghrelin concentrations. In a multivariate regression model controlling for the confounding effects of body mass index (BMI) and age, higher ghrelin concentrations were correlated with lower BULIT-R total scores. The results of this study did not confirm the hypothesis advanced in previous studies that ghrelin concentrations are higher in patients with binge-eating/purging forms of eating disorders. Based on these data, we suggest that, in women with eating disorders, ghrelin concentrations best reflect nutritional status rather than specific patterns of disordered eating behavior.

Effects of Goyazensolide during in vitro cultivation of Schistosoma mansoni

Goyazensolide, a component extracted of Eremanthus goyazensis showed a significant inhibitory effect on egg-laying of Schistosoma mansoni during in vitro cultivation of this parasite. Motility of the worms was also reduced under treatment with goyazensolide and 90 per cent of mortality was reached with concentration up to 4 µg/ml. It has found that separated worms were more susceptible than worms pairing during drug exposition and female alone was significantly more susceptible than male worm in the same conditions of in vitro cultivation. Natural products isolated from plants represent potencial sources for the identification of structures useful for the design of alternative molecules to be used as new drug substances against several infectious deseases.

Oviposition by Schistosoma mansoni during "in vitro" cultivation

A ovoposicao "in vitro" do Schistosoma mansoni durante o cultivo de vermes adultos, durante um periodo de 10 dias mostrou que a cinetica da ovoposicao apresenta caracteristicamente 3 fases bem distintas. Uma fase inicial com baixa producao de ovos, um periodo de maxima ovoposicao e finalmente uma progressiva queda no numero de ovos nas fases tardias do cultivo. A cinetica da ovoposicao, bem como o numero de ovos depositados pelos parasitas nao influenciados pelo numero de casais pela quantidade de meio RPMI 1640, como tambem pelo tempo de desenvolvimento do parasita no interior do hospedeiro vertebrado e finalmente pelo tipo de soro utilizado no meio de cultivo

Aspectos imunologicos do sistema enzimatico fenoloxidase de Schistosoma mansoni / Immunological aspects of the phenol oxidase enzymatic system of Schistosoma mansoni

O sistema enzimatico fenoloxidase (EC1.10.3.1, EC1.10.3.2) esta amplamente distribuido entre os seres vivos, tendo sido descrito em diferentes especies do reino animal e vegetal. Apesar de desempenhar um papel fundamental na formacao da capsula ou parede dos ovos de trematodeos, o sistema enzimatico fenoloxidase (PO) tem sido pouco estudado nesses organismos. No presente trabalho sao apresentados os resultados iniciais de imunizacoes de coelhos contra PO de femeas adultas de S. mansoni e tirosinase de cogumelo (Sigma). As analises imunologicas, realizadas atraves de imunodifusao dupla (teste de Ouchterlony) e imunoeletroforese, revelaram identidade imunitaria parcial entre PO de machos e femeas....

Instrumental quirúrgico maleable para hipofisectomía transesfenoidal / Malleable surgical instruments used for transsphenoidal hypophysectomy

La cirugía de los tumores de hipófisis con o sin extensión suprasillar requiere del uso de instrumental especial. El que se presenta tiene la ventaja de su mayor longitud de diseño, que facilita la visión, y su maleabilidad que permite llegar a los límites del tumor y extirparlo en forma completa

Acceso suprasillar e infrasillar combinado para el tratamiento de los grandes tumores de la región hipofisaria / Combined supra and infrasellar approach for the treatment of large hypophyseal tumors

Se presentan la técnica y la aplicación del acceso suprasillar e infrasillar en un caso de macroprolactinoma para demostrar su utilidad en el tratamiento de los grandes tumores hipofisarios