The effect of thyroid hormones on the white adipose tissue gene expression of PAI-1 and its serum concentration

Metabolic syndrome is associated with an increased risk of developing cardiovascular diseases and Plasminogen activator inhibitor 1 (PAI-1) overexpression may play a significant role in this process. A positive correlation between adipose tissue gene expression of PAI-1 and its serum concentration has been reported. Furthermore, high serum levels of thyroid hormones (T3 and T4) and PAI-1 have been observed in obese children. The present study evaluates the impact of thyroid hormone treatment on white adipose tissue PAI-1 gene expression and its serum concentration. Male Wistar rats (60 days old) were treated for three weeks with T4 (50 µg/day, Hyper) or with saline (control). Additionally, 3T3-L1 adipocytes were treated for 24 h with T4 (100 nM) or T3 (100 nM). PAI-1 gene expression was determined by real-time PCR, while the serum concentration of PAI-1 was measured by ELISA using a commercial kit (Innovative Research, USA). Both the serum concentration of PAI-1 and mRNA levels were similar between groups in retroperitoneal and epididymal white adipose tissue. Using 3T3-L1 adipocytes, in vitro treatment with T4 and T3 increased the gene expression of PAI-1, suggesting non-genomic and genomic effects, respectively. These results demonstrate that thyroid hormones have different effects in vitro and in vivo on PAI-1 gene expression in adipocytes.

There is no difference in hepatic fibrosis rates of patients infected with hepatitis C virus and those co-infected with HIV

Some studies have suggested that human immunodeficiency virus (HIV) infection modifies the natural history of hepatitis C virus (HCV) infection, accelerating the progression of fibrosis and the development of cirrhosis. Our objective was to evaluate the fibrosis progression rate (FPR) in HCV/HIV-co-infected patients, and to identify factors that may influence it. HCV-mono-infected and HCV/HIV-co-infected patients with a known date of HCV infection (transfusion or injection drug use) and a liver biopsy were included. The FPR was defined as the ratio between the fibrosis stage (Metavir score) and the estimated length of infection in years and the result was reported as fibrosis units per year. The factors studied were gender, age at infection, consumption of alcohol, aminotransferase levels, histological activity grade, HCV genotype and viral load, CD4 cell count, HIV viral load, and the use of antiretroviral therapy. Sixty-five HCV-infected (group 1) and 53 HCV/HIV-co-infected (group 2) patients were evaluated over a period of 19 months. The mean FPR of groups 1 and 2 was 0.086 ± 0.074 and 0.109 ± 0.098 fibrosis units per year, respectively (P = 0.276). There was a correlation between length of HCV infection and stage of fibrosis in both groups. The age at infection, the aspartate aminotransferase level (r = 0.36) and the inflammatory activity grade were correlated with the FPR (P < 0.001). No difference in FPR was found between HCV-mono-infected and HCV/HIV-co-infected patients.

The emergence of YMDD mutants precedes biochemical flare by 19 weeks in lamivudine-treated chronic hepatitis B patients: an opportunity for therapy reevaluation

Given the loss of therapeutic efficacy associated with the development of resistance to lamivudine (LMV) and the availability of new alternative treatments for chronic hepatitis B patients, early detection of viral genotypic resistance could allow the clinician to consider therapy modification before viral breakthrough and biochemical relapse occur. To this end, 28 LMV-treated patients (44 ± 12 years; 24 men), on their first therapy schedule, were monitored monthly at four Brazilian centers for the emergence of drug resistance using the reverse hybridization-based INNO-LiPA HBV DR assay and occasionally sequencing (two cases). Positive viral responses (HBV DNA clearance) after 6, 12, and 18 months of therapy were achieved by 57, 68, and 53 percent of patients, while biochemical responses (serum alanine aminotransferase normalization) were observed in 82, 82, and 53 percent of cases. All viral breakthrough cases (N = 8) were related to the emergence of YMDD variants observed in 7, 21, and 35 percent of patients at 6, 12, and 18 months, respectively. The emergence of these variants was not associated with viral genotype, HBeAg expression status, or pretreatment serum alanine aminotransferase levels. The detection of resistance-associated mutations was observed before the corresponding biochemical flare (41 ± 14 and 60 ± 15 weeks) in the same individuals. Then, if highly sensitive LMV drug resistance testing is carried out at frequent and regular intervals, the relatively long period (19 ± 2 weeks) between the emergence of viral resistance and the onset of biochemical relapse can provide clinicians with ample time to re-evaluate drug therapy.

Activity of praziquantel on in vitro transformed Schistosoma mansoni sporocysts

Praziquantel (PZQ) is effective against all the evolutive phases of Schistosoma mansoni. Infected Biomphalaria glabrata snails have their cercarial shedding interrupted when exposed to PZQ. Using primary in vitro transformed sporocysts, labeled with the probe Hoechst 33258 (indicator of membrane integrity), and lectin of Glycine max (specific for carbohydrate of N-acetylgalactosamine membrane), we evaluated the presence of lysosomes at this evolutive phase of S. mansoni, as well as the influence of PZQ on these acidic organelles and on the tegument of the sporocyst. Although the sporocyst remained alive, it was observed that there was a marked contraction of its musculature, and there occurred a change in the parasite's structure. Also, the acidic vesicles found in the sporocysts showed a larger delimited area after contact of the parasites with PZQ. Damages to the tegument was also observed, as show a well-marked labeling either with Hoechst 33258 or with lectin of Glycine max after contact of sporocysts with the drug. These results could partially explain the interruption/reduction mechanism of cercarial shedding in snails exposed to PZQ.

The effects of drugs, ions, and poly-l-lysine on the excretory system of Schistosoma mansoni

We have been able to label the excretory system of cercariae and all forms of schistosomula, immature and adult worms with the highly fluorescent dye resorufin. We have shown that the accumulation of the resorufin into the excretory tubules and collecting ducts of the male adult worm depends on the presence of extracellular calcium and phosphate ions. In the adult male worms, praziquantel (PZQ) prevents this accumulation in RPMI medium and disperses resorufin from tubules which have been prelabelled. Female worms and all other developmental stages are much less affected either by the presence of calcium and phosphate ions, or the disruption caused by PZQ. The male can inhibit the excretory system in paired female. Fluorescent PZQ localises in the posterior gut (intestine) region of the male adult worm, but not in the excretory system, except for the anionic carboxy fluorescein derivative of PZQ, which may be excreted by this route. All stages of the parasite can recover from damage by PZQ treatment in vitro. The excretory system is highly sensitive to damage to the surface membrane and may be involved in vesicle movement and damage repair processes. In vivo the adult parasite does not recover from PZQ treatment, but what is inhibiting recovery is unknown, but likely to be related to immune effector molecules.

Demographic and anthropometrical analysis and genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil

Hepatitis C virus (HCV) infection is a serious public health problem, since 80 percent to 85 percent of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81 percent from public and 19 percent from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62 percent) and white patients (80 percent). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64 percent) over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65 percent of the patients weighed less than 77kg. Overweight and obesity were observed in 37.8 percent and 13.6 percent of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65 percent of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.

In situ variation of cervical mucus pH during exposure to atmospheric air

The objective of the present study was to determine if exposure of cervical mucus to air during specular examination could modify mucus pH. Detection of changes is justified because of their possible interference with sperm-mucus interaction, since an acidic pH is unfavorable to sperm penetration and is associated with infertility due to the cervical factor. Twenty women with good quality mucus were evaluated. pH measurements of ecto- and endocervical mucus were made in situ using a glass electrode after 0-, 5- and 10-min exposure to air. There was a progressive alkalinization of mucus pH. Mean values of ectocervical mucus pH were 6.91, 7.16 and 7.27, while mean values of endocervical mucus pH were 7.09, 7.34 and 7.46 at 0, 5 and 10 min, respectively. Significant differences were found between the mean values obtained at 0 and 5 min, and at 0 and 10 min (P<0.05), whereas the differences in mean values at 5 and 10 min were not significant at either site. We conclude that 5 to 10 min of exposure to atmospheric air affects cervical mucus pH in a significant way. Since tests used to evaluate sperm-mucus interaction generally have not considered this possibility, we suggest that they should be performed immediately after mucus collection in order to avoid misinterpretation of the results.

Neurobehavioral study of the effect of beta-myrcene on rodents

Tea prepared from lemongrass (Cymbopogon citratus) is used for its supposed anxiolytic, hypnotic and analgesic properties in Brazilian folk medicine. beta-Myrcene, a major constituent of lemongrass, produces analgesia in rodents but there is some controversy about whether this actions is central or peripheral or both. Rats and mice received beta-myrcene, 1 g/Kg po in corn oil alone 1 h before being evaluated for a series of responses which included exploratory and emotional behavior, anxiolytic activity in a plus maze and inhibition of conditioned avoidance. No evidence was demonstrable for an effect of beta-myrcene on any f these behaviors. Similarly, beta-myrcene had no protective effect on pentylenetetrazol (PTZ)-induced seizures in mice. These data suggest that beta-myrcene has no benzodiazepine-like anxiolytic activity and that an activity on the central nervous system (antidepressive or antipsychotic) is unlikely. Despite the negative results of this study, folk use of lemongrass tea may still be justified by its analgesic properties

Importância da laparoscopia em ginecologia: análise de 522 casos / Importance of the laparoscopy in gynecology: analysis of 522 cases

Durante 1978 e 1982, 522 pacientes submeteram-se à laparoscopia na Clínica Ginecológica da Universidade de Säo Paulo. Da análise dos resultados obtidos, os autores concluíram que a laparoscopia é recurso propedêutico indispensável para o diagnóstico de certas ginecopatias e sobretudo na investigaçäo da esterilidade. Em 244 pacientes com presumível ginecopatia, 69 (28,3%) tinham pelvis normal. Nas demais 175 (71,7%) a laparoscopia permitiu o diagnóstico correto, seja por visäo direta ou biópsia laparoscópica. Em 43 mulheres referindo algia pélvica crônica e exame ginecológico normal, 18 (41,9%) eram portadoras de ginecopatias compatíveis com a sintomatologia. De 183 pacientes com esterilidade,somente 20 (10,9%) tinham achados laparoscópicos normais.. Em 163 (89,1%), pôde-se diagnosticar fator tubário (35%) endometriose pélvica (5,5%) e esterilizaçäo prévia (13,6%). Das 95 pacientes submetidas à esterilizaçäo, 68 (71,6%) tinham enfermidades sistêmicas graves, indicando-se esterilizaçäo tubária por via laparoscópica. O índice de falha, neste grupo, foi de 2,1%. Näo se registraram óbitos e tampouco graves complicaçöes na presente casuística

Distúrbios da condução atrial / Atrial conduction disorders

Apresenta-se uma revisao dos disturbios da conducao atrial, abrangendo suas bases estruturais e eletrofisiologicas, achados no eletrocardiograma, eletrogramas, vetocardiograma e derivacoes ortogonais, e implicacoes clinicas desses disturbios. A determinacao de multiplos eletrogramas atriais e frequentemente necessaria para o esclarecimento do grau e local de bloqueio atrial. O diagnostico adequado dos disturbios da conducao atrial tem importantes implicacoes prognosticas e terapeuticas

Miocardiopatia hipertrófica. Análise eletrovetocardiográfica da despolarização ventricular / Hypertrophic cardiomyopathy. Electrocardiographyc analysis of ventricular despolarization

A despolarizacao ventricular no eletrovetocardiograma foi analisada em 38 pacientes com miocardiopatia (MCH) e correlacionada com os padroes cineangiograficos apresentados pelos pacientes. A hipertrofia ventricular esquerda ( HVE ) ocorreu em 71,1% dos casos, com predominio da orientacao posterior da alca QRS no plano horizontal (PH). A hipertrofia septal (HS), observada em 55,5% das alcas de HVE (33,4% do total), incidiu tanto nos casos com alca posterior como anterior. No grupo com disturbios da conducao intraventricular (21,1%), predominaram os bloqueios divisionais do ramo esquerdo (BDRE), isolados, associados entre si ou com os bloqueios divisionais do ramo direito ( BDRD ). BDRD ocorreu apenas na vigencia de BDRE. A associcao mais frequente foi bloqueio divisional antero-superior esquerdo e bloqueio divisional superior direito. Nao houve registro de bloqueios tronculares. Houve minima incidencia de hipertrofia ventricular direita, sindrome de pre-exitacao e de tracados normais (2,6% de cada tipo). Conclui-se que a MCH apresenta caracteristicas eletrovetrocardiograficas espectrais, nao sendo possivel a individualizacao de alteracoes especificas da doenca. A falta de correlacao com a cineventriculografia limita o valor do eletrovetocardiograma para previsao do diagnostico cineangiografico

Queimadura extensa na vigencia de gravidez. / Extensive burn in pregnancy

Os autores relatam o caso de uma paciente de 24 anos, gravida na 14a. semana e com extensa area corporal queimada, perfazendo uma superficie de 54,8%. Salientam que o tratametno realizado, foi baseado apenas nos dados clinicos e laboratoriais deixando de labo as formas classicas de hidratacao do grande queimado, pois tratava-se de gestante e, portanto, apresentava alteracoes hemodinamicas peculiares. O prognostico foi favoravel tanto para o feto que nasceu prematuro, mas dentro dos padroes da normalidade, quanto para a mae que sobreviveu

Intoxicação digitálica: eletrofisiológica, clinica e terapêutica / Digitalis poisoning: electrophysiology, clinics and therapeutics

Manifestacoes toxicas sao frequentes em pacientes tratados com glicosideos digitalicos. Diversos fatores interferem com a farmacocinetica dessas substancias, potencializando sua acao. Os digitalicos modificam o potencial de acao das celulas cardiacas, determinando disturbio na formacao e conducao do estimulo. As oscilacoes transitorias do potencial diastolico de membrana constituem um dos principais mecanismos das arritmias digital-depedentes.Doses excessivas, ao induzirem aumento do automatismo e depressao da velocidade de conducao, determinam mais comumente taquiarritmias supraventriculares e ventriculares e disturbio na conducao atrio-ventricular. A precocidade no diagnostico, a suspensao imediata do medicamento e a correcao de desequilibrios hidro-eletroliticos contribuem para o sucesso terapeutico.O melhor conhecimento de farmacodinamica e acao eletrofisiologica dos digitalicos, assim como a determinacao dos niveis sericos e abandono das doses de ataque, propiciam a reducao da incidencia de efeitos toxicos

Traumatismo de la arteria poplitea en las luxaciones de rodilla. / Popliteal artery injuries in knee dislocations

Se analizan los traumatismos de arteria poplitea en las luxaciones de rodilla. Se encuentra casi un 30% de lesion de esta arteria en las luxaciones de esta articulacion. El porcentage de amputaciones es alto, 57%, encontrandose intima relacion con la demora en el tratamiento. Se comenta el mecanismo lesional que se explica por la disposicion anatomica del vaso. El tipo de lesion mas frecuente fue la contusion arterial. Se destaca la importancia del estudio arteriografico precoz para el diagnostico temprano. Se aconseja no plantear como causa de la isquemia el espasmo arterial ni el sindrome compartimental, a fin de no retrasar el diagnostico de lesion arterial. El unico tratamiento posible es el quirurgico, con el restablecimiento de la continuidad arterial como medio de salvar el miembro