Hepatic stellate cell activation in liver transplant patients with hepatitis C recurrence and in non-transplanted patients with chronic hepatitis C.

The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen-producing cells in the liver, can occur in these patients as compared to non-LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer-based morphometric analysis of alpha-smooth muscle actin (alphaSMA)-positive cells and the hepatic TGFbeta(1) expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non-LT patients with chronic hepatitis C, and 16 controls. Hepatic alphaSMA and TGFbeta(1) expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in alphaSMA and TGFbeta(1) expression was observed between LT and non-LT patients with hepatitis C, with the exception of a higher transforming growth factor beta-1 (TGFbeta(1)) expression in non-LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and alphaSMA and TGFbeta(1) expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFbeta(1) expression in the grafts of these patients as compared to non-LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFbeta(1) expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered.     

The main features of central 5-HT1 receptors

The 5-HT1 receptor family comprises five different pharmacologic subtypes, designated 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, and 5-HT1E, whose common property is to bind 5-HT with nanomolar affinity. Recent investigations with molecular biology approaches led to the cloning and sequencing of 5-HT1A receptors in the rat and in the human, and of the 5-HT1C receptor in the rat. Although the 5-HT1A and 5-HT1C protein binding subunits exhibit the same structure with seven hydrophobic transmembrane domains, an extracellular N terminal and an intracellular C tail, their respective amino-acid sequences are markedly different. Indeed, a higher degree of sequence homology is found between the 5-HT1C and 5-HT2 receptors than between the former and 5-HT1A receptors, suggesting that the 5-HT1C subtype in fact belongs to the 5-HT2 class of central 5-HT receptors. All other 5-HT1 receptor subtypes are negatively coupled to adenylyl cyclase, whereas the 5-HT1C subtype, like 5-HT2 receptors, is positively coupled to phospholipase C. The respective regional distributions and regulatory properties, as well as pending questions regarding the ultrastructural localization, synthesis, mutual interactions, and axonal flow of 5-HT1 receptor subtypes, are also discussed.     

Psychosocial factors associated with poor diabetes self-care management in a specialized Center in Mexico City

To examine the relationship between demographic, clinical and psychosocial variables and diabetes self-care management in Mexican type 2 diabetic patients. Cross-sectional study of 176 consecutive patients with type 2 diabetes aged 30-75 years, attending a tertiary health-care center in Mexico City. A brief medical history and previously validated questionnaires were completed. The study group consisted of 64 males/112 females, aged 55 +/- 11 years, mean diabetes duration of 12 +/- 8 years and HbA1c of 9.0 +/- 2.0%, 78.4% reported following the correct dose of diabetes pills or insulin, 58% ate the recommended food portions, and 44.3% did exercise three or more times per week. A good adherence to these three recommendations was observed in only 26.1% of the patients. These patients considered as a group were characterized by a greater knowledge about the disease (P < 0.00001), regular home blood glucose monitoring (P < 0.01), an inner perception of better diabetes control (P = 0.007), good health (P = 0.004) and better communication with their physician (P < 0.02). A poor adherence to two or the three main diabetes care recommendations was associated with a depressive state (OR 2.38, 95% CI 1.1-4.9, P < 0.01) and a history of excessive alcohol intake (OR 4.03, 95% CI 1.1-21.0, P = 0.03). Poor adherence to standard diabetes care recommendations is frequently observed in patients with type 2 diabetes attending a specialized health care center in Mexico City. Depression must be identified and treated effectively.     

Predicting spontaneous early neurological recovery after acute ischemic stroke

We assessed predictors of spontaneous early neurological recovery after acute ischemic stroke by means of multivariate analysis in a cohort of 1,473 consecutive patients treated at one academic center. At hospital discharge, spontaneous neurological improvement or good outcome was defined as grades 0-2 of the Rankin scale, and poor outcome (no improvement or in-hospital death) as grades 3-5. Spontaneous recovery of neurological deficit at the time of discharge from the hospital was observed in 16% of patients with cerebral infarction (n = 238). Dysarthria-clumsy hand syndrome improved in 44% of patients and was the only variable significantly associated with in-hospital functional recovery in three logistic regression models that in addition to lacunar syndromes, included demographic variables, cardiovascular risk factors, and clinical variables [odds ratio (OR) 2.56], neuroimaging findings (OR 2.48), and outcome data (OR 2.39), respectively. Clinical factors related to severity of infarction available at stroke onset have a predominant influence upon in-hospital outcome and may help clinicians to assess prognosis more accurately. Our work gives a contribution into prognostic factors after acute ischemic stroke. With regard to patterns of stroke, dysarthria-clumsy hand syndrome was a significant predictor of spontaneous in-hospital recovery in ischemic stroke patients.     

Propyl gallate delays senescence in Drosophila melanogaster

The effect of propyl gallate (PGL) on life span in Drosophila was investigated. Four groups of flies were supplemented as follows: group 1, no PGL; group 2, no PGL supplement until 28 days followed by 0.3% PGL for remaining life span; group 3, 0.3% PGL from 7 days to 28 days, then none for remaining life span; and group 4, 0.3% PGL from 7 days until death. In all cases, PGL significantly increased mean life span. The largest increase in mean life span (34.2%) was in the group receiving PGL for the entire life span (group 4). Increases of 14.6% and 14.7% were measured in groups 2 and 3, respectively.     

Natural infection of Oryctolagus cuniculus (Lagomorpha, Leporidae) by Gongylonema neoplasticum (Nematoda, Gongylonematidae) in Portugal

Gongylonema neoplasticum was identified in the oesophagus of 14 wild rabbits (Oryctolagus cuniculus) from Portugal. This is the first record of Gongylonema neoplasticum in a naturally infected lagomorph species in Europe. This paper presents the most relevant measurements of adult worms and some of their surface features seen by scanning electron microscopy. Epidemiological aspects of G. neoplasticum such as geographical distribution, host spectrum and biological features are discussed.     

Metabolic disorders in survivors of myocardial infarct

Several lines of evidence have clearly established the role of lipoproteins as risk factors for the development of atherosclerosis. Epidemiologic studies from different countries have found that about one third of myocardial infarction survivors under 60 years of age are hyperlipidemic. The acute stress reaction occurring in the first hours following an acute myocardial infarction causes distinct changes in the patient's metabolic profile, these changes include a significant reduction of total cholesterol and cholesterol associated with low density lipoproteins and a usually mild elevation of blood glucose. With the purpose of establishing the prevalence and severity of lipoprotein disorders found in myocardial infarction survivors living in Mexico city we conducted a prospective study of 106 consecutive admissions to the coronary care unit at the National Institute of Cardiology with the fully proven diagnosis of acute myocardial infarction, we included only patients younger than 60 years of age that could be sampled within the first 72 hours of the appearance of typical symptoms, at this time the coronary risk factor profile was assessed and blood samples were drawn (acute sample). After three months of the diagnosis we sampled 81 of the original 106 patients (chronic sample). The comparison of these 81 patients showed remarkable differences in the lipid values obtained on each sample. The mean value for total cholesterol in the acute sample was 225 mg/dl whereas the corresponding value for the chronic sample was 240.5 mg/dl (p less than 0.005). This difference was also highly significant for the low density fraction. On the basis of the chronic sample analysis we estimated a prevalence of hyperlipoproteinemia of 35.8%. (II: 18.5%, III: 2.5%, IV: 14.8%), an additional subgroup of 10 patients (12.3%) had the hypo-HDL phenotype raising the number of subjects at risk for atherosclerosis to as high as 48.1% considering only the lipoproteins. The prevalence figures for the rest of the risk factors were as follows: 70.3% for tobacco smoking, 35.8% for Systemic Arterial Hypertension, 33.4% for Obesity and 30.8% for Diabetes Mellitus. Among the group of 81 patients, 17 were known diabetics, eight additional cases of Diabetes Mellitus were diagnosed at the chronic phase (two with fasting hyperglycemia and six with diagnostic oral glucose tolerance tests). The "acute plase" glycemia for these eight subjects was significantly higher (mean: 98.4 mg/dl) than the corresponding value for the non diabetic patients (mean: 83.4 mg/dl p less than 0.002), the seventeen known diabetics had a mean glycemia of 150.6 mg/dl in the acute sample.(ABSTRACT TRUNCATED AT 400 WORDS)     

The role of Serratia marcescens porins in antibiotic resistance

The outer membrane permeability of Serratia marcescens was studied by comparing porin-deficient mutants with their parental strains. Omp1-deficient strains were selected by moxalactam resistance, whereas mutants lacking the Omp2 porin were obtained by experimental infection with the SMP2 phage, whose primary receptor is the Omp2 porin. The role of porins was demonstrated in quinolone accumulation assays, where semiquantitative differences in accumulation were observed. Permeability coefficients to cephaloridine of Omp1 mutants were determined and compared with those of the parental strain. The clinical isolates S. marcescens HCPR1 and 866 showed 30- to 200-fold reduced permeability coefficients when Omp1 porin was absent.     

Mutation analysis of the SDHD gene in four kindreds with familial paraganglioma: description of one novel germline mutation.

The familial paraganglioma syndrome is an autosomal dominant disorder characterized by the presence of carotid body paragangliomas and, less frequently, paragangliomas of the glomus jugulare, glomus vagale, and adrenal pheochromocytomas. Germline mutations of the genes for succinate dehydrogenase subunits D, B, or C (SDHD, SDHB, SDHC) have been identified in some kindreds with familial paraganglioma. In this study, we report the clinicopathologic features of four different kindreds with familial paraganglioma, which were screened for germline mutations in the SDHD gene. DNA was obtained from tumor and normal tissue, as well as from peripheral blood. Mutation analysis was performed by single-strand conformation polymorphism analysis and DNA sequencing. SDHD germline mutations were detected in the affected family members of the four families, as well as in several asymptomatic carriers. An identical mutation in exon 4 of SDHD (334-337delACTG) was identified in two apparently unrelated kindreds. The third family showed a germline mutation in exon 2 (W43X). The mutations present in these three families had been previously described in Spanish families, suggesting a founder effect. The fourth family exhibited a mutation in exon 2 of SDHD (170-171delTT), which had not been previously identified. The affected family members of the four kindreds showed paragangliomas, located in the head and neck region, and all of them were benign. These results confirm that genetic testing of SDHD may be a powerful tool for the identification of the syndrome in patients with multiple or bilateral paragangliomas.