Relative abundance and population biology of the non-indigenous crab Charybdis hellerii (Crustacea: Brachyura: Portunidae) in a southwestern Atlantic estuary-bay complex

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparison of peri-operative core temperature in obese and non-obese patients*

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease

Canavan disease, an inherited leukodystrophy, is caused by mutations in the aspartoacylase (ASPA) gene. It is most common among children of Ashkenazi Jewish descent but has been diagnosed in many diverse ethnic groups. Two mutations comprise the majority of mutant alleles in Jewish patients, while mutations in the ASPA gene among non-Jewish patients are different and more diverse. In the present study, the ASPA gene was analysed in 22 unrelated non-Jewish patients with Canavan disease, and 24 different mutations were found. of these,14 are novel, including five missense mutations (E24G, D68A, D249V, C152W, H244R), two nonsense mutations (Q184X, E214X), three deletions (923delT, 33del13, 244delA), one insertion mutation (698insC), two sequence variations in one allele ([10T>G; 11insG]), an elimination of the stop codon (941A>G, TAG-->TGG, X314W), and one splice acceptor site mutation (IVS1 - 2A>T). The E24G mutation resulted in substitution of an invariable amino acid residue (Glu) in the first esterase catalytic domain consensus sequence. The IVS1 - 2A>T mutation caused the retention of 40 nucleotides of intron 1 upstream of exon 2. The results of transient expression of the mutant ASPA cDNA containing these mutations in COS-7 cells and assays for ASPA activity of patient fibroblasts indicated that these mutations were responsible for the enzyme deficiency. In addition, patients with the novel D249V mutation manifested clinically at birth and died early. Also, patients with certain other novel mutations, including C152W, E214X, X314W, and frameshift mutations in both alleles, developed clinical manifestations at an earlier age than in classical Canavan disease.

Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients

Background. About 130 million people are infected with the hepatitis C virus (HCV) worldwide, but effective treatment options are not yet available. One of the most promising targets for antiviral therapy is nonstructural protein 3 (NS3). To identify possible changes in the structure of NS3 associated with virological sustained response or non-response of patients, a model was constructed for each helicase NS3 protein coding sequence. From this, the goal was to verify the interaction between helicases variants and their ligands. Findings. Evidence was found that the NS3 helicase portion of non-responder patients contained substitutions in its ATP and RNA binding sites. K210E substitution can cause an imbalance in the distribution of loads, leading to a decrease in the number of ligations between the essential amino acids required for the hydrolysis of ATP. W501R substitution causes an imbalance in the distribution of loads, leading and forcing the RNA to interact with the amino acid Thr269, but not preventing binding of ribavirin inhibitor. Conclusions. Useful information is provided on the genetic profiling of the HCV genotype 3, specifically the coding region of the NS3 protein, improving our understanding of the viral genome and the regions of its protein catalytic site. © 2010 Rahal et al; licensee BioMed Central Ltd.

Modulation of Immune Response by RAGE and TLR4 Signalling in PBMCs of Diabetic and Non-Diabetic Patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Modulation of immune response by RAGE and TLR4 signalling in PBMCs of diabetic and non-diabetic patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Icodextrin reduces insulin resistance in non-diabetic patients undergoing automated peritoneal dialysis: results of a randomized controlled trial (STARCH)

Insulin resistance is a common risk factor in chronic kidney disease patients contributing to the high cardiovascular burden, even in the absence of diabetes. Glucose-based peritoneal dialysis (PD) solutions are thought to intensify insulin resistance due to the continuous glucose absorption from the peritoneal cavity. The aim of our study was to analyse the effect of the substitution of glucose for icodextrin on insulin resistance in non-diabetic PD patients in a multicentric randomized clinical trial. This was a multicenter, open-label study with balanced randomization (1:1) and two parallel-groups. Inclusion criteria were non-diabetic adult patients on automated peritoneal dialysis (APD) for at least 3 months on therapy prior to randomization. Patients assigned to the intervention group were treated with 2L of icodextrin 7.5%, and the control group with glucose 2.5% during the long dwell and, at night in the cycler, with a prescription of standard glucose-based PD solution only in both groups. The primary end-point was the change in insulin resistance measured by homeostatic model assessment (HOMA) index at 90 days. Sixty patients were included in the intervention (n = 33) or the control (n = 27) groups. There was no difference between groups at baseline. After adjustment for pre-intervention HOMA index levels, the group treated with icodextrin had the lower post-intervention levels at 90 days in both intention to treat [1.49 (95% CI: 1.23-1.74) versus 1.89 (95% CI: 1.62-2.17)], (F = 4.643, P = 0.03, partial η(2) = 0.078); and the treated analysis [1.47 (95% CI: 1.01-1.84) versus 2.18 (95% CI: 1.81-2.55)], (F = 7.488, P = 0.01, partial η(2) = 0.195). The substitution of glucose for icodextrin for the long dwell improved insulin resistance measured by HOMA index in non-diabetic APD patients.

Can Delivery Dialysis Dose Affect Survival of Acute Kidney Injury Patients?

Intensity of dialysis dose in acute kidney injury (AKI) might benefit critically ill patients. The aim of this study was to evaluate the effect of intermittent hemodialysis (IHD) dose on mortality in patients with AKI. Methods: Prospective observational study was performed on AKI patients treated with IHD. The delivered dialysis dose per session was calculated based on single-pool Kt/V urea. Patients were allocated in two groups according to the weekly delivered median Kt/V: higher intensity dialysis dose (HID: Kt/V higher than median) and lower intensity dialysis dose (LID: Kt/V lower than median). Thereafter, AKI patients were divided according to the presence or absence of sepsis and urine output. Clinical and lab characteristics and survival of AKI patients were compared. Results: A total of 121 AKI patients were evaluated. Forty-two patients did not present with sepsis and 45 did not present with oliguria. Mortality rate after 30 days was lower in the HID group without sepsis (14.3% x 47.6%; p = 0.045) and without oliguria (31.8% x 69.5%; p = 0.025). Survival curves also showed that the HID group had higher survival rate when compared with the LID group in non-septic and non-oliguric patients (p = 0.007 and p = 0.003, respectively). Conclusion: Higher dialysis doses can be associated with better survival of less seriously ill AKI patients.

DNA damage in patients infected by Helicobacter pylori

Helicobacter pylori (H. pylori) is considered to predispose carriers to gastric cancer but its role on gastric carcinogenesis is still unknown. The aim of this study was to investigate DNA damage by the comet assay in gastric epithelial cells from antrum and corpus in H. pylori-infected patients with gastritis of different degrees. H. pylori status, gastric histology, and DNA damage were studied in 62 H. pylori-infected and 18 non-infected patients, all of them non-smokers, nonalcoholics, and non-drug users. DNA damage was significantly higher in H. pylori-infected patients presenting gastritis than in non-infected patients with normal mucosa. A direct correlation between the levels of DNA damage and the intensity of gastritis was observed in H. pylori-infected patients. Association between DNA damage and age was also found. The levels of DNA damage were significantly higher in patients older than 50 years than in younger patients with the same degree of gastritis. Our results indicate that H. pylori infection is associated with DNA damage in gastric epithelial cells, which could be a biomarker of risk for gastric cancer in humans.

Cyclosporin A-induced gingival overgrowth in renal transplant patients

Background: the incidence of gingival overgrowth (GO) associated with the use of cyclosporin A (CsA) is controversial. In the present study, we determined the incidence of GO in Brazilian renal transplant patients treated with CsA and the possible associations between periodontal and pharmacological variables.Methods: the test group consisted of 20 renal transplant patients, and the control group included 20 non-transplant patients. Periodontal conditions were evaluated based on the plaque index (PI), gingival index (GI), probing depth (PD), and the rate of gingival overgrowth, together with pharmacological variables (daily CsA dose and duration of treatment).Results: A significant difference in PI (P<0.0001) and PD (P<0.0001) was observed between groups, while GI (P=0.15) did not differ significantly. Using the Pearson correlation coefficient, a significant correlation was observed not only between GI (P<0.001; r=0.8141) and GO, but also for PD (P<0.001; r=0.866) and GO. The other correlations were not statistically significant.Conclusions: We conclude that GO induced by CsA may vary according to the individual sensitivity of each patient and may or may not be correlated with other local factors (periodontal variables).

Psychopathological features in patients with Parkinson's disease and related caregivers' burden

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Use of comet assay to assess DNA damage in patients infected by Helicobacter pylori - Comparisons between visual and image analyses

Studies of DNA damage in gastric epithelial cells of Helicobacter pylori (H. pylori)-infected patients are conflicting, possibly due to different methods used for scoring DNA damage by Comet assay. Therefore, we compared the sensitivity of visual microscopic analysis (arbitrary units-scores and comets%) and image analysis system (tail moment), in the gastric epithelial cells from the antrum and corpus of 122 H. pylori-infected and 32 non-infected patients. The feasibility of cryopreserved peripheral blood lymphocytes and whole-blood cells for DNA damage biomonitoring was also investigated. In the antrum, the levels of DNA damage were significantly higher in H. pylori-infected patients with gastritis than in non-infected patients with normal mucosa, when evaluated by image analysis system, arbitrary units and comets%. In the corpus, the comets% was not sufficiently sensitive to detect the difference between H. pylori-infected patients with gastritis and non-infected patients with normal mucosa. The image analysis system was sensitive enough to detect differences between non-infected patients and H. pylori-infected patients with mild gastritis and between infected patients with moderate and severe gastritis, in both antrum, and corpus, while arbitrary units and comets% were unable to detect these differences. In cryopreserved peripheral blood lymphocytes, the levels of DNA damage (tail moment) were significantly higher in H. pylori-infected patients with moderate and severe gastritis than in non-infected patients. Overall, our results indicate that the image analysis system is more sensitive and adequate to measure the levels of DNA damage in gastric epithelial cells than the other methods assayed. (c) 2005 Elsevier B.V. All rights reserved.

The results of a randomized trial looking at 24 weeks vs 48 weeks of treatment with peginterferon alpha-2a (40 kDa) and ribavirin combination therapy in patients with chronic hepatitis C genotype 1

Peginterferon-alpha plus ribavirin is the most effective therapy for chronic hepatitis C. This study was designed to evaluate the effect of peginterferon alpha-2a (40 kDa) plus ribavirin on sustained virological response (SVR) when administered for 24 vs 48 weeks in genotype 1 naive patients. One hundred and seventeen patients were enrolled in this controlled trial. Genotype 1 patients were randomized to 24 weeks treatment vs 48 weeks treatment. Genotype non-1 patients received 24 weeks treatment as an observational group. Outcomes were SVR (defined by hepatitis C virus-RNA-negative at week 24 of follow-up) and tolerability across the study period. The end-of-treatment response was 59% for genotype 1 (24 weeks treatment), 80% for genotype 1 (48 weeks treatment) and 92% for genotype non-1 (24 weeks treatment). The end-of-follow-up response was 19% (95% confidence interval (CI): 7.2-36.4) (genotype 1, 24 weeks) and 48% (95% CI: 30.2-66.9; P = 0.0175) (genotype 1, 48 weeks). Among genotype non-1, SVR was 76% (95% CI: 62.3-86.5). There were no unexpected adverse events.Almost half of the genotype 1 patients achieved an SVR after 48 weeks treatment with peginterferon alpha-2a (40 kDa) and low-dose ribavirin and confirmed that they should be treated for 48 weeks. Safety profile was acceptable.

Long-term clinical and ultrasonographic evaluation of thrombophilic patients with deep venous thrombosis

OBJECTIVE:The purpose of this study was to evaluate the long term clinical and ultrasonographic outcomes of thrombophilic patients with deep venous thrombosis (DVT).METHOD:Cohort study, retrospective case-control with cross-sectional analysis. Thirty-nine thrombophilic patients and 25 non-thrombophilic patients were assessed 76.3 ± 45.8 months after diagnosis. Demographic and family data were collected, as well as data from clinical and therapeutic progress, and physical and ultrasound examinations of the limbs were performed. Groups were matched for age and gender and the variables studied were compared across groups.RESULTS:Deep venous thrombosis was more frequent in women. The most common thrombophilias were antiphospholipid syndrome and factor V Leiden mutation. There was no difference between groups in terms of the number of pregnancies or miscarriages and the majority of women did not become pregnant after DVT. Non-spontaneous DVT prevailed. Proximal DVT and DVT of the left lower limb were more frequent, and the main risk factor was use of oral contraceptives. All patients were treated with anticoagulation. There was a higher frequency of pulmonary embolism in non-thrombophilic patients. Most patients considered themselves to have a normal life after DVT and reported wearing elastic stockings over at least 2 years. Seventy-one percent of patients had CEAP > 3, with no difference between groups. Deep venous reflux was more frequent in thrombophilic patients.CONCLUSION:There were no significant differences between groups with respect to most of the variables studied, except for a higher frequency of pulmonary embolism in non-thrombophilic patients and greater frequency of deep venous reflux in thrombophilic patients.