Search

Background: The cashew stem borer Anthistarcha binocularis (Meyrick) is a major pest in cashew orchards in Brazil. The damage caused by the larvae results in economic losses, and the available chemical control is not suitable because of the endophytic nature of A. binocularis. The identification of the A. binocularis sex pheromone could provide novel applications for the detection and monitoring of this species., Results: Two compounds from female sex gland extracts elicited electrophysiological responses on male antennae. They were identified as dodec-6-en-1-ol and dodec-6-en-1-yl acetate by gas chromatography-mass spectrometry. E/Z stereoisomers of both compounds were synthesized, and the electroantennograms for the synthetic compounds showed the strongest responses for the (E)-stereoisomers of the alcohol and acetate. In a field trial, the E6-12:OH/E6-12:OAc mixture attracted male A. binocularis, whereas the Z6-12:OH/Z6-12:OAc mixture attracted no specimens., Conclusions: The bioactive compounds from the sex pheromone of A. binocularis have been identified as a mixture of two previously unidentified pheromone compounds: E6-12:OH and E6-12:OAc. The mixture of both compounds was attractive to males in preliminary field experiments, and this study is the first report of Δ6-unsaturated monoenyl pheromone compounds in Lepidoptera. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

The Epstein-Barr virus (EBV)-positive mucocutaneous ulcer is a rare entity in the spectrum of lymphoproliferative diseases associated with the EBV. It occurs typically in patients with immunosuppression associated with immunosenescence, as well as due to iatrogenic causes, posttransplant patients and primary immunodeficiency disorders. It is often a benign and self-limited disease that recedes by stopping or reducing the immunosuppressive agents in most of the cases. Histologically, it is characterized by a population of EBV-positive atypical lymphoid cells. Here, we present a rare case of a 5-month-old pediatric patient, born preterm at 24 weeks of gestational age, presenting a lump on the right shoulder, later evolving to EBV-positive mucocutaneous ulcer.

Background & Aims: Genetic factors may impact nonalcoholic fatty liver disease (NAFLD) severity. We aimed to assess the prevalence of patatin-like phospholipase domain-containing 3 protein (PNPLA3) gene rs738409 C > G polymorphism in Brazilian individuals with type 2 diabetes and to investigate its association with liver disease severity, diabetic chronic degenerative complications, and metabolic control., Methods and Results: PNPLA3 genotyping was performed and classified as CC, CG, and GG. Clinical and laboratory data were obtained, including chronic degenerative diabetes complications. Liver stiffness and steatosis were evaluated by transient hepatic elastography with CAP using FibroScan®. Multiple logistic regression was performed to investigate the association of PNPLA3 G allele with clinical and laboratory variables and with hepatic fibrosis/steatosis. Three hundred three patients were included (118 male, mean age 59 ± 9.5 years). The G allele frequency was 32.5% (CC 47%, CG 41%, and GG 12%). Significant liver fibrosis and severe steatosis were diagnosed in 26% and 43% of patients, respectively. The variables independently associated with the G allele were coronary artery disease (OR: 2.25; 95% CI: 1.03-4.88; p = 0.04), better glycemic control (OR for having an HbA 1c  ≥ 8% [64 mmol/mol]: 0.53; 95% CI: 0.31-0.89; p = 0.01), and significant liver fibrosis (OR: 1.82; 95% CI: 1.04-3.17; p = 0.03)., Conclusion: In individuals with diabetes and NAFLD, PNPLA3 gene rs738409 C > G polymorphism is a marker for the risk of significant liver fibrosis and cardiovascular disease and may be associated with better glycemic control., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect., Materials and Methods: Male Wistar rats received SF juice (4 mL/100 g body weight) by gavage after a 12 h fasting and water deprivation. Fasting and water deprivation continued for 6 h thereafter to warrant juice absorption. Thereafter, animals were allocated to three experimental groups: SF (n = 6): received tap water; SF + NAC (n = 6): received NAC (4.8 g/L) in drinking water for 48 h after gavage; and Sham (n = 6): no interventions. After 48 h, inulin clearance studies were performed to determine glomerular filtration rate. In a second series of experiment, rats were housed in metabolic cages for additional assessments., Results: SF rats showed markedly reduced inulin clearance associated with hyperoxaluria, renal tubular damage, increased oxidative stress and inflammation. NAC treatment ameliorated all these alterations. Under polarized light microscopy, SF rats exhibited intense calcium oxalate birefringence crystals deposition, dilation of renal tubules and tubular epithelial degeneration, which were attenuate by NAC therapy., Conclusions: Our data show that therapeutic NAC attenuates renal dysfunction in a model of acute oxalate nephropathy following SF ingestion by reducing oxidative stress, oxaluria, and inflammation. This might represent a novel indication of NAC for the treatment of SF-induced AKI.

Objective and Background: The aim of this in vitro study was to compare the efficiency of a photodynamic therapy (PDT) technique employing rose bengal (RB) and methylene blue (MB) as photosensitizers (PSs) to reduce the viability of Enterococcus faecalis, a well-known pathogen found in root canal systems. Currently, in several clinical applications, including in the field of endodontics, MB is employed in association with a red laser source for the photoinactivation of pathogenic bacteria., Methods: In this study, MB was used at 0.01% (31.2 mol/L) in association with a red (660 nm) laser as the excitation source in the MB group (MBG). Alternatively, the same test was performed with RB (25 mol/L) that was associated with a green (532 nm) light laser source in the RB group (RBG). A saline solution (0.9%) was used in the control group. The colony-forming units per milliliter (CFU/mL) were calculated after 24 h of incubation at 37°C, and the statistical analysis was performed using ANOVA., Results: The results showed a significant reduction in the CFU/mL in the RBG group (0.12 × 10 8 ) compared with the control (2.82 × 10 8 ) and MBG groups (2.66 × 10 8 ). For the concentration and laser intensity employed in the experiments, the MBG group repeatedly showed no significant reduction in bacterial counts compared with the control. Therefore, the best result regarding the reduction of E. faecalis viable cells was obtained with RB as the PS., Conclusions: PDT may be improved if RB is used in association with a green light laser source for the inactivation of E. faecalis.

Introduction: Members of the Acinetobacter genus are key pathogens that cause healthcare-associated infections, and they tend to spread and develop new antibiotic resistance mechanisms. Oxacillinases are primarily responsible for resistance to carbapenem antibiotics. Higher rates of carbapenem hydrolysis might be ascribed to insertion sequences, such as the ISAba1 sequence, near bla OXA genes. The present study examined the occurrence of the genetic elements bla OXA and ISAba1 and their relationship with susceptibility to carbapenems in clinical isolates of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex., Methods: Isolates identified over 6 consecutive years in a general hospital in Joinville, Southern Brazil, were evaluated. The investigation of 5 families of genes encoding oxacillinases and the ISAba1 sequence location relative to bla OXA genes was conducted using polymerase chain reaction., Results: All isolates presented the bla OXA-51-like gene (n = 78), and 91% tested positive for the bla OXA-23-like gene (n = 71). The presence of ISAba1 was exclusively detected in isolates carrying the bla OXA-23-like gene. All isolates in which ISAba1 was found upstream of the bla OXA-23-like gene (n = 69) showed resistance to carbapenems, whereas the only isolate in which ISAba1 was not located near the bla OXA-23-like gene was susceptible to carbapenems. The ISAba1 sequence position of another bla OXA-23-like-positive isolate was inconclusive. The isolates exclusively carrying the bla OXA-51-like gene (n = 7) showed susceptibility to carbapenems., Conclusions: The presence of the ISAba1 sequence upstream of the bla OXA-23-like gene was strongly associated with carbapenem resistance in isolates of the A. calcoaceticus-A. baumannii complex in the hospital center studied.

Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L(-1) against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

Introduction: Carbapenems are the therapy of choice for treating severe infections caused by the Acinetobacter calcoaceticus-Acinetobacter baumannii complex. We aimed to assess the prevalence and antimicrobial susceptibility profiles of producers of distinct oxacillinases among nosocomial isolates of the A. calcoaceticus-A. baumannii complex in a 249-bed general hospital located in Joinville, Southern Brazil., Methods: Of the 139 A. baumannii clinical isolates with reduced susceptibility to carbapenems between 2010 and 2013, 118 isolates from varying anatomical sites and hospital sectors were selected for genotypic analysis. Five families of genes encoding oxacillinases, namely blaOXA-23-like, blaOXA-24-like, bla(OXA-51-like), bla(OXA-58-like), and blaOXA-143-like, were investigated by multiplex polymerase chain reaction (PCR)., Results: Most (87.3%) isolates simultaneously carried the bla(OXA-23-like) and bla(OXA-51-like) genes, whereas three (2.5%) isolates harbored only blaOXA-51-like ones. The circulation of carbapenem-resistant isolates increased during the study period: from none in 2010, to 22 in 2011, 64 in 2012, and 53 in 2013., Conclusions: Isolates carrying the bla(OXA-23-like) and bla(OXA-51-like) genes were widely distributed in the hospital investigated. Because of the worsening scenario, the implementation of preventive measures and effective barriers is needed.

Purpose: To investigate the association between genetic, behavioral, biological and medical risk factors and the occurrence of preterm birth., Methods: A retrospective case-control study was conducted. The real-time polymerase chain reaction was used to analyze the influence of the rs12473815 polymorphism of the follicle stimulating hormone receptor gene (FSHR) and the rs1942836 polymorphism of the progesterone receptor gene (PGR). Other proposed risk factors were assessed using validated or specifically developed questionnaires and analysis of electronically recorded medical data. A total of 157 patients were included (45 cases who went into labor before 37 weeks of pregnancy and 112 controls who went into labor after 37 and before 42 weeks of pregnancy)., Results: The genotypes CT of rs12473815 and CT and CC of rs1942836 were associated with a higher chance of premature delivery. There was an association between preterm birth and alcohol intake when consumption occurred 2 or more times per month. Low pre-pregnancy body mass index was a predictor of spontaneous preterm birth, while high body mass index reduced this likelihood., Conclusions: The results suggest that excessive alcohol intake, a low level of pre-pregnancy body mass and the risk alleles of rs12473815 and rs1942836 polymorphisms of the FSHR and PGR genes, respectively, influence the occurrence of preterm birth.

Objectives: To evaluate the occurrence of systemic and renal abnormalities in the offspring of Wistar rats exposed to tenofovir disoproxil fumarate (DF) during pregnancy., Methods: Female Wistar rats received a standard diet, with or without addition of tenofovir DF (100 mg/kg diet), 1 week before mating and during pregnancy. Offspring from the tenofovir DF group were placed with an untreated foster mother during breastfeeding and compared with offspring from rats maintained on a standard diet during mating and pregnancy (control). Control and tenofovir DF were followed up at 3 and 6 months of age. Monthly body weight and systolic blood pressure (SBP), glomerular counts, renal function, biochemical parameters, angiotensin II, renal renin angiotensin aldosterone system (RAAS) and renal sodium transporters were analysed., Results: Tenofovir DF offspring showed lower birth weight compared with the control group. After the third month, growth among the tenofovir DF group experienced a rapid catch-up. SBP increased progressively after the second month of age in the tenofovir DF group. Nephron number did not differ between the groups; however, the tenofovir DF group showed glomerular structural changes. Plasma aldosterone was higher in the tenofovir DF group, associated with a significant increase in renal expression of RAAS. The tenofovir DF rats showed up-regulation of renal sodium transporters and consequently lower urinary sodium excretion., Conclusions: This is the first demonstration using an experimental model that maternal exposure to tenofovir DF during gestation results in overactivation of RAAS, up-regulation of renal sodium transporters and hypertension in the offspring., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Single-nucleotide polymorphisms (SNPs) associated with hepatitis C virus (HCV) clearance were identified near the IL28B gene. Coinfection by the human immunodeficiency virus (HIV) influences the course of HCV contributing to liver damage. Nevertheless, little is known about the relationship between these SNPs and HCV/HIV coinfection. Our aim was to estimate the frequencies of the allelic and genotypic variants of the IL28B polymorphisms rs12979860 (C/T) and rs8099917 (T/G) and their possible association with the establishment of HCV infection., Methodology: A total of 199 non-infected controls and 230 patients with chronic hepatitis C, including 53 coinfected with HIV, participated in the study. Genotyping consisted of polymerase chain reaction and subsequent analysis of the restriction patterns resulting from exposure to endonucleases., Results: Among the controls with established results, 47.4% (90/190) exhibited the rs12979860 CC genotype, 43.7 CT, and 8.9% TT, whereas 29.1% (66/227), 51.5%, and 19.4% of the patients exhibited the CC, CT, and TT genotypes, respectively. With respect to rs8099917, 66.8% (133/199) of the controls exhibited the TT genotype, 31.2% TG, and 2.0% GG, whereas 56.1% (129/230), 40.9%, and 3.0% of the patients exhibited the TT, TG, and GG genotypes, respectively., Conclusion: The frequencies of the rs12979860 C allele and CC genotype and of the rs8099917 T allele and TT genotype were significantly higher among controls compared with patients, thus confirming the suggested protective effect against HCV infection. No significant difference was observed in the genotype and allelic distributions between the mono- and coinfected patients.

Objective: To assess the association of the G54D (rs1800450) polymorphism of the gene MBL2 in the gestational diabetes mellitus with the need for additional treatment and the occurrence of large newborns for the gestational age., Subjects and Methods: One hundred and five patients recruited in Joinville--Brazil were evaluated between November 2010 and October 2012. Pregnant women were divided in two groups correspondents to the presence (n = 37) or absence (n = 68) of the mutant allele. The variants of the polymorphism G54D were identified by restriction fragment lengths polymorphisms (RFLP). Anthropometric and biochemical parameters of the mother and the newborn, and the necessity of additional therapy associated with diet were assessed as the primary outcomes., Results: Thirty-five point two percent of the evaluated patients carried at least one mutated allele of G54D polymorphism. There were no significant differences in weight gain, parity, age, body mass index and gestational age of arrival at maternity between the two groups. The groups of patients with or without the mutated allele did not differ in the need for additional treatment associated with diet (16.2% vs. 26.7%) respectively and with the occurrence of large newborns for gestational age (24.3% vs. 13.2%)., Conclusion: Our data showed that the polymorphism G54D of the gene MBL2 had no effect in the need for additional treatment associated with the diet-based therapy and in the occurrence of large newborns for gestational age in the studied population.

Informed consent is recognized as a primary ethical requirement to conduct research involving humans. In the investigations with the use of human biological material, informed consent (IC) assumes a differentiated condition on account of the many future possibilities. This work presents suitable alternatives for IC regarding the storage and use of human biological material in research, according to new Brazilian regulations. Both norms - Resolution 441/11 of the National Health Council, approved on 12 May 2011, and Ordinance 2.201 (NATIONAL GUIDELINES FOR BIOREPOSITORIES AND BIOBANKS OF HUMAN BIOLOGICAL MATERIAL FOR RESEARCH PURPOSE) of the Brazil Ministry of Health, approved on 14 September 2011 - state that the consent of subjects for the collection, storage and use of samples stored in Biobanks is necessarily established by means of a Free and Informed Consent Form (ICF). In order to obtain individual and formal statements, this form should contain the following two mutually exclusive options: an explanation about the use of the stored material in each research study, and the need for new consent or the waiver thereof when the material is used for a new study. On the other hand, ICF suitable for Biorepositories must be exclusive and related to specific research. Although Brazilian and international regulations identify the main aspects to be included in the IC, efforts are still necessary to improve the consent process, so that the document will become a bond of trust between subject and researcher., (© 2012 John Wiley & Sons Ltd.)

Context: Syzygium cumini (L.) Skeels (Myrtaceae) is a tree with dark purple fruits, popularly known as "jambolão" or "jambolan". In folk medicine, this plant is used for the treatment of diabetes and inflammatory conditions., Objective: We investigated the antinociceptive effect of ethanol extract (EE) from S. cumini leaves on orofacial nociception., Material and Methods: The antinociceptive effects of the EE obtained from the leaves of S. cumini were evaluated in mice using formalin- and glutamate-induced orofacial nociception., Results: ESI-MS/MS analyses demonstrated that major constituents in the analyzed samples coincided with the mass of the phenolic acids and flavonoids. In pharmacological approach, pre-treatment with EE (100, 200, or 400 mg/kg, p.o.) significantly reduced (p<0.05 or p<0.01) the percentage of paw licks time during phase 2 (43.2, 47.1, and 57.4%, respectively) of a formalin pain test when compared to control group animals. This effect was prevented by pretreatment with glibenclamide and N(G)-nitro-l-arginine (l-NOARG). The extract, all doses, also caused a marked inhibition (p<0.01 or p<0.001) of glutamate-induced orofacial nociception (38.8, 51.7, and 54.7%) when compared with the control group. No effect was observed with the rota-rod model., Conclusions: We can suggest that the antinociceptive effect of the EE is mediated by peripheral mechanisms, possibly involving KATP channels and the nitric oxide pathways. These effects appear to be related to the presence of flavonoids compounds, such as quercetin.

Context: Crohn's disease is characterized by a chronic and debilitating inflammatory disorder of the gastrointestinal tract. Several factors may contribute to its development. From extensive studies of the human genome, the polymorphism T300A of the gene ATG16L1 (autophagy-related 16-like 1) has been related to increased risk of developing this disease., Objectives: Analyze the role of polymorphism T300A (rs2241880) in patients with Crohn's disease., Methods: 238 samples from (control group) and 106 samples from patients with Crohn's disease recruited at five Southern Brazilian reference centers were evaluated. The genotyping consisted of the amplification via Polymerase Chain Reaction of the genomic segment encompassing T300A, followed by Restriction Fragment Length Polymorphism analysis. The amplicons and fragments were separated by agarose gel electrophoresis and confirmed under ultraviolet light., Results: The genotype AG was more prevalent among patients and controls (50% vs 44.8%), followed by genotypes AA (26.4% vs 35.1%) and GG (23.6% vs 20.1%). The frequency of the allele G of the polymorphism T300A was higher in the group of patients with Crohn's disease (48.6%) than in controls (42.4%), although not reaching statistical significance., Conclusions: It was not possible to confirm the increased susceptibility on development of Crohn's disease conferred by polymorphism T300A.

Indole alkaloids comprise a large and complex class of natural products found in a variety of marine sources. Infectious diseases remain a major threat to public health, and in the absence of long-term protective vaccines, the control of these infectious diseases is based on a small number of chemotherapeutic agents. Furthermore, the emerging resistance against these drugs makes it urgently necessary to discover and develop new, safe and, effective anti-infective agents. In this regard, the aim of this review is to highlight indole alkaloids from marine sources which have been shown to demonstrate activity against infectious diseases.

Aim: To analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians., Methods: A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon α-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients., Results: SNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07)., Conclusion: The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.

Aim: The aim of this study is to assess the coronal marginal leakage of three temporary restorative materials used for root canal sealing after endodontic treatment., Materials and Methods: A total of 88 single-rooted teeth were submitted to biomechanical preparation and filled by lateral condensation technique. After obturation process, the teeth were randomly separated into four groups, being two teeth of each group used as positive and negative control. Temporary sealing was performed as follows: GI - Clip F (VOCO); GII - Bioplic (Biodinβmica); GIII - Vitremer (3M ESPE) and GIV - Ketak N100 (3M ESPE). Next, the specimens were immersed into Indian ink for 30 and 60- days, being 10 specimens for each time interval and then submitted to diaphanization to verify the amount of coronal leakage using a measuring microscope., Results: Leakage mean values within the 30-day period were as follows: Vitremer (0.3 mm), Ketak N100 and Clip F (0.6 mm) and Bioplic (1.7 mm). Within the 60-day period, leakage means were 1.1 mm, 1.5 mm, 2.2 mm and 2.6 mm, respectively., Conclusions: None of the materials was capable of preventing marginal leakage within the 30- and 60-day period. In both time intervals, Bioplic presented the highest mean of leakage and Vitremer the lowest.

Background: High blood pressure represents a major public health problem. Worldwide, approximately one fourth of the adult population has hypertension. Epidemiological and experimental studies suggest a linkage between hyperuricemia and hypertension. Hyperuricemia affects 25-40 % of patients with untreated hypertension. A much lower prevalence has been reported in normotensives or in the general population. However, whether lowering serum uric acid (SUA) might lower blood pressure (BP) is an unanswered question., Objectives: To determine whether uric acid lowering agents reduce BP in patients with primary hypertension., Search Methods: Electronic searches of the following sources were performed without language restriction: Cochrane Hypertension Group Specialised Register (1946 to May 2012), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012 Issue 4), MEDLINE (1946 to May 2012), EMBASE (1974 to May 2012), LILACS (1982 to July 2012), Scirus and ClinicalTrials.gov. Authors of relevant papers were also contacted regarding further published and unpublished work., Selection Criteria: To be included in this review, the studies had to meet the following criteria: 1) Randomised or quasi-randomised with a group assigned to receive a uric acid lowering agent and another group assigned to receive placebo; 2) Double-blind, single-blind or open label; 3) Parallel or crossover trial; 4) For crossover trial, a washout period of at least two weeks; 5) Minimum treatment duration of four weeks; 6) Participants with diagnosis of essential hypertension and hyperuricemia, serum uric acid greater than 6 in women, 7 in men and 5.5 in children/adolescents; 7) Outcome measures includes change in casual or ambulatory, systolic or diastolic blood pressure., Data Collection and Analysis: Two independent reviewers collected the data using a data extraction form. Disagreements were resolved by discussion. Risk of bias was accessed by the Cochrane Collaboration Risk of Bias Tool., Main Results: Three hundred and thirty-six abstracts were examined. One study (enrolling hypertensive and hyperuricemic patients) met the inclusion criteria for the review and was independently rated by both authors. No other studies were identified by the supplementary searches. The study identified as eligible for this review was a randomised controlled trial conducted in the USA (FEIG 2008 ) . This well designed double-blind, placebo-controlled, crossover trial randomised 30 adolescents (11-17 years), newly diagnosed stage 1 primary hypertension and with SUA ≥ 6mg/dl, to receive allopurinol 200 mg twice daily for 4 weeks, and placebo for 4 weeks, with a 2 week washout period between treatments. Casual BP during the allopurinol phase decreased - 6.9 mmHg (95 % CI, - 4.5 to - 9.3), systolic, and - 5.1 mmHg (95 % CI, - 2.5 to - 7.8), diastolic, versus during the placebo phase, - 2.0 mmHg (95 % CI, 0.3 to - 4.3) systolic and - 2.4 mmHg (95 % CI, 0.2 to - 4.1) diastolic. For the secondary outcome (change in 24 ambulatory BP), change in systolic BP with allopurinol was - 6.3 mmHg (95 % CI, - 3.8 to - 8.9), systolic, and - 4.6 mmHg (95% CI, - 2.4 to - 6.8), diastolic, and with placebo, 0.8 mmHg (95 % CI, 3.4 to - 2.9) systolic and - 0.3 mmHg (95 % CI, 2.3 to - 2.1) diastolic. P-value results ranged from 0.004 to 0.05. No participant dropout occurred and no adverse effects were seen in patients treated with allopurinol., Authors' Conclusions: Meta-analysis was not possible in this systematic review. In the one study that matched the inclusion criteria allopurinol decreased "in office" and ambulatory systolic and diastolic BP. Because there was only one included RCT, the number of patients providing data on pharmacotherapy for hyperuricemia in hypertension is small and restricted to adolescents with recently diagnosed mild essential hypertension. Hence, there is insufficient evidence to recommend the use of allopurinol or other hypouricemic drugs as an initial or adjuvant treatment of hypertension and more RCTs are needed.

A sustained virological response is not achieved by a significant proportion of chronic hepatitis C patients treated with interferon-based regimens. Due to the associated side effects and high costs, therapy response markers have been thoroughly sought. Two Single Nucleotide Polymorphisms (SNPs), rs12979860 and rs8099917, which are located upstream from the IL28B gene, have been remarkably described to have a strong association with treatment efficacy. The aim of this study was to develop a straightforward method for genotyping such polymorphisms. A Polymerase Chain Reaction (PCR) followed by enzymatic restriction of amplicons was established for SNPs genotyping. Online computation resources were employed for retrieving reference sequences, such as the selection of oligonucleotides and restriction enzymes. Two pairs of primers were designed and validated for the amplification of segments encompassing rs12979860 (694bp) and rs8099917 (496bp) with common thermocycling parameters. The endonucleases Hpy166II and BsrDI were selected and used for allelic discrimination related to rs12979860 (C/T) and rs8099917 (T/G), respectively. The expected electropherotypes were confirmed for all possible genotypes in 75 blood samples. In addition, the results were validated by sequencing. The method constitutes a simple and reliable assay, which may be readily available for genotyping of rs12979860 and rs8099917 in laboratories that support hepatitis C treatment centers., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Context: The use of thiopurine drugs such as azathioprine and 6-mercaptopurine has become quite common in the treatment of inflammatory bowel disease, transplantation and acute leukemias. Despite their effectiveness, these drugs are capable of causing drug-induced toxicity with the risk of death by myelosuppression. It is now known that these complications occur because of genetic polymorphisms of the thiopurinemethyltransferase (TPMT) enzyme, responsible for its metabolism., Objective: To assess the prevalence of thiopurine methyltransferase polymorphisms in the population of Joinville, SC, Brazil., Methods: We analyzed the frequency of four main allelic variants of the TPMT gene in 199 blood donors from Joinville, from February to April 2010., Results: The normal allele ("wild-type") was found in 93.9% of subjects studied. TPMT variants were detected in 12 subjects (6.03%)., Conclusions: From this study, it was estimated at 6% the risk of toxicity by the administration of azathioprine and 6-mercaptopurine to patients in Joinville.

Hepatitis B virus (HBV) is classified into seven major genotypes (A-H). Brazil, a country of continental proportions, has three prevailing lineages of HBV genotypes A, D, and F. Distinct HBV genotypes have been associated with differential risk of disease progression. Pre-S gene deletions and single nucleotide polymorphisms have also been linked to progression to liver diseases. In this study, the molecular epidemiology of HBV was examined in Southern Brazil. The occurrence of multiple HBV infections, HBV recombination, and genetic markers of disease progression were also evaluated. Seventy-eight persons infected with HBV had their viruses characterized molecularly by nested PCR, DNA sequencing, and phylogenetic inference. Multiple infections and recombinant viruses were evaluated by clonal and bootscanning analyses. The vast majority (96%) of the strains belonged to different D subgenotypes. Three of the four strains with unresolved genotypic classification showed evidence of dual infections with distinct D subgenotypes by clonal analysis. There was also evidence of intragenotype mosaic viruses. While four viruses had pre-S deletions as major variants, another two displayed minor variants with such characteristics. One strain carried the F141L mutation, associated recently with increased risk of hepatocellular carcinoma. These results emphasize the need for monitoring HBV genotype distribution around South America, as well as for the presence of genetic markers of disease progression in subjects diagnosed with HBV recently., (Copyright © 2011 Wiley Periodicals, Inc.)

Introduction: Sepsis is a systemic inflammatory response related to high mortality rates in the hospital environment. Delayed etiological diagnosis and inadequate antimicrobial therapy are associated with treatment failures. Molecular tests based on polymerase chain reaction are regarded as faster and more accurate procedures than culture techniques for microbial identification, providing a higher rate of therapeutic success., Objective: To develop a panel of primers for DNA fragments of sepsis-related microorganisms., Methods: Primers for amplification of Enterobacter spp., Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida spp. were designed and tested for sensitivity and specificity on the basis of their respective standard strains., Results: The intended specificity was obtained for P. aeruginosa, S. aureus and Candida spp primers. Sensitivity tests showed a threshold for detection from 5 ng to 500 fg in blood samples contaminated with microbial DNA., Conclusions: The molecular panel presented offers the advantage of a flexible 'open' system when compared to other multiplex detection methods.

Background: The incidence of bacterbilia in cholelithiasis remains controversial. The positivity of cultures ranges from 0 to 73 per cent. The aim of this study was to employ the polymerase chain reaction (PCR) to detect bacterial DNA in gallbladder bile extracted during elective laparoscopic cholecystectomy, and to compare PCR findings with those of bile culture., Methods: Bile samples from 84 laparoscopic cholecystectomies were collected for culture and PCR analysis., Results: Positive results for bacterbilia were found in 42 (50 per cent) of 84 patients by PCR but in only 16 patients (19 per cent) by culture (P < 0.001). Agreement between the two methods was seen in 44 samples (52 per cent), which were negative in 35 cases. Pathological examination showed chronic cholecystitis in 69 cases (82 per cent) and acute cholecystitis in 15 (18 per cent). Thirty-three (48 per cent) of the patients with chronic cholecystitis were PCR positive but only ten (14 per cent) were culture positive (P < 0.001). Only culture results correlated with findings on pathological examination (P = 0.033)., Conclusion: PCR is more sensitive in detecting bacterial contamination of gallbladder bile in cholecystitis than conventional culture. The clinical relevance of this high sensitivity remains unclear., (Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

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% of patients, while biochemical responses (serum alanine aminotransferase normalization) were observed in 82, 82, and 53% of cases. All viral breakthrough cases (N = 8) were related to the emergence of YMDD variants observed in 7, 21, and 35% 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.

A number of reports have indicated an increased risk of cirrhosis and hepatocellular carcinoma in hepatitis B virus (HBV)-infected individuals carrying HBV e antigen (HBeAg)-negative variants. Although distinct core promoter and precore mutations distributed according to geographical locality and viral genotype have been reported, epidemiological data from South America are still scarce. The prevalences of HBV genotypes and core promoter and precore polymorphisms in 75 HBeAg-negative Argentinean blood donors were surveyed. The observed frequencies of HBV genotypes were 64.0% for genotype F, 17.3% each for genotypes A and D, and 1.3% for genotype C. Genotype F strains were widely distributed and significantly more prevalent in the northern region of the country (P < 0.001). An overall high proportion of a stop codon mutation (UAG) at precore codon 28 (66.7%) was observed. Wild-type codon 28 (UGG) was present in 29.3% of the samples, and the remaining 4.0% of samples had mixed variants. The combination of A at nucleotide (nt) 1762 and G at nt 1764 of the core promoter was found in 58.7% of the samples. The variant profiles--T at nt 1762 and A at nt 1764 or A at nt 1762 and A at nt 1764--were detected in 28.0 and 1.3% of the samples, respectively. The observed core promoter polymorphisms could not be related to the ratio of HBeAg to anti-HBeAg antibody, HBV genotype, or precore codon 28 status. Nevertheless, a clear association of genotype F and a precore stop codon mutation was found (P < 0.05). In conclusion, HBV genotype F and mutant codon 28 strains predominated and were strongly associated in a geographically broad Argentinean blood donor population.