Toxomerus duplicatus Wiedemann, 1830 (Diptera: Syrphidae) preying on Microtheca spp. (Coleoptera: Chrysomelidae) larvae.

Microtheca spp. (Coleoptera: Chrysomelidae) are insect pests primarily related to Brassicaceae crops. In the State of Rio Grande do Sul (RS), southern Brazil, they are found on forage turnip, Raphanus sativus L. var. oleiferus Metzg., which is commonly grown during fall/winter seasons. This work reports the predation of Microtheca spp. larvae by Toxomerus duplicatus Wiedemann, 1830 (Diptera: Syrphidae) larvae, on forage turnip crop, in Santa Maria, RS. This register provides new information about Microtheca spp. natural enemies in Brazil, which might be a new option for integrate pest management of these species.

S-Nitroso-N-acetylcysteine induces de-differentiation of activated hepatic stellate cells and promotes antifibrotic effects in vitro.

Nitric oxide (NO) has been shown to act as a potent antifibrogenic agent by decreasing myofibroblast differentiation. S-Nitroso-N-acetylcysteine (SNAC), a NO donor, attenuates liver fibrosis in rats, but the cellular and molecular mechanisms on liver myofibroblast-like phenotype still remain unknown. Here, we investigate the antifibrotic effects of SNAC on hepatic stellate cells, the major fibrogenic cell type in the liver. A murine GRX cell line was incubated with SNAC (100µM) or vehicle (control group) for 72h. Cell viability was measured by MTT colorimetric assay and the conversion of myofibroblast into quiescent fat-storing cell phenotype was evaluated by Oil-Red-O staining. TGFß-1, TIMP-1, and MMP-13 levels were measure in the supernatant by ELISA. Profibrogenic- and fibrolytic-related gene expression was quantified using real-time qPCR. SNAC induced phenotype conversion of myofibroblast-like phenotype into quiescent cells. SNAC decreased gene and protein expression of TGFß-1 and MMP-2 compared to control groups. Besides, SNAC down-regulated profibrogenic molecules and up-regulated MMP-13 gene expression, which plays a key role in the degradation of interstitial collagen in liver fibrosis. In conclusion, these findings demonstrate that SNAC efficiently can modulate the activation and functionality of murine hepatic stellate cells and could be considered as an antifibrotic treatment to human liver fibrosis.

MR findings of the brain in children and adolescents with portal hypertension and the relationship with blood manganese levels.

BACKGROUND: Few studies have evaluated abnormalities on brain magnetic resonance imaging (MRI) in children and adolescents with chronic liver disease. AIMS: The aim of this study was to investigate the presence of T1 hyperintensity in the basal ganglia of pediatric patients with portal hypertension and its association with blood manganese levels. METHODS: A case control study of 22 patients with portal hypertension (14 Child-Pugh A cirrhosis, 8 non-cirrhotic portal hypertension) and 15 controls was conducted from 2006 to 2007. Blood manganese levels were measured using atomic absorption spectrophotometry. Brain MRI scans were performed using a 1.5 Tesla (Philips) scanner. RESULTS: Blood manganese levels were 26.01+/-12.82 microg/L for patients with portal hypertension (cirrhotic: 22.73+/-11.67 microg/L, non-cirrhotic: 32+/-13.32 microg/L) and 15.64+/-6.61 microg/L for controls (p=0.003). 14/22 patients with portal hypertension presented T1 hyperintensity in the basal ganglia [6/14 cirrhotic; 8/8 non-cirrhotic (p=0.018); zero controls (p=0.001)]. Mean blood manganese levels of patients with liver disease and normal vs. abnormal brain MRI scans were 18.45+/-8.38 microg/L and 30.47+/-13.07 microg/L, respectively (p=0.04). CONCLUSIONS: Brain MRI showed a high frequency (64%) of T1 hyperintensity in the basal ganglia of patients with portal hypertension, which correlated positively with blood manganese levels. This abnormality was found in 100% of the patients with portal hypertension and in 43% of those with mild cirrhotic disease.

Hepatitis A acute liver failure: follow-up of paediatric patients in southern Brazil.

We retrospectively analysed 33 children and adolescents who had been hospitalized in a liver transplant unit within the previous 10 years for acute liver failure (ALF). The patients' age varied between 2 months and 15 years of age (median 6.2 +/- 5.3), and 21 (63%) were male. Thirteen patients (39%) were immunoglobulin-M anti-hepatitis A virus (HAV) sero-positive. Eleven cases (33%) had an undetermined aetiology. The 13 children with HAV ALF were between 17 months and 15.6 years of age (median 5.8 +/- 4.6) and eight were male (61.5%). All were on a list for urgent liver transplant. Of these, five (38%) died while waiting for a liver. Only one patient recovered spontaneously. Seven patients received a liver transplant; three died in the immediate postoperative period and one died 45 days after transplant. Three children are alive 1, 2 and 5 years after transplant. We conclude that HAV was the most frequent cause of ALF, which had high mortality even when a liver transplant was possible. The results support universal HAV vaccination in this area.

Correlation between lactose absorption and the C/T-13910 and G/A-22018 mutations of the lactase-phlorizin hydrolase (LCT) gene in adult-type hypolactasia

The C/T-13910 mutation is the major factor responsible for the persistence of the lactase-phlorizin hydrolase (LCT) gene expression. Mutation G/A-22018 appears to be only in co-segregation with C/T-13910. The objective of the present study was to assess the presence of these two mutations in Brazilian individuals with and without lactose malabsorption diagnosed by the hydrogen breath test (HBT). Ten milk-tolerant and 10 milk-intolerant individuals underwent the HBT after oral ingestion of 50 g lactose (equivalent to 1 L of milk). Analyses for C/T-13910 and G/A-22018 mutations were performed using a PCR-based method. Primers were designed for this study based on the GenBank sequence. The CT/GA, CT/AA, and TT/AA genotypes (lactase persistence) were found in 10 individuals with negative HBT. The CC/GG genotype (lactase non-persistence) was found in 10 individuals, 9 of them with positive HBT results. There was a significant agreement between the presence of mutations in the LCT gene promoter and HBT results (kappa = -0.9, P < 0.001). The CT/AA genotype has not been described previously and seems to be related to lactase persistence. The present study showed a significant agreement between the occurrence of mutations G/A-22018 and C/T-13910 and lactose absorption in Brazilian subjects, suggesting that the molecular test used here could be proposed for the laboratory diagnosis of adult-type primary hypolactasia.

Correlation between lactose absorption and the C/T-13910 and G/A-22018 mutations of the lactase-phlorizin hydrolase (LCT) gene in adult-type hypolactasia.

The C/T-13910 mutation is the major factor responsible for the persistence of the lactase-phlorizin hydrolase (LCT) gene expression. Mutation G/A-22018 appears to be only in co-segregation with C/T-13910. The objective of the present study was to assess the presence of these two mutations in Brazilian individuals with and without lactose malabsorption diagnosed by the hydrogen breath test (HBT). Ten milk-tolerant and 10 milk-intolerant individuals underwent the HBT after oral ingestion of 50 g lactose (equivalent to 1 L of milk). Analyses for C/T-13910 and G/A-22018 mutations were performed using a PCR-based method. Primers were designed for this study based on the GenBank sequence. The CT/GA, CT/AA, and TT/AA genotypes (lactase persistence) were found in 10 individuals with negative HBT. The CC/GG genotype (lactase non-persistence) was found in 10 individuals, 9 of them with positive HBT results. There was a significant agreement between the presence of mutations in the LCT gene promoter and HBT results (kappa = -0.9, P < 0.001). The CT/AA genotype has not been described previously and seems to be related to lactase persistence. The present study showed a significant agreement between the occurrence of mutations G/A-22018 and C/T-13910 and lactose absorption in Brazilian subjects, suggesting that the molecular test used here could be proposed for the laboratory diagnosis of adult-type primary hypolactasia.

Evaluation of the protective effects of quercetin in the hepatopulmonary syndrome.

The hepatopulmonary syndrome (HPS) occurs when intrapulmonary dilatation causes hypoxemia in cirrhosis. The free radicals may play a significant contributory role in the progression of HPS, and flavonoid agents could protect against deleterious effects of free radicals. The flavonoid quercetin was evaluated in an experimental model of biliary cirrhosis induced by bile duct ligation (BDL) in rats. Quercetin was administered at 50mg/kg for 14 days to cirrhotic and non-cirrhotic rats. Bone marrow was extracted from animals to analyze micronuclei. Lung, liver and blood were extracted to detect DNA damage using the comet assay. The results showed that the micronuclei and DNA damages to lung and liver were increased in BDL rats. Quercetin caused no damage to the DNA while decreasing the occurrence of micronucleated cells in bone marrow as well as DNA damage to lung and liver in cirrhotic rats. Quercetin showed antimutagenic activity against hydroperoxides as evaluated by the oxidative stress sensitive bacterial strains TA102 Salmonella typhimurium and IC203 Escherichia coli, suggesting protection by free radical scavenging. In Saccharomyces cerevisie yeast strains lacking mitochondrial or cytosolic superoxide dismutase, these results indicate that quercetin protects cells by induction of antioxidant enzymes. The present study is the first report of genotoxic/antigenotoxic effects of quercetin in a model of animal cirrhosis. In this model, quercetin was not able to induce genotoxicity and, conversely, it increased the genomic stability in the cirrhotic rats, suggesting beneficial effects, probably by its antioxidant properties.

Management of vascular complications after pediatric liver transplantation.

Sixty-five children underwent liver transplantation (LTx) from March 1995 to December 2002. Cirrhosis due to biliary atresia was the main indication, and hepatic artery thrombosis (HAT) the most common vascular complication (n = 5). Other vascular problems were portal vein thrombosis and stenosis. Another patient developed hepatomegaly and ascites due to a late stenosis of the left hepatic vein anastomosis. The two cases of venous stenosis were successfully treated by percutaneous angioplasty. One graft with HAT was saved, but four children died awaiting retransplant.

Potentiation of carbon tetrachloride hepatotoxicity by pentosan polysulfate in rats.

Few data are available in the literature regarding the effect of pentosan polysulfate (PPS) on normal and fibrotic rat livers. In addition, the combination of PPS and carbon tetrachloride (CCl4) has not been studied so far. The objective of this study was to assess the effect of PPS on rat livers treated or not with CCl4 for the induction of liver fibrosis. The study consisted of four stages: 1) hepatic fibrosis induction with CCl4 (N = 36 rats); 2) evaluation of the effect of PPS on CCl4-induced hepatic fibrosis (N = 36 rats); 3) evaluation of the effect of higher doses of PPS in combination with CCl4 (N = 50 rats); 4) evaluation of the presence of an enzymatic inductor effect by PPS (N = 18 rats) using the sodium pentobarbital test which indirectly evaluates hepatic microsomal enzyme activity in vivo. Adult (60 to 70 days) male Wistar rats weighing 180 to 220 g were used. All animals receiving 0.5 ml 8% CCl4 (N = 36) developed hepatic fibrosis, and after 8 weeks they also developed cirrhosis. No delay or prevention of hepatic fibrosis was observed with the administration of 5 mg/kg PPS (N = 8) and 1 mg/kg PPS (N = 8) 1 h after the administration of CCl4, but the increased hepatotoxicity resulting from the combination of the two substances caused massive hepatic necrosis in most rats (N = 45). PPS (40 mg/kg) alone caused hepatic congestion only after 8 weeks, but massive hepatic necrosis was again observed in association with 0.5 ml CCl4 after 1 to 4 weeks of treatment. Unexpectedly, sleeping time increased with time of PPS administration (1, 2, or 3 weeks). This suggests that PPS does not function as an activator of the hepatic microsomal enzymatic system. Further studies are necessary in order to clarify the unexpected increase in hepatotoxicity caused by the combination of CCl4 and high doses of PPS, which results in massive hepatic necrosis.

Potentiation of carbon tetrachloride hepatotoxicity by pentosan polysulfate in rats

Few data are available in the literature regarding the effect of pentosan polysulfate (PPS) on normal and fibrotic rat livers. In addition, the combination of PPS and carbon tetrachloride (CCl4) has not been studied so far. The objective of this study was to assess the effect of PPS on rat livers treated or not with CCl4 for the induction of liver fibrosis. The study consisted of four stages: 1) hepatic fibrosis induction with CCl4 (N = 36 rats); 2) evaluation of the effect of PPS on CCl4-induced hepatic fibrosis (N = 36 rats); 3) evaluation of the effect of higher doses of PPS in combination with CCl4 (N = 50 rats); 4) evaluation of the presence of an enzymatic inductor effect by PPS (N = 18 rats) using the sodium pentobarbital test which indirectly evaluates hepatic microsomal enzyme activity in vivo. Adult (60 to 70 days) male Wistar rats weighing 180 to 220 g were used. All animals receiving 0.5 ml 8 percent CCl4 (N = 36) developed hepatic fibrosis, and after 8 weeks they also developed cirrhosis. No delay or prevention of hepatic fibrosis was observed with the administration of 5 mg/kg PPS (N = 8) and 1 mg/kg PPS (N = 8) 1 h after the administration of CCl4, but the increased hepatotoxicity resulting from the combination of the two substances caused massive hepatic necrosis in most rats (N = 45). PPS (40 mg/kg) alone caused hepatic congestion only after 8 weeks, but massive hepatic necrosis was again observed in association with 0.5 ml CCl4 after 1 to 4 weeks of treatment. Unexpectedly, sleeping time increased with time of PPS administration (1, 2, or 3 weeks). This suggests that PPS does not function as an activator of the hepatic microsomal enzymatic system. Further studies are necessary in order to clarify the unexpected increase in hepatotoxicity caused by the combination of CCl4 and high doses of PPS, which results in massive hepatic necrosis

Hepatitis C virus infection and assisted reproduction.

BACKGROUND: In assisted reproduction, hepatitis C virus (HCV) transmission may pose a risk for the baby, technicians, and gametes or embryos from non-contaminated parents. This study aimed at determining the prevalence and risk factors for HCV infection in a group of infertile couples. METHODS: HCV infection was investigated in 409 patients attending the infertility clinic at Hospital de Clínicas de Porto Alegre, Brazil, between 1997 and 1998. Serum was screened for anti-HCV using ELISA and for hepatitis B surface antigen (HBsAg) using an enzyme-linked fluorescent assay (ELFA). HCV infection and semen viraemia was also investigated using HCV RNA detection. RESULTS: The overall prevalence of anti-HCV was 3.2% (8/248) among women and 3.7% (6/161) among men. All subjects were negative for hepatitis B virus (HBV) and human immunodeficiency virus (HIV). From the 14 HCV-positive patients, two were lost, and serum was collected from the remaining 12 patients for assessment of HCV RNA, resulting in five HCV-positive cases (one woman and four men). Only one of the HCV-positive men had viraemia levels >500 000 RNA copies/ml. There was a significant risk associated with being HCV-positive in women with HCV-positive male partners (P < 0.001). In male patients, the correlation between use of intravenous drugs and HCV-positivity was also significant (P < 0.001). CONCLUSIONS: Since the risk for vertical and laboratory HCV infection is not well determined, and HCV prevalence is not negligible in this group, we recommend that infertile patients be screened before assisted reproductive techniques.

Molecular analysis of the Pi*Z allele in patients with liver disease.

Alpha1-antitrypsin (AAT) is the main protease inhibitor in human plasma. There are more than 75 variants of this protein that differ from each other by their isoelectric point. Most of these alleles cause a reduction in AAT levels; the most common allele is Pi*Z. The main complications related to the Pi*Z allele are obstructive pulmonary disease and liver disease. Some Pi*Z allele carriers present cholestatic jaundice and cirrhosis. The Z type is associated with a secretion defect, which leads to deficiency of AAT and to the formation of intrahepatocytic inclusions in affected subjects. The diagnosis of AAT deficiency can be made by different techniques, including molecular analysis, although the final diagnosis should be done in conjunction with demonstration of the periodic acid-Schiff-positive globules on liver biopsy. In this study, specimens of 29 patients with cryptogenic cirrhosis between age 1 month and 18 years, and of 100 controls were submitted to polymerase chain reaction followed by digestion with TaqI enzyme. Five of the 29 patients had undergone liver transplantation. Three patients were heterozygous for the Pi*Z allele, and two were homozygous (allele frequency = 12.07%; 7/58). Among the controls, who represented the population of Porto Alegre, 1 in 100 individuals was heterozygous for the Pi*Z allele, resulting in an allele frequency of 0.5% (1/200). The high frequency of Pi*Z alleles among the patients indicates the usefulness of AAT molecular testing in children with cholestatic jaundice and cirrhosis.

Evoked potentials for the evaluation of latent hepatic encephalopathy in pediatric liver transplant candidates.

BACKGROUND: Visual evoked potentials (VEPs) and brain stem auditory evoked potentials (BAEPs) have been proposed as tools in the diagnosis of subclinical hepatic encephalopathy (HE). However, little information exists to determine their usefulness in pediatric patients. This study was undertaken to evaluate both methods in the detection of subclinical HE in pediatric liver transplant candidates. METHODS: VEPs and BAEPs were recorded in 15 pediatric liver transplant candidates with no clinical signs of HE. The wave latencies found in these examinations were then compared with those in 16 healthy controls of similar age. Laboratory data on liver function and electroencephalographic data from the patients were also recorded to examine their correlation with the evoked potentials results. RESULTS: No differences were found in the BAEP results between patients and controls. However, in the VEPs, the liver transplant candidates had significantly prolonged N1 (N75) latencies when compared with controls; no significant delay was found in the other waves. In contrast, among the children with liver disease, higher BAEP peak latencies correlated positively with electroencephalographic abnormalities, but this correlation was not observed in VEPs. CONCLUSIONS: Evoked potentials might be of use in detecting alterations related to HE in children. However, further studies are necessary to determine their sensitivity and specificity in this situation.

[Hepatitis A and hepatitis B seroprevalence in 4 centers in Brazil]. / Soroprevalência para hepatite A e hepatite B em quatro centros no Brasil.

The prevalence of antibodies to hepatitis A and B virus was assessed in 3,653 subjects across four regions of Brazil. The anti-HAV and anti-HBc seroprevalence were 64.7% and 7.9%, respectively. The highest anti-HAV (92.8%) and anti-HBc (21.4%) rates were seen in the Northern region. In other regions, anti-HAV seroprevalence over 90% was only reached in the more elderly, indicating an intermediate endemicity and a significantly higher anti-HAV prevalence was seen in the low socioeconomic group between 1-30 years. With respect to anti-HBc seroprevalence an increase was seen in adolescents and there was a significantly higher anti-HBc prevalence in the lower socioeconomic group between 1-20 years. A 3.1% anti-HBc prevalence was seen in one-year-old infants, suggesting a vertical transmission. The major findings of this study indicate that the pre-adolescent and adolescent population in some Brazilian cities are at greatest risk from both hepatitis A and B infection, but for different reasons.

[Liver transplantation] / Transplante hepático.

OBJECTIVE: To review the clinical aspects and the theoretical basis of liver transplantation in children, focusing mainly pre and post surgical periods. METHODS: References were obtained from computerized search in the National Library of Medicine (Medline), recent review articles, and personal files. RESULTS: Great development has occurred in surgical techniques, in organ preservation, in postoperative care, and in immunosuppression methods after the first liver transplantation surgery took place in a child with biliary atresia in 1963. Liver transplantation has become an efficient therapy, widely accepted and used in all age groups. It is a very complex procedure, with many professionals involved and with several legal, ethical and economical implications. We review in this article the clinical aspects before transplantation, including indications, contraindications, clinical and laboratory evaluations, as well as postsurgical aspects, both in the immediate period, after the 1st week, and the long-term outcome, discussing the complications and the treatment of each. CONCLUSIONS: Liver transplantation has dramatically improved the survival of pediatric patients with chronic hepatic diseases. Patients of liver transplantation in the pediatric age group present today survival rates of 90% in the different transplantation centers.

Relationship between nutritional status and histologic findings in small bowel mucosa of children presenting with diarrhoea of more than 14 days' duration.

In order to study the eventual effects of malnutrition on small intestinal mucosa, we evaluated 85 children with diarrhoea of more than 14 days' duration, aged from 4 to 114 months (median 17 months). A proximal small intestinal biopsy was obtained and villus height, crypt depth, mucosal thickness, and total mucosal thickness were measured. Gomez, Waterlow, and Z score criteria were applied. Statistical analyses were performed with the Spearman correlation test and the non-parametrical tests of Wilcoxon, Mann-Whitney, and Kruskal-Wallis. A value of p < 0.05 was considered significant. Average villus height was 269.2 microns (+/- 87.5 microns); crypt depth 113.0 microns (+/- 33.8 microns); mucosal thickness 210.5 microns (+/- 73.2 microns); total mucosal thickness 485.9 microns (+/- 111.8 microns); and villus height/crypt depth ratio 2.5:1 (+/- 0.8:1). Five children had kwashiorkor and 13 had marasmus. Villus height for kwashiorkor children ranged from 151 microns to 353.3 microns (average 286.7 microns), crypt depth from 90.3 microns to 154 microns (average 111.11 microns). According to Gomez criteria, as malnutrition increased, mucosal thickness and the villus/crypt ratio decreased. Waterlow criteria had no relation to mucosal sizes. When distributed in sequential decrease according to their nutritional state, the Z score for weight for age and weight for height indices showed a positive correlation with villus height, total mucosal thickness, and villus/crypt ratio.

Hepatitis B seroprevalence in Latin America.

The seroprevalence of hepatitis B was investigated in over 12,000 subjects in six countries of Latin America: Argentina, Brazil, Chile, the Dominican Republic, Mexico, and Venezuela. Each study population was stratified according to age, gender, and socioeconomic status. Antibodies against hepatitis B core antigen (anti-HBc) were measured in order to determine hepatitis B infection. The highest overall seroprevalence was found in the Dominican Republic (21.4%), followed by Brazil (7.9%), Venezuela (3.2%), Argentina (2.1%), Mexico (1.4%), and Chile (0.6%). In all the countries an increase in seroprevalence was found among persons 16 years old and older, suggesting sexual transmission as the major route of infection. In addition, comparatively high seroprevalence levels were seen at an early age in the Dominican Republic and Brazil, implicating a vertical route of transmission.

[Soroepidemiology of Varicella in Brazil - results of a prospective cross-sectional study] / Soroepidemiologia da varicela no Brasil - resultados de um estudo prospectivo transversal.

OJECTIVES: Varicella has more serious consequences in adolescents and adults. Recent reports from Europe and Asia show an increasing number of adolescents and young adults being seronegative. As there is only limited data on varicella zoster virus (VZV) seroprevalence in Brazil and to facilitate the strategy for varicella vaccination we conducted a VZV seroprevalence study in Brazil. METHODS: This population-based, cross sectional seroepidemiology study was performed in 4 different regions of Brazil. The studied population was stratified according to gender, age and socioeconomic status. VZV IgG antibodies were analyzed by ELISA. RESULTS: 3,879 subjects aged 1-40 years were included into the study. The overall anti-VZV seropositivity rate across all age groups and centers in Brazil was 85.4%. There was a strong age relationship. Especially in the South East and South seroprevalence was low in the age group 1-5 years (44.5% and 57.8%, respectively) while in the North the rate was 88.9%. Overall, Varicella infection was independent of the socioeconomic level, but in the youngest age groups (1-10 years) seroprevalence rates were significantly lower in the high/medium socioeconomic class for most regions. Clinical history of chickenpox correlates well with anti- VZV seropositivity with a predictive value of 95.1% CONCLUSIONS: In preadolescence a substantial proportion of the Brazilian population is susceptible to Varicella infection, and a considerable part of the adolescents and young adults remain VZVseronegative and are thus also at risk.

Caroli's disease: report of 10 cases in children and adolescents in southern Brazil.

PURPOSE: The aim of this study was to describe the authors' experience with Caroli's disease in children and adolescents. METHODS: The authors reviewed the hospital charts of 10 children and adolescents with Caroli's disease diagnosed between 1968 and 1996. RESULTS: The median age at the onset of symptoms was 5.5 months and the median age at diagnosis was 12 months, both much lower than those reported in the literature. Clinical symptoms were compatible with the classical findings of Caroli's disease, but jaundice and hepatosplenomegaly occurred more frequently. There was an association with congenital renal malformation in eight cases (80%), congenital hepatic fibrosis in five cases, and choledochal cyst in two cases. One case presented the pure form of the disease.