Oral 24-week probiotics supplementation did not decrease cardiovascular risk markers in patients with biopsy proven NASH: A double-blind placebo-controlled randomized study.

INTRODUCTION AND OBJECTIVES: Cardiovascular disease (CVD) is the major cause of death in non-alcoholic fatty liver disease (NAFLD), a clinical condition without any approved pharmacological therapy. Probiotics are often indicated for the disease, but their results are controversial in part due to the poor quality of studies. Thus, we investigated the impact of 24-week probiotics supplementation on cardiovascular risk (CVR) in biopsy-proven non-alcoholic steatohepatitis (NASH) patients. PATIENTS AND METHODS: Double-blind, placebo-controlled, single-center study (NCT03467282), adult NASH, randomized for 24 weeks daily sachets of probiotic mix (109CFU of Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus paracasei and Bifidobacterium lactis) or placebo. Clinical scores (atherogenic indexes, atherosclerotic cardiovascular disease-ASCVD and systematic coronary risk evaluation-SCORE), biochemistry, miR-122, miR-33a, plasminogen activator inhibitor-1 (PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), were determined before and after the intervention. RESULTS: Forty-six patients were enrolled (23 received probiotics and 23 placebo), with a mean age of 51.7 years, most of them females and whites. Clinical and demographic features were similar between the groups at the baseline. The Median NAFLD activity score was 4.13 in both groups. Fibrosis was mild in most patients (15.2% and 65.2% F0 and F1, respectively). Treatment did not promote any clinically significant changes in body mass index or laboratory, including lipid and glucose profile. High CVR patients through atherogenic indexes decreased from baseline in both groups, as well as PAI-1 and miR-122 levels, although there was no difference between probiotics and placebo. CONCLUSIONS: A 24-week probiotic mix administration was not superior to placebo in reducing CVR markers in patients with NASH.

Hepatoprotective Effect of Probiotic Lactobacillus rhamnosus GG Through the Modulation of Gut Permeability and Inflammasomes in a Model of Alcoholic Liver Disease in Zebrafish.

Objective: Alcoholic liver disease (ALD) is among the leading causes of death from liver disease. Among the factors involved in its pathogenesis are inflammation and increased intestinal permeability. The aim of this study was to assess the effect of Lactobacillus rhamnosus GG (LGG) on hepatic lipid accumulation, activation of inflammasomes, and gut permeability markers in experimental model of ALD with zebrafish.Methods: An experiment was conducted to assess the effective LGG dose capable of promoting intestinal colonization. Animals were divided into three groups (n = 64/group): ethanol group (E), ethanol + probiotic group (EP), and control group (C). Groups E and EP were exposed to 0.5% ethanol concentration for 28 days. At the end of this period, animals were euthanized, and livers were collected for Oil Red staining and assessment of the inflammasome system. Intestines were collected for evaluation of gut permeability markers.Results: The dose of 1.55 × 106 UFC LGG/fish/d promoted intestinal colonization. Group EP presented lower hepatic lipid accumulation, lower il-1ß expression, and higher cldn15a expression when compared to group E.Conclusions: Supplementation with LGG was protective for hepatic steatosis in ALD model. In addition, LGG influenced the modulation of the inflammatory response and markers of gut permeability, improving the gut barrier structure.

Probiotic supplementation for 24 weeks in patients with non-alcoholic steatohepatitis: the PROBILIVER randomized clinical trial.

Background and aim: Considering the increasing prevalence of non-alcoholic steatohepatitis (NASH) and treatment gaps, this study aimed to evaluate the effect of probiotic supplementation on liver function markers, nutritional status, and clinical parameters. Methods: This double-blind, randomized clinical trial (ClinicalTrials.gov ID: NCT0346782) included adult outpatients with biopsy-proven NASH. The intervention consisted of 24 weeks of supplementation with the probiotic mix Lactobacillus acidophilus (1 × 109 CFU) + Lactobacillus rhamnosus (1 × 109 CFU) + Lactobacillus paracasei (1 × 109 CFU) + Bifidobacterium lactis (1 × 109 CFU), or placebo, twice a day. The following parameters were evaluated: demographic and clinical data, transient elastography (FibroScan), liver enzymes, NAFLD fibrosis score, fatty liver index, laboratory assessment, serum concentration of toll-like receptor-4 (sTLR-4) and cytokeratin 18 (CK-18), anthropometric data, dietary intake, and physical activity. Regarding data analysis, the comparison between the groups was based on the delta of the difference of each variable analyzed (value at the end of treatment minus the baseline value) using the t-test for independent samples or the Mann-Whitney U-test. Results: Forty-four patients with NASH completed the trial (51.4 ± 11.6 years). At baseline, 87% of participants had a mild liver fibrosis degree on biopsy, normal values of liver enzymes, transient elastography values consistent with grade 1 fibrosis in both groups, increased waist circumference (WC), a BMI of 30.97 kg/m2, and 76% presented with metabolic syndrome (MetS). After the intervention, no differences were observed between the probiotic and placebo groups in terms of MetS, WC, BMI scores, or liver enzyme levels (p > 0.05 for all). The elastography values remained consistent with grade 1 fibrosis in both groups. Although CK-18 was reduced in both groups, a larger effect size was noted in the probiotic group (D = 1.336). sTLR-4 was also reduced in both groups, with no difference between groups (p = 0.885). Conclusion: Intervention with probiotics in the early stages of NASH demonstrated no significant change in hepatic and clinical parameters. Clinical trial registration: ClinicalTrials.gov, identifier NCT0346782.

Evaluation of bowel wall flow by color Doppler ultrasound in the assessment of inflammatory bowel disease activity in pediatric patients.

Objective: To assess inflammatory bowel disease (IBD) activity with Doppler ultrasound in pediatric patients, comparing the accuracy of the ultrasound findings with that of the concentrations of fecal calprotectin (FC). Materials and Methods: In a consecutive series, we evaluated 53 examinations of 44 pediatric patients seen between 2014 and 2020: 28 with Crohn's disease, 15 with ulcerative colitis, and one with IBD unclassified. The diagnosis of IBD was made in accordance with the Porto criteria. The alteration studied in the greatest detail was bowel wall flow, which was classified by the lead investigator and two pediatric radiologists, all of whom were blinded to the FC concentrations and the other ultrasound findings. Bowel wall flow was categorized as low if there were up to 2 Doppler ultrasound signals/cm2, moderate if there were 3-5 signals/cm2, and high if there were more than 5 signals/cm2. Results: The agreement among the radiologists was substantial (kappa = 0.73). In cases in which ultrasound showed low bowel wall flow, the median FC concentration was 92 µg/g (interquartile range, 33-661 µg/g), whereas it was 2,286 µg/g (interquartile range, 1,728-5,612 µg/g) in those in which ultrasound showed high bowel wall flow. In the sample as a whole, the sensitivity and specificity of ultrasound was 89.7% and 92.0%, respectively, for the detection of inflammatory activity; 95.5% and 90.9%, respectively, for the detection of Crohn's disease; and 81.3% and 100.0%, respectively, for the detection of ulcerative colitis. Conclusion: Ultrasound of the bowel wall showed a strong correlation with FC concentrations in the assessment of inflammatory activity in pediatric patients with IBD.

Objetivo: Avaliar a atividade da doença inflamatória intestinal (DII) por ultrassonografia (US) com Doppler em cores, comparada à concentração de calprotectina fecal (CF) em pacientes pediátricos. Materiais e Métodos: Em uma série consecutiva, no período entre 2014 e 2020, foram avaliados 53 exames de 44 pacientes pediátricos: 28 casos de doença de Crohn, 15 de colite ulcerativa e um de colite indeterminada. O diagnóstico da DII foi feito pelos critérios de Porto. O fluxo parietal foi a alteração estudada mais detalhadamente e classificada pelo pesquisador principal e por dois radiologistas pediátricos cegados aos valores de CF e de US Doppler. Baixo fluxo parietal foi definido pela captação de até 2 sinais de US Doppler/cm2, fluxo moderado entre 3 e 5 sinais/cm2 e alto fluxo mais de 5 sinais/cm2. Resultados: Houve concordância substancial entre os radiologistas (kappa = 0,73). Nos exames com baixo fluxo parietal a CF média foi 92 µg/g (intervalo interquartil: 33-661 µg/g) e nos exames com alto fluxo a CF média foi 2.286 µg/g (intervalo interquartil: 1.728-5.612 µg/g). Na amostra total, a US demonstrou sensibilidade de 89,7% e especificidade de 92,0% para detecção da atividade inflamatória, 95,5% e 90,9% na doença de Crohn e 81,3% e 100,0% na colite ulcerativa, respectivamente. Conclusão: Houve forte correlação entre a US da parede intestinal e os valores da concentração de CF na avaliação da atividade inflamatória na DII de pacientes pediátricos.

The effect of taurine on hepatic steatosis induced by thioacetamide in zebrafish (Danio rerio).

BACKGROUND: Nonalcoholic fatty liver disease is one of the most prevalent forms of chronic liver disease in the Western world. Taurine is a conditionally essential amino acid in humans that may be a promising therapy for treating this disease. AIM: To evaluate the effect of taurine on hepatic steatosis induced by thioacetamide in Danio rerio. METHODS: Animals were divided into four groups: control (20 µl of saline solution), taurine (1,000 mg/kg), thioacetamide (300 mg/kg), and the taurine-thioacetamide group (1,000 + 300 mg/kg). Thioacetamide was injected intraperitoneally three times a week for 2 weeks. The mRNA expression, lipoperoxidation, antioxidant enzymatic activity, and histological analyses were evaluated in the liver and the triglyceride content was assessed in the serum. RESULTS: Thioacetamide injection induced steatosis, as indicated by histological analyses. The lipoperoxidation showed significant lipid damage in the thioacetamide group compared to the taurine-thioacetamide group (p < 0.001). Superoxide dismutase (SOD) activity in the taurine-thioacetamide group (5.95 ± 0.40) was significantly increased compared to the thioacetamide group (4.14 ± 0.18 U SOD/mg of protein) (p < 0.001). The mRNA expression of SIRT1 (0.5-fold) and Adiponectin receptor 2 (0.39-fold) were lower in the thioacetamide group than the control (p < 0.05). TNF-α mRNA expression was 6.4-fold higher in the thioacetamide group than the control (p < 0.05). SIRT1 mRNA expression was 2.6-fold higher in the taurine-thioacetamide group than in the thioacetamide group. CONCLUSIONS: Taurine seems to improve hepatic steatosis by reducing oxidative stress and increasing SIRT1 expression.

Effect of Melatonin on the Reduction of Hepatic Steatosis and Intestinal Leptin Expression in Zebrafish Exposed to Fructose.

Melatonin is a hormone related to circadian rhythms and has potential clinical applications. Our objectives were to verify the effect of melatonin on the liver of zebrafish exposed to fructose and evaluate the expression of appetite-related genes (leptin, ghrelin, and melanocortin receptor 4 [MC4R]). Animals were divided into three groups: control (CG, n = 25), fructose (FG, n = 25), and fructose+melatonin (FMG, n = 25). The study was carried out in 8 weeks. FG and FMG were exposed to 2% fructose and FMG treated with 1 µM of melatonin. Histological liver studies and gene expression analyses of Leptin, Ghrelin, and MC4R (liver and intestines) were performed. FG developed hepatic steatosis, which did not occur with CG and FMG. Genetic expression of hepatic leptin and MC4R did not show significant difference among the groups. Animals exposed to fructose (FG) presented an increased expression of intestinal leptin compared to those administered with melatonin. Animals exposed to fructose gained weight and developed an important hepatic steatosis, but melatonin reduced significantly the hepatic damage. Intestinal leptin showed increased expression in the group exposed to fructose.

Gut dysbiosis and systemic inflammation promote cardiomyocyte abnormalities in an experimental model of steatohepatitis.

BACKGROUND: Cardiovascular disease is the main cause of death in metabolic-associated fatty liver disease, and gut microbiota dysbiosis is associated with both of them. AIM: To assess the relationship between gut dysbiosis and cardiovascular risk (CVR) in an experimental model of steatohepatitis. METHODS: Adult male Sprague-Dawley rats were randomized to a control group (n = 10) fed a standard diet and an intervention group (n = 10) fed a high-fat choline-deficient diet for 16 wk. Biochemical, molecular, hepatic, and cardiac histopathology. Gut microbiota variables were evaluated. RESULTS: The intervention group had a significantly higher atherogenic coefficient, Castelli's risk index (CRI)-I and CRI-II, interleukin-1ß, tissue inhibitor of metalloproteinase-1 (all P < 0.001), monocyte chemoattractant protein-1 (P = 0.005), and plasminogen activator inhibitor-1 (P = 0.037) than the control group. Gene expression of miR-33a increased (P = 0.001) and miR-126 (P < 0.001) decreased in the intervention group. Steatohepatitis with fibrosis was seen in the intervention group, and heart computerized histological imaging analysis showed a significant decrease in the percentage of cardiomyocytes with a normal morphometric appearance (P = 0.007), reduction in the mean area of cardiomyocytes (P = 0.037), and an increase of atrophic cardiomyocytes (P = 0.007). There were significant correlations between the cardiomyocyte morphometry markers and those of progression and severity of liver disease and CVR. The intervention group had a lower Shannon diversity index and fewer changes in the structural pattern of gut microbiota (both P < 0.001) than controls. Nine microbial families that are involved in lipid metabolism were differentially abundant in intervention group and were significantly correlated with markers of liver injury and CVR. CONCLUSION: The study found a link between gut dysbiosis and significant cardiomyocyte abnormalities in animals with steatohepatitis.

Bone marrow mononuclear cell transplantation improves survival and induces hepatocyte proliferation in rats after CCl(4) acute liver damage.

AIM: The aim of this research was to evaluate the effects of bone marrow mononuclear cell (BMC) transplantation in rats with toxic acute liver damage induced by carbon tetrachloride (CCl(4)). METHODS: Cells from male Wistar rats were obtained using Ficoll density gradient and 0.2 ml (1 × 10(6) cells) were injected into the portal vein of female rats (n = 15) 24 h after damage. Sham group (n = 15) was performed injecting only vehicle in CCl(4)-treated animals. Survival, liver histology, number of mitosis and apoptosis, and identification of stained donor cells were observed 72 h after damage. ALT levels were measured at 0 h, 24 h, 48 h, and 72 h after injury. RESULTS: Donor cells could be detected in recipient rats' livers by fluorescence staining and Sry PCR. The treated group revealed a significant improvement in survival rate after 72 h (p = 0.003). There was also a significant increase in the number of mitotic events in treated livers (p = 0.029). This result was confirmed using an in vitro cell proliferation assay in isolated hepatocytes treated with conditioned medium from BMC. ALT was reduced in the treated group after 72 h (p = 0.034). CONCLUSIONS: Results indicate that BMC transplantation has potential as a new therapeutic option for acute liver disease and suggest that these cells may contribute to hepatic recovery through release of mitotic cytokines.

Tolerability and Effects of the Use of Energy-Enriched Infant Formula After Congenital Heart Surgery: A Randomized Controlled Trial.

BACKGROUND: Undernutrition is a common problem among children with congenital heart disease (CHD) and may lead to poorer surgical outcomes. A higher intake of energy during the postoperative period of CHD surgery seems to be associated with better outcomes. This study aimed to investigate the effect of the use of energy-enriched formula (EE-formula) compared with normocaloric formula during 30 days after CHD surgery. METHODS: A randomized controlled trial with patients undergoing heart surgery in a tertiary hospital in southern Brazil from March 2017 to December 2017 was performed. The intervention group received EE-formula (1 kcal/mL), and the control group received normocaloric formula (0.67 kcal/mL). The researcher in charge of anthropometric evaluation was blinded to the randomization. RESULTS: Fifty-nine patients were included; 30 in control group and 29 in intervention group. There were no statistically significant differences between groups regarding age, gender, anthropometry, and surgical risk classification after randomization. A statistically significant difference in z-score of weight for age and in weight gain variation rate between groups after intervention was observed. Antibiotic use was less frequent in the intervention group, and hospital length of stay was shorter. General gastrointestinal side effects were similar between groups, whereas diarrhea was more frequent in the intervention group. However, this side effect was limited and had spontaneous resolution in 4 out of 6 cases. CONCLUSION: This study demonstrates that EE-formula use after heart surgery of patients with CHD is well tolerated and may improve short-term nutrition outcome, decrease hospital stay, and reduce antibiotic use.

Cholinergic system and exploratory behavior are changed after weekly-binge ethanol exposure in zebrafish.

Binge drinking is characterized by excessive alcohol consumption in a short period of time and is associated with a poor quality of life. Zebrafish are commonly used to investigate neurochemical, behavioral, and genetic parameters associated with ethanol (EtOH) exposure. However, few studies have used zebrafish as a model to investigate binge EtOH exposure. In order to elucidate the potential neurobehavioral impairments evoked by binge EtOH exposure in zebrafish, animals were immersed in 1.4% EtOH for 30 min three consecutive times with intervals of one week. Neurobehavioral parameters were analyzed immediately following the third exposure, as well as 2 and 9 days later. Brain choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were reduced 9 days after the treatment. Thiobarbituric acid-reactive species and dichlorodihydrofluorescein levels were increased immediately after the treatment, but both returned to normal levels 2 days after the treatment. Catalase and glutathione reductase were impaired 2 and 9 days after the treatment. No alteration was observed in superoxide dismutase and glutathione peroxidase activities. EtOH treatment did not alter brain expression of inflammatory genes such as il-1ß, il-10, and tnf-α. Zebrafish displayed anxiolytic-like behavior immediately after the last exposure, though there was no behavioral alteration observed 9 days after the treatment. Therefore, binge EtOH exposure in zebrafish leads to long lasting brain cholinergic alteration, probably related to oxidative stress immediately after the exposure, which is independent of classical inflammatory markers.

Adult derived mononuclear bone marrow cells improve survival in a model of acetaminophen-induced acute liver failure in rats.

INTRODUCTION: Acute liver failure (ALF) is characterized by a rapid loss of hepatic function, with high mortality. Acetaminophen (APAP) intoxication and viral hepatitis are common causes of ALF. Several studies have shown the capacity of adult bone marrow cells to differentiate in hepatocytes, suggesting their use for treating ALF. AIM: In the present study, we tested the use of adult derived mononuclear bone marrow fraction to improve the survival of Wistar rats with APAP-induced ALF. METHODS: Forty-eight female Wistar rats pre-induced with phenobarbital were given APAP in a single dose of 1g/kg via intraperitoneal injection. Bone marrow mononuclear cells were purified from male rats using FICOLL gradient and injected through the portal vein in a volume of 0.2mL containing 1x10(6) cells stained with DAPI. Treatment was administered 24h after APAP injection. The sham group (n=24), received 0.2mL of saline through the portal vein 24h after APAP administration. Survival, liver histology and ALT levels were observed. RESULTS: Survival 72h post-APAP administration was 33% in the sham group and 70.8% in the group receiving bone marrow cells. Liver histology in treated animals showed less intense necrosis and the presence of DAPI-positive cells. CONCLUSIONS: We have shown that bone marrow derived cells are capable of significantly increasing the survival rate of APAP-induced ALF in 37.5% (95% CI, 27.8-40.3%).

Cholinergic System and Oxidative Stress Changes in the Brain of a Zebrafish Model Chronically Exposed to Ethanol.

Ethanol is a widely used drug, and excess or even moderate consumption of ethanol is associated with changes in several neurotransmitter systems, including the cholinergic system. The incidence of alcoholic dementia and its insults are well supported by multiple studies, although the mechanisms of neurotoxicity are still poorly understood. Considering that zebrafish have a complete central nervous system (CNS) and that several signaling systems have already been identified in zebrafish, this neurotoxicological model has become useful. In the present study, we investigated the long-term effects of ethanol consumption on the cholinergic system, on oxidative stress, and on inflammatory parameters in the zebrafish brain. Animals were exposed to 0.5% (v/v) ethanol for 7, 14, and 28 days. Ethanol inhibited choline acetyltransferase activity after 7 and 14 days but not after 28 days. Acetylcholinesterase activity did not change after any of the exposure periods. When compared to the control group, thiobarbituric acid reactive species and dichlorodihydrofluorescein levels were increased after chronic ethanol exposure. Antioxidant activity promoted by the CAT/SOD ratio was altered after chronic ethanol exposure, suggesting that EtOH can induce oxidative damage in the zebrafish brain. In contrast, nitrate and nitrite levels and sulfhydryl content were not altered. Ethanol did not modify gene expression of the inflammatory cytokines il-1b, il-10, or tnf-α in the zebrafish brain. Therefore, the cholinergic system and the oxidative balance were targeted by chronic ethanol toxicity. This neurochemical regulatory mechanism may play an important role in understanding the effects of long-term ethanol consumption and tolerance in zebrafish model studies.

Developmental expression of Commd1 in the liver of the Jackson toxic milk mouse.

Wilson disease (WD) is due to mutations in ATP7B, which encodes an intracellular metal-transporting P-type ATPase. In WD holoceruloplasmin production and biliary excretion of copper are decreased, leading to copper overload, oxidative stress and apoptotic cell death. Other copper-binding proteins include COMMD1, which is inactive in the Bedlington terrier hereditary copper toxicosis, and XIAP, which regulates apoptosis. We examined developmental expression of Commd1 and Xiap in the Jackson toxic milk mouse (Atp7b(tx-J), G712D missense mutation in Atp7b). Expression of Commd1 mRNA appeared unchanged by PCR but real-time PCR demonstrated 3- to 4-fold increase over the first 6 months of life. Immunodetectable Xiap dropped over the first 8 months of life and was nearly undetectable from 6 months onward. Cytosolic NF-kappaB rose then dropped precipitously at 5-6 months. In tx-j mice hepatic copper accumulation leads to decreased Xiap, increased Commd1; these responses ultimately fail to prevent progressive apoptotic cell damage.

Paracrine Effects of Bone Marrow Mononuclear Cells in Survival and Cytokine Expression after 90% Partial Hepatectomy.

Acute liver failure is a complex and fatal disease. Cell-based therapies are a promising alternative therapeutic approach for liver failure due to relatively simple technique and lower cost. The use of semipermeable microcapsules has become an interesting tool for evaluating paracrine effects in vivo. In this study, we aimed to assess the paracrine effects of bone marrow mononuclear cells (BMMC) encapsulated in sodium alginate to treat acute liver failure in an animal model of 90% partial hepatectomy (90% PH). Encapsulated BMMC were able to increase 10-day survival without enhancing liver regeneration markers. Gene expression of Il-6 and Il-10 in the remnant liver was markedly reduced at 6 h after 90% PH in animals receiving encapsulated BMMC compared to controls. This difference, however, was neither reflected by changes in the number of CD68+ cells nor by serum levels of IL6. On the other hand, treated animals presented increased caspase activity and gene expression in the liver. Taken together, these results suggest that BMMC regulate immune response and promote apoptosis in the liver after 90% PH by paracrine factors. These changes ultimately may be related to the higher survival observed in treated animals, suggesting that BMMC may be a promising alternative to treat acute liver failure.

Chronic exposure to ethanol causes steatosis and inflammation in zebrafish liver.

AIM: To evaluate the effects of chronic exposure to ethanol in the liver and the expression of inflammatory genes in zebrafish. METHODS: Zebrafish (n = 104), wild type, adult, male and female, were divided into two groups: Control and ethanol (0.05 v/v). The ethanol was directly added into water; tanks water were changed every two days and the ethanol replaced. The animals were fed twice a day with fish food until satiety. After two and four weeks of trial, livers were dissected, histological analysis (hematoxilin-eosin and Oil Red staining) and gene expression assessment of adiponectin, adiponectin receptor 2 (adipor2), sirtuin-1 (sirt-1), tumor necrosis factor-alpha (tnf-a), interleukin-1b (il-1b) and interleukin-10 (il-10) were performed. Ultrastructural evaluations were conducted at fourth week. RESULTS: Exposing zebrafish to 0.5% ethanol developed intense liver steatosis after four weeks, as demonstrated by oil red staining. In ethanol-treated animals, the main ultrastructural changes were related to cytoplasmic lipid particles and droplets, increased number of rough endoplasmic reticulum cisterns and glycogen particles. Between two and four weeks, hepatic mRNA expression of il-1b, sirt-1 and adipor2 were upregulated, indicating that ethanol triggered signaling molecules which are key elements in both hepatic inflammatory and protective responses. Adiponectin was not detected in the liver of animals exposed and not exposed to ethanol, and il-10 did not show significant difference. CONCLUSION: Data suggest that inflammatory signaling and ultrastructural alterations play a significant role during hepatic steatosis in zebrafish chronically exposed to ethanol.

Viral hepatitis prevention by immunization.

OBJECTIVE: To present an updated review and criticism of viral hepatitis A and B prevention by immunization. SOURCES OF DATA: Review of medical articles obtained from the MEDLINE database. The most recent and representative articles on the subject (2000-2006) were selected. The Centers for Disease Control and Prevention (CDC), American Academy of Pediatrics (AAP), Brazilian Society of Pediatrics and Brazilian Ministry of Health websites were also researched. SUMMARY OF THE FINDINGS: Viral hepatitis prevention is an enormous challenge to the public health systems of countries and the medical and scientific communities. Hepatitis viruses produce important morbidity and mortality in the world, causing acute and chronic hepatic disease. There are highly efficient vaccines available on the market to prevent new infections by the A and B viruses. However, A and B viruses continue to be among the most commonly notified diseases preventable by vaccines. In this article, we discuss the vaccines used to prevent these infections, with the aim of expanding knowledge and the practice of prevention of these infectious diseases. CONCLUSIONS: Although the vaccines against A and B hepatitis are recommended for various risk groups, estimated vaccine coverage is still modest and many vaccination opportunities are lost. In order to reduce the incidence of A and B hepatitis, which are preventable by vaccines, it is necessary for physicians to encourage their patients to be vaccinated.

Lactobacillus rhamnosus GG Effect on Behavior of Zebrafish During Chronic Ethanol Exposure.

Ethanol is a widely consumed drug, which acts on the central nervous system to induce behavioral alterations ranging from disinhibition to sedation. Recent studies have produced accumulating evidence for the therapeutic role of probiotic bacteria in behavior. We aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) on the behavior of adult zebrafish chronically exposed to ethanol. Adult wild-type zebrafish were randomly divided into four groups, each containing 15 fish. The following groups were formed: Control (C), received unsupplemented feed during the trial period; Probiotic (P), fed with feed supplemented with LGG; Ethanol (E), received unsupplemented feed and 0.5% of ethanol directly added to the tank water; and Probiotic+Ethanol (P+E), group under ethanol exposure (0.5%) and fed with LGG supplemented feed. After 2 weeks of exposure, the novel tank test was used to evaluate fish behavior, which was analyzed using computer-aided video tracking. LGG alone did not alter swimming behavior of the fish. Ethanol exposure led to robust behavioral effects in the form of reduced anxiety levels, as indicated by increased vertical exploration and more time spent in the upper region of the novel tank. The group exposed to ethanol and treated with LGG behaved similarly to animals exposed to ethanol alone. Taken together, these results show that zebrafish behavior was not altered by LGG per se, as seen in murine models. This was the first study to investigate the effects of a probiotic diet on behavior after a chronic ethanol exposure.

Encapsulated Whole Bone Marrow Cells Improve Survival in Wistar Rats after 90% Partial Hepatectomy.

Background and Aims. The use of bone marrow cells has been suggested as an alternative treatment for acute liver failure. In this study, we investigate the effect of encapsulated whole bone marrow cells in a liver failure model. Methods. Encapsulated cells or empty capsules were implanted in rats submitted to 90% partial hepatectomy. The survival rate was assessed. Another group was euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy to study expression of cytokines and growth factors. Results. Whole bone marrow group showed a higher than 10 days survival rate compared to empty capsules group. Gene expression related to early phase of liver regeneration at 6 hours after hepatectomy was decreased in encapsulated cells group, whereas genes related to regeneration were increased at 12, 24, and 48 hours. Whole bone marrow group showed lower regeneration rate at 72 hours and higher expression and activity of caspase 3. In contrast, lysosomal-ß-glucuronidase activity was elevated in empty capsules group. Conclusions. The results show that encapsulated whole bone marrow cells reduce the expression of genes involved in liver regeneration and increase those responsible for ending hepatocyte division. In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival.

Ontogenetic changes in serum S100B in Down syndrome patients.

BACKGROUND: It has been shown that Down syndrome (DS) patients have elevated S100B levels in brain tissue. DESIGN: Measurements of S100B were performed in serum samples from 48 DS patients and 42 ostensibly healthy age-matched controls. RESULTS: We observed higher levels of S100B in the DS group than in the control group. Moreover, serum S100B in DS patients was not age-dependent as it is in normal individuals. CONCLUSION: The higher levels of S100B in DS patients may reflect a general and persistent increase in the extracellular space and may be associated with neurodegenerative lesions observed in DS patients.

Cirrhosis in children and adolescents: An overview.

Several conditions, especially chronic liver diseases, can lead to cirrhosis in children and adolescents. Most cases in clinical practice are caused by similar etiologies. In infants, cirrhosis is most often caused by biliary atresia and genetic-metabolic diseases, while in older children, it tends to result from autoimmune hepatitis, Wilson's disease, alpha-1-antitrypsin deficiency and primary sclerosing cholangitis. The symptoms of cirrhosis in children and adolescents are similar to those of adults. However, in pediatric patients, the first sign of cirrhosis is often poor weight gain. The complications of pediatric cirrhosis are similar to those observed in adult patients, and include gastrointestinal bleeding caused by gastroesophageal varices, ascites and spontaneous bacterial peritonitis. In pediatric patients, special attention should be paid to the nutritional alterations caused by cirrhosis, since children and adolescents have higher nutritional requirements for growth and development. Children and adolescents with chronic cholestasis are at risk for several nutritional deficiencies. Malnutrition can have severe consequences for both pre- and post-liver transplant patients. The treatment of cirrhosis-induced portal hypertension in children and adolescents is mostly based on methods developed for adults. The present article will review the diagnostic and differential diagnostic aspects of end-stage liver disease in children, as well as the major treatment options for this condition.