Detection of Escherichia coli O157H7 and Campylobacter jejuni in Bovine Carcasses in Two Slaughterhouses in Bio-Bío District, Chile.

Escherichia coli O157:H7 (E. coli O157:H7) and Campylobacter jejuni (C. jejuni) are pathogenic microorganisms that can cause severe clinical symptoms in humans and are associated with bovine meat consumption. Specific monitoring for E. coli O157: H7 or C. jejuni in meat is not mandatory under Chilean regulations. In this study, we analyzed 544 samples for the detection of both microorganisms, obtained from 272 bovine carcasses (280 kg average) at two slaughterhouses in the Bio-Bío District, Chile. Sampling was carried out at post-shower of carcasses and after channel passage through the cold chamber. Eleven samples were found to be positive for E. coli O157:H7 (4.0%) using microbiological and biochemical detection techniques and were subjected to a multiplex PCR to detect fliC and rfbE genes. Six samples (2.2%) were also found to be positive for the pathogenicity genes stx1, stx2, and eaeA. Twenty-two carcasses (8.0%) were found to be positive for C. jejuni using microbiological and biochemical detection techniques, but no sample with amplified mapA gene was found.

Are silymarin and N-acetylcysteine able to prevent liver damage mediated by multiple factors? Findings against ethanol plus LPS-induced liver injury in mice.

This study investigated the effect of N-acetylcysteine (NAC) and silymarin (SIL) in the liver of mice exposed to ethanol and lipopolysaccharides (LPS). Mice were divided into four groups (n = 6): naive, vehicle, NAC (200 mg/kg), and SIL (200 mg/kg). Treatments were given orally (po) once daily for 10 days. Liver injury was induced by administration of ethanol (30%, po) for 10 days, once daily, followed by a single administration of LPS (2 mg/kg, ip) 24 h before euthanasia. After the treatment period, animals were euthanized, and liver and blood samples were collected. NAC, but not SIL, prevented the increase in oxalacetic glutamic transaminase (OGT) and pyruvic glutamic transaminase (PGT) serum levels. NAC and SIL did not restore levels of reduced glutathione or hepatic malonaldehyde. The treatments with NAC or SIL showed no difference in the activity of glutathione S-transferase, superoxide dismutase, and catalase compared to vehicle group. Myeloperoxidase and N-acetylglucosaminidase activities are increased, as well as the IL-6 and IL-10 levels in the liver. The treatment with NAC, but not SIL, reduced the N-acetylglucosamines activity and the IL-6 and IL-10 amount in the liver. Histological findings revealed microsteatosis in the vehicle group, which was not prevented by SIL but was partially reduced in animals receiving NAC. Unlike other liver injury models, NAC (200 mg/kg) or SIL (200 mg/kg) did not positively affect antioxidant patterns in liver tissue of animals exposed to ethanol plus LPS, but NAC treatment displays anti-inflammatory properties in this model.

Marcadores humorales y estudio ultrasonográfico en pacientes diabéticos con enfermedad hepática por acumulación de grasa / Humoral markers and ultrasonographic study in diabetic patients with liver disease due to fat accumulation

Introducción: La enfermedad hepática grasa no alcohólica se caracteriza por: una acumulación de grasa en el hígado en forma de triacilglicéridos, ausencia de inflamación, fibrosis y un consumo de menos de 30 grados de alcohol al día. Esta afección se asocia a la diabetes mellitus (sobre todo tipo 2), y se observa un creciente aumento en el número de consultas hospitalarias por esta causa. Objetivo: Determinar la relación de los marcadores humorales y el estudio ultrasonográfico en pacientes diabéticos con enfermedad hepática grasa no alcohólica. Métodos: Se realizó una investigación descriptiva y transversal en la Consulta Provincial de Hepatología del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro», en el período de marzo 2019 a diciembre 2020. El universo de estudio estuvo conformado por 89 pacientes (con edades mayores o iguales a 19 años, de ambos sexos); la muestra estuvo constituida por 66 pacientes que fueron seleccionados por muestreo no probabilístico. Resultados: Predominaron los pacientes con edades entre 40 y 59 años, masculinos, de piel blanca, y procedencia urbana. El grado de esteatosis predominante fue el grado 1 (leve). Los marcadores humorales (glicemia, gamma glutamil transpeptidasa, albúmina e índice de Ritis) fueron los más afectados patológicamente. Conclusiones: Los estudios ultrasonográficos mostraron una asociación estadísticamente significativa con alteración de los marcadores humorales de lesión hepática, lo cual puede alertar de una posible evolución desfavorable de esta enfermedad.

Introduction: non-alcoholic fatty liver disease is characterized by an accumulation of fat in the liver in the form of triacylglycerides, absence of inflammation, fibrosis and a consumption of less than 30 degrees of alcohol per day. This condition is associated with diabetes mellitus (especially type 2), and there is a growing increase in the number of hospital visits for this cause. Objective: to determine the relationship between humoral markers and ultrasonographic study in diabetic patients with non-alcoholic fatty liver disease. Methods: a descriptive and cross-sectional investigation was carried out in the provincial hepatology consultation at "Arnaldo Milián Castro" Clinical and Surgical University Hospital from March 2019 to December 2020. The study universe consisted of 89 patients (older than or equal to 19 years, of both genders); the sample consisted of 66 patients who were selected by non-probabilistic sampling. Results: white male patients aged between 40 and 59 years living in urban areas predominated. The predominant degree of steatosis was grade 1 (mild). Humoral markers (glycemia, gamma- glutamyl transpeptidase, albumin and De Ritis ratio) were the most pathologically affected. Conclusions: ultrasonographic studies showed a statistically significant association with changes in humoral markers of liver injury, which may alert to a possible unfavorable evolution of this disease.

MINIMAL LIVER ENZYMES ABNORMALITIES AT ADMISSION ARE RELATED TO SEVERE COVID-19 CLINICAL COURSE IN A LARGE BRAZILIAN COHORT.

BACKGROUND: COVID-19 is a multisystemic disease, primarily affecting the respiratory system. Liver involvement is frequent, but the impact on the clinical course and outcomes are controversial. OBJECTIVE: The aim was to assess liver function at the admission and evaluate its effects on severity and mortality in hospitalized patients with COVID-19. METHODS: This is a retrospective study of hospitalized patients in a tertiary hospital in Brazil, with a PCR-confirmed SARS-CoV-2 infection between April and October 2020. 1080 out of 1229 patients had liver enzymes on admission and were divided in two cohorts, based on the presence or absence of abnormal liver enzymes (ALE). Demographic, clinical, laboratory, imaging, clinical severity, and mortality were evaluated. Patients were followed until discharge, death or transfer to another institution. RESULTS: Median age was 60 years and 51.5% were male. The more frequent comorbidities were hypertension (51.2%), and diabetes (31.6%). Chronic liver disease and cirrhosis were present in 8.6% and 2.3%, respectively. ALE (aminotransferases higher than 40 IU/L) were present in 56.9% of patients [mild (1-2 times): 63.9%; moderate (2-5 times): 29.8%; severe (>5 times): 6.3%]. Male gender [RR 1.49, P=0.007], increased total bilirubin [RR 1.18, P<0.001] and chronic liver disease [RR 1.47, P=0.015] were predictors of abnormal aminotransferases on admission. Patients with ALE had a higher risk of disease severity [RR 1.19; P=0.004]. There was no association among ALE and mortality. CONCLUSION: ALE is common in COVID-19 hospitalized patients and were independently correlated with severe COVID-19. Even mild ALE at admission may be a severity prognostic marker.

Alcoholic liver disease and intestinal microbiota in an experimental model: Biochemical, inflammatory, and histologic parameters.

OBJECTIVES: Alcoholic liver disease (ALD) is the leading cause of alcohol-related deaths worldwide. Experimental ALD models are expensive and difficult to reproduce. A low-cost, reproducible ALD model was developed, and liver damage compared with the gut microbiota. The aims of this study were to develop an experimental model of ALD, through a high-fat diet, the chronic use of ethanol, and intragastric alcohol binge; and to evaluate the composition of the gut microbiota and its correlation with markers of inflammatory and liver disease progression in this model. METHODS: Adult male Wistar rats were randomized (N = 24) to one of three groups: control (standard diet and water + 0.05% saccharin), ALC4 and ALC8 (sunflower seed, 10% ethanol + 0.05% saccharin for 4 and 8 wk, respectively). On the last day, ALC4/8 received alcoholic binge (5 g/kg). Clinical, nutritional, biochemical, inflammatory, pathologic, and gut microbiota data were analyzed. RESULTS: ALC4/8 animals consumed more alcohol and lipids (P < 0.01) and less total energy, liquids, solids, carbohydrates, and proteins (P < 0.01), and gained less weight (P < 0.01) than controls. ALC8 had lower Lee index scores than controls and ALC4 (P < 0.01). Aminotransferases increased and albumin diminished in ALC4/8 but not in the control group (P < 0.03 for all). Glucose and aspartate transaminase/alanine aminotransaminase ratios were higher in the ALC8 rats than in the controls (P < 0.03). Cholesterol was higher in ALC4 and lower in ALC8 compared with controls (P < 0.03). Albumin and high-density lipoprotein cholesterol levels were lower in ALC8 (P < 0.03). Hepatic concentration of triacylglycerols was higher in ALC8 than in ALC4 and controls (P < 0.05). ALC4/8 presented microvesicular grade 2 and 3 steatosis, respectively, and macrovesicular grade 1. No change in the gene expression of inflammatory markers between groups was seen. ALC4/8 had lower fecal bacterial α-diversity and relative abundance of Firmicutes (P < 0.005) and greater Bacterioidetes (P < 0.0007) and Protobacteria (P < 0.001) than controls. Gut microbiota correlated with serum and liver lipids, steatosis, albumin, and aminotransferases (P < 0.01 for all). CONCLUSION: The model induced nutritional, biochemical, histologic, and gut microbiota changes, and appears to be useful in the study of therapeutic targets.

Hiperferritinemia y sospecha de sobrecarga de hierro en pacientes del Hospital Pablo Tobón Uribe, entre los años 2010 a 2020 / Hyperferritinemia and suspected iron overload in patients at the Pablo Tobón Uribe Hospital, between 2010 and 2020

Introducción. El objetivo de esta investigación fue comparar el perfil bioquímico y clínico de los pacientes con hiperferritinemia secundaria a hemocromatosis hereditaria (HH), frente a aquellos con hiperferritinemia por causas sospechosas de sobrecarga de hierro (Fe) diferentes a la HH. Metodología. Se estudiaron 92 pacientes (61 hombres y 31 mujeres), remitidos tras la detección de valores de ferritina >300 µg/L en hombres y >200 µg/L en mujeres. En todos se analizaron datos demográficos generales, comorbilidades, motivo de remisión para estudios de hiperferritinemia, manifestaciones clínicas, antecedente familiar de HH y tratamiento reci-bido. Los resultados de las pruebas de laboratorio, imagenología, hallazgos histopatológicos y estudios genéticos, se describieron según la disponibilidad. Resultados. El 96,74 % de los pacientes fueron evaluados en consulta externa, 86,96 % procedían de Medellín o de otros municipios de Antioquia, Colombia. La edad promedio de los participantes fue de 52 años, la principal razón para ser derivados para estudios fue la elevación de los marcadores de Fe sérico, la causa más frecuente de hiperferritinemia fueron los diagnósticos diferentes a la HH (64,13 %) y entre quienes no tenían HH, la etiología metabólica fue la más común (59,32 %). Los pacientes con HH tuvieron niveles más elevados de ferritina y Fe sérico, mientras que en el grupo sin HH se presentaron mayores elevaciones en la saturación de transferrina, transfe-rrina y transaminasas. En pacientes con sobrecarga de Fe, la mutación más frecuentemente encontrada fue la homocigota H63D (36,67 %). Finalmente, 93,94 % de los pacientes con HH recibieron tratamiento con flebotomías, mientras que los cambios en el estilo de vida fueron indicados en el 55,93 % de los pacientes sin HH. Conclusiones. La hiperferritinemia es una presentación clínica frecuente y es importante hacer un abordaje sistemático para identificar sus causas. Aunque la HH es una causa importante de elevación persistente de ferritina, en el enfoque de los pacientes con esta condición, se deben descartar etiologías más frecuentes como la hiperferritinemia de etiología metabólica.

Introduction. The aim of this investigation was to compare the biochemical and clinical profile of patients with secondary hyperferritinemia caused by hereditary hemochromatosis (HH), versus those with hyperferritinemia due to suspected causes of iron (Fe) overload other than HH. Methodology. A total of 92 patients (61 men and 31 women) referred after the detection of ferritin values >300 µg/L in men and >200 µg/L in women were studied. General demographic data, comorbidities, referral reasons for hyperferritinemia studies, clinical manifestations, family history of HH, and treatment received were analyzed in all patients. The results of laboratory tests, medical imaging, histopatho-logical findings, and genetic studies were described based on availability. Results. Of all patients, 96.74% were evaluated as outpatients, 86,96% from the municipality of Medellin in Antioquia, Colombia. The average age of the participants was 52 years, the main reason for being referred for studies was the elevation of serum Fe markers, the most frequent cause of hyperferritinemia in the population studied were conditions other than HH (64.13%), and among those who did not have HH, the metabolic etiology was the most common cause (60%). Patients with HH had higher levels of ferritin and serum Fe, while in the group without HH there were greater elevations of transferrin saturation, transferrin and transaminases. In patients with iron overload, the most frequently found mutation was the homozygous H63D (36.67%). Finally, 93.94% of the patients with HH received phlebotomy treatment, while changes in lifestyle were indicated in 55.93% of patients without HH. Conclusions. Hyperferritinemia is a frequent clinical presentation and it is important to make a systematic approach to identify its causes. Although HH is an important cause of persistent ferritin elevation, in the approach to patients with this condition, more frequent etiologies such as hyperfe-rritinemia of metabolic etiology should be ruled out.

Normal transaminases in obese patients with metabolic associated steatohepatitis (MASH): a cohort of Peruvian patients.

INTRODUCTION: Metabolic associated steatohepatitis (MASH) is one of the most frequent causes of chronic liver disease. Liver transaminases are important biomarkers to measure liver injury, however, a proportion of patients with MASH may present with normal levels of transaminases. The levels of serum transaminases may not correlate with the severity of histopathological changes. OBJECTIVE: We aimed to identify the frequency of normal transaminases in obese patients with MASH, as well as to describe the clinical, biochemical and histological characteristics in this specific group of patients. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted in the bariatric surgery service of a private clinic. Obese patients older than 18 years with a body mass index (BMI) >30Kg/m2 and 2 co-morbidities undergoing a gastric sleeve surgery were included. Measurement of biochemical routine laboratory exams was performed. Insulin resistance was calculated using the homeostasis evaluation model (HOMA-IR). All patients underwent liver biopsies prior to surgery and the diagnosis of MASH was based on the Brunt criteria. RESULTS: 159 obese patients with MASH were included, of which 47.2% had normal transaminases and 52.8% elevated transaminases. Factors associated with alteration in transaminases were: being male OR=4.02 (95% CI: 2.03- 7.96; p<0.01), diagnosis of type 2 diabetes mellitus OR=4.86 (95% CI: 1.97- 11.95; p<0.01) and levels of GGT >50 IU/L OR=7.50 (95% CI: 3.40-16.56; p<0.01). The values of HOMA-IR and GGT were significantly higher in the group of high transaminases (p<0.01). Differences in the degree of fibrosis were not associated with transaminases levels. CONCLUSION: In conclusion we found that the frequency of normal transaminases was 47.2% in obese patients with MASH. Factors associated with elevation in liver enzymes were being male, diagnosis of diabetes mellitus and elevation in GGT levels. The degree of fibrosis was not associated with elevations in liver transaminases. These findings suggest that transaminases levels alone are not accurate markers to assess liver injury, as they do not necessarily correlate with histological liver damage.

DIFFERENTIAL DIAGNOSIS BETWEEN BILIARY AND NONBILIARY ACUTE PANCREATITIS: WHAT IS THE IMPORTANCE OF LABORATORY TESTS?

BACKGROUND: The differential diagnosis of the causal factors of acute pancreatitis is fundamental for its clinical follow-up, becoming relevant to establishing laboratory criteria that elucidate the difference between biliary and nonbiliary causes. AIM: The aim of this study was to establish criteria based on laboratory tests for the differential diagnosis between acute pancreatitis of biliary and nonbiliary causes and to identify laboratory tests with sufficient sensitivity to propose the creation of an algorithm for differential diagnosis between the causes. METHODS: The research consisted of observational analysis, with a cross-sectional design of laboratory tests of two groups of patients with acute pancreatitis: group A: nonbiliary cause and group B: biliary cause. Hematocrit, white blood cell count, lactate dehydrogenase, glucose, lipase, amylase, total bilirubin, oxalacetic transaminase, pyruvic transaminase, gamma-glutamyltransferase, and alkaline phosphatase were investigated. Data were submitted to nonparametric tests and receiver operating characteristics. RESULTS: Hematocrit values, number of leukocytes, lactate dehydrogenase, and glucose showed no significant difference between the groups (p>0.1). Lipase, amylase, total bilirubin, oxalacetic transaminase, pyruvic transaminase, gamma-glutamyltransferase, and alkaline phosphatase values showed a significant difference between groups (p<0.05). The oxalacetic transaminase, pyruvic transaminase, and alkaline phosphatase tests were most sensitive in determining the biliary cause, allowing the establishment of a cutoff point by the receiver operating characteristic test: pyruvic transaminase: 123.0 U/L (sensitivity: 69.2%; specificity: 81.5%), oxalacetic transaminase: 123.5 U/L (sensitivity: 57.3%; specificity: 78.8%), and alkaline phosphatase: 126.5 U/L (sensitivity: 66.1%; specificity: 69.4%), from which the probability of a correct answer increases. CONCLUSION: It was possible to establish criteria based on laboratory tests for the differential diagnosis between acute pancreatitis of biliary and nonbiliary origin; however, the tests did not show enough sensitivity to propose the creation of an algorithm for differential diagnosis between the same causes.

Daily Intake of Smallanthus sonchifolius (Yacon) Roots Reduces the Progression of Non-alcoholic Fatty Liver in Rats Fed a High Fructose Diet.

High-fructose diet is associated with an increased risk of dyslipidemia, metabolic syndrome, and the development of non-alcoholic fatty liver disease (NAFLD) through chronic inflammation. The present study aimed to elucidate the potential benefit of daily consumption of Smallanthus sonchifolius (yacon) roots, rich in fructooligosaccharides (FOS), on the progression to liver fibrosis, in a rat model of NAFLD induced by a high-fructose diet. Male Wistar rats were fed a standard diet (CD, n = 6) or a standard diet plus 10% fructose solution (FD; n = 18). After 20 weeks, FD rats were randomly separated into the following groups (n = 6, each): FD; FD treated with yacon flour (340 mg FOS/body weight; FD + Y) and FD treated with fenofibrate (30 mg/kg body weight; FD + F), for 16 weeks. Daily intake of yacon flour significantly reduced body weight gain, plasma lipid levels, transaminase activities, and improved systemic insulin response in FD rats. In the liver, yacon treatment decreased fructose-induced steatosis and inflammation, and reduced total collagen deposition (64%). Also, yacon decreased TGF-ß1 mRNA expression (78%), followed by decreased nuclear localization of p-Smad2/3 in liver tissue. Yacon significantly reduced the expression of α-smooth muscle actin (α-SMA), Col1α1, and Col3α1 mRNAs (85, 44, and 47%, respectively), inhibiting the activation of resident hepatic stellate cells (HSCs). These results suggested that yacon roots have the potential to ameliorate liver damage caused by long-term consumption of a high-fructose diet, being a promising nutritional strategy in NAFLD management.

Antihyperlipidemic Activity of Glycoconjugated Phthalimides in Mice Submitted to a Model of Dyslipidemia and Insulin Resistance.

Alterations in lipid and lipoprotein metabolism are factors that trigger several negative metabolic complications. Hyperlipidemia is the starting point for the development of comorbidities of the cardiovascular system, such as atherosclerosis. The search for compounds that reduce high levels of total cholesterol and triglycerides has been widely reported in several publications in the literature. Phthalimide derivatives have been extensively researched with various biological actions. In this study we evaluated the antihyperlipidemic ability of three phthalimide derivatives (FGT-2, FGT-3 and FGT-4) on a model of obesity and insulin resistance in mice. The animals were submitted to a hyperlipid diet for 60 days. On the thirtieth day they were treated with phthalimides (20 mg/kg). The positive control group was treated with Simvastatin (20 mg/kg) and the negative control received only the carboxymethylcellulose vehicle. Biochemical and histological analyzes of all groups were analyzed. The animals treated with phthalimidic derivatives had a reduction in total cholesterol, low density and very low density lipoproteins (LDL-c and VLDL-c), triglycerides and fasting glycemia when compared to the negative control group. The treated animals also showed good results when analyzing the atherogenic indexes Castelli i and II and the ratio Triglycerides/HDL-c. In the oral glucose tolerance test and in the insulin tolerance test, animals treated with phthalimides were more sensitive to the action of the hormone regulating carbohydrate uptake. In the evaluation of the transaminases (AST/ALT), the animals of the group treated with phthalimides presented a lower elevation than the other groups of the experiment, the same observed with the uric acid evaluation. Histological analyzes were performed on liver, kidney, heart and pancreas samples. The groups treated with the compounds FGT-2 and FGT3 presented discrete alterations in the liver and kidney. FGT-4 did not present histological alterations for both tissues and the three phthalimide derivatives did not cause alterations in the other organs. These results suggest that the phthalimides tested can act as antihyperlipidemic agents and have a pleiotropic action, by acting also reducing glycemia in insulin resistance model mimicking diabetes mellitus type 2. These compounds may appear as a new approach in the treatment of obesity and complications, which are multifaceted.

Perinatal exposure to a glyphosate pesticide formulation induces offspring liver damage.

The present study investigated the effects of perinatal exposure to glyphosate-based herbicide (GBH) in offspring's liver. Pregnant Wistar rats were exposed to GBH (70 mg glyphosate/Kg body weight/day) in drinking water from gestation day 5 to postnatal day 15. The perinatal exposure to GBH increased 45Ca2+ influx in offspring's liver. Pharmacological tools indicated a role played by oxidative stress, phospholipase C (PLC) and Akt pathways, as well as voltage-dependent Ca2+ channel modulation on GBH-induced Ca2+ influx in offspring's liver. In addition, changes in the enzymatic antioxidant defense system, decreased GSH content, lipid peroxidation and protein carbonylation suggest a connection between GBH-induced hepatotoxic mechanism and redox imbalance. The perinatal exposure to GBH also increased the enzymatic activities of transaminases and gamma-glutamyl transferase in offspring's liver and blood, suggesting a pesticide-induced liver injury. Moreover, we detected increased iron levels in liver, blood and bone marrow of GBH-exposed rats, which were accompanied by increased transferrin saturation and decreased transferrin levels in blood. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were increased in the liver of rats perinatally exposed to GBH, which were associated with. Increased phospho-p65NFκB immunocontent. Therefore, we propose that excessive amounts of iron in offspring's liver, blood and bone marrow induced by perinatal exposure to GBH may account for iron-driven hepatotoxicity, which was associated with Ca2+ influx, oxidative damage and inflammation. Further studies will clarify whether these events can ultimately impact on liver function.

Effectiveness of Direct-acting Agents After Liver Transplantation A Real-life Study in Rio de Janeiro.

BACKGROUND: Data concerning hepatitis C virus (HCV) treatment using direct-acting agents (DAAs) post liver transplantation (LT) remains scarce in low- and average-income countries. AIM OF THE STUDY: To evaluate the safety and efficacy of post-LT HCV treatment using DAAs in Rio de Janeiro (Brazil), and to assess the course of hepatic biomarkers after sustained virological response (SVR). METHODS: Data from LT recipients with recurrent HCV treated using DAAs was retrospectively analyzed. HCV was defined by detectable HCV-RNA with elevated aminotransferases and/or histological signs of infection on liver biopsy post LT. SVR was defined as undetectable HCV-RNA 12 weeks after the end of treatment. Aspartate-to-Platelet Ratio Index (APRI) and Fibrosis-4 score (FIB-4) were calculated before treatment and after SVR. RESULTS: 116 patients (63% male, median age 62 years, 75% genotype 1 and 62% with hepatocellular carcinoma [HCC] prior to LT) were included. Cirrhosis was identified in the allograft of 21 subjects (18%). The overall SVR was 96.6% without differences in SVR proportion according to clinical/demographic characteristics, genotype or presence of cirrhosis. SVR rates were similar in individuals with and without HCC pre-LT (95.8% [95% CI: 87.6-98.7] vs. 97.7% [95% CI: 85.0-99.7%], p = 0.588). No serious adverse events were observed and the use of ribavirin was associated with at least one adverse event (OR = 8.71 [95% CI: 3.17-23.99]). SVR was associated with regression of APRI (OR = 26.00 [95% CI 4.27-1065.94]) and FIB-4 (OR = 15.00 [95% CI: 2.30-631.47]). CONCLUSION: Post-LT HCV treatment with DAAs was safe and effective and associated with a significant decrease in hepatic biomarker levels after SVR.

Indicación de N-acetilcisteína en distintas formas de toxicidad por paracetamol / Indication of n-acetylcysteine in differents forms of paracetamol toxicity

Introducción: la hepatotoxicidad por paracetamol está relacionada con la formación del metabolito N-acetil-parabenzoquinoneimina (NAPQI) y su falta de detoxificación a través del glutatión, cuyas reservas se deplecionan en el contexto de una sobredosis. La administración de N-acetilcisteína (NAC) como sustancia dadora de grupos tioles (-SH) contribuye a la prevención del daño hepático que puede desarrollarse con dosis terapéuticas o tóxicas. Métodos: se comentan 5 casos de exposición a paracetamol en los cuales se administró NAC por alteración de la función hepática. La gravedad de los cuadros varió en función de las dosis y del tiempo de latencia hasta la consulta. Resultados: cuatro pacientes ingirieron una única dosis tóxica y una paciente recibió la dosis diaria máxima de paracetamol de 4000 mg/día durante 5 días. La paciente que consultó dentro de las 4 horas posteriores a la ingesta no presentó elevación de transaminasas. Todas las pacientes recibieron NAC y sus valores de enzimas hepáticas se normalizaron al momento del alta. Conclusión: la administración temprana de NAC puede ser útil para prevenir daño hepático tanto en ingestas de dosis tóxicas, como en casos de utilización de dosis terapéuticas máximas durante varios días. (AU)

Introduction: paracetamol hepatotoxicity is related to the formation of the metabolite N-acetyl-parabenzoquinoneimine (NAPQI) and its lack of detoxification through glutathione, whose reserves are depleted in paracetamol overdose. The administration of N-acetylcysteine (NAC) as a donor of sulfhydryl groups (-SH) can prevent liver damage that could even occur with therapeutic or toxic doses. Methods: 5 cases of exposure to paracetamol are discussed, in which NAC was administered due to impaired liver function. These manifestations presented different severity depending on the drug doses and the time until medical consultation. Results: four patients ingested single toxic doses and one patient received the maximum daily dose of paracetamol of 4000 mg/day for 5 days. The patient who consulted within 4 hours after ingestion did not present elevation of transaminases. All patients received NAC, with normal liver enzymes at discharge. Conclusion: the early administration of NAC may be useful to prevent liver damage both in toxic dose intakes and in cases of use of maximum therapeutic doses for several days. (AU)

The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance.

Chagas disease (CD) affects at least 6 million people in 21 South American countries besides several thousand in other nations all over the world. It is estimated that at least 14,000 people die every year of CD. Since vaccines are not available, chemotherapy remains of pivotal relevance. About 30% of the treated patients cannot complete the therapy because of severe adverse reactions. Thus, the search for novel drugs is required. Here we tested the benznidazole (BZ) combination with the repositioned drug disulfiram (DSF) and its derivative diethyldithiocarbamate (DETC) upon Trypanosoma cruzi in vitro and in vivo. DETC-BZ combination was synergistic diminishing epimastigote proliferation and enhancing selective indexes up to over 10-fold. DETC was effective upon amastigotes of the BZ- partially resistant Y and the BZ-resistant Colombiana strains. The combination reduced proliferation even using low concentrations (e.g., 2.5 µM). Scanning electron microscopy revealed membrane discontinuities and cell body volume reduction. Transmission electron microscopy revealed remarkable enlargement of endoplasmic reticulum cisternae besides, dilated mitochondria with decreased electron density and disorganized kinetoplast DNA. At advanced stages, the cytoplasm vacuolation apparently impaired compartmentation. The fluorescent probe H2-DCFDA indicates the increased production of reactive oxygen species associated with enhanced lipid peroxidation in parasites incubated with DETC. The biochemical measurement indicates the downmodulation of thiol expression. DETC inhibited superoxide dismutase activity on parasites was more pronounced than in infected mice. In order to approach the DETC effects on intracellular infection, peritoneal macrophages were infected with Colombiana trypomastigotes. DETC addition diminished parasite numbers and the DETC-BZ combination was effective, despite the low concentrations used. In the murine infection, the combination significantly enhanced animal survival, decreasing parasitemia over BZ. Histopathology revealed that low doses of BZ-treated animals presented myocardial amastigote, not observed in combination-treated animals. The picrosirius collagen staining showed reduced myocardial fibrosis. Aminotransferase de aspartate, Aminotransferase de alanine, Creatine kinase, and urea plasma levels demonstrated that the combination was non-toxic. As DSF and DETC can reduce the toxicity of other drugs and resistance phenotypes, such a combination may be safe and effective.

Experimental infection with Schistosoma mansoni isolated from the wild rodent Holochilus sciureus shows a low parasite burden but induces high schistosomiasis severity in BALB/c mice.

Wild mammals, especially rodents, can participate in the life cycle of Schistosoma mansoni; however, the impact of these parasite strains on the severity of schistosomiasis remains unclear. The aim of this study was to comparatively evaluate the parasitological and immunopathological alterations induced by an S. mansoni strain isolated from the wild rodent Holochilus sciureus (HS strain) and a parasite strain isolated from a human (LE strain) in experimentally infected mice. Male BALB/c mice were subcutaneously infected with 50 cercariae/mouse of either the HS or the LE strain and were evaluated for 12 weeks. In the experimental groups, the parasite burden was estimated by worm and egg (feces and tissues) count, and immunopathological alterations were evaluated in the liver and intestines. Compared to experimental infection with the LE parasite strain, HS-infected mice showed reduced number of parasite worms but higher fecundity rate, significant reduction in IL-5, IL-10 and IL-13 concentrations, lower EPO-activity in liver homogenate and higher concentrations of TNF-α, IFN-γ, IL-12 and IL-17 in the small intestine homogenate. Moreover, HS infection resulted in higher concentrations of NO end-products in both the liver and intestine, suggesting a predominance of the Th1/Th17 immune response. HS-infected mice also showed higher plasma transaminase levels, formed larger granulomas, and had a higher mortality rate in comparison with LE-infected mice. Data indicate that BALB/c mice infected with the HS strain of S. mansoni showed reduced susceptibility to the parasite but stronger tissue inflammation and high disease severity.

Computer Modeling Explains the Structural Reasons for the Difference in Reactivity of Amine Transaminases Regarding Prochiral Methylketones.

Amine transaminases (ATAs) are pyridoxal-5'-phosphate (PLP)-dependent enzymes that catalyze the transfer of an amino group from an amino donor to an aldehyde and/or ketone. In the past decade, the enzymatic reductive amination of prochiral ketones catalyzed by ATAs has attracted the attention of researchers, and more traditional chemical routes were replaced by enzymatic ones in industrial manufacturing. In the present work, the influence of the presence of an α,ß-unsaturated system in a methylketone model substrate was investigated, using a set of five wild-type ATAs, the (R)-selective from Aspergillus terreus (Atr-TA) and Mycobacterium vanbaalenii (Mva-TA), the (S)-selective from Chromobacterium violaceum (Cvi-TA), Ruegeria pomeroyi (Rpo-TA), V. fluvialis (Vfl-TA) and an engineered variant of V. fluvialis (ATA-256 from Codexis). The high conversion rate (80 to 99%) and optical purity (78 to 99% ee) of both (R)- and (S)-ATAs for the substrate 1-phenyl-3-butanone, using isopropylamine (IPA) as an amino donor, were observed. However, the double bond in the α,ß-position of 4-phenylbut-3-en-2-one dramatically reduced wild-type ATA reactivity, leading to conversions of <10% (without affecting the enantioselectivity). In contrast, the commercially engineered V. fluvialis variant, ATA-256, still enabled an 87% conversion, yielding a corresponding amine with >99% ee. Computational docking simulations showed the differences in orientation and intermolecular interactions in the active sites, providing insights to rationalize the observed experimental results.

Hipertransaminasemia en coledocolitiasis / Hypertransaminasemia in choledocholithiasis

Introducción. La coledocolitiasis aguda se presenta cuando un cálculo se impacta en el conducto biliar distal. Usualmente se manifiesta con un patrón colestásico, con aumento de la AST y ALT leve o moderado. Sin embargo, se han reportado series de casos de coledocolitiasis con AST y ALT con valores >400 UI/L, lo que puede llevar al médico a considerar una hepatitis como diagnóstico presuntivo, en vez de una coledocolitiasis. Con esta revisión exploratoria se pretende explicar esta forma de presentación, y sugerir los pasos que debe dar el clínico para identificar estos casos y brindar un diagnóstico oportuno y certero. Metodología. Se realizó una revisión exploratoria utilizando los buscadores PubMed, BIREME (BVS), LILACS y Google Académico, con las palabras MeSH "choledocholithiasis", "transaminases" y el conector "and", así como los términos DeCS "coledocolitiasis", "transaminasas" y el conector "y". Resultados. Se incluyeron en el análisis un total de 20 estudios relacionados con el tema coledocolitiasis y elevación de AST o ALT >400 UI/L. Se encontró que el aumento de AST o ALT entre 400 UI/L y 500 UI/L se presentó en el 5,76% de los casos, valores entre 500 UI/L y 800 UI/L en el 36,8%, entre 800 UI/L y 1.000 UI/L en el 9%, y valores >1.000 UI/L en el 6,43% de los casos. Conclusión. La coledocolitiasis con elevación de transaminasas AST o ALT >400 UI/L es una situación que debe tenerse presente, en particular en personas jóvenes, y en aquellos sin historia de problemas hepáticos previos. Es necesario que el médico tenga el diagnóstico presuntivo de coledocolitiasis, aun con niveles de transaminasas que puedan sugerir una hepatitis, y analizar las diferentes variables que son indispensables para lograr un diagnóstico preciso.

Introduction. Acute choledocholithiasis occurs when a stone impacts the distal bile duct. It usually manifests with a cholestatic pattern, with a mild or moderate increase in ASL and ALT. However, series of cases of choledocholithiasis have been reported with AST and ALT values >400 IU/L, which may lead the physician to consider hepatitis as a presumptive diagnosis, instead of choledocholithiasis. This scoping review is intended to explain this form of presentation, and to suggestthe steps that the clinician should take to identify these cases and provide a timely and accurate diagnosis. Methodology. A scoping review was carried out using PubMed, BIREME (BVS), LILACS and Google Scholar search engines, with the MeSH words "choledocholithiasis", "transaminases" and the "and" connector, as well as the DeCS terms "coledocolitiasis", "transaminasas" and the "y" connector. Results. A total of 20 studies related to the topic of choledocholithiasis and elevation of AST or ALT >400 IU/L were included in the analysis. It was found that the increase in AST or ALT between 400 IU/L and 500 IU/L occurred in 5.76% of the cases, values between 500 IU/L and 800 IU/L in 36.8%, between 800 IU/L and 1,000 IU/L in 9%, and values >1,000 IU/L in 6.43% of the cases. Conclusion. Choledocholithiasis with elevated AST or ALT transaminases >400 IU/L is an occurrence that should be taken into account, particularly in young people, and in those without a history of previous liver problems. It is necessary for the specialist to have a presumptive diagnosis of choledocholithiasis, even with transaminase levels that may suggest hepatitis, and to analyze the different variables that are essential to achieve an accurate diagnosis.