1,721,038 research outputs found
Metabolomics reveals that aldose reductase activity due to AKR1B10 is upregulated in hepatitis C virus infection
No full textTo understand the changes in the metabolome of hepatitis C virus (HCV)-infected persons, we conducted a metabolomic investigation in both plasma and urine of 30 HCV-positive individuals using plasmas from 30 HCV-negative blood donors and urines from 30 healthy volunteers. Samples were analysed by gas chromatography-mass spectrometry and data subjected to multivariate analysis. The plasma metabolomic phenotype of HCV-positive persons was found to have elevated glucose, mannose and oleamide, together with depressed plasma lactate. The urinary metabolomic phenotype of HCV-positive persons comprised reduced excretion of fructose and galactose combined with elevated urinary excretion of 6-deoxygalactose (fucose) and the polyols sorbitol, galactitol and xylitol. HCV-infected persons had elevated galactitol/galactose and sorbitol/glucose urinary ratios, which were highly correlated. These observations pointed to enhanced aldose reductase activity, and this was confirmed by real-time quantitative polymerase chain reaction with AKR1B10 gene expression elevated sixfold in the liver. In contrast, AKR1B1 gene expression was reduced 40% in HCV-positive livers. Interestingly, persons who were formerly HCV infected retained the metabolomic phenotype of HCV infection without reverting to the HCV-negative metabolomic phenotype. This suggests that the effects of HCV on hepatic metabolism may be long lived. Hepatic AKR1B10 has been reported to be elevated in hepatocellular carcinoma and in several premalignant liver diseases. It would appear that HCV infection alone increases AKR1B10 expression, which manifests itself as enhanced urinary excretion of polyols with reduced urinary excretion of their corresponding hexoses. What role the polyols play in hepatic pathophysiology of HCV infection and its sequelae is currently unknown
Cirrhotic cardiomyopathy: A cardiologist’s perspective
Full text linkCardiac dysfunction is frequently observed in patients with cirrhosis, and has long been linked to the direct toxic effect of alcohol. Cirrhotic cardiomyopathy (CCM) has recently been identified as an entity regardless of the cirrhosis etiology. Increased cardiac output due to hyperdynamic circulation is a pathophysiological hallmark of the disease. The underlying mechanisms involved in pathogenesis of CCM are complex and involve various neurohumoral and cellular pathways, including the impaired β-receptor and calcium signaling, altered cardiomyocyte membrane physiology, elevated sympathetic nervous tone and increased activity of vasodilatory pathways predominantly through the actions of nitric oxide, carbon monoxide and endocannabinoids. The main clinical features of CCM include attenuated systolic contractility in response to physiologic or pharmacologic strain, diastolic dysfunction, electrical conductance abnormalities and chronotropic incompetence. Particularly the diastolic dysfunction with impaired ventricular relaxation and ventricular filling is a prominent feature of CCM. The underlying mechanism of diastolic dysfunction in cirrhosis is likely due to the increased myocardial wall stiffness caused by myocardial hypertrophy, fibrosis and subendothelial edema, subsequently resulting in high filling pressures of the left ventricle and atrium. Currently, no specific treatment exists for CCM. The liver transplantation is the only established effective therapy for patients with end-stage liver disease and associated cardiac failure. Liver transplantation has been shown to reverse systolic and diastolic dysfunction and the prolonged QT interval after transplantation. Here, we review the pathophysiological basis and clinical features of cirrhotic cardiomyopathy, and discuss currently available limited therapeutic options
A closer look at the spectrum of drug-induced liver injury in sub-Saharan Africa.
No full textDrug-induced liver injury (DILI) has become the most frequent cause of acute liver failure in high-income countries. However, little is known about the determinants of DILI in sub-Saharan Africa (SSA), where the prescription of antimicrobials as well as the use of potentially hepatotoxic traditional medicine are common. : Based on an extensive literature search, we summarize current data available on the epidemiology and risk factors of DILI in SSA. We discuss the most likely causes of DILI in the region, including antimicrobial therapies and traditional medicine. We also highlight research gaps as well as barriers to diagnosis and management of the condition, and explore ways to address these important challenges. : DILI is underestimated in SSA and several factors challenge its early diagnosis, including lack of information on the causes of DILI in the region, sub-optimal knowledge about the condition among clinicians, and structural difficulties faced by health care systems. In order to better prevent the occurrence of DILI and its complications, it is crucial to enhance awareness among health care providers and patients, adapt drug prescription habits and regulations, and improve current knowledge on the main risk factors for DILI, including host genetic and environmental determinants
Autoimmune hepatitis triggered by SARS-CoV-2 vaccination.
Full text linkThe development of autoimmune diseases has been reported after SARS-CoV-2 infection. Vaccination against SARS-CoV-2 could also trigger auto-immunity, as it has been described with other vaccines. An aberrant immune response induced by molecular mimicry and bystander activation, especially in predisposed individuals, is a potential mechanism. We report the case of a 76-year-old woman with Hashimoto thyroiditis and prior COVID-19 infection who developed severe autoimmune hepatitis (with typical features including strongly positive anti-smooth muscle antibody and markedly elevated immunoglobulins G, as well as typical histological findings) following SARS-CoV-2 vaccination (mRNA-1273 SARS-CoV-2 vaccine, Moderna®). The link between SARS-CoV-2 vaccination and the development of autoimmune diseases needs to be further investigated. Although a causality relationship cannot be proven, caution may be warranted when vaccinating individuals with known autoimmune diseases
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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