In-herd prevalence of Fasciola hepatica and Calicophoron / Paramphistomum spp. infections in German dairy cows with comparison of two coproscopical methods and establishment of real-time pyrosequencing for rumen fluke species differentiation.

Infections with liver and rumen flukes are among the most frequent parasitic diseases in cattle worldwide. In Europe, the predominant liver fluke species is Fasciola hepatica, and the recently rapidly spreading rumen flukes are mostly Calicophoron daubneyi and occasionally Paramphistomum leydeni. In this study, 1638 faecal samples from individual dairy cows from 24 northern and 18 southern German farms as well as one central German farm, all preselected for potential F.

Comparative Intra-Subject Analysis of Gene Expression and Protein Abundance of Major and Minor Drug Metabolizing Enzymes in Healthy Human Jejunum and Liver.

First pass metabolism by phase I and phase II enzymes in the intestines and liver is a major determinant of the oral bioavailability of many drugs. Several studies analyzed expressions of major drug-metabolizing enzymes (DMEs), such as CYP3A4 and UGT1A1 in the human gut and liver. However, there is still a lack of knowledge regarding other DMEs (i.

Importance of ACE2 for SARS-CoV-2 Infection of Kidney Cells.

In late 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the causative agent of coronavirus disease 2019 (COVID-19) emerged in China and spread rapidly around the world, causing an ongoing pandemic of global concern. COVID-19 proceeds with moderate symptoms in most patients, whereas others experience serious respiratory illness that requires intensive care treatment and may end in death. The severity of COVID-19 is linked to several risk factors including male sex, comorbidities, and advanced age.

Protein Abundance of Drug Metabolizing Enzymes in Human Hepatitis C Livers.

Hepatic drug metabolizing enzymes (DMEs), whose activity may be affected by liver diseases, are major determinants of drug pharmacokinetics. Hepatitis C liver samples in different functional states, i.e.

Effects of knockout and overexpression on local cortisol production and differentiation of mesenchymal stem cells.

Exogenous glucocorticoids increase the risk for osteoporosis, but the role of endogenous glucocorticoids remains elusive. Here, we describe the generation and validation of a loss- and a gain-of-function model of the cortisol producing enzyme 11β-HSD1 () to modulate the endogenous glucocorticoid conversion in SCP-1 cells - a model for human mesenchymal stem cells capable of adipogenic and osteogenic differentiation. CRISPR-Cas9 was successfully used to generate a cell line carrying a single base duplication and a 5 bp deletion in exon 5, leading to missense amino acid sequences after codon 146.

Gene Expression and Protein Abundance of Nuclear Receptors in Human Intestine and Liver: A New Application for Mass Spectrometry-Based Targeted Proteomics.

Background: Unwanted drug-drug interactions (DDIs), as caused by the upregulation of clinically relevant drug metabolizing enzymes and transporter proteins in intestine and liver, have the potential to threaten the therapeutic efficacy and safety of drugs. The molecular mechanism of this undesired but frequently occurring scenario of polypharmacy is based on the activation of nuclear receptors such as the pregnane X receptor (PXR) or the constitutive androstane receptor (CAR) by perpetrator agents such as rifampin, phenytoin or St. John's wort.

Protein Abundance of Drug Transporters in Human Hepatitis C Livers.

Transmembrane drug transport in hepatocytes is one of the major determinants of drug pharmacokinetics. In the present study, ABC transporters (P-gp, MRP1, MRP2, MRP3, MRP4, BCRP, and BSEP) and SLC transporters (MCT1, NTCP, OAT2, OATP1B1, OATP1B3, OATP2B1, OCT1, and OCT3) were quantified for protein abundance (LC-MS/MS) and mRNA levels (qRT-PCR) in hepatitis C virus (HCV)-infected liver samples from the Child-Pugh class A ( = 30), B ( = 21), and C ( = 7) patients. Protein levels of BSEP, MRP3, MCT1, OAT2, OATP1B3, and OCT3 were not significantly affected by HCV infection.

Rumen and Liver Fluke Infections in Sheep and Goats in Northern and Southern Germany.

Paramphistomidosis has recently been identified as an emerging parasitosis in Europe. This study estimated the prevalence of rumen flukes, and , in small ruminants in Germany and identified occurring rumen fluke species and potential predictors for fluke infections. Pooled fecal samples from 223 sheep farms and 143 goat farms in northern and southern Germany were examined by the sedimentation technique, and molecular species identification was performed on rumen-fluke-positive samples.

Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver Pathology.

Hepatic drug metabolizing enzymes (DMEs) markedly affect drug pharmacokinetics. Because liver diseases may alter enzymatic function and in turn drug handling and clinical efficacy, we investigated DMEs expression in dependence on liver pathology and liver failure state. In 5 liver pathologies (hepatitis C, alcoholic liver disease, autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis) and for the first time stratified according to the Child-Pugh score, 10 CYPs (CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5) and 4 UGTs (UGT1A1, UGT1A3, UGT2B7 and UGT2B) enzymes were quantified for protein abundance (LC-MS/MS) and gene expression (qRT-PCR).

Rumen (/ spp.) and Liver Flukes () in Cattle-Prevalence, Distribution, and Impact of Management Factors in Germany.

This study was carried out to determine the prevalence of rumen flukes on German cattle farms via the sedimentation technique, and to identify the rumen fluke species occurring in Germany. Additionally, the prevalence of patent infections was determined. Furthermore, a short questionnaire was answered by the farmers.

Mass spectrometry-based targeted proteomics method for the quantification of clinically relevant drug metabolizing enzymes in human specimens.

Biotransformation by phase I and II metabolizing enzymes represents the major determinant for the oral bioavailability of many drugs. To estimate the pharmacokinetics, data on protein abundance of hepatic and extrahepatic tissues, such as the small intestine, are required. Targeted proteomics assays are nowadays state-of-the-art for absolute protein quantification and several methods for quantification of drug metabolizing enzymes have been published.

Comparative Hepatic and Intestinal Efflux Transport of Statins.

Previous studies have shown that lipid-lowering statins are transported by various ATP-binding cassette (ABC) transporters. However, because of varying methods, it is difficult to compare the transport profiles of statins. Therefore, we investigated the transport of 10 statins or statin metabolites by six ABC transporters using human embryonic kidney cell-derived membrane vesicles.

Organic Cation Transporter 1 an Intestinal Uptake Transporter: Fact or Fiction?

Intestinal transporter proteins are known to affect the pharmacokinetics and in turn the efficacy and safety of many orally administered drugs in a clinically relevant manner. This knowledge is especially well-established for intestinal ATP-binding cassette transporters such as P-gp and BCRP. In contrast to this, information about intestinal uptake carriers is much more limited although many hydrophilic or ionic drugs are not expected to undergo passive diffusion but probably require specific uptake transporters.

Drug-Drug Interactions Involving Intestinal and Hepatic CYP1A Enzymes.

Cytochrome P450 (CYP) 1A enzymes are considerably expressed in the human intestine and liver and involved in the biotransformation of about 10% of marketed drugs. Despite this doubtless clinical relevance, CYP1A1 and CYP1A2 are still somewhat underestimated in terms of unwanted side effects and drug-drug interactions of their respective substrates. In contrast to this, many frequently prescribed drugs that are subjected to extensive CYP1A-mediated metabolism show a narrow therapeutic index and serious adverse drug reactions.

Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations.

The most commonly used oral antidiabetic drug, metformin, is a substrate of the hepatic uptake transporter OCT1 (gene name ). However, OCT1 deficiency leads to more pronounced reductions of metformin concentrations in mouse than in human liver. Similarly, the effects of OCT1 deficiency on the pharmacokinetics of thiamine were reported to differ between human and mouse.

[Paramphistomidosis - an overview on epidemiology and clinical signs].

Paramphistosis is a globally occurring parasitic disease in various ruminants caused by a range of rumen flukes (including , and ). In Europe, local occurrences of rumen fluke infection in domestic and wild ruminants have been described for decades. There is now evidence that paramphistomidosis is gaining in importance, because high prevalence rates were reported in the United Kingdom, Ireland, France, Spain, Belgium and The Netherlands.