Genetic Variants Determine Treatment Response in Autoimmune Hepatitis.

Background: Autoimmune hepatitis (AIH) is a rare entity; in addition, single-nucleotide polymorphisms (SNPs) may impact its course and outcome. We investigated liver-related SNPs regarding its activity, as well as in relation to its stage and treatment response in a Central European AIH cohort.

Methods: A total of 113 AIH patients (i.

Effect of the Tubing Material Used in Peristaltic Pumping in Tangential Flow Filtration Processes of Biopharmaceutics on Particle Formation and Flux.

Tangential flow filtration (TFF) is a central step in manufacturing of biopharmaceutics. Membrane clogging leads to decreased permeate flux, longer process time and potentially complete failure of the process. The effect of peristaltic pumping with tubings made of three different materials on protein particle formation during TFF was monitored via micro flow imaging, turbidity and photo documentation.

Afamin predicts the prevalence and incidence of nonalcoholic fatty liver disease.

Objectives: In the general population, increased afamin concentrations are associated with the prevalence and incidence of metabolic syndrome as well as type 2 diabetes. Although metabolic syndrome is commonly associated with nonalcoholic fatty liver disease (NAFLD), there exist no information on afamin and NAFLD.

Methods: Afamin concentrations were cross-sectionally measured in 146 Austrian patients with NAFLD, in 45 patients without NAFLD, and in 292 age- and sex-matched healthy controls.

Optic nerve injury in preoperative imaging is associated with visual improvement outcome in endoscopic optic nerve decompression.

Objective: To evaluate potential clinical parameters having an impact on visual outcome after endoscopic optic nerve decompression in acute optic neuropathy patients.

Methods: A retrospective chart review of patients with acute optic neuropathy, who underwent endoscopic optic nerve decompression between June 2001 and November 2018 at an academic center was performed. Patients were divided into groups according to visual improvement after surgical treatment (yes/no).

Shaker-related voltage-gated potassium channels Kv1 in human hippocampus.

In this study, we investigated the tissue expression levels, alpha subunit composition and distribution of Shaker-related voltage-dependent potassium Kv1 channels in human hippocampus by combining western blotting experiments, toxin autoradiography, in vivo radioligand binding studies, immunoprecipitation and immunohistochemistry. Tissue expression of Kv1.1 and Kv1.

Exploring blended group interventions for depression: Randomised controlled feasibility study of a blended computer- and multimedia-supported psychoeducational group intervention for adults with depressive symptoms.

Background: Blended interventions aim to capitalise on the strengths of both computer-based and face-to-face therapy. Studies on this innovative treatment format remain scare. This especially accounts for the group treatment of depression.

Diagnostic and prognostic accuracy of galectin-3 and soluble ST2 for acute heart failure.

Background: We aimed to compare head-to-head the diagnostic and prognostic capabilities of galectin-3, soluble ST2 (sST2) and B-type natriuretic peptide (BNP) for heart failure (HF) in an emergency setting.

Methods: We studied 251 consecutive patients with dyspnoea as a chief compliant presenting to an emergency department. The diagnosis of HF was based on the Framingham score for HF plus echocardiographic evidence of systolic or diastolic dysfunction.

Small-conductance calcium-activated potassium type 2 channels (SK2, KCa2.2) in human brain.

SK2 (KCa2.2) channels are voltage-independent Ca-activated K channels that regulate neuronal excitability in brain regions important for memory formation. In this study, we investigated the distribution and expression of SK2 channels in human brain by Western blot analysis and immunohistochemistry.

Interleukin 6, galectin 3, growth differentiation factor 15, and soluble ST2 for mortality prediction in critically ill patients.

Purpose: The aim of this study was to compare the prognostic value of interleukin 6 (IL-6), galectin 3, growth differentiation factor 15 (GDF-15), and soluble ST2 (sST2) in an unselected cohort of critically ill patients.

Methods: During a study period of 1 year, we recruited 530 consecutive patients admitted to a medical intensive care unit of a tertiary care hospital. We examined a combination of inflammatory, renal, and cardiac biomarkers for the prediction of 90-day all-cause mortality.

Reference values of galectin-3 and cardiac troponins derived from a single cohort of healthy blood donors.

Background: Here we describe the determination of upper reference limits (URL) for galectin-3, high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) in a single cohort of healthy blood donors using routine assays.

Methods: For this reference value study, we used a cohort of 402 consecutive blood donors (64% were male and 36% were female). The median individuals' age was 35.

Plasma concentrations of novel cardiac biomarkers before and after hemodialysis session.

Objectives: Biomarkers are useful for establishing disease severity or prognosis in patients with chronic kidney disease. The aim of our study was to determine the plasma concentrations of novel cardiovascular biomarkers in patients on chronic hemodialysis in the context of published upper reference limits (URL) of these biomarkers; and to compare the plasma concentrations of those same analytes before and after hemodialysis session.

Design And Methods: Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-A-type natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), C-terminal pro-arginine vasopressin (CT-proAVP, also known as Copeptin) and soluble ST2 (sST2) were measured in 28 patients before and after dialysis session.

The single nucleotide polymorphism Gly482Ser in the PGC-1α gene impairs exercise-induced slow-twitch muscle fibre transformation in humans.

PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes.

Association of the biomarkers soluble ST2, galectin-3 and growth-differentiation factor-15 with heart failure and other non-cardiac diseases.

Background: The biomarkers soluble ST2 (sST2), galectin-3, and growth-differentiation factor-15 (GDF-15) provide prognostic information in patients with heart failure (HF). The aim of this study was to evaluate to which extent plasma concentrations of these biomarkers are increased in HF compared with diverse non-cardiac conditions such as infectious disease or chronic kidney disease.

Methods: We recruited 15 patients in each of the following clinical categories: HF without co-morbidity, pneumonia without co-morbidity, chronic obstructive pulmonary disease (COPD) without co-morbidity, HF and a co-morbidity of pneumonia, renal disease without co-morbidity, and sepsis.

Chromogranin peptides in brain diseases.

Synaptic disturbances may play a key role in the pathophysiology of neuropsychiatric diseases. In this article, we review immunohistological findings of chromogranin peptides in neurodegenerative and neurodevelopmental disorders, with particular emphasis on Alzheimer's disease, the disorder chromogranins have been studied most extensively. Data was collected from existing and new experimental data and medline research.

The third-generation P-glycoprotein inhibitor tariquidar may overcome bacterial multidrug resistance by increasing intracellular drug concentration.

Objectives: The use of efflux pump inhibitors may be a powerful strategy to overcome transporter-mediated bacterial multidrug resistance. In the present study, we set out to investigate the potency of tariquidar, a third-generation P-glycoprotein inhibitor in clinical development, for overcoming bacterial resistance towards ciprofloxacin.

Methods: Staphylococcus aureus 29213 (SA29213) and S.

Plasma protein binding of fluoroquinolones affects antimicrobial activity.

Objectives: In contrast to most antimicrobial classes, there is a doubt about the impact of protein binding (PB) on the antimicrobial activity of fluoroquinolones. We set out to evaluate the suitability of previously used models for investigating the influence of PB on bacterial killing by fluoroquinolones.

Methods: PB of moxifloxacin and trovafloxacin was determined in Mueller-Hinton broth (MHB) containing different concentrations of human serum or albumin.

Clinical scoring system for the prediction of target site penetration of antimicrobials in patients with sepsis.

Background And Objectives: The present study investigated the usefulness of routinely employed scoring systems in predicting tissue penetration of antimicrobials. In addition, a novel, easy to use scoring system was designed for the estimation of tissue penetration of antimicrobials in patients with sepsis.

Methods: Tissue pharmacokinetics were assessed in skeletal muscle and subcutaneous adipose tissue by use of the microdialysis technique in 34 patients with sepsis.

Biological, biochemical, and molecular characterization of a new clinical Trichophyton rubrum isolate resistant to terbinafine.

We have characterized a new clinical strain of Trichophyton rubrum highly resistant to terbinafine but exhibiting normal susceptibility to drugs with other mechanisms of action. Resistance to terbinafine in this strain is caused by a missense mutation in the squalene epoxidase gene leading to the amino acid substitution F397L.

Amino acid substitution in Trichophyton rubrum squalene epoxidase associated with resistance to terbinafine.

There has only been one clinically confirmed case of terbinafine resistance in dermatophytes, where six sequential Trichophyton rubrum isolates from the same patient were found to be resistant to terbinafine and cross-resistant to other squalene epoxidase (SE) inhibitors. Microsomal SE activity from these resistant isolates was insensitive to terbinafine, suggesting a target-based mechanism of resistance (B. Favre, M.

No association of clock gene T3111C polymorphism and affective disorders.

CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation. Using PCR and RFLP, we investigated in patients with unipolar depression and bipolar disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders (n=102) compared to healthy controls (n=103).

Antifungal drug response in an in vitro model of dermatophyte nail infection.

Despite terbinafine being fungicidal against Trichophyton rubrum in standard NCCLS assays and rapidly accumulating in nails in vivo, onychomycosis patients require prolonged terbinafine treatment to be cured. To investigate this, we developed a more clinically relevant onychomycosis in vitro test model. Human nail powder inoculated with T.

Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine.

The in vitro antifungal susceptibilities of six clinical Trichophyton rubrum isolates obtained sequentially from a single onychomycosis patient who failed oral terbinafine therapy (250 mg/day for 24 weeks) were determined by broth microdilution and macrodilution methodologies. Strain relatedness was examined by random amplified polymorphic DNA (RAPD) analyses. Data obtained from both broth micro- and macrodilution assays were in agreement and revealed that the six clinical isolates had greatly reduced susceptibilities to terbinafine.

In vitro susceptibility of Microsporum canis and other dermatophyte isolates from veterinary infections during therapy with terbinafine or griseofulvin.

We investigated the in vitro activity of terbinafine against fresh veterinary isolates of Microsporum canis and the potential of this organism to develop resistance in vivo during oral therapy. Dermatophyte cultures (n = 300) were obtained from naturally infected cats and dogs undergoing oral therapy with terbinafine or griseofulvin. M.