Investigating a New Way to Assess Metabolic Risk in Pregnant Females with Prior RYGB Surgery.

Background: Obesity in pregnancy is linked to adverse clinical outcomes such as gestational diabetes. Recently, a risk score calculated by different ceramide concentrations was recognized as a new way to investigate cardiovascular risk. The aim was to analyze if the ceramide risk score and cardiometabolic risk vary between normal-weight, obese, and females with prior Roux-en-Y bypass surgery (RYGB) during pregnancy.

Pharmacokinetics of isavuconazole at different target sites in healthy volunteers after single and multiple intravenous infusions.

Background: Invasive aspergillosis is a severe fungal infection that affects multiple organ systems including the CNS and the lungs. Isavuconazole, a novel triazole antifungal agent, has demonstrated promising activity against Aspergillus spp. However, data on the penetration of isavuconazole into the CNS and ELF and intracellular accumulation remain limited.

The impact of biological sex in peripheral nerve blockade: A prospective pharmacodynamic, pharmacokinetic and morphometric study in volunteers.

Study Objective: The impact of biological sex in peripheral regional anaesthesia is largely unknown. We therefore designed a prospective study in volunteers to investigate the impact of biological sex on pharmacodynamic, pharmacokinetic and morphometric characteristics for peripheral nerve blockade.

Methods: The initial study plan was powered to include 90 volunteers to find a difference of 35 min in duration of sensory block (primary outcome variable) with 80% power and alpha error at 5%.

Plasma and intraperitoneal pharmacokinetics of ceftazidime/avibactam in peritoneal dialysis patients.

Objectives: Peritonitis is a serious complication in patients undergoing automated peritoneal dialysis (APD) that increases morbidity and frequently disqualifies patients from the peritoneal dialysis programme. Ceftazidime/avibactam (CAZ/AVI) is a potential treatment option for APD patients with peritonitis caused by resistant Gram-negative bacteria, but limited data exist on systemic and target-site pharmacokinetics (PK) in patients undergoing APD. This study set out to investigate the PK of CAZ/AVI in plasma and peritoneal dialysate (PDS) of patients undergoing APD.

Simvastatin therapy in higher dosages deteriorates bone quality: Consistent evidence from population-wide patient data and interventional mouse studies.

Background: Combining mouse experiments with big data analysis of the Austrian population, we investigated the association between high-dose statin treatment and bone quality.

Methods: The bone microarchitecture of the femur and vertebral body L4 was measured in male and ovariectomized female mice on a high-fat diet containing simvastatin (1.2 g/kg).

Increased left dorsolateral prefrontal cortex density following escitalopram intake during relearning: a randomized, placebo-controlled trial in healthy humans.

Background: Serotonergic agents affect brain plasticity and reverse stress-induced dendritic atrophy in key fronto-limbic brain areas associated with learning and memory.

Objectives: The aim of this study was to investigate effects of the antidepressant escitalopram on gray matter during relearning in healthy individuals to inform a model for depression and the neurobiological processes of recovery.

Design: Randomized double blind placebo control, monocenter study.

ABCB1 variants and sex affect serotonin transporter occupancy in the brain.

Strategies to personalize psychopharmacological treatment promise to improve efficacy and tolerability. We measured serotonin transporter occupancy immediately after infusion of the widely prescribed P-glycoprotein substrate citalopram and assessed to what extent variants of the ABCB1 gene affect drug target engagement in the brain in vivo. A total of 79 participants (39 female) including 31 patients with major depression and 48 healthy volunteers underwent two PET/MRI scans with the tracer [C]DASB and placebo-controlled infusion of citalopram (8 mg) in a cross-over design.

Comparison of pharmacokinetics and stability of generics of cefepime, linezolid and piperacillin/tazobactam with their respective originator drugs: an intravenous bioequivalence study in healthy volunteers.

Objectives: The efficacy and quality of generic antibacterial drug formulations are often questioned by both healthcare specialists and patients. Therefore, the present study investigated the interchangeability of generic drugs with their originators by comparing bioequivalence parameters and stability data of generic cefepime, linezolid and piperacillin/tazobactam with their respective originator drugs.

Methods: In this open-label, randomized, crossover bioequivalence study, three groups of 12 healthy volunteers each received a single intravenous infusion of either 2 g of cefepime or 4.

Ethyl glucuronide in hair detects a high rate of harmful alcohol consumption in presumed non-alcoholic fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) cannot reliably be distinguished by routine diagnostics, and the role of alcohol consumption in metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. We investigated alcohol consumption in patients with presumed NAFLD and ALD using novel objective alcohol markers.

Methods: In total, 184 consecutive patients were included in this prospective observational study.

The Effect of Pregabalin on the Minimum Alveolar Concentration of Sevoflurane: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

Background: Pregabalin is commonly used perioperatively to reduce post-operative pain and opioid consumption and to prevent the development of chronic pain. It has been shown to reduce anesthetic consumption in balanced anesthesia, but studies investigating its effect on the minimum alveolar concentration (MAC) of volatile anesthetics are lacking. The aim of this study was to investigate the effect of two different doses of pregabalin on the MAC of sevoflurane.

Microdosing as a Potential Tool to Enhance Clinical Development of Novel Antibiotics: A Tissue and Plasma PK Feasibility Study with Ciprofloxacin.

Background And Objective: In microdose studies, drug pharmacokinetics is measured in humans after administration of subtherapeutic doses. While previous microdose studies focused primarily on plasma pharmacokinetics, we set out to evaluate the feasibility of microdosing for a pharmacokinetic assessment in subcutaneous tissue and epithelial lining fluid.

Methods: Healthy subjects received a single intravenous bolus injection of a microdose of [C]ciprofloxacin (1.

Ethanol reduces the minimum alveolar concentration of sevoflurane in rats.

A high number of trauma patients are under the influence of alcohol. Since many of them need immediate surgical procedures, it is imperative to be aware of the interaction of alcohol with general anesthesia. To counter challenges that arise from clinical studies, we designed an animal experiment in which 48 adult Wistar rats either received 1 g · kg ethanol, 2 g · kg ethanol or placebo via intraperitoneal application.

High Dose Lopinavir/Ritonavir Does Not Lead to Sufficient Plasma Levels to Inhibit SARS-CoV-2 in Hospitalized Patients With COVID-19.

Despite lopinavir/ritonavir (LPV/RTV) demonstrating activity against SARS-CoV-2, large trials failed to show any net clinical benefit. Since SARS-CoV-2 has an EC50 of 16.4 μg/ml for LPV this could be due to inadequate dosing.

/ Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model.

Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine blood based pharmacokinetic model for intermittent renal replacement therapy.

Metabo-tip: a metabolomics platform for lifestyle monitoring supporting the development of novel strategies in predictive, preventive and personalised medicine.

Background/aims: Exposure to bioactive compounds from nutrition, pharmaceuticals, environmental contaminants or other lifestyle habits may affect the human organism. To gain insight into the effects of these influences, as well as the fundamental biochemical mechanisms behind them, individual molecular profiling seems to be a promising tool and may support the further development of predictive, preventive and personalised medicine.

Methods: We developed an assay, called metabo-tip for the analysis of sweat, collected from fingertips, using mass spectrometry-by far the most comprehensive and sensitive method for such analyses.

Effect of Ketamine on Human Neurochemistry in Posterior Cingulate Cortex: A Pilot Magnetic Resonance Spectroscopy Study at 3 Tesla.

Ketamine is a powerful glutamatergic long-lasting antidepressant, efficient in intractable major depression. Whereas ketamine's immediate psychomimetic side-effects were linked to glutamate changes, proton MRS (H-MRS) showed an association between the ratio of glutamate and glutamine and delayed antidepressant effect emerging ∼2 h after ketamine administration. While most H-MRS studies focused on anterior cingulate, recent functional MRI connectivity studies revealed an association between ketamine's antidepressant effect and disturbed connectivity patterns to the posterior cingulate cortex (PCC), and related PCC dysfunction to rumination and memory impairment involved in depressive pathophysiology.

Generic versus reference listed ropivacaine for peripheral nerve blockade: A randomised, triple-blinded, crossover, equivalence study in volunteers.

Background: Generic drug preparations do not require the same degree of scrutiny as the originally licensed preparation before they can be approved for clinical use. The permitted tolerance limits for bioequivalent preparations might be associated with clinically relevant differences for drugs with a narrow therapeutic index, such as local anaesthetics.

Objective: We compared pharmacokinetic and pharmacodynamic characteristics of generic and reference listed or original preparations of ropivacaine.

Effect of Ketamine on Limbic GABA and Glutamate: A Human Multivoxel Magnetic Resonance Spectroscopy Study.

Introduction: Converging evidence suggests that ketamine elicits antidepressant effects enhanced neuroplasticity precipitated by a surge of glutamate and modulation of GABA. Magnetic resonance spectroscopic imaging (MRSI) illustrates changes to cerebral glutamate and GABA immediately following ketamine administration during dissociation. However, few studies assess subacute changes in the first hours following application, when ketamine's antidepressant effects emerge.

The effect of oral Δ-9-tetrahydrocannabinol on the minimal alveolar concentration of sevoflurane: A randomised, controlled, observer-blinded experimental study.

Background: Cannabis has increasingly been used for medical and recreational purposes. The main pharmacological compound in cannabis is tetrahydrocannabinol (THC), which has sedative, anxiolytic and analgesic effects. In some animal models, THC has also been shown to reduce the minimum alveolar concentration (MAC) of halothane and cyclopropane, but its effect on sevoflurane, currently the most commonly used inhalational anaesthetic agent, has not been investigated.

Caffeine Uptake into the Vitreous after Peroral Coffee Consumption.

Introduction: Caffeine and its metabolites have antioxidant activity, scavenging reactive oxygen species. The aim of our study was to measure caffeine concentrations in vitreous samples after peroral caffeine intake.

Methods: This prospective study included patients scheduled for 23-G pars plana vitrectomy with membrane peeling due to epiretinal membranes.

On the relationship of first-episode psychosis to the amphetamine-sensitized state: a dopamine D receptor agonist radioligand study.

Schizophrenia is characterized by increased behavioral and neurochemical responses to dopamine-releasing drugs. This prompted the hypothesis of psychosis as a state of "endogenous" sensitization of the dopamine system although the exact basis of dopaminergic disturbances and the possible role of prefrontal cortical regulation have remained uncertain. To show that patients with first-episode psychosis release more dopamine upon amphetamine-stimulation than healthy volunteers, and to reveal for the first time that prospective sensitization induced by repeated amphetamine exposure increases dopamine-release in stimulant-naïve healthy volunteers to levels observed in patients, we collected data on amphetamine-induced dopamine release using the dopamine D receptor agonist radioligand [C]-(+)-PHNO and positron emission tomography.

Low pH reduces the activity of ceftolozane/tazobactam in human urine, but confirms current breakpoints for urinary tract infections.

Background: Acidic pH has been shown to impact the antibiotic activity of non-β-lactams in urine.

Objectives: To investigate the in vitro activity of ceftolozane/tazobactam compared with meropenem at different pH settings in urine.

Methods: We determined the MICs for 30 clinical isolates of Escherichia coli, 25 clinical isolates of Klebsiella pneumoniae and 24 clinical isolates of Proteus mirabilis in pooled human urine and standard growth medium at pH 5 and 7.

Impact of thrombocytes, on bacterial growth and antimicrobial activity of selected antibiotics.

In vitro pharmacodynamic models are used to optimize in vivo dosing regimens in antimicrobial drug development. One limiting factor of such models is the lack of host factors such as corpuscular blood components as erythrocytes which have already been shown to impact activity of antibiotics and/or growth of the pathogen. However, the impact of thrombocytes has not previously been investigated.