Intranasal Administration of Bedaquiline-Loaded Fucosylated Liposomes Provides Anti-Tubercular Activity while Reducing the Potential for Systemic Side Effects.

Liposomal formulations of antibiotics for inhalation offer the potential for the delivery of high drug doses, controlled drug release kinetics in the lung, and an excellent safety profile. In this study, we evaluated the performance of a liposomal formulation for the poorly soluble, antituberculosis agent, bedaquiline. Bedaquiline was encapsulated within monodisperse liposomes of ∼70 nm at a relatively high drug concentration (∼3.

Sex Matters-Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer.

Preclinical studies rarely test the efficacy of therapies in both sexes. The field of oncology is no exception in this regard. In a model of syngeneic, orthotopic, metastasized pancreatic ductal adenocarcinoma we evaluated the impact of sex on pathological features of this disease as well as on the efficacy and possible adverse side effects of a novel, small molecule-based therapy inhibiting KRAS:SOS1, MEK1/2 and PI3K signaling in male and female C57BL/6J mice.

Chiral analysis of amphetamine, methamphetamine, MDMA and MDA enantiomers in human hair samples.

A novel analytical method was developed for the simultaneous quantification of the R/S-enantiomers of amphetamine, methamphetamine, MDA and MDMA in hair samples using liquid chromatography-tandem mass spectrometry (LC-MS-MS). This method involved a straightforward derivatization step with dansyl chloride and the use of a chiral column, enabling the separation and quantification of all eight enantiomers in a single analysis. The method exhibited excellent linearity across a concentration range of 0.

Morphine concentrations in fatalities after palliative treatment of acute burn injury.

The evaluation of a morphine concentration in postmortem blood is routine for a forensic toxicologist. We here report three fatal cases where we found high morphine concentrations with 7.96, 4.

Stability of PEth 16:0/18:1, 16:0/18:2, 16:0/20:4, 18:0/18:1, 18:0/18:2, and 18:1/18:1 in authentic whole blood samples (at room temperature).

Phosphatidylethanol (PEth) is a direct alcohol biomarker to monitor individuals' drinking behavior that has gained recognition in clinical and forensic settings. The increasing application of the marker makes investigation of the preanalytical handling necessary, and analyte stability deserves major attention. This study was conducted to investigate the change of six PEth homologues' concentration, stored in authentic samples of EDTA blood over a course of 30 days at room temperature (n = 62).

PEth 16:0/18:1 and 16:0/18:2 after consumption of low doses of alcohol-A contribution to cutoff discussion.

Phosphatidylethanol in blood has gained recognition as a direct alcohol biomarker. Although different cutoffs have been suggested, there is no consensus for differentiating abstinence from alcohol consumption. In this study, 75 participants (72% female) consumed 20 g of ethanol on three consecutive evenings.

Beta-Glucuronidase Activity: Another Source of Ethyl Glucuronide.

Numerous classes of endogenous and xenobiotic compounds are conjugated to uridine-5'-diphospho (UDP)-alpha-D-glucuronic acid which is catalyzed by human UDP-Glucuronosyltransferases (UGTs). The resulting beta-D-glucuronides can be hydrolyzed to β-D-glucuronic acid and the corresponding aglycone in a configuration retaining manner by beta-glucuronidases (GUSBs), which are widely distributed in mammalians, microbiota, insects, molluscs, nematodes, fishes and plants. This study investigates GUSBs' activity in the presence of ethanol (0-70% by volume) using different β-D-glucuronides (phenolphthalein-β-D-glucuronide, 4-nitrophenol-β-D-glucuronide, morphine-3-O-β-D-glucuronide, quercetin-3-O-β-D-glucuronide and 1-/2-propyl-β-D-glucuronide) as substrates.

Investigating the use of PEth, CDT and MCV to evaluate alcohol consumption in a cohort of homeless individuals- A comparison of different alcohol biomarkers.

In a cohort including individuals with suspected high alcohol consumption, the concentrations of the indirect alcohol biomarkers carbohydrate-deficient transferrin (CDT) and mean corpuscular volume (MCV) and the direct alcohol biomarker phosphatidylethanol (PEth) were investigated. Blood alcohol concentration (BAC) was analysed as a marker for acute alcohol ingestion. In addition to questions about subjective alcohol consumption behaviour, 147 homeless persons underwent a physical examination with blood sampling.

Phosphatidylethanol in patients with liver diseases of different etiologies: Analysis of six homologues and comparison with other alcohol markers.

Background And Aims: Phosphatidylethanol (PEth) is a direct alcohol biomarker. Aim of the study was to evaluate the performance of six homologues of PEth in comparison to other alcohol markers in patients with liver diseases.

Methods: The study included 234 patients with liver disease, who gave statements about alcohol consumption during the three months prior to the doctor's appointment.

Impaired diagnostic accuracy of hair ethyl glucuronide testing in patients with renal dysfunction.

The impact of renal impairment and hemodialysis on ethyl glucuronide concentrations in hair (hEtG) is not well known. Here, hEtG levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patients presenting to the transplant outpatient clinic and compared with the self-reported alcohol consumption in an anonymous validated questionnaire. Estimated daily alcohol intake (EDI) was calculated.

Analysis of six different homologues of phosphatidylethanol from dried blood spots using liquid chromatography-tandem mass spectrometry.

Phosphatidylethanol (PEth) is a direct biomarker for alcohol consumption consisting of a fraction of different ethanol-modified, homologue phospholipids. The aim of this study was to validate an ultra-high-performance liquid chromatography-tandem mass spectrometry method to quantitate six different homologues of PEth (16:0/18:1, 16:0/18:2, 16:0/20:4, 18:0/18:1, 18:0/18:2, and 18:1/18:1) from dried blood spots (DBSs). DBSs were prepared volumetrically (20 μL of whole blood) and extracted with 1 mL of methanol (0.