Integration Analysis of Pharmacokinetics and Metabolomics to Predict Metabolic Phenotype and Drug Exposure of Remdesivir

Remdesivir has displayed pharmacological activity against SARS-CoV-2. However, no pharmacometabolomics (PM) or correlation analysis with pharmacokinetics (PK) was revealed. Rats were intravenously administered remdesivir, and a series of blood samples were collected before and after treatment. Comprehensive metabolomics profile and PK were investigated and quantitated simultaneously using our previous reliable HPLC-MS/MS method. Both longitudinal and transversal metabolic analyses were conducted, and the correlation between PM and PK parameters was evaluated using Pearson’s correlation analysis and the PLS model. Multivariate statistical analysis was employed for discovering candidate biomarkers which predicted drug exposure or toxicity of remdesivir. The prominent metabolic profile variation was observed between pre- and posttreatment, and significant changes were found in 65 metabolites. A total of 15 metabolites—12 carnitines, one N-acetyl-D-glucosamine, one allantoin, and one corticosterone—were significantly correlated with the concentration of Nuc (active metabolite of remdesivir). Adenosine, spermine, guanosine, sn-glycero-3-phosphocholine, and l-homoserine may be considered potential biomarkers for predicting drug exposure or toxicity. This study is the first attempt to apply PM and PK to study remdesivir response/toxicity, and the identified candidate biomarkers might be used to predict the AUC and Cmax, indicating capability of discriminating good or poor responders. Currently, this study originally offers considerable evidence to metabolite reprogramming of remdesivir and sheds light on precision therapy development in fighting COVID-19.

Profile variation of bla genes among non-lactose fermenting Gram-negative bacilli between clinical and environmental isolates of Dr. Soetomo Hospital, Surabaya, Indonesia

Endraputra PN, Kuntaman K, Wasito EB, Shirakawa T, Raharjo D, Setyarini W. 2021. Profile variation of bla genes among non-lactose fermenting Gram negative bacilli between clinical and environmental isolates of Dr. Soetomo Hospital, Surabaya, Indonesia. Biodiversitas 22: 5047-5054. Carbapenem-resistant non-fermenter Gram-negative bacilli are notorious opportunistic pathogens in hospitalized patients and hospital environments. This study explored the carbapenemase gene among non-fermenter Gram-negative bacilli from hospital wastewater and clinical isolates in Dr. Soetomo Hospital, Surabaya, Indonesia. All samples were screened on MacConkey agar with meropenem 2 µg/ml and gene detected by Multiplex PCR. All samples were screened on MacConkey agar with meropenem 2 µg/ml and gene detected by Multiplex PCR. A total of 121 isolates consisted of 76 clinical (41 carbapenem-resistant Acinetobacter baumannii and 35 carbapenem-resistant Pseudomonas aeruginosa), 45 environmental isolates (6 carbapenem-resistant Pseudomonas aeruginosa and 32 carbapenem-resistant Pseudomonas spp.), and 7 screening samples (all CRPAs). Clinical isolates carbapenemase genes were identified, blaOXA-23-like 21 (28%), blaOXA-24-like 30 (39%), blaNDM-1 1 (1%), and blaIMP-1 6 (8%) while environmental isolates were blaOXA-23-like 5 (13%), blaOXA-24-like 4 (11%), blaOXA-48-like 2 (5%), blaNDM-1 13 (34%), blaVIM 12 (32%), and blaIMP-1 4 (11%). Rectal swab screening specimens presented blaOXA-23-like 3 (43%), blaOXA-24-like 3 (43%), and blaNDM-1 1 (14%). The carbapenemase gene pattern was different between clinical and environmental isolates. The blaOXA-23-like and blaOXA-24-like were most prevalent among in both clinical and wastewater, while blaVIM was mostly in wastewater. The presence of carbapenem-resistant non-fermenter Gram-negative bacilli carrying carbapenemase genes in hospital effluents indicated that the community river was seeded with an antimicrobial resistance gene.

Aromatic Profile Variation of Essential Oil from Dried Makwhaen Fruit and Related Species

The aim of this research is to evaluate the relationship between genotype, phenotype, and chemical profiles of essential oil obtained from available Zanthoxylum spp. Three specimens of makhwaen (MK) distributed in Northern Thailand were genetically and morphologically compared with other Zanthoxylum spices, known locally as huajiao (HJ) and makwoung (MKO), respectively. HJ was taxonomically confirmed as Z. armatum while MKO and MK were identified as Z. rhetsa and Z. myriacanthum. Genetic sequencing distributed these species into three groups accordingly to their confirmed species. Essential oil of the dried fruits from these samples was extracted and analyzed for their chemical and physical properties. Cluster analysis of their volatile compositions separated MKO and MK apart from HJ with L-limonene, terpinen-4-ol, β-phellandrene, and β-philandrene. By using odor attributes, the essential oil of MKO and MK were closely related possessing fruity, woody, and citrus aromas, while the HJ was distinctive. Overall, the phenotypic characteristic can be used to elucidate the species among makhwaen fruits of different sources. The volatile profiling was nonetheless dependent on the genotypes but makwoung and makhwaen showed similar profiles.

Исследование динамики выходной оптической мощности полупроводниковых лазеров (1070 nm) с маломодовым латеральным волноводом мезаполосковой конструкции при сверхвысоких токах накачки

At ultrahigh levels of pulsed current pumping, the characteristics of semiconductor lasers based on an asymmetric heterostructure with a broadened lateral waveguide of a mesa-stripe design are studied. A peak power of 5.1 W is demonstrated at a pump current amplitude of 10 A. Three types of spatial dynamics of laser radiation are determined: the first one is a slow (~ 200 ns) intensity profile variation along the lateral near field at initial level of pump currents; the second one is a presence of fast (~ 10 ns) processes of mode competition at moderate pump currents; the third one is a chaotic temporal behavior of the output power at maximum pump currents.