Anti-HNA testing of allo-exposed COVID-19 convalescent plasma donors including genetic human neutrophil antigen screening to prevent anti-HNA antibody-mediated transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury caused by antibodies against human neutrophil antigens (HNA) is a serious but rare complication associated with blood transfusion. The presence of such antibodies is most probable in donors with a transfusion/pregnancy history. During the COVID-19 pandemic period convalescent plasma (CP) containing neutralizing antibodies against SARS-CoV-2 was widely used for COVID-19 patients as a therapy in the absence of any treatment. The aim of the study was to work out a simple diagnostic algorithm of anti-HNA testing of allo-exposed CP donors including genetic HNA screening. MATERIALS AND METHODS: A total of 457 anti-HLA-negative allo-exposed CP donors were genotyped for HNA-1a/1b, HNA-3a/3b, and HNA-2, and only donors with homozygous HNA-1a/1a; HNA-3b/3b; or HNA-2null genotypes were tested for anti-HNA antibody using LabScreenMulti (One Lambda) and homozygous HNA-1b/1b using the granulocyte immunofluorescence test (GIFT) but verified using LabScreenMulti. RESULTS: Testing of 83 homozygous HNA-3b/3b; HNA-2null; or HNA-1a/1a donors revealed anti-HNA-3a antibody in one case. Testing of 181 HNA-1b/1b donors using GIFT gave 10 ambiguous results verified using LabScreenMulti which confirmed anti-HNA-1a antibody in one case. The frequency of FCGR3B*01 and *04 encoding HNA-1a was 0.34; FCGR3B*02, *03, and *05 encoding HNA-1b-0.66; SLC44A2*01 encoding HNA-3a-0.80; and SLC44A2*02 encoding HNA-3b-0.20. In 3.7% cases the HNA-2null genotype was revealed. DISCUSSION: Due to applying HNA genotyping as a primary test before anti-HNA antibody testing the serological work was limited only to HNA-homozygous donors revealing two anti-HNA immunized donors. The distribution of HNA genotypes in the cohort was similar to other Caucasian populations.

Development and Validation of a UPLC-MS/MS Method for Therapeutic Drug Monitoring, Pharmacokinetic and Stability Studies of First-Line Antituberculosis Drugs in Urine.

Tuberculosis (TB) remains one of the leading global causes of mortality. Several methods have been established to detect anti-TB agents in human plasma and serum. However, there is a notable absence of studies analyzing TB drugs in urine. Thus, our objective was to validate a method for quantifying first-line anti-TB agents: isoniazid (INH), pyrazinamide (PZA), ethambutol (ETH), and rifampicin (RIF), along with its metabolite 25-desacetylrifampicin, and degradation products: rifampicin quinone and 3-formyl-rifampicin in 10 µL of urine. Chromatographic separation was achieved using a Kinetex Polar C18 analytical column with gradient elution (5 mM ammonium acetate and acetonitrile with 0.1% formic acid). Mass spectrometry detection was carried out using a triple-quadrupole tandem mass spectrometer operating in positive ion mode. The lower limit of quantification (LLOQ) was 0.5 µg/mL for INH, PZA, ETH, and RIF, and 0.1 µg/mL for RIF's metabolites and degradation products. The method was validated following FDA guidance criteria and successfully applied to the analysis of the studied compounds in urine of TB patients. Additionally, we conducted a stability study of the anti-TB agents under various pH and temperature conditions to mimic the urine collection process in different settings (peripheral clinics or central laboratories).

Pharmacokinetic Drug-Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients.

Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug-drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.

Analysis of retinol, α-tocopherol, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in plasma of patients with cardiovascular disease by HPLC-MS/MS method.

Fat-soluble vitamins play a pivotal role in the progression of atherosclerosis and the development of cardiovascular disease. Therefore, plasma monitoring of their concentrations may be useful in the diagnosis of these disorders as well as in the process of treatment. The study aimed to develop and validate an HPLC-MS/MS method for determination of retinol, α-tocopherol, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in plasma of patients with cardiovascular disease. The analytes were separated on an HPLC Kinetex F5 column via gradient elution with water and methanol, both containing 0.1% (v/v) formic acid. Detection of the analytes was performed on a triple-quadrupole MS with multiple reaction monitoring via electrospray ionization. The analytes were isolated from plasma samples with liquid-liquid extraction using hexane. Linearity of the analyte calibration curves was confirmed in the ranges 0.02-2 µg/mL for retinol, 0.5-20 µg/mL for α-tocopherol, 5-100 ng/mL for 25-hydroxyvitamin D2 and 2-100 ng/mL for 25-hydroxyvitamin D3. Intra- and inter-assay precision and accuracy of the method were satisfactory. Short- and long-term stabilities of the analytes were determined. The HPLC-MS/MS method was applied for the determination of the above fat-soluble vitamin concentrations in patient plasma as potential markers of the cardiovascular disease progression.

A review of chromatographic methods for the determination of water- and fat-soluble vitamins in biological fluids.

Vitamins are an essential element of nutrition and thus contribute to human health. Vitamins catalyze many biochemical reactions and their lack or excess can cause health problems. Therefore, monitoring vitamin concentrations in plasma or other biological fluids may be useful in the diagnosis of various disorders as well as in the treatment process. Several chromatographic methods have been developed for the determination of these compounds in biological samples, including high-performance liquid chromatography with UV and fluorescence detection. Recently, high-performance liquid chromatography with tandem mass spectrometry methods have been widely used for the determination of vitamins in complex matrices because of their high sensitivity and selectivity. This method requires preconditioning of samples for analysis, including protein precipitation and/or various extraction techniques. The choice of method may depend on the desired cost, convenience, turnaround time, specificity, and accuracy of the information to be obtained. This article reviews the recently reported chromatographic methods used for determination of vitamins in biological fluids. Relevant papers published mostly during the last 5 years were identified by an extensive PubMed search using appropriate keywords. Particular attention was given to the preparation steps and extraction techniques. This report may be helpful in the selection of procedures that are appropriate for certain types of biological materials and analytes.

Selected Psychosocial Factors, Nutritional Behavior, and the Analysis of Concentrations of Selected Vitamins in Patients with Cardiovascular Diseases.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, influenced by the interaction of factors, including age, sex, genetic conditions, overweight/obesity, hypertension, an abnormal lipid profile, vitamin deficiencies, diabetes, and psychological factors. This study aimed to assess the relationships between psychosocial and nutritional factors in a group of 61 patients with CVD (i.e., atherosclerosis, hypertension, ischemic heart disease, and myocardial infarction) and their possible impact on the course of the disease. The plasma concentrations of vitamins A, E, D, and ß-carotene were determined using validated HPLC-MS/MS, while the lipid profile was analyzed enzymatically. Psychosocial factors and nutritional behaviors were assessed using author-designed questionnaires. Over 50% of patients had 25-OH-D3 and retinol deficiencies, while >85% of patients exhibited significant deficiencies in α-tocopherol and ß-carotene. The lipid profile showed no specific relationship with any particular CVD. Dietary behavior minimally impacted biochemical parameters except for higher ß-carotene concentrations in the group with higher fruit and vegetable intake. The negative impact of the CVD on selected parameters of quality of life was noticed. To increase the effectiveness of the prevention and treatment of CVD, the need for interdisciplinary cooperation observed between doctors, psychologists, and specialists in human nutrition seems to be justified.

Trend research of vitamin D receptor: Bibliometric analysis.

Studies on vitamin D receptor (VDR) and its association with multiple disorders are expanding. This bibliometric study aims to find and summarize VDR-related publications, and compare them across various countries, organizations, and journals to demonstrate trends in VDR research. VOSviewer and Excel 2019 were used to classify and summarize Web of Science articles from 1900 to mid-2021. Total records of 8762 articles were analyzed, and maps of co-citations bibliometric keywords co-occurrence were designed. In conclusion, relative research interest and published papers related to VDR were growing in the past 30 years. The United States of America dominates the research regarding VDR. The highest quality of VDR research was achieved by the University of California System, University of Wisconsin System, and Harvard University. J Steroid Biochem Mol Biol, PLoS One, and J Biol Chem are the leading three productive journals on VDR. Various aspects of vitamin D deficiency associated disorders and genetic studies regarding VDR, including single nucleotide polymorphism, gene variants, epigenome, long non-coding ribonucleic acid (lncRNA), and small nucleolar RNA host gene 6 are potentially the recent research hotspot in this field. Moreover, coronavirus disease, polycystic ovary syndrome, non-alcoholic fatty liver disease, gut microbiota, gestational diabetes, systemic sclerosis, and chemoresistance are the trending medical conditions associated with VDR.

Clinical Significance of Analysis of Vitamin D Status in Various Diseases.

Vitamin D plays a role not only in the proper functioning of the skeletal system and the calcium-phosphate equilibrium, but also in the immune system, the cardiovascular system and the growth and division of cells. Although numerous studies have reported on the analysis of vitamin D status in various groups of patients, the clinical significance of measurements of vitamin D forms and metabolites remains ambiguous. This article reviews the reports analyzing the status of vitamin D in various chronic states. Particular attention is given to factors affecting measurement of vitamin D forms and metabolites. Relevant papers published during recent years were identified by an extensive PubMed search using appropriate keywords. Measurement of vitamin D status proved to be a useful tool in diagnosis and progression of metabolic syndrome, neurological disorders and cancer. High performance liquid chromatography coupled with tandem mass spectrometry has become the preferred method for analyzing the various forms and metabolites of vitamin D in biological fluids. Factors influencing vitamin D concentration, including socio-demographic and biochemical factors as well as the genetic polymorphism of the vitamin D receptor, along with vitamin D transporters and enzymes participating in vitamin D metabolism should be considered as potential confounders of the interpretation of plasma total 25(OH)D concentrations.

Comparison of antioxidative properties of raw vegetables and thermally processed ones using the conventional and sous-vide methods.

The study determines the antioxidant properties of methanol vegetable extracts from raw vegetables, conventionally cooked vegetables and sous-vide. In the research, two methods were used: free radical scavenging DPPH (µM Trolox) and the reduction of Fe3+to Fe2+ - FRAP (µM Fe2+). Antioxidative properties for raw vegetables were obtained with the range of 7.47-235 (µM Trolox/100g of vegetables) and 2.66-103 (µM Fe2+/100g of vegetables), for vegetables after the conventional cooking process 6.15-657 (µM Trolox/100g of vegetables) and 3.03-99.9 (µM Fe2+/100g of vegetables), for vegetables after the sous-vide process 4.45-648 (µM Trolox/100g of vegetables) and 3.06-99.9 (µM Fe2+/100g of vegetables). For some vegetables, an increase in the antioxidative potential was observed as a result of cooking processes; however, it was much higher for the sous-vide technique. All results were subjected to a one-way analysis of variance (ANOVA) and, if significant differences were revealed, the POST-HOC Duncan test was used (α=0.05).

Genetic and Non-Genetic Determinants of the Pharmacological Activity of Statins.

Statins are cholesterol-lowering agents which belong to the group of the most commonly prescribed drugs. The use of statins has become the standard treatment in patients with an increased risk of cardiovascular and coronary heart diseases. However, many clinical studies have shown that 13 - 75% of patients fail to achieve LDL-cholesterol and total cholesterol target levels. The clinical implications of insufficient response include cardiovascular complications caused by atherosclerosis leading to acute myocardial infarction, stroke and death. The mechanism underlying statin resistance has been associated with genetic polymorphisms and nongenetic factors (e.g. concomitant diseases, drug-drug interactions, interactions with food and dietary supplements). The article provides a comprehensive update of the current knowledge regarding the role of genetic polymorphism and non-genetic determinants of cholesterol-lowering effect of statins. Dietary aspects of statin efficacy were also presented. The Pubmed search was performed to identify relevant papers from the last ten years which were included in the review. Consideration of the genetic and non-genetic determinants of pharmacological action of statins as well as mechanisms of drug-drug interactions may be useful in clinical practice for improving safety and efficacy of statin treatment.