Volume 38, Issue 4

Introduction Despite the ever-increasing occurrences of the coronavirus disease (COVID-19) cases around the world, very few medications have been validated in the clinical trials to combat COVID-19. Although several vaccines have been developed in the past quarter, the time elapsed between deployment and administration remains a major impediment. Content Repurposing of pre-approved drugs, such as phosphodiesterase 5 (PDE5) inhibitors, could be a game-changer while lessening the burden on the current healthcare system. Repurposing and developing phosphodiesterase 5 (PDE5) inhibitors could extrapolate their utility to combat the SARS-CoV-2 infection, and potentially aid in the management of the symptoms associated with its newer variants such as BF.7, BQ.1, BQ.1.1, XBB.1.5, and XBB.1.16. Summary Administration of PDE5 inhibitors via the oral and intravenous route demonstrates other potential off-label benefits, including anti-apoptotic, anti-inflammatory, antioxidant, and immunomodulatory effects, by intercepting several pathways. These effects can not only be of clinical importance in mild-to-moderate, but also moderate-to-severe SARS-CoV-2 infections. This article explores the various mechanisms by which PDE5 inhibitors alleviates the symptoms associated with COVID-19 as well as well as highlights recent studies and findings. Outlook These benefits of PDE5 inhibitors make it a potential drug in the physicians’ armamentarium in alleviating symptoms associated with SARS-CoV-2 infection. However, adequate clinical studies must be instituted to eliminate any untoward adverse events.

Objectives Diplazium esculentum (Retz.) Sw. is an edible vegetable fern of the Himalayan region with high nutritional and therapeutic value owing to its richness in various secondary metabolites and both macro and micronutrients. Content This updated review discusses the general traditional use, ethnopharmacology, phytochemistry, nutritional value, pharmacology, and toxicity concerns of D. esculentum. Summary The plant parts, viz. rhizomes, shoots, fronds and leaves, have immense ethnomedicinal importance, being traditionally used to cure several health disorders. Among other pharmacological effects, this botanical reveals excellent anti-inflammatory, analgesic, antifungal, antibacterial, antioxidant, anti-leishmanial, antioxidant, anaphylactic, antipyretic, anthelmintic and hepatoprotective activities, directly attributed to the presence of many secondary metabolites. From a pharmacological point of view, the excellent antioxidant potential of D. esculentum suggests its promising use for nutraceutical or functional food formulation purposes. Outlook Considering the evidences on popular ethnomedicinal uses of D. esculentum as an edible vegetable, its immense bio-potential, and multiple pharmacological roles, there is a huge need to evaluate its therapeutic applications in light of standard clinical trials.

Objectives Tamsulosin is a first-line drug for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Despite its high ratings for efficacy and safety, these parameters may vary due to genetic polymorphisms of CYP2D6 enzyme, which is involved in the metabolism of the drug. This variability may have great impact on the therapy of LUTS associated with BPH and may require an individualized approach to drug selection. The aim of the study was to assess the impact of genetic polymorphisms in CYP2D6 on the efficacy and safety of tamsulosin therapy in patients with LUTS associated with BPH. Methods The study included 106 patients with LUTS/BPH (N40 according to ICD-10). All patients received monotherapy with tamsulosin 0.4 mg/day for at least 8 weeks. Depending on the severity of symptoms, all patients were divided into 2 groups based on the IPSS score: the first group of patients had moderate symptoms (n=57), and the second group of patients had severe symptoms (n=49). The results of treatment were assessed using the IPSS questionnaire with determination of quality of life (QoL), transrectal ultrasound of the prostate with determination of prostate volume and postvoid residual urine volume, and uroflowmetry. The carriage of allelic variants of CYP2D6 (*3, *4, *9, *10, and *41) were determined by polymerase chain reaction in all patients. Results In patients with moderate symptoms who was classified as «intermediate» metabolizers by CYP2D6, a statistically significant greater reduction in symptoms according to the overall IPSS scale at 8 weeks (p=0.046) and the obstructive symptom subscale starting from 4 weeks of treatment (p<0.05) was shown. Allelic variants of the CYP2D6 gene did not affect the frequency of adverse reactions to tamsulosin. Conclusions The results of the study show that in patients with moderate LUTS associated with BPH who are «intermediate» metabolizers by CYP2D6, there is a better therapeutic effect of tamsulosin.

Objectives Rhinitis is classified into several types with allergic rhinitis (AR) being the most common. AR is among the inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), in which corticosteroids are administered to overcome the decrease in cortisol production. The treatment options available for AR vary with 1 st line treatment being intranasal corticosteroids (INCS). The responsiveness to corticosteroids is due to their binding to corticotropin-releasing hormone receptor-1 (CRHR1). Various studies have studied the responsiveness to corticosteroids treatment in patients with asthma and COPD in association with CRHR1 gene single nucleotide polymorphisms (SNPs). Methods In our study, we investigated the association of three SNPs of CRHR1 gene (rs242941, rs242940, and rs72834580) with symptoms improvement post-treatment in AR patients. Blood samples were collected from 103 patients for DNA extraction and gene sequencing. Those patients started to receive INCS for 8 weeks and their symptoms were assessed, through a questionnaire, before treatment and post-treatment to check for symptoms improvement. Results Our data showed that improvement of eye redness is significantly less following INCS treatment in patients with allele (C) (AOR=0.289, p-value-0.028, 95 % CI=0.096–0.873) and genotype (CC) (AOR=0.048, p-value-0.037, 95 % CI=0.003–0.832) of rs242941 SNP. There was no correlation with other genotypes, alleles, or haplotypes of the investigated SNPs. Conclusions Our findings show that there is no correlation between CRHR1 gene polymorphism and symptoms improvement following INCS treatment. Further studies are required to evaluate the association of INCS and symptoms improvement post-treatment with larger sample size.

Objectives The present study investigated the analysis of adverse drug reactions (ADRs) to tamoxifen (TAM) in breast cancer patients in relation to the carriage of genetic polymorphisms of genes encoding enzymes of CYP system and transporters of P-glycoprotein (Pg) and predictive models based on it. Methods A total of 120 women with breast cancer taking adjuvant TAM were examined for the gene polymorphisms such as CYP2D6*4 , CYP3A5*3 , CYP2C9*2 , CYP2C9*3 , CYP2C19*2 , CYP2C19*3 and ABCB1 ( C3435T ). Allelic variants were determined using the real-time polymerase chain reaction method. The research material was double sampling of buccal epithelium. Medical history data and extracts from case histories were used as sources of medical information, on the basis of which questionnaires specially created by us were filled out. Results An associative analysis showed association with the development of ADRs to TAM indicating their clinical significance from different genetic polymorphisms of CYP2D6 , CYP3A5 , CYP2C9 and ABCB1 . The complex associative analysis performed using mathematical modeling made it possible to build predictive risk models for the development of ADRs such as hot flashes, dyspepsia, bone pain, and asthenia. Conclusions Models that include both genetic and non-genetic determinants of ADRs of TAM may further improve the prediction of individual response to TAM.

Objectives To evaluate the role of ABCB1 (C3435T rs1045642, rs1128503, rs2032582, rs4148738), SLCO1B1 T521C rs4149056 genetic polymorphisms in the development of major types of methotrexate (MTX) toxicities and the occurrence of a terminal event (death, relapse) in pediatric АLL. Methods The study included 124 patients diagnosed with pediatric ALL. All patients treated according to the protocols of the German BFM group (2002/2009) with high-dose (1,000, 2,000 and 5,000 mg/m 2 ) methotrexate. MTX-related toxicities, including hematologic, hepatic and renal, were evaluated according to the common terminology criteria for adverse events version 5.0 (CTCAE v.5.0). Real-time PCR method was used to investigate polymorphisms of ABCB1 and SLCO1B1 genes. The study material was peripheral blood. Results A competitive analysis demonstrated significant relationships between MTX ADRs. The results of the study support the existence of relationships between some ADRs and MTX kinetics. An associative analysis showed association with the development of AEs to methotrexate indicating their clinical significance from different genetic polymorphisms protein-transporters. The available results confirm the associations of the studied genes with the increased risk of high doses MTX toxic ADRs and terminal events. Conclusions Complementing the existing criteria for pediatric ALL risk groups with pharmacogenetic indicators will allow further individualization of therapy.

Objectives Antibiotic resistance is rising, prompting innovative strategies for eradicating the epidemic. This study investigated the antibacterial properties of the leaves of a widely used medicinal plant, Adhatoda vasica . Methods The plant’s polar (water, methanol) and non-polar (hexane) extracts were tested against several different bacterial strains using the disc diffusion technique. Results In a study, it was found that the water extract had the greatest inhibitory effect on Staphylococcus simulans and Staphylococcus aureus , with minimum inhibitory concentrations of 16.444 and 19.315 g/mL, respectively. Gram-negative strains were more susceptible to plant extracts than Gram-positive strains. The phytochemical analysis indicated the presence of secondary metabolites such as alkaloids, saponins, flavonoids, tannins, and steroids, where absorbance was recorded at 415 nm. The water extract had the highest amount of phenolics, with a total phenolic content of 53.92 0.47 mg and a total flavonoid content of 7.25 0.08 mg. Results suggest that the extract may have potential therapeutic applications for antimicrobial properties. Conclusions The study concluded that the extract’s phenolic group of secondary metabolites were responsible for its antibacterial activity. The study highlights A. vasica as a promising source for discovering new and effective antibacterial compounds.