Search

Natchaya Vanwong,1,2 Sayanit Tipnoppanon,1 Chalitpon Na Nakorn,3 Pornpen Srisawasdi,4 Punyanuch Rodcharoen,4 Sadeep Medhasi,5 Pajaree Chariyavilaskul,2,6,7 Sarawut Siwamogsatham,2,8,9 Yongkasem Vorasettakarnkij,2,9 Chonlaphat Sukasem10– 12 1Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand; 2Cardiovascular Precision Medicine Research Group, Special Task Force of Activating Research (STAR), Chulalongkorn University, Bangkok, Thailand; 3Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, Thailand; 4Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 5Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand; 6Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 7Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Chulalongkorn University, Bangkok, Thailand; 8Chula Clinical Research Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 9Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 10Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 11Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand; 12Pharmacogenomics and Precision Medicine, The Preventive Genomics & Family Check-up Services Center, Bumrungrad International Hospital, Bangkok, ThailandCorrespondence: Chonlaphat Sukasem, Division of Pharmacogenetics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand, Tel +66-2-200-4331, Fax +66-2-200-4332, Email chonlaphat.suk@mahidol.ac.thPurpose: Statins are increasingly widely used in the primary and secondary prevention of cardiovascular disease. However, there is an inter-individual variation in statin response among patients. The study aims to determine the association between genetic variations in drug-metabolizing enzyme and transporter (DMET) genes and lipid-lowering response to a statin in Thai patients with hyperlipidemia.Patients and Methods: Seventy-nine patients who received statin at steady-state concentrations were recruited. Serum lipid profile was measured at baseline and repeated after 4-month on a statin regimen. The genotype profile of 1936 DMET markers was obtained using Affymetrix DMET Plus genotyping microarrays.Results: In this DMET microarray platform, five variants; SLCO1B3 (rs4149117, rs7311358, and rs2053098), QPRT (rs13331798), and SLC10A2 (rs188096) showed a suggestive association with LDL-cholesterol-lowering response. HDL-cholesterol-lowering responses were found to be related to CYP7A1 gene variant (rs12542233). Seven variants, SLCO1B3 (rs4149117, rs7311358, and rs2053098); SULT1E1 (rs3736599 and rs3822172); and ABCB11 (rs4148768 and rs3770603), were associated with the total cholesterol-lowering response. One variant of the ABCB4 gene (rs2109505) was significantly associated with triglyceride-lowering response.Conclusion: This pharmacogenomic study identifies new genetic variants of DMET genes that are associated with the lipid-lowering response to statins. Genetic polymorphisms in DMET genes may impact the pharmacokinetics and lipid-lowering response to statin. The validation studies confirmations are needed in future pharmacogenomic studies.Keywords: drug-metabolizing enzymes, drug transporters, gene polymorphisms, statin

The mechanisms of Pythium insidiosum -antigen (PIA) immunotherapy activating a patient's immune system are unknown. We evaluated the interleukin-8 (IL-8) serum levels during P. insidiosum infection and after vaccination with PIA in vascular pythiosis cases. Furthermore, we studied the anti- P. insidiosum activity of neutrophils stimulated with various concentrations of PIA ex vivo in 3 strains of P. insidiosum isolated from vascular pythiosis patients. IL-8 serum levels were evaluated using the ELISA technique. We assessed the effect of PIA-stimulated neutrophils on the viability of zoospores using MTT assay, visualized neutrophil extracellular trap (NET) formation via microscopy, and measured the levels of double-stranded DNA (dsDNA) using PicoGreen dsDNA quantitation assay in 3 strains of P. insidiosum isolated from vascular pythiosis patients. Serum levels of IL-8 gradually lowered from the early to the end phases of vaccination with PIA among the surviving group of vascular pythiosis cases. Neutrophils stimulated with 0.01 µg/ml PIA reduced zoospore viability significantly compared to PIA-unstimulated neutrophils for strain 1 and strain 3 ( p  < .05). Neutrophils stimulated with 0.01, 0.1, 1, and 10 µg/ml PIA exhibited significantly lower zoospore viability than PIA-unstimulated neutrophils for strain 2 ( p  < .05). IL-8 can be used as a biomarker for monitoring vascular pythiosis cases treated with the PIA vaccine. Also, anti- P. insidiosum activity of PIA-stimulated neutrophils was probably due to the disruption of cellular activity in zoospores rather than the mechanisms based on the formation of NETs.

There has been limited research into the role of the Pythium insidiosum antigen (PIA) in modulating immune response in patients with pythiosis. This study investigated the balance of T helper type 2 (Th2) and T helper type 1 (Th1) responses after receiving PIA immunotherapy in patients with pythiosis. Next, the phagocytic activity and phagocytic index of IFN-γ primed PIA-treated macrophages were examined. Furthermore, the phagocytosis of infective P. insidiosum zoospores by macrophages was investigated. This work showed that the PIA vaccine induced Th1 response and M1 macrophages in patients with vascular pythiosis who survived and those with localized pythiosis. Phagocytic activity and phagocytic index were increased considerably in localized pythiosis patients compared to vascular pythiosis patients with hematological diseases. IFN-γ priming of PIA-treated macrophages against P. insidiosum zoospores enhanced the phagocytic activity and phagocytic index in vascular and localized pythiosis patients. Macrophages engulfed P. insidiosum zoospores, but the zoospores continued germination, resulting in macrophage death. Overall, our results suggest that PIA can modulate the immune responses, contributing to higher levels of Th1-type cytokine and potentially improving the survival of patients with vascular pythiosis. This study is the first to uncover that P. insidiosum zoospores can survive within macrophages., (© 2024. The Author(s).)

The human leukocyte antigen (HLA) system is one of the most crucial host factors influencing disease progression in bacterial and viral infections. This review provides the basic concepts of the structure and function of HLA molecules in humans. Here, we highlight the main findings on the associations between HLA class I and class II alleles and susceptibility to important infectious diseases such as tuberculosis, leprosy, melioidosis, Staphylococcus aureus infection, human immunodeficiency virus infection, coronavirus disease 2019, hepatitis B, and hepatitis C in populations worldwide. Finally, we discuss challenges in HLA typing to predict disease outcomes in clinical implementation. Evaluation of the impact of HLA variants on the outcome of bacterial and viral infections would improve the understanding of pathogenesis and identify those at risk from infectious diseases in distinct populations and may improve the individual treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Sadeep Medhasi and Narisara Chantratita.)

Human pythiosis is associated with poor prognosis with significant mortality caused by Pythium insidiosum . Antimicrobials' in vitro and in vivo results against P . insidiosum are inconsistent. Although antimicrobials are clinically useful, they are not likely to achieve therapeutic success alone without surgery and immunotherapy. New therapeutic options are therefore needed. This non-exhaustive review discusses the rationale antimicrobial therapy, minimum inhibitory concentrations, and efficacy of antibacterial and antifungal agents against P. insidiosum . This review further provides insight into the immunomodulating effects of antimicrobials that can enhance the immune response to infections. Current data support using antimicrobial combination therapy for the pharmacotherapeutic management of human pythiosis. Also, the success or failure of antimicrobial treatment in human pythiosis might depend on the immunomodulatory effects of drugs. The repurposing of existing drugs is a safe strategy for anti- P. insidiosum drug discovery. To improve patient outcomes in pythiosis, we suggest further research and a deeper understanding of P. insidiosum virulence factors, host immune response, and host immune system modification by antimicrobials.