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Mohan Anant,Bhatnagar Anuj,Gupta Tarang,Ujjalkumar Das,Kanswal Sunita,Velpandian Thirumurthy,Guleria Randeep,Singh Urvashi B. 한국약제학회 2022 Journal of Pharmaceutical Investigation Vol.52 No.4
Purpose Patients with pulmonary tuberculosis (PTB) who fail therapy or develop a relapse are initiated on a retreatment regimen. These patients are at high risk for adverse outcomes. This study aimed to assess the relationship between plasma levels of anti-tubercular drugs and therapy outcome in patients on retreatment. Methods Pharmacokinetics of retreatment regimen drugs [isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), ethambutol (EMB), and streptomycin (STM)] were compared between cured and not-cured patients using liquid chromatographytandem mass spectrometry (LC-MS/MS) in 134 patients with PTB on a retreatment regimen. Results Of 134 patients, 108 were cured, 17 developed multi-drug resistant TB (MDR-TB), and 9 remained smear-positive after completion of the retreatment (8 months). Two-hour plasma levels ( C2hr) at Day 0 were lower in ‘not cured’ subjects than ‘cured’ subjects and reflected the drug levels achieved later in the duration of retreatment. Notably, in the 26 ‘not cured’ subjects, C2hr plasma levels after the first dose at Day 0 were significantly low (INH: 0.86 vs. 2.94 mg/L, p ≤ 0.002, RIF: 0.56 vs. 2.55 mg/L, p ≤ 0.003, PZA: 1.85 vs. 26.58 mg/L, p ≤ 0.001 and EMB: 0.72 vs. 1.53 mg/L, p ≤ 0.010). Conclusion Therapeutic failure in patients with PTB on a retreatment regimen is associated with lower plasma drug levels. Therapeutic drug monitoring would prove useful for obtaining a favorable clinical outcome. C2hr levels on Day 0 reflected drug levels achieved later and could be a good predictor of patient outcome.
Tiwari Jagesh Kumar,Mandadi Nagesh,Sridhar Jandrajupalli,Mandal Vikramjit,Ghosh Arpita,Kardile Hemant B.,Naga Kailash C.,Shah Mohd Abas,Rawat Shashi,Venkateswarlu Vallepu,Malik Kamlesh,Bhatnagar Anuj 한국응용곤충학회 2021 Journal of Asia-Pacific Entomology Vol.24 No.2
The foxglove aphid (or glasshouse potato aphid, Aulacorthum solani Kaltenbach) transmits serious potato viruses (potato virus Y, and potato leaf roll virus) which cause heavy yield losses. Our aim of this study was to pre liminary analysis of draft genome sequence to uncover virulence genes in the aphid. The genome assembly size (316.39 Mb) was very close to its genome size (318.19 Mb) estimated by flow cytometry. The genome completeness (81.8%) was confirmed by the Benchmarking Universal Single Copy Orthologs (BUSCO) analysis indicating 14.90% transposable elements (TEs) in the genome. Of total 22,021 predicted genes, 16,610 were annotated with putative functions of other aphids mainly Myzus persicae, Acyrthosiphon pisum and Diuraphis noxia. We identified virulence genes such as defensive and detoxification genes, salivary genes and chemore ceptors, insecticide resistance genes, virus transmission genes, transcription factors and mitochondrial genes. Importantly, analysis of detoxification genes particularly 53 cytochrome P450s (CYPs) indicated involvement of 23 CYPs families in aphid genome. Further, GO and KEGG pathways analyses showed gene enrichment pre dominantly with molecular function and signal transduction, respectively. Phylogeny analysis revealed genetic divergence among 12 aphid species and Au. solani is closely related with M. persicae. Further, non-synonymous (Ka)/synonymous (Ks) substitutions (Ka/Ks) indicated positive selection for 6 (Ka/Ks > 1) and 122 (Ka/Ks = 0.5–1) single copy orthologous gene pairs between Au. solani and with the pea aphid. Thus, our preliminary draft genome analysis provides new insights of Au. solani to understand molecular basis of aphid biology, host-aphid interactions and adaptation mechanism.