Allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: Signal detection and preventability from Vietnam National pharmacovigilance database.

WHAT IS KNOWN AND OBJECTIVE: Allopurinol, the first-line medication for hyperuricemia is well-known for its association with severe cutaneous adverse reactions, especially Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In the current study, we analysed the Vietnamese spontaneous reporting database to identify signals and preventability of allopurinol-induced SJS/TEN in Vietnam from 2010 to 2019. METHODS: Signal generation was assessed using the case/non-case method. Reporting odds ratios (RORs) and 95% confidence intervals (95% CI) were calculated. RESULTS: Among 72,822 spontaneous ADR reports submitted to the Vietnam National Drug Information and Adverse Drug Reaction Monitoring Centre, 392 reports were on SJS/TEN, of which, 65 cases (16.6%) were related to allopurinol. The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 (ROR of 3.531, 95% CI: 1.830-6.810) and annually increased until 2019 (ROR of 11.923, 95% CI: 8.508-16.710). The preventability assessment showed that no allopurinol-induced SJS/TEN case was definitely unpreventable. 61.6% of the SJS/TEN cases were avoidable because they were associated with inappropriate prescribing such as unapproved indications, too high initial dose and even rechallenging in patients with a history of allopurinol allergy. WHAT IS NEW AND CONCLUSION: The signals of allopurinol-induced SJS/TEN in Vietnam started in 2014 and annually increased until 2019. Our first report specifically focusing on the ADR preventability of allopurinol showed that correction of medical errors relating to prescription could prevent more than 60% of SJS/TEN cases in Vietnamese allopurinol users. This is a feasible and practical solution, provided that there would be a systematic change in both healthcare systems and public awareness.

Phylogeny of Alpinia coriandriodora D. Fang and Implications for Character Evolution and Conservation.

BACKGROUND AND OBJECTIVE: Alpinia, the largest genus of Zingiberaceae, includes ca. 250 species. The A. coriandriodora D. Fang was recognized for Vietnamese flora. However, the systematic position of this species within Alpinia genus was unclear. The study aimed to understand the phylogenetic placement of A. coriandriodora based on the molecular data and interpret evolution of the key morphological characters. MATERIALS AND METHODS: The phylogenetic analysis were conducted by using the combined dataset of two DNA regions by both Maximum Likelihood (ML) and Bayesian Inference (BI) methods. Seven morphological characters were selected for morphological character evolution and the analysis was performed in Mesquite. RESULTS: Alpinia coriandriodora was supported closely related to southern Chinese species of Alpinia. Morphological character optimizations suggest that the presence/absence of tomentum in leaf, inflorescence rachis and ovary is an important character for the taxonomy of Alpinia. The character evolution analyses indicated that panicle is ancestral character in Alpinia. The A. coriandriodora shares different evolutionary histories based on our character re-construction to most members of Southeast Asian Alpinia. The presence of filament is supposed to be an adaptation to the pollination by insects for species of Alpinia. CONCLUSION: The present study revealed the molecular phylogenetic relationship of A. coriandriodora within Alpinia. The presence of filament could be an adaptation to the pollination by insects for species of Alpinia. Some reasonable conservation strategies are proposed to protect the species including maintenance of the plant's natural habitats, seeds or seedlings collection for germplasm storage and artificial breeding using biotechnology.

Development and potential use of an Edwardsiella ictaluri wzz mutant as a live attenuated vaccine against enteric septicemia in Pangasius hypophthalmus (Tra catfish).

Edwardsiella ictaluri is a causative agent of enteric septicemia of catfish (ESC), a seriously lethal disease in Vietnamese catfish (Pangasius hypophthalmus). A safe and effective vaccine against ESC is currently an urgent demand due to antibiotic overuse in pangasius farms has led to an alarming antimicrobial resistance. In this study, two E. ictaluri wzzE mutants (WzM-L3, deficient in a 1038bp-entire wzzE gene and WzM-S3, a 245bp-partial deletion of wzzE) were developed and their protection efficiacy was evaluated in hatched pangasius against ESC by immersion vaccination. As comparing to the high virulent wild-type strain who caused 73.33% of death on pangasius fingerlings immersed at 7.1 × 106 CFU ml-1, both mutants showed extremely low mortality rates at 3.33% (WzM-S3) and 0% (WzM-L3) on pangasius fingerlings immersed at high concentration of 1.5 × 107 CFU mL-1 and 9.7 × 106 CFU ml-1, respectively. Interestingly, both WzM-S3 and WzM-L3 had a remarkably high protection against ESC, as RPS % were found at 89.29% and 90%, respectively. The mutant WzM-L3 is a potential live attenuated vaccine against ESC in Vietnamese catfish farms with good protection and simple practice.

Two new simple iridoids from the ant-plant Myrmecodia tuberosa and their antimicrobial effects.

Six iridoid derivatives (1-6), including two new compounds myrmecodoides A and B (1 and 2), were isolated from the ant-plant Myrmecodia tuberosa. Their structures were determined on the basis of spectroscopic data ((1)H and (13)C NMR, HSQC, HMBC, (1)H-(1)H COSY, NOESY and HR-ESI-MS) and by comparison with the literature values. Among isolates, 3 and 4 exhibit weak antibacterial effect against Staphylococcus aureus subsp. aureus with MIC value of 100.0 µg/mL.

Tirucallane Glycoside from the Leaves of Antidesma bunius and Inhibitory NO Production in BV2 Cells and RAW264.7 Macrophages.

One new tirucallane-type triterpene glycoside, antidesoside (1), along with two biflavones, podocarpusflavone A (2) and amentoflavone (3) and two megastigmane glycosides, byzantionoside B (4), and (6S,9R)-roseoside (5) were isolated from the methanol extract of Antidesma bunius leaves. Their structures were determined by spectroscopic methods and in comparison with the published data. Compounds 1 - 3 were found to show strong inhibitory effect of NO production in BV2.cells and RAW264.7 macrophages LPS-stimulated, with IC50 values ranging from 8.5 to 26.9 µM.

Vasorelaxing activity of two coumarins from Murraya paniculata leaves.

In the search for novel chemical scaffolds leading to potential antihypertensive agents, the methanol extract of Murraya paniculata leaves was assessed for its effects on isolated rat aorta rings. The vasorelaxing effect of the chloroform fraction of the methanol plant extract was the most potent for its vasorelaxing activity on rat aorta rings contracted by 60 mM K(+) (K60). Two coumarins were isolated from the chloroform fraction: the novel kimcuongin (1) and the known murracarpin (2). Their structures were determined from spectroscopic evidences including (1)H- and (13)C-NMR, correlation spectroscopy (COSY), nuclear Overhauser effect spectroscopy (NOESY), heteronuclear multiple bond correlation (HMBC), heteronuclear single quantum correlation (HSQC), and high resolution mass spectrometry (HR-MS). Kimcuongin and, to a lesser extent, murracarpin, showed vasorelaxing activity with IC50 values of 37.7 µM and 139.3 µM, respectively. The coumarins kimcuongin and murracarpin may thus represent a novel class of vasodilators of natural source.