Primary vesicoureteral reflux mediated renal scarring after urinary tract infection in Thai children

AIM: To evaluate the association between primary vesicoureteral reflux (VUR) and renal scarring in children using 99 m Technetium-labelled dimercaptosuccinic acid (DMSA). METHODS: Children attending at Songklanagarind Hospital from 1987 to 2002 were evaluated. RESULTS: Ages at diagnosis of VUR in 46 boys and 52 girls were 1.1+/-1.6 and 2.9+/-2.5 years, median 0.6 and 2.3 years, respectively (P<0.001). DMSA scans were performed at 4.1+/-3.6 years. Renal parenchymal damage was detected in 34 kidneys (22%) of 154 demonstrated refluxing ureters, and one kidney (2%) of 42 non-refluxing ureters (P=0.002). Of 79 refluxing ureters in boys and 75 refluxing ureters in girls, there were 25 and nine renal scars, respectively (32% and 12%, P=0.003). Renal scars in VUR grades I-V were 11%, 7%, 12%, 44% and 64%, respectively (P<0.001). Multivariate analysis revealed that high grade VUR (P<0.001), age of diagnosis of VUR greater than 5 years (P=0.001), and male gender (P=0.002) were the most significant risk factors for renal scarring. CONCLUSION: High-grade VUR, age of diagnosis of VUR greater than 5 years and male gender were the most significant risk factors for renal scarring.     

Lupinifolin from Albizia myriophylla wood: A study on its antibacterial mechanisms against cariogenic Streptococcus mutans

ObjectiveTo determine the anti-Streptococcus mutans mechanisms of action of lupinifolin from Albizia myriophylla Benth. (Fabaceae) wood and provide scientific evidence to support the traditional use of the plant against dental caries.MethodsThe minimum inhibitory concentration (MIC) was evaluated using the broth micro-dilution method. The effects of lupinifolin on bactericidal activity, bacterial cell walls, and membranes were investigated by time-kill, lysis, and leakage assays, respectively. Electron microscopy was utilized to observe any cell morphological changes caused by the compound. Localization of lupinifolin in S. mutans was detected using the thin layer chromatography technique.ResultsThe MIC range of lupinifolin against S. mutans (n = 6) was 2–4 μg/ml. This compound displayed bactericidal effects on S. mutans ATCC 25175 by 90–99.9% killing at 4MIC-16MIC after 8–24 hours. Lupinifolin-treated cells demonstrated no lysis. However, significant cytoplasmic leakage through the bacterial membrane was observed after treatment with lupinifolin at 4MIC-16MIC. As revealed by ultrastructural analysis, lupinifolin produced some changes in bacterial cell walls and membranes. Moreover, the compound was observed in the cytoplasmic fraction of the lupinifolin-treated cells. These results suggest that lupinifolin can enter the cell of bacteria but does not accumulate in the cell envelope and subsequently disrupts the integrity of the cytoplasmic membrane, leading to cell death.ConclusionThe scientific evidence from this study offers valuable insights into the potential role of lupinifolin in pharmaceutical and antibiotic applications and supports the therapeutic effects of A. myriophylla, which has traditionally been used as an alternative treatment for dental caries.     

NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine

6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT15¹3 and NUDT15¹2 genotypes were at a 10–15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT15¹3 and NUDT15¹2, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients.     

Dose optimization with population pharmacokinetics of ritonavir-boosted lopinavir for Thai people living with HIV with and without active tuberculosis

BackgroundPrior to dolutegravir availability, ritonavir-boosted lopinavir (LPV/r) was an alternative recommendation when first-line drugs could not be used. A high concentration of protease inhibitors was observed in the Thai people living with HIV (PLWH). Thus, dose reduction of LPV/r may be possible. However, the pharmacokinetics and dose optimization of LPV/r have never been investigated. This study aimed to develop a population pharmacokinetic model of LPV/r and provide dosage optimization in Thai PLWH.MethodsLPV and RTV trough concentrations from Thai PLWH were combined with intensive data. The data were analyzed by the nonlinear mixed-effects modeling approach. The influence of RTV concentration on LPV oral clearance (CL/F) was investigated.ResultsRifampicin (RIF) use increased LPV and RTV CL/F by 2.16-fold and 1.99-fold, respectively. The reduced dose of 300/75 and 200/150 mg twice daily provided a comparable percentage of patients achieving LPV target trough concentration to the standard dose for PI-naïve patients. For HIV/TB co-infected patients receiving RIF who could not tolerate the recommended dose, the reduced dose of 600/150 mg twice daily was recommended.ConclusionThe population pharmacokinetic model was developed by integrating the interaction between LPV and RTV. The reduced LPV/r dosage offers sufficient LPV exposure for Thai PLWH.     

The dopaminergic system in the brain of the native Thai chicken, Gallus domesticus: localization and differential expression across the reproductive cycle

Dopamine (DA) has a pivotal role in avian prolactin (PRL) secretion, acting centrally through D₁ DA receptors to stimulate PRL secretion by operating through vasoactive intestinal peptide (VIP). DA also inhibits PRL secretion by activating D₂ DA receptors at the pituitary level. This study was designed to investigate the distribution of DA neurons in the native Thai chicken, utilizing tyrosine hydroxylase (TH) as a marker for dopaminergic neurons. The differential expression of hypothalamic TH immunoreactive (TH-ir) neurons was also compared across the reproductive cycle. The results revealed that TH-ir neurons and fibers were found throughout the brain of the laying hen and were predominantly located within the diencephalon and mesencephalon. The observed distribution pattern of TH immunoreactivity was consistent with that reported previously in several avian species. However, changes in the number of TH-ir neurons in the nucleus intramedialis (nI) were observed across the reproductive cycle and correlated directly with variations in PRL levels. The population of TH-ir neurons in the nI increased significantly during the egg incubation period, where circulating PRL levels were the greatest. This study indicates, for the first time, that an association exists between DA neurons and the regulation of the reproductive system in the native Thai chicken. There is a paucity of information about the reproductive neuroendocrine regulation of tropical non-seasonally breeding avian species and it is suggested that the differential expression of DA neurons in the nI might play a role in the control of VIP secretion and subsequent PRL release in such birds.     

Development and testing of the Resilience Factors Scale for Thai adolescents

Abstract   The growing body of knowledge related to resilience supported the need for the development of an instrument that can be used to assess resilience factors, that is, individual protective factors, but to date, no established instrument for Thai adolescents exists. The purposes of this study were to develop and test the psychometric properties of the Resilience Factors Scale for Thai adolescents. Derived from the resilience theory of Grotberg and a literature review, 27 items compose the scale. The content validity was evaluated by five experts. The construct, contrast-group, and predictive validity, as well as the internal reliability, were evaluated with a multistage random sample of 638 tenth-to-twelfth graders in four high schools in Bangkok, Thailand. An exploratory factor analysis in the final step indicated that the scale consists of six components with 25 items. Evidence of validity and reliability was obtained. This scale has demonstrated good psychometric properties and has provided an objective tool for assessing the resilience factors of Thai adolescents.     

Red Cell Indices and Formulas Used in Differentiation of β-Thalassemia Trait from Iron Deficiency in Thai School Children

Red cell indices and formulas have been established as simple, fast, and inexpensive means for discrimination between the β-thalassemia (β-thal) trait and iron deficiency. However, there were no reports of the diagnostic reliability of different red cell indices and formulas in discrimination of β-thal trait from iron deficiency in the Thai population. The aim of this study was to examine the diagnostic accuracy of five red cell indices [red blood cell (RBC) count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (Hb) (MCH), mean corpuscular Hb concentration (MCHC), and red cell distribution width (RDW)] and eight formulas (Sirdah, Green & King, RDW Index, Menzler, England & Fraser, Ehsani, Srivastava, and Shine & Lal). Their sensitivity, specificity, positive and negative prognostic value and efficiency, were analyzed in 77 Thai school children, 21 with the β-thal trait and 56 with iron deficiency. The Sirdah and Srivastava formulas proved to be the most reliable indexes as they had 100.0% sensitivity and negative predictive value, the highest efficiency (97.4%), and the highest Youden’s Index value (96.4%). Therefore, these formulas could be used in initial discrimination of the β-thal trait from iron deficiency in Thai school children.