G6PD genetic variations in neonatal Hyperbilirubinemia in Indonesian Deutromalay population.

BACKGROUND: Neonatal jaundice is a common finding in newborns in Asia, including Indonesia. In some cases, the serum total bilirubin levels exceeds the 95th percentile for hours of life (neonatal hyperbilirubinemia). Severe neonatal hyperbilirubinemia (NH) could lead to kernicterus and neonatal death. Glucose-6-Phosphage Dehydrogenase (G6PD) genetic variations and deficiency have been reported in several studies to be associated with NH. This study aimed to analyze the G6PD genetic variations and its activity in neonates with and without hyperbilirubinemia in the Deutromalay Indonesian population. METHODS: Deoxyribose Nucleic Acid (DNA) was isolated from peripheral blood of 116 and 115 healthy term neonates with and without hyperbilirubinemia. All infants underwent the following laboratory examinations: routine hematologic evaluation, Coombs test, G6PD activity measurement using the Randox kit method, and serum total bilirubin level. All exons of the G6PD gene were targeted for deep sequencing using MiSeq (Illumina). An association study of G6PD polymorphisms with NH was performed using PLINK. RESULTS: The prevalence of G6PD deficiency in neonates with and without hyperbilirubinemia in Indonesian Deutromalay population were 1.72% (95% Confidence Interval (CI): 0.6-4.1%) and 1.74% (95% CI: 0.7-4.1%), respectively. The most common G6PD polymorphisms, i.e. rs1050757/c.* + 357A > G, rs2230037/c.1311C > T, and rs2071429/c.1365-13 T/IVS11, were identified. However, none of those polymorphisms and their haplotype were associated with NH (p > 0.05, Odds Ratio (OR) ~1.00). The prevalence of G6PD mutations in neonates with and without hyperbilirubinemia were 6.8% (95% CI: 2.3-11.5%) and 6.9% (95% CI: 2.3-11.6%), respectively. The most frequently identified G6PD mutation was the Viangchan variant (p.V291 M), which was followed by the Canton (p.R459L) and Vanua Lava (p.L128P) variants. Two novel mutations were identified both in case (p.V369A, p.I167F) and control (p.L474=, p.I36T) groups. CONCLUSION: The prevalence of G6PD deficiency is low in neonates with or without hyperbilirubinemia in Deutromalay Indonesian population. The majority of G6PD mutations identified among Indonesian Deutromalay population in this study are Viangchan, Canton and Vanua Lava variants.

UGT1A1 Genetic Variations and a Haplotype Associated with Neonatal Hyperbilirubinemia in Indonesian Population.

Neonatal hyperbilirubinemia (NH) is a common finding in newborn babies in Indonesia. Common and rare variants of UGT1A1 have been known to contribute to NH etiology. This study aims to identify UGT1A1 genetic variation and haplotype associated with NH in Indonesian population. DNA was isolated from 116 cases and 115 controls and a targeted-deep sequencing approach was performed on the promoter, UTRs, and exonic regions of UGT1A1. Determining association of common variants and haplotype analysis were performed using PLINK and Haploview. Ten and 4 rare variants were identified in cases and controls, respectively. The UGT1A1 rare variants frequency in cases (5.17%) was higher than that in controls (1.7%). Four of those rare variants in cases (p.Ala61Thr, p.His300Arg, p.Lys407Asn, and p.Tyr514Asn) and three in controls (p.Tyr79X, p.Ala346Val, and p.Thr412Ser) are novel variants. The frequencies of p.Gly71Arg, p.Pro229Gln, and TA7 common variants were not significantly different between cases and controls. A haplotype, consisting of 3 major alleles of 3' UTRs common variants (rs8330C>G, rs10929303C>T, and rs1042640C>G), was associated with NH incidence (p = 0.025) in this population. Using targeted-deep sequencing and haplotype analysis, we identified novel UGT1A1 rare variants and disease-associated haplotype in NH in Indonesian population.

Endothelial dysfunction in the young adult: a retrospective cohort study on the effect of low birth weight.

AIM: to investigate the effect of low birth weight (LBW) on endothelial function, and to determine the role of plasma adiponectin in endothelial dysfunction by conducting flow mediated brachial artery (FMBA) test or vasodilation response (VR) and by measuring plasma asymmetrical dimethylarginine (ADMA) of young adults born with LBW. METHODS: in a retrospective cohort study, subjects were randomly selected from the growth study cohort of Tanjungsari Sumedang district West Java. They consisted of 67 LBW and 67 NBW (Normal Birth Weight) young adults. Dependent variables were plasma adiponectin, plasma ADMA, and VR. The correlation between plasma adiponectin and ADMA level was examined using Pearson's correlation. RESULTS: the relative risk for LBW to have low brachialis artery vasodilation response was 2.94, (95% CI:1.91-4.53), and to have low of plasma adiponectin concentration 1.53, (95% CI: 1.07-2.18). There was a statistically significant difference for all variables studied (FMBA, plasma ADMA, and plasma Adiponectin concentrations), while simultaneous confidence interval measurements indicated that the value of FMBA and the concentration of plasma adiponectin were significantly lower, respectively p<0.001, 95% CI: -4.409-(-2.114), and p=0.015, 95% CI: -1.083-(-0.082) in LBW compared to NBW subjects. The correlation between plasma adiponectin concentration and plasma ADMA concentration in LBW subjects was not significant. CONCLUSION: there is an effect of LBW on endothelial function. LBW compared to NBW subjects have lower VR and plasma adiponectin concentration. There may be a small role of plasma adiponectin in endothelial dysfunction of young adults with LBW.

Potential activity of fevicordin-A from Phaleria macrocarpa (Scheff) Boerl. seeds as estrogen receptor antagonist based on cytotoxicity and molecular modelling studies.

Fevicordin-A (FevA) isolated from Phaleria macrocarpa (Scheff) Boerl. seeds was evaluated for its potential anticancer activity by in vitro and in silico approaches. Cytotoxicity studies indicated that FevA was selective against cell lines of human breast adenocarcinoma (MCF-7) with an IC50 value of 6.4 µM. At 11.2 µM, FevA resulted in 76.8% cell death of T-47D human breast cancer cell lines. Critical pharmacophore features amongst human Estrogen Receptor-α (hERα) antagonists were conserved in FevA with regard to a hypothesis that they could make notable contributions to its pharmacological activity. The binding stability as well as the dynamic behavior of FevA towards the hERα receptor in agonist and antagonist binding sites were probed using molecular dynamics (MD) simulation approach. Analysis of MD simulation suggested that the tail of FevA was accountable for the repulsion of the C-terminal of Helix-11 (H11) in both agonist and antagonist receptor forms. The flexibility of loop-534 indicated the ability to disrupt the hydrogen bond zipper network between H3 and H11 in hERα. In addition, MM/GBSA calculation from the molecular dynamic simulations also revealed a stronger binding affinity of FevA in antagonistic action as compared to that of agonistic action. Collectively, both the experimental and computational results indicated that FevA has potential as a candidate for an anticancer agent, which is worth promoting for further preclinical evaluation.

Severity of psychiatric and physical problems is associated with lower quality of life in methadone patients in Indonesia.

BACKGROUND AND OBJECTIVES: The goal of methadone maintenance treatment (MMT) is to reduce the harm and to improve patients' quality of life (Qol). However, the Qol is also influenced by other co-occurring disorders. Data regarding the Qol and the co-occurrence of these disorders is lacking in low-middle income countries. We therefore describe the prevalence of physical, psychiatric, and drug abuse co-occurring disorders among MMT patients in Indonesia and determine the association between the severity of the co-occurring disorders and the Qol. METHODS: Data were collected in 112 injection drug abusers (IDUs) attending a MMT program in West Java, Indonesia, using validated questionnaires, medical records and laboratory testing. For comparison, 154 IDUs not enrolled in MMT were recruited by respondent driven sampling. RESULTS: The most frequent co-occurring disorders were hepatitis C (92%), HIV (77%), benzodiazepine abuse (56%), and anxiety disorders (32%). IDUs in MMT had one (26%), two (47%), or three (27%) co-occurring disorders. Higher severity in psychiatric and physical problems was associated with poorer Qol. IDUs not enrolled in MMT had similar co-occurring problems. CONCLUSIONS: The prevalence of co-occurring disorders in IDUs in Indonesia is high and they influence their Qol. SCIENTIFIC SIGNIFICANCE: Therefore, comprehensive treatment, especially focusing on the common co-occurring disorders should be provided in MMT to improve the Qol.

Kaempferol-3-O-rhamnoside isolated from the leaves of Schima wallichii Korth. inhibits MCF-7 breast cancer cell proliferation through activation of the caspase cascade pathway.

Plants consumed by non-human primates represent potential drug sources for human disease management. In this study, we isolated kaempferol-3-O-rhamnoside as an active compound from the leaves of Schima wallichii Korth., a plant commonly consumed by non-human primates. Its anti-cancer activities, including its ability to induce apoptotic mechanisms, were investigated in MCF-7 breast cancer cells. Results showed that in MCF-7 cells, kaempferol-3-O-rhamnoside inhibits cell proliferation in a dose-dependent manner and promotes apoptosis via the activation of the caspase signaling cascade, which includes caspase-9, caspase-3 and PARP. Our results provide a basis for further exploration of kaempferol-3-O-rhamnoside as an active compound for potential anti-cancer therapeutics.

Successful testing and treating of HIV/AIDS in Indonesia depends on the addiction treatment modality.

BACKGROUND: In many settings, people who inject drugs (PWID) have limited access to human immunodeficiency virus (HIV) care which is provided in several hospitals and primary health centers in big cities. Substance abuse treatment (SAT) can be used as the entry-point to HIV programs. The aim of this study is to describe the characteristics of the PWID who had accessed SAT and determine which SAT modality associates significantly with HIV programs. METHODS: PWID were recruited by respondent-driven sampling in an urban setting in Java, Indonesia and interviewed with the Addiction Severity Index (ASI), Blood-Borne Virus Transmission Risk Assessment Questionnaires, and Knowledge Questionnaire on HIV/AIDS. The information regarding the use of substance abuse treatment and HIV program were based on questions in ASI. RESULTS: Seventy-seven percent of 210 PWID had accessed SAT at least once. PWID who had accessed a SAT modality reported more severe drug problems. The most widely used SAT were opioid substitution (57%) and traditional/faith-based treatment (56%). Accessing substitution treatment (adjusted odds ratio [OR] = 5.8; 95% confidence interval [CI]: 2.5-13.9) or residential drug-free treatment (adjusted OR = 3.7; 95% CI: 1.4-9.7) was significantly associated with HIV testing, whereas accessing substitution treatment (adjusted OR = 3.8; 95% CI: 1.9-7.5) or other medical services (adjusted OR = 3.1; 95% CI: 1.1-8.7) was significantly associated with HIV treatment. There was no significant association between accessing traditional/faith-based treatment and HIV testing and treatment. CONCLUSION: Efforts should be made to link HIV services with traditional/faith-based treatment to increase the coverage of HIV programs.

A comparison of cryopreservation methods: Slow-cooling vs. rapid-cooling based on cell viability, oxidative stress, apoptosis, and CD34+ enumeration of human umbilical cord blood mononucleated cells.

BACKGROUND: The finding of human umbilical cord blood as one of the most likely sources of hematopoietic stem cells offers a less invasive alternative for the need of hematopoietic stem cell transplantation. Due to the once-in-a-life time chance of collecting it, an optimum cryopreservation method that can preserve the life and function of the cells contained is critically needed. METHODS: Until now, slow-cooling has been the routine method of cryopreservation; however, rapid-cooling offers a simple, efficient, and harmless method for preserving the life and function of the desired cells. Therefore, this study was conducted to compare the effectiveness of slow- and rapid-cooling to preserve umbilical cord blood of mononucleated cells suspected of containing hematopoietic stem cells. The parameters used in this study were differences in cell viability, malondialdehyde content, and apoptosis level. The identification of hematopoietic stem cells themselves was carried out by enumerating CD34+ in a flow cytometer. RESULTS: Our results showed that mononucleated cell viability after rapid-cooling (91.9%) was significantly higher than that after slow-cooling (75.5%), with a p value = 0.003. Interestingly, the malondialdehyde level in the mononucleated cell population after rapid-cooling (56.45 µM) was also significantly higher than that after slow-cooling (33.25 µM), with a p value < 0.001. The apoptosis level in rapid-cooling population (5.18%) was not significantly different from that of the mononucleated cell population that underwent slow-cooling (3.81%), with a p value = 0.138. However, CD34+ enumeration was much higher in the population that underwent slow-cooling (23.32 cell/µl) than in the one that underwent rapid-cooling (2.47 cell/µl), with a p value = 0.001. CONCLUSIONS: Rapid-cooling is a potential cryopreservation method to be used to preserve the umbilical cord blood of mononucleated cells, although further optimization of the number of CD34+ cells after rapid-cooling is critically needed.