Norlelawati A.Talib

Beneficial effect of the leaves of Murraya koenigii (Linn.) Spreng (Rutaceae) on diabetes-induced renal damage in vivo

ETHNOPHARMACOLOGICAL RELEVANCE Murraya koenigii (Linn.) Spreng (curry leaf) is widely used as a nephroprotective agent in kidneys infirmities among diabetics by the traditional practitioners in Malaysia. However, the latter role of curry leaf has been grossly under reported and is yet to receive proper scientific evaluation. AIM OF THE STUDY The present study was designed to investigate the beneficial effect of the leaves of Murraya koenigii (Linn.) on diabetes-induced renal damage in vivo with regard to prove its efficacy by local traditional practitioners in the treatment of kidney frailties in diabetics. MATERIALS AND METHODS Aqueous (AQ) extract of the leaves of Murraya koenigii (Linn.) was administered to both normal and streptozotocin (STZ) induced diabetic male rats (Sprague-Dawley strain). Animals were divided into six groups (n=6) and treated with variable dose levels of AQ extract (200 and 400mg/kg body weight/day) for 30 days. At the end of 30 days, animals were sacrificed, blood was collected, processed and stored at -70°C for the zestimation of serum urea and creatinine, changes in plasma antioxidant capacity by FRAP assay, and glutathione peroxidase levels, in the normal and STZ-induced diabetic rats. Histological changes of the kidneys of these animals were also evaluated by light microscopy to determine the beneficial effect of the leaves. RESULTS Daily oral administration of variable dose levels of the AQ extract for 30 days, produced significant dose dependant decrease in serum urea and creatinine levels (p<0.001), and marked increase in the levels of plasma antioxidant capacity (p<0.01) in diabetic treated rats, compared to the control (non-diabetic) subjects. However, the normal treated rats showed minimal variation in these parameters in comparison to normal controls. Histological studies of the kidneys of these animals showed comparable tissue regeneration by the AQ extract. CONCLUSION The results of our study scientifically support the traditional belief for using the leaves of Murraya koenigii (Linn.) as adjuvant, in the treatment of pain disorders related to renal impairments among diabetics.

Frequencies of A(TA)7TAA, G71R, and G493R Mutations of the UGT1A1 Gene in the Malaysian Population

Background: Gilbert syndrome is caused by defects in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. These mutations differ among different populations and many of them have been found to be genetic risk factors for the development of neonatal jaundice. Objectives: The objective was to determine the frequencies of the following mutations in the UGT1A1 gene: A(TA)7TAA (the most common cause of Gilbert syndrome in Caucasians), G71R (more common in the Japanese and Taiwanese population), and G493R (described in a homozygous Malay woman with Crigler-Najjar syndrome type 2) in a group of Malaysian babies with hyperbilirubinemia and a group of normal controls. Methods: The GeneScan fragment analysis was used to detect the A(TA)7TAA variant. Mutation screening of both G71R and G493R was performed using denaturing high performance liquid chromatography. Results: Fourteen out of fifty-five neonates with hyperbilirubinemia (25%) carried the A(TA)7TAA mutation (10 heterozygous, 4 homozygous). Seven out of fifty controls (14%) carried this mutation (6 heterozygous, 1 homozygous). The allelic frequencies for hyperbilirubinemia and control patients were 16 and 8%, respectively (p = 0.20). Heterozygosity for the G71R mutation was almost equal among both groups (5.5% for hyperbilirubinemia patients and 6.0% for controls; p = 0.61). One subject (1.8%) in the hyperbilirubinemia group and none of the controls were heterozygous for the G493R mutation (p = 0.476). Conclusions: The A(TA)7TAA seems more common than the G71R and G493R mutations in the Malaysian population.

Screening for G71R mutation of the UGT1A1 gene in the Javanese‐Indonesian and Malay‐Malaysian populations

Abstract Background : There are significant differences in the prevalence and severity of neonatal jaundice among various populations. Recently, it has been reported that a mutation of the UGT1A1 gene, glycine to arginine at codon 71 (G71R), is related to the development of neonatal jaundice in East Asian populations. However, whether the G71R mutation contributes to the high incidence of neonatal jaundice in different Asian populations remains unknown. The authors screened for this mutation in the Javanese‐Indonesian and Malay‐Malaysian populations.

Disrupted-in-Schizophrenia-1 (DISC1) gene as genetic markers of schizophrenia susceptibility

Abstract Introduction There are substantial evidences that suggest DISC1 function in neurodevelopment thus support the locus as candidate gene of schizophrenia and potential target for the treatment of schizophrenia. Objectives: The aim of the study is to assess the association of DISC1 gene as genetic susceptibility marker of schizophrenia. Methods This is an unmatched case control study with the total of 225 unrelated schizophrenia patients and 350 control healthy individuals. Seventeenth SNPs within DISC1 gene were selected based on HapMap data constructed using the Haploview. The SNPs were genotyped using PCR-RFLP assay. Results & Discussion We found significant differences in genotypes and allele frequencies between patients and controls for two SNPs, rs4658971 [p=0.0303,OR=1.435(1.035–1.990)] and rs1538979 [p=0.036, OR=1.351(1.02–1.79)]. Conclusion The study provided significant evidence of DISC1 gene as a marker of schizophrenia susceptibility.

p16 Tumor Suppressor Gene Methylation in Diffuse Large B Cell Lymphoma: A Study of 88 Cases at Two Hospitals in the East Coast of Malaysia

Introduction: p16 gene plays an important role in the normal cell cycle regulation. Methylation of p16 has been reported to be one of the epigenetic events contributing to the pathogenesis of diffuse large B-cell lymphoma (DLBCL) which occurring at varying frequency. DLBCL is an aggressive and high-grade malignancy which accounts for approximately 30% of all non-Hodgkin lymphoma cases. However, little is known regarding the epigenetic alterations of p16 gene in DLBCL cases in Malaysia. Therefore, the objective of this study was to examine the status of p16 methylation in DLBCL. Methods: A total of 88 formalin-fixed paraffin-embedded DLBCL tissues retrieved from two hospitals located in the east coast of Malaysia, namely Hospital Tengku Ampuan Afzan (HTAA) Pahang and Hospital Universiti Sains Malaysia (HUSM) Kelantan, were chosen for this study. DNA specimens were isolated and subsequently subjected to bisulfite treatment prior to methylation specific-PCR. Two pairs of primers were used to amplify methylated and unmethylated regions of p16 gene. The PCR products were then separated using agarose gel electrophoresis and visualised under UV illumination. SPSS version 12.0 was utilised to perform all statistical analysis. Result: p16 methylation was detected in 65 of 88 (74%) samples. There was a significant association between p16 methylation status and patients aged >50 years old (p=0.04). Conclusion: Our study demonstrated that methylation of p16 tumor suppressor gene in our DLBCL cases is common and significantly increased among patients aged 50 years and above. Aging is known to be an important risk factor in the development of cancers and we speculate that this might be due to the increased transformation of malignant cells in aging cell population. However, this has yet to be confirmed with further research and correlate the findings with clinicopathological parameters.