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Fulltext The presence of single-nucleotide polymorphisms in Hps4 gene in a subset of schizophrenic patients in Pahang: a preliminary study

Norafiza Zainuddin, Maizatul Akma Mamat, Norlelawati A. Talib

International Journal of Allied Health Sciences, 2017;1(2):14-27.
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Schizophrenia is a devastating mental disorder that affects people’s normal life with heterogeneous features of its clinical presentation, as well as its molecular attribute. In order to identify the potential molecular aberration, particularly single nucleotide polymorphism (SNP) which could be important in the aetiology of schizophrenia, polymerase chain reaction (PCR)-DNA sequencing approach was utilized for targeting the exon (and intron) 9 of the Hermansky-Pudlak syndrome type 4 (HPS4) gene. DNAs were extracted from peripheral blood of nine schizophrenic patients and one normal individual prior to PCR-DNA sequencing. Following DNA sequencing, a SNP (A>G) which is rs713998 at nucleotide position 22618 of exon 9 of the HPS4 gene was observed in eight schizophrenia samples. Moreover, DNA sequencing results also revealed an intronic aberration/SNP which is rs3747129 (C>T) at nucleotide position 22789 of intron 9 of the HPS4 gene in four schizophrenia samples. A SNP which is rs739289 (G>T) at nucleotide position 22677 of the intron was also found in eight schizophrenia samples. The importance of both the exonic and intronic aberrations is yet to be confirmed with further research involving larger population and other relevant clinical parameters. That notwithstanding, these preliminary results suggested that single nucleotide aberrations, particularly SNPs might have a role in the development of schizophrenia
Fulltext Effects of Chronic Organic Arsenic Exposure on Rats Kidney - Light Microscopy and Electron Microscopy Study

Wan Muhamad SalahudinWan Salleh, Norlelawati A. Talib, Nor Zamzila Abdullah, Sanda Aung, Zunariah Buyong

IIUM Medical Journal Malaysia, 2019;18(102):41-0.
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Monosodium methylarsonate (MSMA) is an organic arsenical pesticide widely used in agriculture. Humans are exposed to arsenic through drinking water and anthropogenic activities. Exposure to inorganic arsenic has been linked with multiple health problems. However, studies focusing on chronic organic arsenic exposure and its adverse effects on kidney were limited. The purpose of current study was to determine the effects of chronic organic arsenic exposure in rats kidney by light and electron microscopy. Materials and Method: Thirty-six male SpragueDawley rats were divided into six groups (n=6); three control and three treatment group respectively. All the control group was given distilled water via oral gavage. The treatment group was given oral gavage of MSMA at 42.10 mg/kg body weight (BW) which is equivalent 1/30 LD50 of MSMA. The control and treatment groups were sacrificed at two month, four month and six months interval. Both kidneys harvested for light microscopy and electron microscopy study. Results: Showed progressive changes. The changes initially focal and became diffused involving glomerular; such as glomerular hypercellularity, glomerular shrinkage and dilated Bowman's space. Meanwhile, in proximal tubules, showed diminished brush borders, detachment of nucleus and basement membrane thickening. Electron microscopy showed flattened cell bodies of podocytes, effacement and fusion of podocytes foot processes, thickening of glomerular basement membrane, and discontinuity of brush border. The control and two-months treated group appeared to be normal. Conclusion: Chronic organic arsenic (MSMA) exposure induced chronic kidney injury.
Fulltext Liver Sinusoidal Endothelial Cell (LSEC) isolation following a liver profusion technique

Shahida Saharudin, Norlelawati A. Talib, Nor Zamzila Abdullah, Jamalludin Ab. Rahman, Zunariah Buyong

International Medical Journal Malaysia, 2017;16(11):27-27.
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Liver perfusion has been the standard method to digest and isolate liver
cells including liver sinusoidal endothelial cells (LSEC). Poor cannulating skills through
portal vein results in a waste of animal resource. Familiarization of both liver perfusion
technique and adhering strictly to aseptic technique during cell handling ensure high
cell yield, minimum morphology disruption and cell contamination. We aimed to present
a method of liver perfusion procedure followed by the isolation of LSEC. (Copied from article).
Fulltext Epigenetic changes of DRD2 gene in Pathogenesis of Schizophrenia

Nour El Huda Abd Rahim, Mohd Nabil Fikri Rahim, Norsidah Ku Zaifah, Hanisah Mohd Noor, Kartini Abdullah, Norlelawati A. Talib

International Medical Journal Malaysia, 2017;16(11):3-3.
MyJurnal

The dopamine hypothesis has earlier dominated the theories for the
development of schizophrenia based on the early pharmacologic evidence. The
antipsychotic drugs, among others, is thought to interfere with the function of the
dopamine D2 receptor (DRD2) resulting in clinical improvement. Accumulating evidence
suggest the role of epigenetic mechanisms in the pathophysiology of schizophrenia.
Despite this, specific evidence linking the DRD2 DNA methylation with schizophrenia is
insufficient mainly due to the poor accessibility and limited brain samples. Of late, new
data has suggested the global impact of DNA methylation in the development of
schizophrenia, thus methylation in the peripheral blood could infer changes in the brain.
The aim of this study was to assess the DRD2 DNA methylation in the peripheral blood of
schizophrenia.
Fulltext Acquired Platelet Dysfunction with Eosinophilia (APDE): Contemplating Physical Abuse

Muhamad Azamin Anua, Norlelawati A. Talib,, Nur Farah Izzati Misaridin, Asrar Abu Bakar, Mossad Abdelhak Mohamed, Taufiq Hidayat Hasan

IIUM Medical Journal Malaysia, 2019;18(102):11-0.
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APDE is an acquired, transient bleeding disorder characterised by normal platelet counts with eosinophilia. It was previously known as ‘nonthrombocytopenic purpura with eosinophilia’. We report a case of a 3-year-old boy with prolonged history of spontaneous unexplained bruising which was initially investigated by SCAN team for non-accidental injury (NAI). Case report: A 3-yearold boy attended clinic with a 4-month history of recurrent bruising. Parents were unsure of preceded illness, but he remained well with no history of trauma. He has unremarkable medical history and father is a thalassaemia carrier. Upon assessment in clinic, he was subsequently referred for suspected NAI and SCAN team led to a police report with a plan to review in 2-months. Parents later decided to bring the child for further medical assessments which revealed multiple bruises over both thighs, back of shoulder, loin and trunk with varying sizes and ages. They were all non-tender on palpation with no recognisable shapes or patterns. Blood results showed normal liver functions with slightly prolonged APTT 39.8 secs. He has normal platelet count with significant eosinophilia 2.2 x 10^9/L and occasional reactive lymphocytes. Reflecting this result, plan for platelet functions and von Willebrand tests were made. However, due to costs, we decided to treat the child with antihelminthic agent for possible parasitic infestation. He had 3 days course of albendazole and no further bruises appeared after 5 days of completing treatment. Discussion: The clinical presentation of APDE can mimic Idiopathic Thrombocytopenic Purpura in many ways yet normal platelet counts often leads to a delay in diagnosis. Reassuringly, the course of APDE is benign and no treatment is often required. Conclusion: Investigations however are costly, therefore treatment with anti-helminthic agent would be an alternative option in providing assurance to family and medical practitioners dealing with suspected cases.
Fulltext Prediction of clinical symptoms of Schizophrenia based on COMT Methylation marker

Nour El Huda Abd Rahim, Mohd Nabil Fikri Rahim, Norsidah Ku Zaifah, Hanisah Mohd Noor, Kartini Abdullah, Norlelawati A. Talib

International Medical Journal Malaysia, 2017;16(11):19-19.
MyJurnal

The dopamine hypothesis of schizophrenia is based on the fact that hyperdopaminergic
state is involved in causing psychosis and antipsychotic drugs block the
dopamine receptor. COMT regulates the homeostatic levels of neurotransmitter
dopamine in the synapses and plays a role in the neurocognitive function. The
dysregulation of dopamine in the prefrontal cortex influences the cognitive function and
the severity of the psychotic symptoms in schizophrenia. During epigenetic event,
methylated COMT gene may cause reduction in its expression and contribute to the
clinical presentation of schizophrenia. Therefore, the aim of this study was to assess the
feasibility of using COMT DNA methylation for the prediction of specific psychotic
presentation of schizophrenia. (Copied from article).
Fulltext MGMT and SPOCK2 Promoter Methylation in diffuse large B-Cell Lymphoma: a study in two tertiary health centres in the East Coast of Malaysia

Norafiza Zainuddin, Lailatul Jalilah Mohd Ridah, Aqilah Nabihah Omar, Norlelawati A. Talib, Naznin Muhammad, Faezahtul Arbaeyah Hussain

Jurnal Sains Kesihatan Malaysia, 2017;15(2):77-82.
MyJurnal

MGMT (O6
-Methylguanine-DNA Methyltransferase) suppresses tumor development by removing alkyl adduct, while
SPOCK2 (SPARC/Osteonectin CWCV and Kazal-like domains proteoglycan) abolishes the inhibition of membrane-type
matrix metalloproteinases (MT-MMP) which leads to angiogenesis. Hence, MGMT methylation may initiate malignant cells
transformation. In contrast, SPOCK2 methylation is hypothesized not to be a common event in diffuse large B-cell lymphoma
(DLBCL). In this study, we examined the methylation status of MGMT and SPOCK2 in DLBCL as in Malaysia the information
is extremely lacking. A total of 88 formalin-fixed paraffin-embedded tissue of patients diagnosed with DLBCL from the
year 2006 to 2013 were retrieved from Hospital Universiti Sains Malaysia, Kelantan and Hospital Tengku Ampuan Afzan,
Pahang. Methylation-specific polymerase chain reaction (MSP) was used to examine the methylation status of both genes.
Interestingly, methylation of MGMT was detected in all the 88 DLBCL samples, whereas SPOCK2 was found to be methylated
in 83 of 88 (94.3%) DLBCL cases. Our study showed a remarkably high percentage of promoter methylation of both
MGMT and SPOCK2 genes. Our finding also negates initial expectation that SPOCK2 methylation would be an uncommon
event in the majority of DLBCL cases. This study has shown a very high percentage of promoter methylation of MGMT and
SPOCK2 in the DLBCL cases studied by MSP, using archival lymphoma tissues. Nonetheless, additional research is needed
to quantitatively evaluate MGMT and SPOCK2 methylation, and to analyse gene expression and/or protein expression in
order to further understand the role of MGMT and SPOCK2 methylation in the pathogenesis of DLBCL.
Fulltext Anti-atherosclerotic effects of Eurycoma Longifolia (Tongkat Ali) in rats fed on High-fat diet

Fakhria Al-Joufi, Anil K. Saxena, Imad M. Al-Ani, Norlelawati A. Talib, Rafidah H. Mokhtar, Norsidah Ku -Zaifah

International Medical Journal Malaysia, 2017;16(1):83-90.
MyJurnal

Atherosclerosis in cardiovascular disease (CVD) is a growing health problem, especially in developing countries. Hyperlipidemia is known as a dominant risk factor for the development of atherosclerosis. This study was designed to investigate the effects of Eurycoma Longifolia (EL) also known as Malaysian Ginseng/ Tongkat Ali on the testosterone level, biochemical changes of lipid profile and intima media thickness (IMT) in rats fed on high-fat diet. Twenty young, adult male Sprague-Dawley (SD) rats were housed for 12 weeks. After one week of acclimatization, they were randomly divided into four groups of 5 animals each and treated for 12 weeks as follow: Group ND was given only normal diet, group NDEL was given normal diet and EL extracts (15mg/kg) dissolved in distilled water, group HFD was given only high fat diet and group HFDEL was given high fat diet and EL extracts (15mg/kg). Rats which were treated with EL (NDEL and HFDEL) showed a significant increase (p
Fulltext Disrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from Malaysia

Norlelawati AT, Kartini A, Norsidah K, Ramli M, Tariq AR, Wan Rohani WT

Psychiatry Investig, 2015 Jan;12(1):103-11.
PMID: 25670952 DOI: 10.4306/pi.2015.12.1.103

Even though the role of the DICS1 gene as a risk factor for schizophrenia is still unclear, there is substantial evidence from functional and cell biology studies that supports the connection of the gene with schizophrenia. The studies associating the DISC1 gene with schizophrenia in Asian populations are limited to East-Asian populations. Our study examined several DISC1 markers of schizophrenia that were identified in the Caucasian and East-Asian populations in Malaysia and assessed the role of rs2509382, which is located at 11q14.3, the mutual translocation region of the famous DISC1 translocation [t (1; 11) (p42.1; q14.3)].
Relationship of psychological symptoms, antipsychotics and social data with psychosocial function in schizophrenia patients in Malaysia

Norlelawati AT, Kartini A, Norsidah K, Ramli M, Wan Azizi WS, Tariq AR

Asia Pac Psychiatry, 2015 Mar;7(1):45-53.
PMID: 23857669 DOI: 10.1111/appy.12089

INTRODUCTION: The present study investigated the relationship between psychological symptoms and psychosocial function and the role of relevant sociodemographic data and antipsychotic use in the prediction of psychosocial function among multiracial schizophrenia outpatients in Malaysia.
METHODS: A total of 223 participants were recruited in this cross-sectional study conducted from December 2010 to April 2011. Psychological symptoms were assessed using the Positive and Negative Syndrome Scale whilst the psychosocial function was assessed using the Personal and Social Performance scale. Sociodemographic and treatment variables were gathered through interview or review of the medical records.
RESULTS: All dimensions of psychosocial functions were inversely correlated with Positive and Negative Syndrome Scale sub-domains. Only the disorganization sub-domain significantly predicts all dimensions of psychosocial function. For social data, body mass index and employment status were significant predictors of all dimensions of psychosocial functions. Typical antipsychotics significantly predict social function negatively as compared to sulpiride (β = -0.152, P = 0.028).
DISCUSSION: We found that the relationship between psychological symptoms and psychosocial functions were relatively consistent with the findings from the Caucasian population. Additionally, disorganization was the only significant predictor of all dimensions of psychosocial functions. This further emphasized the importance of cognition in psychosocial function. The roles of sulpiride, body mass index and employment status as predictors of psychosocial function were also discussed.
KEYWORDS: antipsychotics; psychosocial function; schizophrenia; symptoms
Study site: Psychiatric clinic, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia
Fulltext Preliminary study on association of beta2-adrenergic receptor polymorphism with hypertension in hypertensive subjects attending Balok Health Centre, Kuantan

Atia AE, Norsidah K, Nor Zamzila A, Rafidah Hanim M, Samsul D, Aznan MA, et al.

Med J Malaysia, 2012 Feb;67(1):25-30.
PMID: 22582545

Polymorphisms within the beta2-adrenergic receptor (ADRB2) gene have been repeatedly linked to hypertension. Among the ADRB2 polymorphisms detected, Arg16Gly and Gln27Glu codons are considered the two most important variations. The amino acid substitution at these codons may lead to abnormal regulation of ADRB2 activity. The aim of the present study was to assess the association between ADRB2 polymorphisms and hypertension. This case-control study consisted of 100 unrelated subjects (50 hypertensive and 50 matched normal controls). Arg16Gly and the Gln27Glu polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay. There were no significant evidence of association in allelic and genotypes distribution of Arg16Gly and Glu27Gln with blood pressure and hypertension. These findings suggest that the variation within codon 16 and 27 of ADRB2 gene were unlikely to confer genetic susceptibility for hypertension in our population samples.
DNA methylation of membrane-bound catechol-O-methyltransferase in Malaysian schizophrenia patients

Nour El Huda AR, Norsidah KZ, Nabil Fikri MR, Hanisah MN, Kartini A, Norlelawati AT

Psychiatry Clin Neurosci, 2018 Apr;72(4):266-279.
PMID: 29160620 DOI: 10.1111/pcn.12622

AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relations with the clinical variables of schizophrenia patients.
METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays. The extracted DNA was bisulfite converted, and the percentage methylation ratio value was calculated based on the results following a MethyLight protocol analysis.
RESULTS: The percentage methylation ratio of COMT was lower in schizophrenia than it was in the healthy controls (P
Relationship of selective complement markers with schizophrenia

Mohd Asyraf AJ, Nour El Huda AR, Hanisah MN, Norsidah KZ, Norlelawati AT

J Neuroimmunol, 2022 02 15;363:577793.
PMID: 34990981 DOI: 10.1016/j.jneuroim.2021.577793

Immune system dysregulation may be involved in schizophrenia, but biomarker studies have thus far reported inconsistent findings. The relationship of plasma levels of complement markers C3 and C4, with schizophrenia, sociodemographic and clinico-psychological factors were here studied in 183 patients and 212 controls. C3 and C4 levels were significantly higher in the patients and in subjects with elevated C-reactive protein (CRP), and positively correlated with body mass index (BMI) (p
Reelin (RELN) DNA methylation in the peripheral blood of schizophrenia

Nabil Fikri RM, Norlelawati AT, Nour El-Huda AR, Hanisah MN, Kartini A, Norsidah K, et al.

J Psychiatr Res, 2017 05;88:28-37.
PMID: 28086126 DOI: 10.1016/j.jpsychires.2016.12.020

The epigenetic changes of RELN that are involved in the development of dopaminergic neurons may fit the developmental theory of schizophrenia. However, evidence regarding the association of RELN DNA methylation with schizophrenia is far from sufficient, as studies have only been conducted on a few limited brain samples. As DNA methylation in the peripheral blood may mirror the changes taking place in the brain, the use of peripheral blood for a DNA methylation study in schizophrenia is feasible due to the scarcity of brain samples. Therefore, the aim of our study was to examine the relationship of DNA methylation levels of RELN promoters with schizophrenia using genomic DNA derived from the peripheral blood of patients with the disorder. The case control studies consisted of 110 schizophrenia participants and 122 healthy controls who had been recruited from the same district. After bisufhite conversion, the methylation levels of the DNA samples were calculated based on their differences of the Cq values assayed using the highly sensitive real-time MethyLight TaqMan® procedure. A significantly higher level of methylation of the RELN promoter was found in patients with schizophrenia compared to controls (p = 0.005) and also in males compared with females (p = 0.004). Subsequently, the RELN expression of the methylated group was 25 fold less than that of the non-methylated group. Based upon the assumption of parallel methylation changes in the brain and peripheral blood, we concluded that RELN DNA methylation might contribute to the pathogenesis of schizophrenia. However, the definite effects of methylation on RELN function during development and also in adult life still require further elaboration.

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