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  1. Hazwani Ahmad Yusof, Rabinderjeet Singh, Zainuddin Zafarina, Kieron Rooney, Ahmad Munir Che Muhamed
    MyJurnal
    The purpose of this study was to examine the effect of the ACE I/D gene polymorphism on athletic status and physical performance of well-trained Malaysian athletes. The distribution of ACE I/D gene polymorphism among 180 well trained athletes was compared with 180 sedentary controls. 20 meter Yo-Yo intermittent recovery and leg strength tests were used to measure maximal oxygen consumption (VO2max) and leg strength value of athletes with different ACE I/D genotype, respectively. Chi-Square and one way ANOVA tests were used for data analysis. The II and DD genotype were more prevalent among the endurance athletes and the strength/ power athletes compared to the other groups, respectively (p=0.00). The VO2max was not significantly associated with ACE genotype in athlete (p=0.828). However, athletes with the DD genotype had recorded a greater result for leg strength (113.8 ± 36.2) than those with the II (96.2 ± 28.0) and the ID (112.2 ± 33.5) genotype (p=0.047). This study supports the notion that ACE I/D gene polymorphism might be a genetic factor associated with athletic status and strength performance among the Malaysian population. Future studies with more representation of endurance athletes might able to detect the association between I allele and endurance performance.
  2. Tengku Baharudin N, Jaafar H, Zainuddin Z
    Malays J Med Sci, 2012 Jan;19(1):36-42.
    PMID: 22977373 MyJurnal
    BACKGROUND: The mitochondrial DNA (mtDNA) 10398 polymorphism is hypothesised to alter a mitochondrial subunit of the electron transfer chain and is associated with several neurodegenerative disorders and cancers.

    METHODS: In this study, an mtDNA polymorphism at nucleotide position 10398 was screened in 101 Malay female patients with invasive breast cancer and 90 age-matched healthy female controls using minisequencing analysis.

    RESULTS: The Malay women with the 10398G variant showed a significantly increased risk of invasive breast cancer (OR = 2.29, 95% CI 1.25-4.20, P = 0.007). Immunohistochemistry analysis was conducted to investigate the effect of this polymorphism on the levels of apoptosis in breast cancer cells. The level of Bax (a pro-apoptotic protein) expression was significantly higher than that of Bcl-2 (an anti-apoptotic protein) in patients carrying the G allele (P = 0.016) but not in those carrying the A allele (P = 0.48).

    CONCLUSION: Based on these findings, we propose that the mtDNA 10398 polymorphism may be a potential risk marker for breast cancer susceptibility in the Malay population.

  3. Lim KT, Zahari Z, Amanah A, Zainuddin Z, Adenan MI
    Exp Parasitol, 2016 Mar;162:49-56.
    PMID: 26772786 DOI: 10.1016/j.exppara.2016.01.002
    To accelerate the discovery of novel leads for the treatment of Human African Trypanosomiasis (HAT), it is necessary to have a simple, robust and cost-effective assay to identify positive hits by high throughput whole cell screening. Most of the fluorescence assay was made in black plate however in this study the HTS assay developed in 384-well format using clear plate and black plate, for comparison. The HTS assay developed is simple, sensitive, reliable and reproducible in both types of plates. Assay robustness and reproducibility were determined under the optimized conditions in 384-well plate was well tolerated in the HTS assay, including percentage of coefficient of variation (% CV) of 4.68% and 4.74% in clear and black 384-well plate, signal-to-background ratio (S/B) of 12.75 in clear 384-well plate and 12.07 in black 384-well plate, Z' factor of 0.79 and 0.82 in clear 384-well plate and black 384-well plate, respectively and final concentration of 0.30% dimethylsulfoxide (DMSO) in both types of plate. Drug sensitivity was found to be comparable to the reported anti-trypanosomal assay in 96-well format. The reproducibility and sensitivity of this assay make it compliant to automated liquid handler use in HTS applications.
  4. Zainal SA, Md Daud MK, Abd Rahman N, Zainuddin Z, Alwi Z
    Int J Pediatr Otorhinolaryngol, 2012 Aug;76(8):1175-9.
    PMID: 22613756 DOI: 10.1016/j.ijporl.2012.04.027
    To identify the mutations in the GJB2 gene and to determine its association with non-syndromic hearing loss in Malays.
  5. Lim KT, Amanah A, Chear NJ, Zahari Z, Zainuddin Z, Adenan MI
    Exp Parasitol, 2018 Jan;184:57-66.
    PMID: 29175017 DOI: 10.1016/j.exppara.2017.11.007
    In our ongoing work searching for new trypanocidal lead compounds from Malaysian plants, two known piperidine alkaloids (+)-spectaline (1) and iso-6-spectaline (2) were isolated from the leaves of Senna spectabilis (sin. Cassia spectabilis). Analysis of the 1H and 13C NMR spectra showed that 1 and 2 presented analytical and spectroscopic data in full agreement with those published in the literature. All compounds were screened in vitro against Trypanosoma brucei rhodesiense in comparison to the standard drug pentamidine. Compound 1 and 2 inhibited growth of T. b. rhodesiense with an IC50 value of 0.41 ± 0.01 μM and 0.71 ± 0.01 μM, without toxic effect on L6 cells with associated a selectivity index of 134.92 and 123.74, respectively. These data show that piperidine alkaloids constitute a class of natural products that feature a broad spectrum of biological activities, and are potential templates for the development of new trypanocidal drugs. To our knowledge, the compounds are being reported for the first time to have inhibitory effects on T. b. rhodesiense. The ultrastructural alterations in the trypanosome induced by 1 and 2, leading to programmed cell death were characterized using electron microscopy. These alterations include wrinkling of the trypanosome surface, formation of autophagic vacuoles, disorganization of kinetoplast, and swelling of the mitochondria. These findings evidence a possible autophagic cell death.
  6. Gan CY, Zainuddin Z, Muhamad Noh H, Rahmat R, Mohd Akir F, Mahad NH, et al.
    Forensic Sci Int, 2019 Sep;302:109865.
    PMID: 31279278 DOI: 10.1016/j.forsciint.2019.06.023
    Consumption of curry containing poppy seeds has raised an issue concerning the opiate content in the urine that might exceed the cut-off value (300ng/mL). The main objective of this study was to examine the morphine and codeine contents in the urine of the consumers after partaking poppy seed-enriched curry in. The volunteers were asked to partake: (a) a single meal and their urines were collected within 24h, or (b) Two meals a day for three consecutive days and their urines were collected within 72h. Two different dosages were also tested in this study: (a) low dosage: 1g/100ml curry (containing 138μg of morphine and 66μg of codeine) and (b) high dosage: 5g/100ml curry (containing 690μg of morphine and 330μg of codeine). The subjects were randomised into the groups using the method of stratified randomization with age and gender groups as covariates. A total of 6 subjects was allocated for each group and placebos were used as control. Results showed that all subjects who consumed low dosage of poppy seeds either in single meal or multiple meals experiment were found negative. However, 1 out of 6high dosage subjects was confirmed positive at a period of 3-6h after the consumption of curry in the single meal study. This outlier maybe due to the lack of water consumption after consuming the curry, thus the low volume of urine was collected and the opiate was concentrated in the urine. On the other hand, 5 out of 6high dosage subjects in the multiple meals experiment were found positive. Majority of these subjects were found positive on the second and third day of the experiment after the second curry meal was consumed. The outlier (negative) in this group might be due to the high consumption of water throughout the experiment and the subject's urine volumes and frequency of urine collection were much higher compared to other subjects. From the result of this study, it can be concluded that partaking high dosages of poppy seed in curry could give a positive response (>300ng/ml+uncertainty of measurement) in the urine, and the water consumption after partaking curry has significant influence for the opiate contents in the urine.
  7. Macaulay V, Hill C, Achilli A, Rengo C, Clarke D, Meehan W, et al.
    Science, 2005 May 13;308(5724):1034-6.
    PMID: 15890885
    A recent dispersal of modern humans out of Africa is now widely accepted, but the routes taken across Eurasia are still disputed. We show that mitochondrial DNA variation in isolated "relict" populations in southeast Asia supports the view that there was only a single dispersal from Africa, most likely via a southern coastal route, through India and onward into southeast Asia and Australasia. There was an early offshoot, leading ultimately to the settlement of the Near East and Europe, but the main dispersal from India to Australia approximately 65,000 years ago was rapid, most likely taking only a few thousand years.
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