1.The synthetic molecules YK51 and YK73 attenuate replication of dengue virus serotype 2
Gan, C.S. ; Yusof, R. ; Othman, S.
Tropical Biomedicine 2017;34(2):270-283
Dengue virus infection has been posing alarming economic and social burden on
affected nations. It is estimated that 50-100 million dengue infections occur annually with
over 2.5 billion people at risk for endemic transmission. In the effort to develop effective
antiviral agents, we previously reported potential antiviral activities from selected array of
natural products and compounds against dengue virus serotype 2 (DV2). In this study, we
report the synthesis of two efficacious novel compounds, YK51 and YK73, and their activities
against DV2 replication. Both compounds were chemically synthesised from nicotinic acid
using a modified method for the synthesis of dihydropyridine. The products were tested with
cell-based assays against DV2 followed by a serine protease assay. As a result, both YK51 and
YK73 exhibited intriguing antiviral properties with EC50 of 3.2 and 2.4 µM, respectively. In
addition, YK51 and YK73 were found to attenuate the synthesis of intracellular viral RNA and
protect the switching of non-classic mechanism of protein translation. These compounds
demonstrated inhibitory properties toward the activity of DV2 serine protease in a dose
dependent manner. These findings demonstrate that both YK51 and YK73 serve as DV2 serine
protease inhibitors that abrogate viral RNA synthesis and translation. Further investigation
on these compounds to corroborate its therapeutic properties towards dengue is warranted.
2.Oligodontia: challenges in dental rehabilitation
Nur Adilah Ahmad Othman ; S. Nagarajan M.P. Sockalingam
Archives of Orofacial Sciences 2014;9(2):96-100
Oligodontia, although rare, may have significant impact on the quality of life of those affected with it. Provision of restorative treatment for these patients can be very challenging and demanding for clinicians, especially during the active growth phase. Nevertheless, the dental needs of these patients are real and should be addressed appropriately. The present case report described a restorative rehabilitative plan and execution of different restorative treatment modalities in a 14-year-old patient with oligodontia. The challenges faced in the provision of dental care were highlighted. The treatment outcome showed a positive psychological impact on the well-being of the patient based on parental observations.
Anodontia
3.Real space flight travel is associated with ultrastructural changes, cytoskeletal disruption and premature senescence of HUVEC
MY Kapitonova ; S Muid ; GRA Froemming ; WNW Yusoff ; S Othman ; AM Ali ; HM Nawawi
The Malaysian Journal of Pathology 2012;34(2):103-113
Microgravity, hypergravity, vibration, ionizing radiation and temperature fluctuations are major factors
of outer space flight affecting human organs and tissues. There are several reports on the effect
of space flight on different human cell types of mesenchymal origin while information regarding
changes to vascular endothelial cells is scarce.
Ultrastructural and cytophysiological features of macrovascular endothelial cells in outer space
flight and their persistence during subsequent culturing were demonstrated in the present investigation.
At the end of the space flight, endothelial cells displayed profound changes indicating cytoskeletal
lesions and increased cell membrane permeability. Readapted cells of subsequent passages
exhibited persisting cytoskeletal changes, decreased metabolism and cell growth indicating cellular
senescence.
4.Alteration of cell cytoskeleton and functions of cell recovery of normal human osteoblast cells caused by factors associated with real space flight.
Kapitonova, My ; Salim, N ; Othman, S ; Muhd Kamauzaman, Tmht ; Ali, Am ; Nawawi, Hm ; Froemming, Gra
The Malaysian Journal of Pathology 2013;35(2):153-63
Experiments involving short-term space flight have shown an adverse effect on the physiology, morphology and functions of cells investigated. The causes for this effect on cells are: microgravity, temperature fluctuations, mechanical stress, hypergravity, nutrient restriction and others. However, the extent to which these adverse effects can be repaired by short-term space flown cells when recultured in conditions of normal gravity remains unclear. Therefore this study aimed to investigate the effect of short-term spaceflight on cytoskeleton distribution and recovery of cell functions of normal human osteoblast cells. The ultrastructure was evaluated using ESEM. Fluorescent staining was done using Hoechst, Mito Tracker CMXRos and Tubulin Tracker Green for cytoskeleton. Gene expression of cell functions was quantified using qPCR. As a result, recovered cells did not show any apoptotic markers when compared with control. Tubulin volume density (p<0.001) was decreased significantly when compared to control, while mitochondria volume density was insignificantly elevated. Gene expression for IL-6 (p<0.05) and sVCAM-1 (p<0.001) was significantly decreased while alkaline phosphatase (p<0.001), osteocalcin and sICAM (p<0.05) were significantly increased in the recovered cells compared to the control ones. The changes in gene and protein expression of collagen 1A, osteonectin, osteoprotegerin and beta-actin, caused by short-term spaceflight, were statistically not significant. These data indicate that short term space flight causes morphological changes in osteoblast cells which are consistent with hypertrophy, reduced cell differentiation and increased release of monocyte attracting proteins. The long-term effect of these changes on bone density and remodeling requires more detailed studies.
5.Expression analysis of SIR2 and SAPs1-4 gene expression in Candida albicans treated with allicin compared tofluconazole
Alireza Khodavandi ; Fahimeh Alizadeh ; Nabil S Harmal ; Shiran M Sidik, ; Fauziah Othman ; Zamberi Sekawi ; Pei Pei Chong,
Tropical Biomedicine 2011;28(3):589-598
One of the main factors for virulence of fungus such as Candida albicans is the
ability to change its morphology from yeast to hyphae. Allicin, one of the volatile sulfur-oil
compounds from freshly crushed garlic, has a variety of antifungal activities. In this study,
the effect of allicin on growth and hyphae production in C. albicans as compared to fluconazole,
an antifungal drug was investigated using survival time in vitro and microscopic image at
different time intervals. Additionally, the expression of selected genes involved in hyphae
formation and development such as SIR2 and SAP1-4 was evaluated by semi-quantitative RTPCR
and relative real time RT-PCR. Allicin was shown to down-regulate the expression of
SIR2 (5.54 fold), similar to fluconazole (3.48 fold) at 2x MIC concentrations. Interestingly,
allicin had no effect on SAPs1-4 expression, whereas fluconazole was able to suppress SAP4
expression. Our findings showed that allicin was effective in suppressing hyphae development
of C. albicans to an extent that is sometimes equal or more than fluconazole. Moreover, allicin
and fluconazole seemed to share a common anti-Candida mechanism through inhibition of
SIR2 gene, while fluconazole appeared to also exert its fungistatic effect through another
pathway that involved SAP4 suppression.
6.Optimal protein extraction methods from diverse sample types for protein profiling by using Two-Dimensional Electrophoresis (2DE)
Tan, A.A. ; Azman, S.N. ; Abdul Rani, N.R. ; Kua, B.C. ; Sasidharan, S. ; Kiew, L.V. ; Othman, N. ; Noordin, R. ; Chen, Y.*
Tropical Biomedicine 2011;28(3):620-629
There is a great diversity of protein samples types and origins, therefore the
optimal procedure for each sample type must be determined empirically. In order to obtain a
reproducible and complete sample presentation which view as many proteins as possible on
the desired 2DE gel, it is critical to perform additional sample preparation steps to improve
the quality of the final results, yet without selectively losing the proteins. To address this, we
developed a general method that is suitable for diverse sample types based on phenolchloroform
extraction method (represented by TRI reagent). This method was found to yield
good results when used to analyze human breast cancer cell line (MCF-7), Vibrio cholerae,
Cryptocaryon irritans cyst and liver abscess fat tissue. These types represent cell line,
bacteria, parasite cyst and pus respectively. For each type of samples, several attempts were
made to methodically compare protein isolation methods using TRI-reagent Kit, EasyBlue Kit,
PRO-PREPTM Protein Extraction Solution and lysis buffer. The most useful protocol allows the
extraction and separation of a wide diversity of protein samples that is reproducible among
repeated experiments. Our results demonstrated that the modified TRI-reagent Kit had the
highest protein yield as well as the greatest number of total proteins spots count for all type
of samples. Distinctive differences in spot patterns were also observed in the 2DE gel of
different extraction methods used for each type of sample.
7.Genetic Markers for Idiopathic Scoliosis in Arab Population: A Pilot Study.
Abdallah S AL-OMRAN ; Mir SADAT-ALI ; Abdallah A AL-OTHMAN
Asian Spine Journal 2009;3(2):53-57
STUDY DESIGN: Cross-sectional screening. PURPOSE: This study was conducted to determine if there is any association of the three microsatellite markers on chromosome 19p 13.3 in unrelated Saudi Arabian girls who were suffering with adolescent idiopathic scoliosis (AIS) and their healthy siblings. OVERVIEW OF LITERATURE: The genetic influence on the development of familial scoliosis has been previously described, but the genetic influence on AIS still remains unknown. Three microsatellite markers (D19S216, D19S894, and DS1034) of chromosome 19p 13.3 were reported to be significantly associated with familial scoliosis. This cross-sectional screening was carried out in AIS patients and their siblings. METHODS: For eleven Saudi Arabian girls who were treated for AIS and their 11 siblings, we performed a linkage analysis using parametric and nonparametric methods and using GENEHUNTER ver. 2.1. Multipoint linkage analysis was used to specify an autosomal dominant trait with a gene frequency of 0.01 at the genotypic and the allelic levels. One sided Fisher's exact tests were used in the analysis of the contingency tables for the D19S216, D19S894 and DS1034 markers. RESULTS: The analysis between the patient group and the healthy siblings showed that at the genotypic level there was a significant association of the markers and scoliosis (D19S894 [p=0.036], D19S216 [p=0.004], and DS1034 [p=0.013]). Yet at the allelic level, there was no statistically significant association of the markers between the AIS patients and their siblings. CONCLUSIONS: Our pilot study shows that there is a genetic influence between the AIS patients and the siblings. We believe large scale genetic screening is warranted for the patients with AIS to identify beyond any doubt the influence of these markers.
Adolescent
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Arabs
;
Genes, vif
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Genetic Markers
;
Genetic Testing
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Humans
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Mass Screening
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Microsatellite Repeats
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Pilot Projects
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Scoliosis
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Siblings
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Stress, Psychological
8.Cytotoxicity and scanning electron microscopy study of gentamycin-coated HA effect on biofilm.
Au LF ; Othman F ; Mustaffa R ; Vidyadaran S ; Rahmat A ; Besar I ; Akim AM ; Khan MA ; Saidi M ; Shamsudin MN ; Froemming GA ; Ishak AK
The Medical Journal of Malaysia 2008;63 Suppl A():16-17
Biofilms are adherent, multi-layered colonies of bacteria that are typically more resistant to the host immune response and routine antibiotic therapy. HA biomaterial comprises of a single-phased hydroxyapatite scaffold with interconnected pore structure. The device is designed as osteoconductive space filler to be gently packed into bony voids or gaps following tooth extraction or any surgical procedure. Gentamycin-coated biomaterial (locally made hydroxyapatite) was evaluated to reduce or eradicate the biofilm on the implant materials. The results indicated that the HA coated with gentamycin was biocompatible to human osteoblast cell line and the biofilm has been reduced after being treated with different concentrations of gentamycin-coated hydroxyapatite (HA).
10.Twin reverse arterial perfusion sequence.
N A Z Nik LAH ; C A Che YAAKOB ; M S OTHMAN ; N M Z Nik MAHMOOD
Singapore medical journal 2007;48(12):e335-7
Twin reverse arterial perfusion sequence occurs in approximately one percent of monochorionic twins. This condition is always fatal for the recipient twin and carries a high mortality rate for the pump twin. Various treatment options are described, but management is continually evolving with the publication of new data. We report an acardiac acephalic monochorionic twin who was diagnosed at 31 weeks gestation. Serial ultrasonographical examinations of the normal pump twin showed intrauterine growth restriction but with no evidence of heart failure. A healthy pump twin was delivered by caesarean section at 34 weeks.
Abnormalities, Multiple
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diagnostic imaging
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Cesarean Section
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Female
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Fetofetal Transfusion
;
diagnostic imaging
;
Follow-Up Studies
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Gestational Age
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Heart Defects, Congenital
;
diagnostic imaging
;
Humans
;
Infant, Newborn
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Pregnancy
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Pregnancy Outcome
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Pregnancy Reduction, Multifetal
;
methods
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Pregnancy, Multiple
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Twins, Monozygotic
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Ultrasonography, Prenatal