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Formation and characterization of pDNA-loaded alginate microspheres for oral administration in mice

Nograles N, Abdullah S, Shamsudin MN, Billa N, Rosli R

J Biosci Bioeng, 2012 Feb;113(2):133-40.
PMID: 22093752 DOI: 10.1016/j.jbiosc.2011.10.003

Alginate, a natural polysaccharide, was explored in this study as an oral delivery vehicle of a mammalian expression vector into the murine intestinal mucosa. Alginate microspheres were produced through water-in-oil (W/O) emulsification method. Average diameter sizes of microspheres were 46.88 μm±3.07 μm with significant size reduction upon utilization of 1.0% Span80. Plasmid DNA (pDNA) carrying green fluorescent protein reporter gene (GFP), pVAX-GFP, was encapsulated within microspheres at efficiencies of 72.9 to 74.4%, carrying maximum load of 6 μg pDNA. Alginate microspheres demonstrated shrinkage in pH 1.2 and swelling in pH 9.0 with pDNA release about twice the amount released in acidic environment. Oral delivery of pVAX-GFP loaded-microspheres, at 50 μg, 100 μg and 150 μg dose, was performed on BALB/c mice. Tissue biodistribution, investigated through flow cytometric analysis, demonstrated GFP positive intestinal cells (<1.0%) with 1.3-fold higher levels for the 100 μg dose; therefore suggesting feasibility of the approach for oral gene delivery and vaccination.
Transcriptome profiling of endothelial cells during infections with high and low densities of C. albicans cells

Lim CS, Rosli R, Seow HF, Chong PP

Int J Med Microbiol, 2011 Aug;301(6):536-46.
PMID: 21371935 DOI: 10.1016/j.ijmm.2010.12.002

Systemic infections of Candida albicans, the most prevalent fungal pathogen in humans, are on the rise in recent years. However, the exact mode of pathogenesis of this fungus is still not well elucidated. Previous studies using C. albicans mutants locked into the yeast form via gene deletion found that this form was avirulent and did not induce significant differential expression of host genes in vitro. In this study, a high density of C. albicans was used to infect human umbilical vein endothelial cells (HUVEC), resulting in yeast-form infections, whilst a low density of C. albicans resulted in hyphae infections. Transcriptional profiling of HUVEC response to these infections showed that high densities of C. albicans induced a stronger, broader transcriptional response from HUVEC than low densities of C. albicans infection. Many of the genes that were significantly differentially expressed were involved in apoptosis and cell death. In addition, conditioned media from the high-density infections caused a significant reduction in HUVEC viability, suggesting that certain molecules released during C. albicans and HUVEC interactions were capable of causing cell death. This study has shown that C. albicans yeast-forms, at high densities, cannot be dismissed as avirulent, but instead could possibly contribute to C. albicans pathogenesis.
Using fuzzy association rule mining in cancer classification

Mahmoodian H, Hamiruce Marhaban M, Abdulrahim R, Rosli R, Saripan I

Australas Phys Eng Sci Med, 2011 Apr;34(1):41-54.
PMID: 21327594 DOI: 10.1007/s13246-011-0054-8

The classification of the cancer tumors based on gene expression profiles has been extensively studied in numbers of studies. A wide variety of cancer datasets have been implemented by the various methods of gene selection and classification to identify the behavior of the genes in tumors and find the relationships between them and outcome of diseases. Interpretability of the model, which is developed by fuzzy rules and linguistic variables in this study, has been rarely considered. In addition, creating a fuzzy classifier with high performance in classification that uses a subset of significant genes which have been selected by different types of gene selection methods is another goal of this study. A new algorithm has been developed to identify the fuzzy rules and significant genes based on fuzzy association rule mining. At first, different subset of genes which have been selected by different methods, were used to generate primary fuzzy classifiers separately and then proposed algorithm was implemented to mix the genes which have been associated in the primary classifiers and generate a new classifier. The results show that fuzzy classifier can classify the tumors with high performance while presenting the relationships between the genes by linguistic variables.
Fulltext Induced pluripotent stem cells: history, properties and potential applications

Nordin N, Lai MI, Veerakumarasivam A, Ramasamy R, Abdullah S, Wendy-Yeo WY, et al.

Med J Malaysia, 2011 Mar;66(1):4-9.
PMID: 23765134 MyJurnal

The development of induced pluripotent stem cells (iPSCs) has been met with much enthusiasm and hailed as a breakthrough discovery by the scientific and research communities amidst the divisive and ongoing debates surrounding human embryonic stem cells (hESC) research. The discovery reveals the fact that embryonic pluripotency can be generated from adult somatic cells by the induction of appropriate transcriptional factor genes essential for maintaining the pluripotency. They provide an alternative source for pluripotent stem cells, thus representing a powerful new research tool besides their potential application in the field of regenerative medicine. In this review, the historical background of iPSCs generation will be discussed together with their properties and characteristics as well as their potential therapeutic applications.
Newcastle disease virus infection promotes Bax redistribution to mitochondria and cell death in HeLa cells

Molouki A, Hsu YT, Jahanshiri F, Rosli R, Yusoff K

Intervirology, 2010;53(2):87-94.
PMID: 19955813 DOI: 10.1159/000264198

Newcastle disease virus (NDV) is an avian paramyxovirus that has gained a lot of interest in cancer viro-therapeutic applications because of its ability to selectively induce apoptosis in human cancer cells. However, the underlying mechanisms by which NDV induces apoptosis in human cancer cells are still not entirely understood.
An alternative Candida spp. cell wall disruption method using a basic sorbitol lysis buffer and glass beads

Lim CS, Tung CH, Rosli R, Chong PP

J Microbiol Methods, 2008 Dec;75(3):576-8.
PMID: 18727938 DOI: 10.1016/j.mimet.2008.07.026

This report describes a modified, cost-effective method of cell wall disruption for the yeast Candida spp., which employs the use of glass beads in a simple sorbitol lysis buffer. This method can be used in conjunction with a commercial RNA or genomic DNA isolation method to obtain high-quality RNA or DNA.
DNA vaccine constructs against enterovirus 71 elicit immune response in mice

Tung WS, Bakar SA, Sekawi Z, Rosli R

Genet Vaccines Ther, 2007;5:6.
PMID: 17445254

Enterovirus 71 (EV71) is a major causative viral agent responsible for large outbreaks of hand, foot and mouth disease (HFMD), a common rash illness in children and infants. There is no effective antiviral treatment for severe EV71 infections and no vaccine is available. The objectives of this study were to design and construct a DNA vaccine against Enterovirus 71 using the viral capsid protein (VP1) gene of EV71 and to verify the functionality of the DNA vaccine in vitro and in vivo.
Cellulose acetate phthalate microencapsulation and delivery of plasmid DNA to the intestines

Hanafi A, Nograles N, Abdullah S, Shamsudin MN, Rosli R

J Pharm Sci, 2013 Feb;102(2):617-26.
PMID: 23192729 DOI: 10.1002/jps.23389

Cellulose acetate phthalate (CAP) microcapsules were formulated to deliver plasmid DNA (pDNA) to the intestines. The microcapsules were characterized and were found to have an average diameter of 44.33 ± 30.22 μm, and were observed to be spherical with smooth surface. The method to extract pDNA from CAP was modified to study the release profile of the pDNA. The encapsulated pDNA was found to be stable. Exposure to the acidic and basic pH conditions, which simulates the pH environment in the stomach and the intestines, showed that the release occurred in a stable manner in the former, whereas it was robust in the latter. The loading capacity and encapsulation efficiency of the microcapsules were low but the CAP recovery yield was high which indicates that the microcapsules were efficiently formed but the loading of pDNA can be improved. In vitro transfection study in 293FT cells showed that there was a significant percentage of green-fluorescent-protein-positive cells as a result of efficient transfection from CAP-encapsulated pDNA. Biodistribution studies in BALB/c mice indicate that DNA was released at the stomach and intestinal regions. CAP microcapsules loaded with pDNA, as described in this study, may be useful for potential gene delivery to the intestines for prophylactic or therapeutic measures for gastrointestinal diseases.
Fulltext Angiotensinogen M235T gene variants and its association with essential hypertension and plasma renin activity in Malaysian subjects: a case control study

Say YH, Ling KH, Duraisamy G, Isaac S, Rosli R

BMC Cardiovasc Disord, 2005;5(1):7.
PMID: 15811183

Essential hypertension is a major public health concern worldwide where its prevalence accounts for various cerebrovascular diseases. A common molecular variant of angiotensinogen (AGT), the precursor of potent vasoactive hormone angiotensin II, has been incriminated as a marker for genetic predisposition to essential hypertension in some ethnics. This case-control study was designed not only to determine the association of the AGT M235T gene variants with essential hypertension, but also its relationship to Plasma Renin Activity (PRA) in subjects attending the Health Clinic, Kuala Lumpur, Malaysia.
Fulltext Genotypic and Phenotypic Detection of AmpC β-lactamases in Enterobacter spp. Isolated from a Teaching Hospital in Malaysia

Mohd Khari FI, Karunakaran R, Rosli R, Tee Tay S

PLoS One, 2016;11(3):e0150643.
PMID: 26963619 DOI: 10.1371/journal.pone.0150643

OBJECTIVES: The objective of this study was to determine the occurrence of chromosomal and plasmid-mediated β-lactamases (AmpC) genes in a collection of Malaysian isolates of Enterobacter species. Several phenotypic tests for detection of AmpC production of Enterobacter spp. were evaluated and the agreements between tests were determined.
METHODS: Antimicrobial susceptibility profiles for 117 Enterobacter clinical isolates obtained from the Medical Microbiology Diagnostic Laboratory, University Malaya Medical Centre, Malaysia, from November 2012-February 2014 were determined in accordance to CLSI guidelines. AmpC genes were detected using a multiplex PCR assay targeting the MIR/ACT gene (closely related to chromosomal EBC family gene) and other plasmid-mediated genes, including DHA, MOX, CMY, ACC, and FOX. The AmpC β-lactamase production of the isolates was assessed using cefoxitin disk screening test, D69C AmpC detection set, cefoxitin-cloxacillin double disk synergy test (CC-DDS) and AmpC induction test.
RESULTS: Among the Enterobacter isolates in this study, 39.3% were resistant to cefotaxime and ceftriaxone and 23.9% were resistant to ceftazidime. Ten (8.5%) of the isolates were resistant to cefepime, and one isolate was resistant to meropenem. Chromosomal EBC family gene was amplified from 36 (47.4%) E. cloacae and three (25%) E. asburiae. A novel blaDHA type plasmid-mediated AmpC gene was identified for the first time from an E. cloacae isolate. AmpC β-lactamase production was detected in 99 (89.2%) of 111 potential AmpC β-lactamase producers (positive in cefoxitin disk screening) using D69C AmpC detection set. The detection rates were lower with CC-DDS (80.2%) and AmpC induction tests (50.5%). There was low agreement between the D69C AmpC detection set and the other two phenotypic tests. Of the 40 isolates with AmpC genes detected in this study, 87.5%, 77.5% and 50.0% of these isolates were positive by the D69C AmpC detection set, CC-DDS and AmpC induction tests, respectively.
CONCLUSIONS: Besides MIR/ACT gene, a novel plasmid-mediated AmpC gene belonging to the DHA-type was identified in this study. Low agreement was noted between the D69C AmpC detection set and two other phenotypic tests for detection of AmpC production in Enterobacter spp. As plasmid-mediated genes may serve as the reservoir for the emergence of antibiotic resistance in a clinical setting, surveillance and infection control measures are necessary to limit the spread of these genes in the hospital.
Fulltext DNA methylation and histone modifications are the molecular lock in lentivirally transduced hematopoietic progenitor cells

Ngai SC, Rosli R, Al Abbar A, Abdullah S

Biomed Res Int, 2015;2015:346134.
PMID: 25961011 DOI: 10.1155/2015/346134

Stable introduction of a functional gene in hematopoietic progenitor cells (HPCs) has appeared to be an alternative approach to correct genetically linked blood diseases. However, it is still unclear whether lentiviral vector (LV) is subjected to gene silencing in HPCs. Here, we show that LV carrying green fluorescent protein (GFP) reporter gene driven by cytomegalovirus (CMV) promoter was subjected to transgene silencing after transduction into HPCs. This phenomenon was not due to the deletion of proviral copy number. Study using DNA demethylating agent and histone deacetylase (HDAC) inhibitor showed that the drugs could either prevent or reverse the silencing effect. Using sodium bisulfite sequencing and chromatin immunoprecipitation (ChIP) assay, we demonstrated that DNA methylation occurred soon after LV transduction. At the highest level of gene expression, CMV promoter was acetylated and was in a euchromatin state, while GFP reporter gene was acetylated but was strangely in a heterochromatin state. When the expression declined, CMV promoter underwent transition from acetylated and euchromatic state to a heterochromatic state, while the GFP reporter gene was in deacetylated and heterochromatic state. With these, we verify that DNA methylation and dynamic histone modifications lead to transgene silencing in HPCs transduced with LV.
Fulltext The prevalence of MTHFR 677C-->T missense mutation, total plasma homocysteine levels and associated risk factors in Malay subjects

Ling KH, Rosli R, Duraisamy G, Mohd Nasir MT

Med J Malaysia, 2003 Jun;58(2):243-54.
PMID: 14569745

The missense mutation of the methylenetetrahydrofolate reductase (MTHFR) gene 677C-->T is associated with modest elevation of homocysteine levels. The bio-ecogenetics factors of total homocysteine levels (tHcy) were investigated in a cross sectional study involving 53 randomly selected healthy Malay subjects. Results indicated that the prevalence of the homozygous 677T/T was 3.8% and heterozygous 677C/T was 17.0%. The levels of tHcy was higher in subjects aged more than 50 years (n = 7, 11.53 +/- 4.45 mumol/l) and in males (10.99 +/- 3.77 mumol/l) especially smoking males (12.19 +/- 3.62 mumol/l). THcy levels were low in the 3 pregnant subjects (4.44 mumol/l, p = 0.036) who were under folate supplementation.
Fulltext In Vivo Anti-Tumor Effects of Citral on 4T1 Breast Cancer Cells via Induction of Apoptosis and Downregulation of Aldehyde Dehydrogenase Activity

Nigjeh SE, Yeap SK, Nordin N, Rahman H, Rosli R

Molecules, 2019 Sep 05;24(18).
PMID: 31492037 DOI: 10.3390/molecules24183241

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among females globally. The tumorigenic activities of cancer cells such as aldehyde dehydrogenase (ALDH) activity and differentiation have contributed to relapse and eventual mortality in breast cancer. Thus, current drug discovery research is focused on targeting breast cancer cells with ALDH activity and their capacity to form secondary tumors. Citral (3,7-dimethyl-2,6-octadienal), from lemon grass (Cymbopogoncitrates), has been previously reported to have a cytotoxic effect on breast cancer cells. Hence, this study was conducted to evaluate the in vivo effect of citral in targeting ALDH activity of breast cancer cells. BALB/c mice were challenged with 4T1 breast cancer cells followed by daily oral feeding of 50 mg/kg citral or distilled water for two weeks. The population of ALDH+ tumor cells and their capacity to form secondary tumors in both untreated and citral treated 4T1 challenged mice were assessed by Aldefluor assay and tumor growth upon cell reimplantation in normal mice, respectively. Citral treatment reduced the size and number of cells with ALDH+ activity of the tumors in 4T1-challenged BALB/c mice. Moreover, citral-treated mice were also observed with smaller tumor size and delayed tumorigenicity after reimplantation of the primary tumor cells into normal mice. These findings support the antitumor effect of citral in targeting ALDH+ cells and tumor recurrence in breast cancer cells.
Antioxidant Potential and Angiotensin-Converting Enzyme (ACE) Inhibitory Activity of Orotic Acid-Loaded Gum Arabic Nanoparticles

Hassani A, Hussain SA, Abdullah N, Kamarudin S, Rosli R

AAPS PharmSciTech, 2019 Jan 07;20(2):53.
PMID: 30617521 DOI: 10.1208/s12249-018-1238-2

Orotic acid (OA) nanoparticles were prepared using the freeze-drying method. The antihypertensive activity and antioxidant capacity of OA and orotic acid-loaded gum arabic nanoparticles (OAGANPs) were examined using the angiotensin-converting enzyme (ACE), 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO), and β-carotene assays, as well as the quantification of total phenolic content (TPC). The DPPH and NO scavenging activities of OAGANPs were significantly higher than those of the OA solution. The β-carotene bleaching assay of OAGANPs showed a dose-dependent trend, while 500 μg/ml was significantly more effective than the other concentrations, which exerted 63.4% of the antioxidant activity. The in vitro antihypertensive assay revealed that the OAGANPs exhibited the most potent ACE inhibition activity, when compared to the OA solution. Hence, results revealed the potential of preparing the OA as a nanoparticle formulation in enhancing the antioxidant and antihypertensive properties compared to the OA solution.
Epicatechin and scopoletin-rich Morinda citrifolia leaf ameliorated leukemia via anti-inflammatory, anti-angiogenesis, and apoptosis pathways in vitro and in vivo

Ahmadi N, Mohamed S, Sulaiman Rahman H, Rosli R

J Food Biochem, 2019 07;43(7):e12868.
PMID: 31353737 DOI: 10.1111/jfbc.12868

The anti-leukemia mechanisms of Morinda citrifolia L. leaf extract were investigated on human Jurkat leukemia cells and in leukemia-induced BALB/c mice. The leukemia-induced mice were fed daily with the extract (100 or 200 mg/kg BW) and compared to ATRA (All-trans-retinoic-acid; 5 mg/kg BW). After 4 weeks' treatment, the extract (standardized to epicatechin and scopoletin), arrested Jurkat cell-cycle at the G0/G1 phase and activated the caspase-3 and caspase-8 (death-receptor extrinsic pathways). The extract dose-dependently reduced the blood and bone marrow myeloblasts levels of leukemia-induced mice; upregulated cancer suppressor genes CSF3, SOCS1, PTEN and TRP53; increased anti-inflammatory IL10 and IL4; downregulated anti-apoptotic or proliferation genes; decreased the pro-inflammatory NF-κβ; suppressed pro-angiogenesis VEGFA mRNA expressions, and restored the homeostatic immune or leukocytes levels. The extract directly ameliorated leukemia via cancer cells apoptosis, suppressed inflammation and angiogenesis; and mitigated bone marrow myeloblasts imbalance, without any observable toxicity on the animals. PRACTICAL APPLICATIONS: The scopoletin (coumarin) and epicatechin (flavonoid)-rich Morinda citrifolia (Noni) leaves may be used as functional food ingredient, vegetables, or dietary supplements to treat and suppress leukemia progression by directly killing the cancer cells and preventing new cancer cells development and bone marrow myeloblast imbalance in the bone marrow, without being toxic to normal cells. The M. citrifolia leaf extract suppressed inflammation, and potential metastasis by inhibiting new cancer-related blood vessel formation.
Fulltext The Roles of Non-Coding RNAs in Tumor-Associated Lymphangiogenesis

Md Yusof K, Rosli R, Abdullah M, A Avery-Kiejda K

Cancers (Basel), 2020 Nov 06;12(11).
PMID: 33172072 DOI: 10.3390/cancers12113290

Lymphatic vessels are regarded as the "forgotten" circulation. Despite this, growing evidence has shown significant roles for the lymphatic circulation in normal and pathological conditions in humans, including cancers. The dissemination of tumor cells to other organs is often mediated by lymphatic vessels that serve as a conduit and is often referred to as tumor-associated lymphangiogenesis. Some of the most well-studied lymphangiogenic factors that govern tumor lymphangiogenesis are the vascular endothelial growth factor (VEGF-C/D and VEGFR-2/3), neuroplilin-2 (NRP2), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF), to name a few. However, recent findings have illustrated that non-coding RNAs are significantly involved in regulating gene expression in most biological processes, including lymphangiogenesis. In this review, we focus on the regulation of growth factors and non-coding RNAs (ncRNAs) in the lymphatic development in normal and cancer physiology. Then, we discuss the lymphangiogenic factors that necessitate tumor-associated lymphangiogenesis, with regards to ncRNAs in various types of cancer. Understanding the different roles of ncRNAs in regulating lymphatic vasculature in normal and cancer conditions may pave the way towards the development of ncRNA-based anti-lymphangiogenic therapy.
Fulltext Oral health literacy of first year university students [Abstract]

Jaafar A, Rosli R, Shamsulhuda N, Samsudin AD, Ab Mumin N

International Medical Journal Malaysia, 2017;16(21):5-5.
MyJurnal

1st IIUM International Dental Conference 2017
Introduction: Oral health literacy (OHL) can be different between science stream and non-science stream students as the exposure to knowledge of science is low among non-science stream. This situation can lead to unhealthy oral health behaviour and later increase the oral health problem among the non-science stream group. Thus, the study conducted aimed to compare the oral health literacy among science stream and non-science stream students and other factors associated, among first year students of Universiti Sains Islam Malaysia (USIM).
Materials and Methods: A cross-sectional study was conducted among 256 students from various faculties of USIM consisted of both science and non-science stream group. A validated Malay version, self-administered questionnaire of Oral Health Literacy Instrument (OHLI) was used to assess their OHL. Data gathered was later
analysed using IBM SPSS version 21.0. Multiple logistics regression was used to determine the associated risk factors of OHL.
Results: Study indicated that science stream students compared to non-science stream students have higher oral health literacy (OR= 6.98; 95% CI= 3.64, 13.39; p<0.001). Besides, students whom their mother's education level are high have higher OHL compared to their counterparts (OR= 2.31; 95%CI= 1.24, 4.28; p= 0.008).
Conclusion(s): An exposure to in-depth knowledge of science has an effect on OHL. Science stream students have high oral health literacy compared to non-science group. This finding give some ideas on suitable methods of oral health promotion that can be implemented among science and non-science stream background of students especially in school.
KEYWORDS: oral health literacy, science stream, first year students, Universiti Sains Islam Malaysia
Fulltext Chemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines

Fakiruddin KS, Lim MN, Nordin N, Rosli R, Abdullah S

Biology (Basel), 2021 Oct 26;10(11).
PMID: 34827096 DOI: 10.3390/biology10111103

Pre-clinical studies have demonstrated the efficacy of mesenchymal stem cells (MSCs) expressing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) or MSC-TRAIL against several tumors. However, due to the existence of cancer stem cells (CSCs), some tumors, including non-small cell lung cancer (NSCLC), exhibit TRAIL resistance. This study was designed to evaluate the capacity of using first-line chemotherapies including cisplatin, 5-fluorouracil (5-FU) and vinorelbine to act as a chemo-sensitizer on CD133+ (prominin-1 positive) CSCs derived from NSCLC cell lines (A549, H460 and H2170) for the purpose of MSC-TRAIL-induced inhibition. We showed that MSC-TRAIL was resistant to all three chemotherapies compared to the NSCLC cell lines, suggesting that the chemotherapies had little effect on MSC-TRAIL viability. Pre-treatment using either cisplatin or 5-FU, but not with vinorelbine, was able to increase the efficacy of MSC-TRAIL to kill the TRAIL-resistant A549-derived CSCs. The study also demonstrated that both 5-FU and vinorelbine were an effective chemo-sensitizer, used to increase the anti-tumor effect of MSC-TRAIL against H460- and H2170-derived CSCs. Furthermore, pre-treatment using cisplatin was noted to enhance the effect of MSC-TRAIL in H460-derived CSCs; however, this effect was not detected in the H2170-derived CSCs. These findings suggest that a pre-treatment using certain chemotherapies in NSCLC could enhance the anti-tumor effect of MSC-TRAIL to target the CSCs, and therefore the combination of chemotherapies and MSC-TRAIL may serve as a novel approach for the treatment of NSCLC.
Fulltext A Retrospective Analysis of Spontaneous Adverse Drug Reactions Reports Relating to Paediatric Patients

Rosli R, Ming LC, Abd Aziz N, Manan MM

PLoS One, 2016;11(6):e0155385.
PMID: 27249414 DOI: 10.1371/journal.pone.0155385

BACKGROUND: Spontaneous reporting on adverse drug reactions (ADR) has been established in Malaysia since 1987, and although these reports are monitored by the Malaysia drug monitoring authority, the National Pharmaceutical Control Bureau, information about ADRs in the paediatric patient population still remains unexplored. The aims of this study, therefore, were to characterize the ADRs reported in respect to the Malaysian paediatric population and to relate the data to specific paediatric age groups.
METHODS: Data on all ADRs reported to the National Pharmaceutical Control Bureau between 2000 and 2013 for individuals aged from birth to 17 years old were analysed with respect to age and gender, type of reporter, suspected medicines (using the Anatomical Therapeutic Chemical classification), category of ADR (according to system organ class) as well as the severity of the ADR.
RESULTS: In total, 11,523 ADR reports corresponding to 22,237 ADRs were analysed, with half of these reporting one ADR per report. Vaccines comprised 55.7% of the 11,523 ADR reports with the remaining being drug related ADRs. Overall, 63.9% of ADRs were reported for paediatric patients between 12 and 17 years of age, with the majority of ADRs reported in females (70.7%). The most common ADRs reported were from the following system organ classes: application site disorders (32.2%), skin and appendages disorders (20.6%), body as a whole general disorders (12.8%) and central and peripheral nervous system disorders (11.2%). Meanwhile, ADRs in respect to anti-infectives for systemic use (2194/5106; 43.0%) were the most frequently reported across all age groups, followed by drugs from the nervous system (1095/5106; 21.4%). Only 0.28% of the ADR cases were reported as fatal. A large proportion of the reports were received from healthcare providers in government health facilities.
DISCUSSION: ADR reports concerning vaccines and anti-infectives were the most commonly reported in children, and are mainly seen in adolescents, with most of the ADRs manifesting in skin reactions. The majority of the ADR reports were received from nurses in the public sector, reporting ADRs associated with vaccine administration. The low fatality rate of ADR cases reported could potentially be caused by reporting bias due to the very low reporting percentage from the private healthcare institutions. This study indicates that ADR rates among Malaysian children are higher than in developed countries. Constant ADR reporting and monitoring, especially in respect to paediatric patients, should be undertaken to ensure their safety.
Fulltext The impact of vitamin D deficiency on caries, periodontitis, and oral cancer: A systematic review

Hussein AS, Rosli RA, Ramle RS, Khor GH

Saudi Dent J, 2024 Jul;36(7):970-979.
PMID: 39035557 DOI: 10.1016/j.sdentj.2024.04.012

BACKGROUND: The relationship between vitamin D deficiency with dental caries, periodontitis and oral cancer is controversial.
OBJECTIVES: This review aimed to systematically evaluate the published literature and summarise the available evidence about the impact of vitamin D deficiency (VDD) on the oral diseases mentioned above.
METHODS: PubMed, Web of Science, Scopus and ScienceDirect databases were used. The search terms included were vitamin D, caries, periodontitis, and oral cancer. All papers published between January 2017 and November 2022 were included. The PRISMA process was used for the screening and selection studies.
RESULTS: Initially, 3001 studies were identified. However, after evaluating 46 full-text articles that explored the link between VDD and caries, periodontitis, and oral cancer, only 32 studies met the inclusion criteria for this systematic review. Among these, 15 studies focused on caries, 16 on periodontitis, and only one on oral cancer. Regarding study quality and risk of bias, 25 out of the 32 studies were deemed to have low risk. A total of 12 studies on periodontitis showed the impact of VDD.
CONCLUSION: The review highlights that most evidence suggests an association between VDD and periodontitis. However, findings concerning the association between VDD and dental caries were controversial. Thus, further research is required to clarify the impacts of VDD on caries and oral cancer.

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