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Fulltext Emerging therapeutic potential of anti-psychotic drugs in the management of human glioma: A comprehensive review

Kamarudin MNA, Parhar I

Oncotarget, 2019 Jun 11;10(39):3952-3977.
PMID: 31231472 DOI: 10.18632/oncotarget.26994

Despite numerous advancements in the last decade, human gliomas such as astrocytoma and glioblastoma multiforme have the worst prognoses among all cancers. Anti-psychotic drugs are commonly prescribed to treat mental disorders among cancer patients, and growing empirical evidence has revealed their antitumor, anti-metastatic, anti-angiogenic, anti-proliferative, chemo-preventive, and neo-adjuvant efficacies in various in vitro, in vivo, and clinical glioma models. Anti-psychotic drugs have drawn the attention of physicians and researchers owing to their beneficial effects in the prevention and treatment of gliomas. This review highlights data on the therapeutic potential of various anti-psychotic drugs as anti-proliferative, chemopreventive, and anti-angiogenic agents in various glioma models via the modulation of upstream and downstream molecular targets involved in apoptosis, autophagy, oxidative stress, inflammation, and the cell cycle in in vitro and in vivo preclinical and clinical stages among glioma patients. The ability of anti-psychotic drugs to modulate various signaling pathways and multidrug resistance-conferring proteins that enhance the efficacy of chemotherapeutic drugs with low side-effects exemplifies their great potential as neo-adjuvants and potential chemotherapeutics in single or multimodal treatment approach. Moreover, anti-psychotic drugs confer the ability to induce glioma into oligodendrocyte-like cells and neuronal-like phenotype cells with reversal of epigenetic alterations through inhibition of histone deacetylase further rationalize their use in glioma treatment. The improved understanding of anti-psychotic drugs as potential chemotherapeutic drugs or as neo-adjuvants will provide better information for their use globally as affordable, well-tolerated, and effective anticancer agents for human glioma.
Fulltext Transitioning pre-clinical glioblastoma models to clinical settings with biomarkers identified in 3D cell-based models: A systematic scoping review

Phon BWS, Kamarudin MNA, Bhuvanendran S, Radhakrishnan AK

Biomed Pharmacother, 2022 Jan;145:112396.
PMID: 34775238 DOI: 10.1016/j.biopha.2021.112396

Glioblastoma (GBM) remains incurable despite the overwhelming discovery of 2-dimensional (2D) cell-based potential therapeutics since the majority of them have met unsatisfactory results in animal and clinical settings. Incremental empirical evidence has laid the widespread need of transitioning 2D to 3-dimensional (3D) cultures that better mimic GBM's complex and heterogenic nature to allow better translation of pre-clinical results. This systematic scoping review analyses the transcriptomic data involving 3D models of GBM against 2D models from 22 studies identified from four databases (PubMed, ScienceDirect, Medline, and Embase). From a total of 499 genes reported in these studies, 313 (63%) genes were upregulated across 3D models cultured using different scaffolds. Our analysis showed that 4 of the replicable upregulated genes are associated with GBM stemness, epithelial to mesenchymal transition (EMT), hypoxia, and migration-related genes regardless of the type of scaffolds, displaying close resemblances to primitive undifferentiated tumour phenotypes that are associated with decreased overall survival and increased hazard ratio in GBM patients. The upregulation of drug response and drug efflux genes (e.g. cytochrome P450s and ABC transporters) mirrors the GBM genetic landscape that contributes to in vivo and clinical treatment resistance. These upregulated genes displayed strong protein-protein interactions when analysed using an online bioinformatics software (STRING). These findings reinforce the need for widespread transition to 3D GBM models as a relatively inexpensive humanised pre-clinical tool with suitable genetic biomarkers to bridge clinical gaps in potential therapeutic evaluations.
Fulltext A laboratory study of fluoride concentration in infant formulas marketed in Malaysia and estimation of daily intake

Mohd Desa, S. N. F., Muhamad, N. A., Mohd Nor, N. A., Abdul Razak, F., Abdul Manan, N. S., Abdul Manan, N. S., et al.

International Food Research Journal, 2020;27(5):893-902.
MyJurnal

The window of maximum susceptibility for the development of dental fluorosis for anterior
teeth is during the first two to three years of life. The primary source of fluoride intake for
infants at this age is mainly from the diet including infant formula. Thus, the present work
aimed to investigate the fluoride concentration in commercially available Malaysian infant
formulas that required reconstitution before consumption. A total of 29 infant formulas available in the Malaysian market were reconstituted with deionised water, fluoridated tap water,
and filtered tap water. The fluoride concentration of the infant formulas was analysed directly
using a fluoride ion selective electrode. The daily fluoride intake estimation from the infant
formulas was calculated using the median infant body weight and recommended volumes for
formula consumption from newborn to > 12 months of age. Results showed that the fluoride
concentration of the infant formulas when reconstituted with deionised water ranged between
0.009 to 0.197 mg/L that contributed to the estimated daily fluoride intake ranging from 0.005
to 0.100 mg (total intake per day) or 0.001 to 0.025 mg/kg (total intake per body weight/day).
The fluoride concentration in the selected infant formulas was low, but after reconstitution
with fluoridated tap water, the overall fluoride concentration in infant formulas sample significantly increased (p < 0.001). Nevertheless, the estimated daily fluoride intake from infant
formulas alone did not exceed the lowest-observed-adverse-effect level (LOAEL) of fluoride
at 0.10 mg/kg/day.
Fulltext Internal jugular vein height and inferior vena cava diameter measurement using ultrasound to determine central venous pressure: a correlation study

Nik Muhamad NA, Safferi RS, Robertson CE

Med J Malaysia, 2015 Apr;70(2):63-6.
PMID: 26162379 MyJurnal

OBJECTIVE: To determine the correlation between central venous pressure (CVP) measured by conventional central venous access and ultrasonographic measurement of internal jugular vein (IJV) height and inferior vena cava (IVC) diameter.
METHODS: A prospective, cross-sectional, convenience sampling observational study.
RESULTS: 25 patients from the Emergency Department (ED) Universiti Kebangsaan Malaysia Medical Centre (UKMMC) were studied between 1st March and 30th April 2013. The median age was 63 years (95% CI 54-67). There was a significant correlation between IJV height and CVP using central venous access (r=0.64 p<0.001). Correlation between IVC diameter in end expiration and CVP was 0.74 (p<0.001). An IJV height measurement >8cm predicted a CVP >8cm H2O (sensitivity 71.4%, specificity of 83.3%).
CONCLUSION: Measurement of IJV height and IVC diameter by ultrasonography correlates well with invasive CVP and is useful for the assessment of volume status in critically ill patients in the ED.
Study site: Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur
Compliance of Malaysian healthcare workers towards tuberculosis prevention programmes in workplace: An exploratory sequential mixed method study protocol

Halim I, Reffin N, Sharifa Ezat WP, Muhamad NA, Harith AA

Med J Malaysia, 2021 Nov;76(6):857-864.
PMID: 34806673

INTRODUCTION: The World Health Organization (WHO) stated that the incidence of tuberculosis among healthcare workers is increasing yearly and exceeds the incidence of tuberculosis in the community in almost all the countries that report to the WHO. The problem is greater in countries with high burden of tuberculosis disease in the community. The cause of this problem may be contributed by the attitudes of the healthcare workers themselves, such as non-compliance of the procedures at their work tasks meant to prevent them from contracting the disease. Therefore, this study aims to assess the perceptions and the behaviours of healthcare workers in relation to compliance towards prevention activities on tuberculosis at their workplace.
MATERIALS AND METHODS: We plan to conduct a two-phase exploratory sequential mixed method study to determine the factors affecting compliance of Malaysian healthcare workers towards tuberculosis prevention programmes in their workplace based on the guidelines of the Ministry of Health, Malaysia. Phase one is a qualitative study with a focus group discussion and questionnaire development and phase two is a quantitative study where data will be collected among healthcare workers in government clinics and hospitals in Selangor. The data from phase one will be analysed using Atlas.Ti software for thematic analysis and data from phase two will be analysed using SEM AMOS software for structural equation modelling.
Pulmonary thromboembolic disease associated with COVID-19 infection: a comparison between geriatric and non-geriatric populations

Tan TL, Illa NE, Ting SY, Hwong PL, Makhtar NK, Sim YH, et al.

Med J Malaysia, 2023 May;78(3):379-388.
PMID: 37271849

INTRODUCTION: The magnitude of Coronavirus Disease 2019 (COVID-19) infection among the elderly population is expected to rise. Our study compares the clinical and computed tomographical (CT) features of pulmonary thromboembolic (PTE) disease associated with COVID-19 infection in geriatric and non-geriatric cases, and explores the 60-day mortality rate in these two groups.
MATERIALS AND METHODS: We conducted this retrospective cross-sectional study in Hospital Tengku Ampuan Rahimah, Selangor, Malaysia. Patients admitted in April 2021 and May 2021 with concomitant COVID-19 infection and PTE disease were included. Demographic, clinical and laboratory data were retrieved, whilst CTPA images were analysed by a senior radiologist.
RESULTS: A total of 150 patients were recruited, comprising 45 geriatric patients and 105 non-geriatric patients. The prevalence rate of hypertension, diabetes mellitus and dyslipidaemia were higher among the geriatric cohort. Evidently, the percentage of patients with fever and diarrhoea were significantly higher among the non-geriatric cohort. The geriatric cohort also recorded a significantly lower absolute lymphocyte count at presentation and albumin level during admission. Despite earlier presentation, the geriatric cohort suffered from more severe diseases. Analysis of the CT features demonstrated that the most proximal pulmonary thrombosis specifically limited to the segmental and subsegmental pulmonary arteries in both cohorts. The elderly suffered from a significantly higher inhospital mortality rate and their cumulative probability of survival was significantly lower.
CONCLUSION: Typical COVID-19 symptoms may be absent among the elderly, prompting a lower threshold of suspicion during the COVID-19 pandemic. Additionally, the elderly demonstrated a higher probability of adverse outcomes despite earlier presentation and treatment.