IIUM Medical Journal Malaysia (IMJM)
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PTEN as A Candidate Molecular Target That Links MVA Pathway and Anti-HER2 Therapy Resistance
Get PDFDrug resistance remains a major problem hampering the success of targeted treatment in cancer therapy. Despite the promising future of targeted therapy, the occurrence of drug resistance leading to poor therapeutic response has been recorded in a large number of patients. The underlying mechanism however is not conclusive. Cholesterol has been associated with the development of breast cancer and its link to drug resistance in this type of cancer could be a new branch of study. Targeting cholesterol biosynthesis for cancer therapy via mevalonate (MVA) pathway is currently demonstrated as an attractive approach for overcoming treatment resistance in HER2+ breast cancer. Here, we discuss the overview of MVA pathway components in breast cancer treatment and resistance as well as the potential use of MVA pathway inhibitors in breast cancer therapy as a new approach to the problem. We also highlight the role of PTEN deficiency, a well-known resistance mechanism in HER2+ breast cancer cells, as a possible new target of the HMGCR inhibition that could be exploited to reverse anti-HER2 resistance
A Review on Complete Freund’s Adjuvant-Induced Arthritic Rat Model: Factors Leading to its Success
Get PDFArthritis-induced adjuvant (AIA) is an established animal model reflecting several clinical manifestations of human arthritis. It provides more understanding of pathogenesis and pathways involved in arthritic development and for testing various treatment modalities. Complete Freund’s adjuvant (CFA) is one of the most known algogenic agents used to develop AIA rodent model. Its wide application increases understanding of CFA effects locally and systemically following adjuvant-containing mycobacterium exposure in-vivo. This study aims to review possible factors involved in producing a successful CFA-induced arthritic rat model. We conducted a review of previous studies to determine critical factors to be emphasized. Since arthritis can be classified as gout, osteoarthritis, and rheumatoid arthritis, among others, factors that should be assessed include different dosage and volume, injection site, remission, arthritic and animal gender, and strain selections to successfully develop an arthritic rat model
Minocycline Ameliorated LPS-Induced Learning and Memory Impairment by Inhibiting Microglia and Astrocytes Activation in the Hippocampus
Get PDFINTRODUCTION: Many studies support the notion that neuroinflammation involving glial cells may be the fundamental pathogenic event that lead to brain damage and degeneration in Alzheimer’s disease (AD). The effects of minocycline on glial cells activation in the lipopolysaccharide (LPS) rat model is studied here. MATERIALS AND METHODS: Fifty adult male Sprague Dawley rats were split into five groups: control, LPS, LPS-treated with minocycline 25 mg/kg, LPS-treated with minocycline 50 mg/kg, and LPS treated with memantine 10 mg/kg. For two weeks, rats were treated with minocycline and memantine intraperitoneally daily, while were injected with LPS intraperitoneally once on day 5. Morris water maze (MWM) test was performed to evaluate the learning and working memory behaviour. Immunohistochemistry and Western blot were performed to measure ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) expressions in the hippocampal tissue. RESULTS: LPS injection caused significant learning and working memory deficits (p<0.05) as well as increased expressions of Iba-1 and GFAP (p<0.05), indicating microglia and astrocytes activation, respectively. Minocycline treatment significantly improved learning and working memory performance (p<0.05) and reduced microglia/astrocytes activation (p<0.05) in a dose-dependent manner, similar to the effect of memantine. CONCLUSIONS: Our results suggest that minocycline modulates LPS-induced microglia and astrocytes activation as well as improves learning and working memory comparable to memantine. Thus, minocycline may have preventive-therapeutic effect in diseases involving neuroinflammation such as AD
MicroRNAs Expression Profile in Young Patients with Acute Myocardial Infarction
Get PDFIntroduction: Acute myocardial infarction (AMI) is a severe coronary heart disease. Targeted miRNAs studies implicated two main pathways in the regulation of AMI namely pro-apoptosis (miR-29b and miR-194-5p on PTEN) and pro-necroptosis (miR-325 & miR-105 on RIPK3 ) pathways. This study aims to profile the miRNAs in Healthy Controls, Young AMI, and Mature AMI patients with matching criteria. MATERIALS AND Methods: Total RNA was extracted from plasma and the miRNA expression profiling using small RNA was done on the BGISEQ500 SE5 sequencing platform with BGI sequencing libraries. The sequence data were analysed using Gene Ontology (GO) to determine the function of the differently expressed genes, while Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were applied to identify the biological pathways in Young AMI against Mature AMI. Results: Of 1497 differentially expressed miRNAs, 1090 miRNAs were upregulated, and 407 miRNAs were downregulated in Young AMI against Mature AMI. The top 10 upregulated miRNAs were miR-552, miR-4446-3p, miR-432-5p, miR-548j-5p, miR-219, miR-982, miR-181a-2-3p, miR-654-5p, miR-58 and miR-548k; while the top 10 downregulated were miR-16-5p, miR-1064, miR-431-5p, miR-790 miR-1177, miR-201, miR-105, miR-518, miR-419 and miR-1103. There were 9 novel miRNAs discovered in this study; miR-58, miR-982, miR-548k, miR-1064, miR-790, miR-1177, miR-201, miR-419, and miR-1103. The target genes of differentially expressed miRNAs that were mapped to the signal transduction pathway in KEGG indicated that 346 classes were enriched. Conclusion: Our miRNA profiling revealed differentially expressed miRNAs including 9 novel miRNAs in Young and Mature AMI that require further evaluations for their roles in AMI.
A Rare Cause of Acute Abdomen in Adults: Adult Intussusception
Get PDFAdult intussusception is rare, less common and differs from childhood intussusception in its presentation, aetiology and treatment. It is common in paediatrics of less than three years of age.1,2 Unlike in paediatric population, most adult cases presented to emergency department with intestinal obstruction, and rarely, the actual diagnosis of intussusception is made during clinical setting. Top causes of adult intussusception include malignant or benign lesions, post-operative complications such as adhesions, Meckel diverticulum and bowel inflammatory disease. 8-20% of cases are idiopathic with no lead point lesion.3 Preliminary radiograph may show signs of intestinal obstruction, but computed tomography (CT) is the gold standard imaging for intussusception. This is a case report of an adult intussusception in Hospital Tengku Ampuan Afzan, Kuantan which was not detected during clinical examination, but diagnosed by CT imaging.
A Study of Risk Factors in Acute Myocardial Infarction of Adults Ages 18 To 45 in A Tertiary Referral Centre for Cardiology Services in Malaysia's East Coast.
Get PDFIntroduction: Acute myocardial infarction (AMI) is the major cause of death worldwide. There is limited data on the characteristics of afflicted young adults. Recent increase in recreational drugs has been associated. No local studies have ever reliably attributed this in young adults. This study aims to study the characteristic of AMI cases among young adults and these associations. Materials and Methods: This cross-sectional study was conducted at a tertiary referral centre for Cardiology services, Hospital Tengku Ampuan Afzan (HTAA), Kuantan, Pahang. It involved screening 818 patients presenting with AMI at the Emergency Department of HTAA over a one-year duration. Malaysian citizens aged 18 to 45 years old diagnosed with new AMI were included. Urinary samples were collected for recreational drug screening. Results: The incidence of AMI cases among young adults in HTAA Kuantan, Pahang were 10.3 per 100 persons of total AMI cases in a one-year period (95% Confidence Interval, 8.4%-12.6%). Fifty-eight patients who met the inclusion criteria were recruited, 1.7 % tested positive for amphetamines. Males made up 96.6% of the patients and the most common risk factor identified for young adults with AMI was smoking (N=45, 77.6%) followed by obesity (N=33, 56.9%). Conclusion: Recreational drug use at AMI presentation was negligible. Males made up the majority and smoking was the most prevalent risk factor. To date, this is the first study in Malaysia looking at the incidence of young adults with AMI and their preponderant characteristics
Appropriateness of Proton-Pump Inhibitor Usage among Hospitalized Patients in a Johor Government Hospital
No full textIntroduction: Proton pump inhibitors (PPIs) are potent and effective acid suppressant agents. There are emerging concerns that PPI overuse leads to escalating healthcare costs, drug-drug interactions, and adverse clinical outcomes. Exploring the appropriateness of PPI therapy among hospitalised patients in Malaysia is crucial. Thus, this study aims to determine the appropriateness of proton pump inhibitors utilisation in Sultan Ismail Hospital, Malaysia. Materials and Methods: This single-center retrospective cross-sectional study was conducted at a public tertiary hospital situated in the Johore state of Malaysia. Patients recruited were 12 years and above who had received PPI in January 2017. Medical information was reviewed from electronic medical records. Patients were classified into three subgroups based on indications adopted from evidence-based guidelines. Results: 422 patients were enrolled, 47.4% (n=200) fulfilled the Food Drug Administration (FDA) approved indications, 25.4% (n=107) had borderline indications, and 27.2% (n=115) had inappropriate PPI usage. Improper PPI therapy was observed with a similar fraction of patients in medical (24.5%, n= 58 ) and non-medical disciplines (30.8 %, n=57). Stress ulcer prevention in low-risk subjects and individuals with no apparent indication were reasons for PPI overuse. Conclusion: PPI overuse is prevailing in hospitalised adult patients. Promoting the awareness of guideline-based indications and adverse clinical events of PPI among clinicians is imperative in improving PPI prescribing.
Balance Disorders: A Review of Patients at a Specialized Vestibular Clinic
Get PDFIntroduction: With recent advancements in vestibular assessments, new ancillary tests can assist clinicians to better understand underlying cause of a balance problem. The recently established specialized vestibular clinic in Sultan Ahmad Shah Medical Centre @IIUM is equipped with these tests. This study aimed to determine the prevalence of the different diagnoses of balance disorders in a specialized vestibular clinic in Kuantan, Malaysia. Materials and Methods: This is a retrospective review of 121 walk-in patients over an 18-month period at a specialized Vestibular Clinic in Sultan Ahmad Shah Medical Centre @IIUM. The variables analysed in this review include the age, gender, ethnicity, diagnoses, and total number of visits before diagnoses were achieved. Results: Meticulous history taking, focused otorhinolaryngological examination and detailed vestibular assessment through the specialized vestibular clinic helped us in reaching a conclusive diagnosis. The most common cause of balance disorders in our review was Benign Paroxysmal Positional Vertigo (BPPV), constituting 41.3% of the cases. Among the canals, the posterior canal is the most affected (70%) and is usually treated with Epley manoeuvre. Other common diagnoses include Vestibular Migraine, Meniere’s Disease and Vestibular Neuritis. Conclusion: Vestibular clinics play a vital role in helping to pinpoint the accurate diagnosis of patients with balance disorders
Uric Acid: Friend or Foe?
Get PDFIntroduction. Adverse Pregnancy outcomes (APO) continue to trouble physicians worldwide, and uric acid has become a marker of interest in its prediction. Despite this, the correlation of uric acid in the third trimester is rarely studied, and the reference value for normal uric acid levels in pregnancy has yet to be established. This study was done to evaluate the association of uric acid levels in the third trimester of pregnancy and the development of APO, specifically gestational hypertension (GH), pre-eclampsia (PE), gestational diabetes mellitus (GDM), small for gestational age (SGA) and to determine a cut-off value of serum uric acid levels for screening of the APO. Materials and methods. A retrospective observational study was conducted among 374 women who delivered at Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM) and developed the APO of interest and had serum uric acid levels taken during the third trimester of pregnancy. A cut off value of 309 µmol/L was used to assess the sensitivity and specificity in predicting the APO. Results. Associations are observed between 309 µmol/L and the development of GH (p<0.0005), PE (p<0.0005), GDM (p<0.0005), SGA (p=0.0264). Plotted ROC curves with cutoff point of 309 µmol/L demonstrated moderate predictive value of serum uric acid and the development of GH (AUC 0.639), PE (AUC 0.713), SGA (AUC 0.649) and low predictive value for GDM (AUC 0.4). Conclusion. Serum uric acid level of 309 µmol/L in the third trimester of pregnancy is a moderate predictor of GH, PE, SGA and a poor predictor of GDM.
KEYWORDS: Uric acid; pregnancy trimester, third; pregnancy outcom
