Pusat Pengajian Sains Perubatan - Tesis
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- PublicationAnti-diabetic and anti-lethargic effects of stichopus horrens extract in type 2 diabetes-induced sprague dawley male rats(2025-01)Vixuan, EngDiabetes mellitus is a chronic metabolic disorder, that is attributed to either insufficient insulin production by the pancreas or impaired response of body cells to insulin. Present medication like metformin has brought significant therapeutic effects in treating this disease but the side effects prompt the researchers to explore other alternative treatments especially natural products. This study aimed to investigate the potential of different sea cucumber samples of Stichopus horrens, differentiated by extraction methods, in reducing fasting blood glucose level, minimising fatigue condition, and restoring structure and function in organs of diabetic type 2-induced rats. Two extraction methods were utilised in this study, which are hydrolysis and high-pressure processing (HPP). The first extract of sea cucumber was subjected to hydrolysis only, while the second extract was exposed to HPP only. The last extract of sea cucumber was subjected to both hydrolysis and HPP. In the in-vitro assay, human umbilical vein endothelial cells (HUVECs) were exposed to three Stichopus horrens body wall samples, and a positive control, metformin with concentrations ranging from 6.25 to 4000 µg/mL in MTT assay to obtain starting dosage of treatments for animal study. The in-vivo study involved Sprague Dawley (SD) rats, which included the induction of high fat diet for five weeks, 110 mg/kg of nicotinamide injection, followed by 55 mg/kg of streptozotocin (STZ) into creating Type 2 diabetes mellitus (T2DM) rat model. Rats were randomly grouped into six groups; normal control (n=3), diabetic control (n=3), metformin-treated group (n=3), sea cucumber extract (hydrolysis only) (n=3), sea cucumber extract (HPP only) (n=3), and sea cucumber extract (HPP and hydrolysis) (n=4). The findings displayed a decreasing trend in cell viability with increasing sea cucumber concentration with ICS0 values of 3.771 ± 0.152 µg/mL in sea cucumber extract (hydrolysis only), 3.783 ± 0.063 µg/mL in sea cucumber extract (HPP only), and 4.006 ± 0.054 µg/mL in sea cucumber extract (HPP and hydrolysis) while metformin depicted an increasing trend of cell viability with ECS0 value of 4.931 ± 4.044 µg/mL. As a result, the starting dosage for animal study pertaining to different treatments is 150 mg/kg each. The findings depicted decreasing trend of blood glucose level after four weeks of treatments with 150 mg/kg sea cucumber samples and increased exercise tolerance in sea cucumber extract (HPP and hydrolysis) group with 150 mg/kg. Apart from that, sea cucumbers exhibited mild restoration in histological changes of liver, kidney, and pancreas. The short treatment duration of sea cucumber on diabetic rats might prove that sea cucumber is a promising candidate for the development of novel product in the future.
- PublicationEffect of birth asphyxia on the thyroid hormone in term newborn delivered in hospital Universiti Sains Malaysia(2023)Fikri, Ahmad Zafrullah Afham AhmadIntroduction The objectives of this study are to compare thyroid hormone levels in term asphyxiated newborns versus healthy controls and to determine potential correlations between the severity of birth asphyxia and the thyroid hormone levels. Methods A prospective case-control study was performed by comparing cases of birth asphyxia with the healthy controls. The primary outcomes included cord blood Thyroid Stimulating Hormone (TSH), and TSH and Free Thyroxine 4 (FT4) levels at 24-36 hours after birth. Correlations were sought between the severity of birth asphyxia with the thyroid hormone levels for the cases. Results The study included 20 cases and 21 controls. Demographic data were similar for the two groups except for a significantly higher Caesarean section rate in the control group. There were no significant differences between the groups in the cord TSH and the 24-36 hours FT4 levels, but the median (IQR) TSH level at 24 to 36 hours was significantly lower in the case group than in the control group, (8.3 mIU/L(4.5-13.7) versus 14.1 mIU/L(9.4-17.0); p<0.05). The highest Thompson scores within the first six hours after birth was significantly correlated with lower TSH levels (r of -0.468; p<0.05). There was also a significant correlation between the Apgar score at 10 minutes and the level of FT4 at 24-36 hours after birth (r of 0.501; p<0.05). Conclusion This study showed that TSH at 24-36 hours after birth was significantly lower in asphyxiated newborns. Selected parameters of the severity of birth asphyxia correlated with thyroid hormone levels at 24-36 hours.
- PublicationOutcomes of temporary vascular access and factors influencing delayed arteriovenous fistula creation among intermittent hemodialysis patients: a study in hospital Universiti Sains Malaysia, Kelantan(2023)Abdullah @ Mohd Baharudin, Abdul HananIntroduction: Haemodialysis is the main modality of Renal Replacement Therapy (RRT) in Malaysia. However, most of the patients are initiated with intermittent haemodialysis via a central venous catheter as their main vascular access before placement of arteriovenous fistula (AVF) or graft (AVG). Objectives: This study aimed to identify types of vascular access among intermittent haemodialysis patients, and to determine the proportion of vascular access-related complications. We also aimed to study the factor that contributed to the delay of AVF creation at our institution. Methods: This is a single-centre retrospective, cross-sectional analysis of CKD stage 5 patients who were initiated on intermittent haemodialysis between 1 January 2021 and 31 December 2021. Data were collected from the medical record unit of Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan. Demographic data, comorbidities, catheterrelated complications, associated mortality, and factors of delayed AVF creation were analyzed using SPSS version 27. The association between types of a catheter with complication were analyzed by chi-square test. A P-value of less than 0.05 was considered statistically significant. Results: A total of 74 patients with intermittent haemodialysis were identified. Of these, males were 52.7 % and females were 47.3 %. Most patients were of Malay ethnicity with a mean age of 55 years old. Most of them have comorbidities of hypertension 95.9%, diabetes 79.7 % and ischemic heart diseases 23%. Most of them initiate haemodialysis with an Introduction: Haemodialysis is the main modality of Renal Replacement Therapy (RRT) in Malaysia. However, most of the patients are initiated with intermittent haemodialysis via a central venous catheter as their main vascular access before placement of arteriovenous fistula (AVF) or graft (AVG). Objectives: This study aimed to identify types of vascular access among intermittent haemodialysis patients, and to determine the proportion of vascular access-related complications. We also aimed to study the factor that contributed to the delay of AVF creation at our institution. Methods: This is a single-centre retrospective, cross-sectional analysis of CKD stage 5 patients who were initiated on intermittent haemodialysis between 1 January 2021 and 31 December 2021. Data were collected from the medical record unit of Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan. Demographic data, comorbidities, catheterrelated complications, associated mortality, and factors of delayed AVF creation were analyzed using SPSS version 27. The association between types of a catheter with complication were analyzed by chi-square test. A P-value of less than 0.05 was considered statistically significant. Results: A total of 74 patients with intermittent haemodialysis were identified. Of these, males were 52.7 % and females were 47.3 %. Most patients were of Malay ethnicity with a mean age of 55 years old. Most of them have comorbidities of hypertension 95.9%, diabetes 79.7 % and ischemic heart diseases 23%. Most of them initiate haemodialysis with an uncuffed femoral catheter, 93.2% and later, they change to the uncuffed internal jugular catheter 71.6%. The highest complication seen was central line-associated bloodstream infections (CLABSI) which were in 17.6% of patients, followed by hematoma in 8.5% of patients. We found no significant association between the types of haemodialysis catheters used with their complications. With regards to the delay in AVF creation, the majority of patients (36.2%) mention dialysis fear as their main concern, followed by small venous access, 34%. A total of 18 patients died during this study period. The major causes of death are due to CLABSI (5 patients) and sepsis-not related to catheter insertion (5 patients). Conclusion: In conclusion, the use of a haemodialysis central venous catheter among intermittent haemodialysis patients carries a significant risk for catheter-related complications, particularly infections and bleeding, with a risk of mortality. Early creation of arteriovenous fistula in pre-dialysis patients is vital in improving the outcomes of the patients.
- PublicationGenetic determinants excluding GBCR::ABL mutations of imatinib mesylate therapy response among chronic myeloid leukaemia patients in Malaysia(2023-04)Ismail, Siti MariamDespite imatinib mesylate (IM) being the frontline drug for successful treatment of chronic myeloid leukaemia (CML), a significant proportion of CML patients on IM therapy develop resistance and attain poor outcome. The objective of the present study was to investigate the contribution of selected polymorphisms of VEGFA (+936 C>T and -634 G>C), VEGFR2 (1192 C>T, ivs25-29 G>A and 1416 T>A), BIM (intron 2 deletion and c465 C>T), TP53 mutation at exon 8 and additional chromosome abnormalities (ACAs) in modulating IM treatment response and disease progression in 249 Malaysia CML patients undergoing IM treatemnt. For this study, CML patients comprising of 127 IM resistant and 122 IM good response were recriuted. For VEGFA +936 C>T and -634 G>C, VEGFR2 1192 C>T, ivs25-29 G>A and 1416 T>A and BIM c465 C>T Polymerase Chain Reaction- Restriction Enzyme Fragment Length Polymorphims (PCR – RFLP) was employed and allele specific – PCR (AS – PCR) for BIM intron 2 deletion polymorphims, TP53 mutation at exon 8 was investigated using PCR amplification followed by DNA sequencing. ACAs were investigated employing standard cytogenetic procedures and FISH. With regard to VEGFA, both the SNPs +936 C>T and -634 G>C showed significant lower risk for the development of resistance. For the homozygous variant (TT) +936 C>T, of showed OR: 0.11 (95 % CI = 0.02 – 0.56, p = 0.008) and CC of the -634 G>C showed OR: 0.17 (95 % CI = 0.07 – 0.41, p = 0.001). The C allele of -634 G>C was also significantly associated with lower risk for development of IM resistance (OR: 0.49, 95 % CI = 0.34 – 0.71, p = 0.001). In the case of VEGFR2, ivs25-29 G>A SNP, only homozygous variant (AA) showed significant lower risk association with development of resistance with OR, 0.17 (95 % CI = 0.04 – 0.84, p = 0.029). For SNP of 1416 T>A, the heterozygous variant (TA) and homozygous variant (AA) showed significant lower risk for development of resistance (OR: 0.25, 95 % CI: 0.11 – 0.59, p = 0.002 for heterozygous variant and OR: 0.27, 95 % CI = 0.12 – 0.62, p = 0.002 for homozygous variant respectively). In the case of TP53 exon 8 and BIM intron 2 deletion, all study subjects showed wildtype genotype with no mutation in exon 8 and no deletion detected in intron 2. For BIM c465 C>T, the heterozygous variant (CT) and dominant genetic model CT + TT (OR: 2.14, 95 % CI = 1.24 – 3.67, p = 0.006 and OR: 1.99, 95 % CI = 1.19 – 3.34, p = 0.009) and variant allele T (OR: 1.57, 95 % CI = 1.03 – 2.39, p = 0.036) showed higher risk for the development of resistance to IM. ACAs were detected in 40/ 249 patients (16.1 %). For determining the prognosis impact of ACAs, these 40 patients were categorized to those with Ph+/ ACAs and Ph-/ ACAs and further stratified into four groups based on the type of abnormalities. Patients with group 1 and group 2 abnormalities showed comparatively better prognosis while patients with group 3 and 4 abnormalities showed higher risk for disease progression. Novel ACAs consisting of rearrangements involving chromosomes 11 and 12 were found to lead to myeloid BP. Stratification based on individual ACAs found to have differential prognostic impact and might be a potential risk predictive system to prognosticate and guide treatment of CML patients. These findings from the present study demonstrated obvious relationships of host genetic and tumour genomic factors with IM treatment response and disease progression These genetic factors could be potential biomarkers to predict IM treatment response and disease progression in Malaysian CML patients.
- PublicationThe recovery and detection of trace methamphetamine residues deposited on laboratory coat materials(2023-05)Chien, Quah SuIllicit drugs handling and processing could potentially contaminate the surfaces and personal protection equipment used by the analysts in drug testing laboratories. Such drug contamination, if any, might lead to long-term harmful exposure. Therefore, the monitoring of possible contamination is crucial to reduce the harmfulness resulted from the exposures. Using methamphetamine as a contamination indicator, this study aimed to recover and detect trace methamphetamine residues deposited on the laboratory coat material. In this study, methamphetamine was chosen as the target substance due to its high prevalence of seizures in Malaysia which is often ended up in the forensic laboratory for analysis. A dispersive liquid-liquid microextraction (DLLME) procedure was firstly optimised, followed by the derivatisation of methamphetamine using trifluoroacetic acid anhydride and finally the detection by gas chromatography-mass spectrometry (GC-MS) method. Known concentrations of methamphetamine were deposited on seven types of laboratory coat materials, and their recovery percentages were then determined and compared. Based on the response surface methodology optimisation, DLLME procedure utilising 685 μL dichloromethane as extraction solvent and 1000 μL 2-propanol as disperser solvent in combination with vortexing for 90 seconds and centrifugation at 500 rpm for 5 minutes was used for the recovery of methamphetamine from fabric substrate. Derivatised methamphetamine was found to provide enhanced responses for the detection of trace methamphetamine through the application of validated GC method (linearity: y= 0.0017 x - 0.4698, R2= 0.9993; limit of detection: 7.80 ng/mL; limit of quantification: 23.40 ng/mL; intra-day precision: 3.35 - 3.76%; inter-day precision: 4.65 - 6.50%; accuracy: 94.92% - 106.01%). The presence of methamphetamine was also confirmed through the comparison and matching with mass spectral database. Percentage recoveries of methamphetamine from seven types of laboratory coat materials were determined to be more than 45% at three different concentration levels covering 0.5, 1.5, and 3 μg/100 cm2. To conclude, this study had successfully recovered and detected the trace methamphetamine residues deposited on laboratory coat materials based on the proposed DLLME-GC-MS procedure.