Pusat Pengajian Sains Perubatan - Monograf
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- PublicationThe anxiety effect of a generalized epilepsy rat model treated with zolpidem(2025-07)Murugan, Sutharshinnii A/PGeneralized epilepsy, characterized by recurrent seizures originating from both cerebral hemispheres, is often associated with anxiety, significantly impacting patients' quality of life. This study investigated the anxiolytic effects of zolpidem, a GABAA receptor modulator, in a kainic acid (KA)-induced generalized epilepsy rat model. A total of 24 male Sprague-Dawley (SD) rats were assigned to six groups: Sham, KA only, KA + 1mg/kg zolpidem, KA + 3mg/kg zolpidem, 1mg/kg zolpidem only, and 3mg/kg zolpidem only. Generalized epilepsy induced through intraperitoneal (i.p.) administration of KA (7.5mg/kg to 15mg/kg, as needed). Zolpidem was administered orally at a daily dose for 14 consecutive days. Anxiety-related behaviours were assessed using the open-field test (OFT) before and after zolpidem treatment, while body weight, feed intake, and water consumption were monitored daily. Histopathological analysis of the hippocampus was performed using haematoxylin and eosin (H&E) staining to assess morphological alterations, including neuronal loss and disruption of tissue architecture, associated with anxiety-related pathology in kainic acid-induced generalized epilepsy, and to evaluate the potential neuroprotective effects of zolpidem treatment. KA injection successfully induced generalised epilepsy, with all KA-injected rats reaching a seizure severity score of 4 on the Modified Racine Scale. In the OFT, central zone entries significantly increased (p < 0.01) following intervention in the KA + 1mg/kg ZOL group, indicating a potential anxiolytic effect. The KA + 3mg/kg zolpidem group also showed a significant increase (p < 0.05), but the effect was less pronounced than at the lower dose. In contrast, the 3mg/kg zolpidem-only group exhibited reduced entries and time spent in the central zone post-intervention (both) showing p < 0.01), suggesting a potential anxiogenic effect at higher doses in non-epileptic animals. However, total distance travelled showed no significant differences across groups, indicating zolpidem’s effects were more specific to anxiety-related exploratory behaviour than general locomotion. These behavioural findings align with cage-side observations, which associated KA-induced generalized epilepsy with anxiety-like behaviour. No significant differences in body weight, feed efficiency, or water consumption were observed across groups. Histological analysis revealed characteristic neuronal damage in the hippocampus of KA-treated rats, including hypereosinophilia of the cytoplasm, pyknotic nuclei, and granule cell dispersion (GCD). Notably, the KA + 1mg/kg zolpidem group exhibited reduced neuronal damage compared to the KA only and KA + 3mg/kg zolpidem groups. Paradoxically, both zolpidem-only groups also displayed neurodegenerative changes, suggesting potential adverse effects of prolonged zolpidem exposure in the absence of epilepsy. These findings suggest that zolpidem at 1mg/kg reduces anxiety in generalized epilepsy, potentially mitigating the epilepsy-associated psychiatric comorbidity. However, a higher dose of 3mg/kg may exacerbate anxiety and neuronal damage, highlighting the importance of precise dosing to optimize therapeutic outcomes while minimizing adverse effects.
- PublicationCytogenomic profiling of chronic lymphocytic leukaemia patients using dna microarray.(2021)Zamri, Wan Norizzati Wan MohamadChronic lymphocytic leukaemia (CLL) accounts approximately 5 – 11% of lymphoproliferative disorders in Western countries. Despite the indolent disease progression, it had been reported that Asian CLL is more aggressive and had shorter time to first therapy compared to Western counterpart due to its complex genomic landscape. Even though chromosomal aberration of CLL can be detected by Fluorescence in situ Hybridization (FISH) and Multiplex Ligation-dependent Probe Amplification (MLPA) together with conventional cytogenetic analysis (CCA), however some of the abnormality can be missed due to method’s limitation. This study investigated chromosomal aberration using DNA microarray to detect cryptic chromosomal abnormality that could escape detection of FISH and MLPA which able to overcome both methods limitation and subsequently identify candidate genes that could involve in our population CLL. In this retrospective study, archive genomic DNA of 7 newly diagnosed CLL in 2012 from previous study (USM Short Term grant title: Analysis of Hypermethylation Status of Tumor Suppressor Genes p16INK4a, p15INK4b, ADAM12 and PCDHGB7 in Chronic Lymphocytic Leukemia Patients and Normal Individuals)(JEPeM code: USMKK/PPP/JEPeM/234.3(07)) were used. They were subjected to DNA microarray analysis using Affymetrix CytoScan® 750K Array using manufacture procedure. Detailed clinical information was extracted from patient’s cytogenetic request form and patient’s medical records. Chromosomal aberration were identified in all patients using DNA microarray. Result showed deletion of chromosome 13q and 14q varied in size ranging 0.42MB to 39.97MB. Interestingly, there were also additional CAs in form of trisomy 3, cryptic interstitial deletion of chromosome 13q, 14q, 16p, Xp and duplication of 14q32.33 and 22q11.2. Deletion 14q32.33 region closely related to mutational status of IGH while other cryptic aberrations need further investigation to explore contribution to CLL pathogenesis. All the cryptic deletion and duplication of these chromosome unable to be detected by CCA due to small size (<5MB). The findings can help the clinicians to stratify patients accordingly and more close monitoring warranted. DNA microarray are valuable tool in detecting relevant genomic aberrations in CLL patients especially cryptic abnormalities. Implementation of DNA microarray in CLL diagnosis will help clinicians to give precise treatment that tailored to patient’s need.
- PublicationUnveiling safety profile of Pereskia bleo leaf extract: A comprehensive study on female toxicity and teratogenicity in Sprague Dawley rats.(2024-05-28)
- PublicationThe effect of light resistance training using dumbbells and ankle-wrist weights on modifiable cardiovascular disease risk factors.(2013)Yaacob, Najib MajdiCardiovascular diseases which account for the majority of the population disease burden are closely linked to unhealthy lifestyles. One of the global strategies to reduce the burden is by promoting physical activity which includes both aerobic activity and resistance training. Resistance training is an important component of physical activity which has a great potential for improvement of overall health. This study aimed to determine and compare the effect of light resistance training using either dumbbells or ankle-wrist weights on body composition, blood pressure, health related physical fitness and biochemical parameters among overweight and obese adults in Kelantan. One hundred and thirty eight overweight and obese adults, aged 18-60 years were randomized to two groups; dumbbell group (n=69) and ankle-wrist weight group (n=69). Participants in dumbbell group performed group exercises three times per week using a pair of one kilogram dumbbells. The exercise consisted of a one sets of 12 movements, 12 repetitions for each movements which lasted for 20 minutes. Participants in ankle-wrist weight groups were given a pair of 500 gm ankle and a pair of 500 gm wrist weights to be used during activities of daily living for at least 20 minutes, three days per week. For both groups, resistances training for the first three months were closely monitored for adherence and the last three months were not directly monitored. Eighty nine participants completed this sixth month study. At third month, both groups showed significant reduction from baseline in waist circumference (WC) (dumbbell group: mean difference: 4.26, 95% CI: 2.10, 6.42; p<0.001; ankle-wrist weight group: mean difference: 3.31, 95% CI: 2.07, 4.55; p<0.001), waist to hip ratio (WHR) (dumbbell group: mean difference: 0.022,95% CI: 0.003, 0.041; p—0.016; ankle-wrist weight group: mean difference: 0.011, 95% CI: 0.001, 0.022; p—0.035) body fat percentage (dumbbell group: mean difference: 1.14, 95% CI: 0.60, 1.68; p<0.001; ankle-wrist weight group: mean difference: 1.20, 95% CI: 0.72, 1.69; p<0.001) and significant increase in skeletal muscle percentage (dumbbell group: mean difference: -0.66, 95% CI: -1.06, -0.27; p<0.001; ankle-wrist weight group: mean difference: -0.82, 95% CI: -1.13, -0.51; p<0.001), cardiorespiratory fitness (dumbbell group: mean difference: 17.23, 95% CI: 14.63, 19.83; p<0.001; anklewrist weight group: mean difference: 15.57, 95% CI: 13.18, 17.96; p<0.001), muscular endurance (Push up test: dumbbell group: mean difference: -5.78, 95% CI: -7.04, -4.51; p<0.001; ankle-wrist weight group: mean difference: -5.41, 95% CI: - 6.48, -4.34; p<0.001; Sit up test: dumbbell group: mean difference: -8.33, 95% CI: - 10.18, -6.47; p<0.001; ankle-wrist weight group: mean difference: -8.96, 95% CI: - 10.46, -7.46; p<0.001), muscular strength (Handgrip strength: dumbbell group: mean difference: -6.30, 95% CI: -8.77, -3.83; p<0.001; ankle-wrist weight group: mean difference: -4.16, 95% CI: -5.51, -2.82; p<0.001; Leg strength: dumbbell group: mean difference: -16.43, 95% CI: -19.84, -13.02; p<0.001; ankle-wrist weight group: mean difference: -21.49, 95% CI: -25.89, -17.09; p<0.001) and flexibility (dumbbell group: mean difference: -5.40, 95% CI: -6.63, -4.17; p<0.001; ankle-wrist weight group: mean difference: -1.67, 95% CI: -2.40, -0.95; p<0.001). Participants in dumbbell group showed significant reduction in total cholesterol (mean difference: 0.30, 95% CI: 0.03, 0.57; p=0.033), low density lipoprotein cholesterol (LDL-C) (mean difference: 0.36, 95% CI: 0.09, 0.63; p=0.004) and non-high density lipoprotein cholesterol (mean difference: 0.39, 95% CI: 0.12, 0.66; p=0.002) while participants in ankle-wrist weight group showed significant increase in high density lipoprotein cholesterol (HDL-C) (mean difference: -0.14, 95% CI: -0.25, -0.02; p=0.014) at the end of the third month. At the end of sixth month, significant reduction from baseline in WC and WHR, and significant increase in cardiorespiratory fitness, muscular strength, muscular endurance and flexibility were maintained with addition of significant reduction of systolic blood pressure (SBP) for both groups (dumbbell group: mean difference: 5.60, 95% CI: 1.24, 9.96; p=0.006; ankle-wrist weight group: mean difference: 5.27, 95% CI: 0.99, 9.54; p=0.008) and significant increase in HDL-C were maintained for ankle-wrist weight group. After adjustment of age only improvement of WC, SBP, cardiorespiratory fitness, muscular strength, muscular endurance and flexibility were still significant. Effect of six months light resistance training between using dumbbells and ankle-wrist weights were similar with exception of leg strength which was better in ankle-wrist weight group (at month 3: 62.38 vs. 68.43; at month 6: 58.38 vs. 70.96; p<0.001) and flexibility was better for dumbbell group (at month 3: 36.70 vs. 32.59; at month 6: 37.83 vs. 33.35; p<0.001). Resistance exercise using either dumbbells or ankle-wrist weight produce significant improvement in certain components of body composition, blood pressure, health related physical fitness and biochemical parameters. Light resistance training should be considered to be an integral component of healthy lifestyle promotion programs aiming to reduce cardiovascular risk and to improve overall health.
- PublicationScreening of laryngopharyngeal reflux disease in patients with gastroesophageal reflux disease symptoms in Hospital Universiti Sains.(2013)Apparau, HemaLaryngopharyngeal reflux (LPR) has been recognized as an extraesophageal manifestation of gastro esophageal reflux disease (GERD). However, many questions still exist as how to diagnose this disease accurately and to identify patients with silent reflux. This study was conducted to determine the prevalence of LPR in patients with GERD symptoms in Hospital Universiti Sains Malaysia, Kubang Kerian. This is a cross sectional study involving 115 patients presenting to Gastroenterology clinic and Outpatient clinic in HUSM from December 2011 to June 2012. Participants were required to answer the Symptomatic GERD questionnaire and Reflux Symptom Index questionnaire. This was followed by laryngeal examination and documentation of Reflux Finding Score. The prevalence of LPR in patients with symptomatic GERD was 33.04%. The commonest symptom in RSI was ‘heartbum, chest pain, indigestion or stomach acid coming up’. The most commonest sign seen in RFS is ‘erythema’. There was significant correlation between RSI and RFS. LPR is present in patients with symptoms of GERD. RSI and RFS play an important role to identify patients with LPR and aid the clinician to deliver the appropriate treatment to them.