Displaying publications 1 - 20 of 89 in total

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  1. Fulltext What information and the extent of information research participants need in informed consent forms: a multi-country survey
    Karbwang J, Koonrungsesomboon N, Torres CE, Jimenez EB, Kaur G, Mathur R, et al.
    BMC Med Ethics, 2018 09 15;19(1):79.
    PMID: 30219106 DOI: 10.1186/s12910-018-0318-x
    BACKGROUND: The use of lengthy, detailed, and complex informed consent forms (ICFs) is of paramount concern in biomedical research as it may not truly promote the rights and interests of research participants. The extent of information in ICFs has been the subject of debates for decades; however, no clear guidance is given. Thus, the objective of this study was to determine the perspectives of research participants about the type and extent of information they need when they are invited to participate in biomedical research.

    METHODS: This multi-center, cross-sectional, descriptive survey was conducted at 54 study sites in seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to determine the importance of each element in the ICF among research participants of a biomedical study, with an anchored rating scale from 1 (not important) to 5 (very important).

    RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%) were returned. The majority of respondents considered most elements required in the ICF to be 'moderately important' to 'very important' for their decision making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct benefit, and common adverse effects of the intervention were considered to be of most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45, respectively).

    CONCLUSIONS: Research participants would like to be informed of the ICF elements required by ethical guidelines and regulations; however, the importance of each element varied, e.g., risk and benefit associated with research participants were considered to be more important than the general nature or technical details of research. Using a participant-oriented approach by providing more details of the participant-interested elements while avoiding unnecessarily lengthy details of other less important elements would enhance the quality of the ICF.

  2. Fulltext Relationship between coping styles and lipid profile among public university staff
    Ariaratnam S, Krishnapillai AD, Daher AM, Fadzil MA, Razali S, Omar SA, et al.
    Lipids Health Dis, 2017 Feb 28;16(1):50.
    PMID: 28245847 DOI: 10.1186/s12944-017-0438-1
    BACKGROUND: The scarcity of data about coping styles with a biochemical marker namely lipid profile, potentially associated with cardiovascular risk factors is most striking among professionals working in public university. Hence, this research aimed to investigate the relationship between coping styles and lipid profile comprising total cholesterol (TC), triglyceride (TG), HDL-cholesterol (high density lipoprotein-cholesterol) and LDL-cholesterol (Low density lipoprotein-cholesterol) among this group of professionals.

    METHODS: A cross sectional survey was conducted among staff from a tertiary education centre. Subjects were contacted to ascertain their medical history. A total of 320 subjects were interviewed and 195 subjects were eligible and subsequently recruited on a suitable date for taking blood and administration of the questionnaires. The subjects completed questionnaires pertaining to demographic details and coping styles. Pearson's correlation coefficient was used to measure the strength of association between lipid profile and coping styles.

    RESULTS: Majority of the subjects were non-academic staff (60.0%), female (67.2%), Malay (91.8%), married (52.3%) and educated until Diploma level (34.9%). Academic staff scored significantly higher mean scores in task-oriented coping styles (Mean = 64.12). Non-academic staff scored significantly higher mean scores in emotion (Mean = 48.05) and avoidance-oriented coping styles (Mean = 57.61). Malay subjects had significantly higher mean scores in emotion (Mean = 47.14) and avoidance-oriented coping styles (Mean = 55.23). Non-malay subjects (Mean = 66.00) attained significantly higher mean scores in task-oriented coping styles. Single/divorced/widowed individuals scored significantly higher mean scores in emotion (Mean = 48.13) and avoidance-oriented coping styles (Mean = 56.86). There was a significant negative correlation between TC (r = -0.162) and LDL (r = -0.168) with avoidance-oriented coping styles (p = 0.023, p = 0.019 respectively).

    CONCLUSION: Avoidance-oriented coping style was more likely to engender favourable lipid profile. Hence, assessment of coping styles would certainly assist health care practitioners in predicting subjects who would be at a greater risk of developing cardiovascular diseases.

  3. Evaluation of toxicity profile of kratom (Mitragyna speciosa Korth) decoction in rats
    Hassan Z, Singh D, Suhaimi FW, Chear NJ, Harun N, See CP, et al.
    Regul Toxicol Pharmacol, 2023 Sep;143:105466.
    PMID: 37536550 DOI: 10.1016/j.yrtph.2023.105466
    Mitragyna speciosa Korth also known as kratom, is an herbal drug preparation for its therapeutic properties and opioid-replacement therapy. Kratom is consumed in a brewed decoction form in Malaysia and to date, no studies have characterized its chemical and toxicity profile. Thus, this study aims to evaluate kratom decoction's safety and toxicity profile after 28 days of treatment. Mitragynine content was quantified in kratom decoction and used as a marker to determine the concentration. Male and female Sprague Dawley rats were orally treated with vehicle or kratom decoction (10, 50 or 150 mg/kg) and two satellite groups were treated with vehicle and kratom decoction (150 mg/kg). Blood and organs were collected for hematology, biochemical and histopathology analysis at the end of treatment. No mortality was found after 28 days of treatment and no significant changes in body weight and hematology profile, except for low platelet count. High amounts of uric acid, AST, ALT and alkaline phosphatase were found in the biochemical analysis. Histological investigation of the heart and lungs detected no alterations except for the kidney, liver and brain tissues. In conclusion, repeated administration of kratom decoction provided some evidence of toxicity in the kidney and liver with no occurrence of mortality.
  4. Lymph node metastasis of primary endometrial cancers: Associated proteins revealed by MALDI imaging
    Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Lokman NA, Zhang C, et al.
    Proteomics, 2016 06;16(11-12):1793-801.
    PMID: 27061135 DOI: 10.1002/pmic.201500455
    Metastasis is a crucial step of malignant progression and is the primary cause of death from endometrial cancer. However, clinicians presently face the challenge that conventional surgical-pathological variables, such as tumour size, depth of myometrial invasion, histological grade, lymphovascular space invasion or radiological imaging are unable to predict with accuracy if the primary tumour has metastasized. In the current retrospective study, we have used primary tumour samples of endometrial cancer patients diagnosed with (n = 16) and without (n = 27) lymph node metastasis to identify potential discriminators. Using peptide matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI), we have identified m/z values which can classify 88% of all tumours correctly. The top discriminative m/z values were identified using a combination of in situ sequencing and LC-MS/MS from digested tumour samples. Two of the proteins identified, plectin and α-Actin-2, were used for validation studies using LC-MS/MS data independent analysis (DIA) and immunohistochemistry. In summary, MALDI-MSI has the potential to identify discriminators of metastasis using primary tumour samples.
  5. Fulltext Human iPS-derived pre-epicardial cells direct cardiomyocyte aggregation expansion and organization in vitro
    Tan JJ, Guyette JP, Miki K, Xiao L, Kaur G, Wu T, et al.
    Nat Commun, 2021 08 17;12(1):4997.
    PMID: 34404774 DOI: 10.1038/s41467-021-24921-z
    Epicardial formation is necessary for normal myocardial morphogenesis. Here, we show that differentiating hiPSC-derived lateral plate mesoderm with BMP4, RA and VEGF (BVR) can generate a premature form of epicardial cells (termed pre-epicardial cells, PECs) expressing WT1, TBX18, SEMA3D, and SCX within 7 days. BVR stimulation after Wnt inhibition of LPM demonstrates co-differentiation and spatial organization of PECs and cardiomyocytes (CMs) in a single 2D culture. Co-culture consolidates CMs into dense aggregates, which then form a connected beating syncytium with enhanced contractility and calcium handling; while PECs become more mature with significant upregulation of UPK1B, ITGA4, and ALDH1A2 expressions. Our study also demonstrates that PECs secrete IGF2 and stimulate CM proliferation in co-culture. Three-dimensional PEC-CM spheroid co-cultures form outer smooth muscle cell layers on cardiac micro-tissues with organized internal luminal structures. These characteristics suggest PECs could play a key role in enhancing tissue organization within engineered cardiac constructs in vitro.
  6. Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer
    Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Kaur G, Anderson L, et al.
    Biochim Biophys Acta Proteins Proteom, 2017 Jul;1865(7):846-857.
    PMID: 27784647 DOI: 10.1016/j.bbapap.2016.10.010
    The prediction of lymph node metastasis using clinic-pathological data and molecular information from endometrial cancers lacks accuracy and is therefore currently not routinely used in patient management. Consequently, although only a small percentage of patients with endometrial cancers suffer from metastasis, the majority undergo radical surgery including removal of pelvic lymph nodes. Upon analysis of publically available data and published research, we compiled a list of 60 proteins having the potential to display differential abundance between primary endometrial cancers with versus those without lymph node metastasis. Using data dependent acquisition LC-ESI-MS/MS we were able to detect 23 of these proteins in endometrial cancers, and using data independent LC-ESI-MS/MS the differential abundance of five of those proteins was observed. The localization of the differentially expressed proteins, was visualized using peptide MALDI MSI in whole tissue sections as well as tissue microarrays of 43 patients. The proteins identified were further validated by immunohistochemistry. Our data indicate that annexin A2 protein level is upregulated, whereas annexin A1 and α actinin 4 expression are downregulated in tumours with lymph node metastasis compared to those without lymphatic spread. Moreover, our analysis confirmed the potential of these markers, to be included in a statistical model for prediction of lymph node metastasis. The predictive model using highly ranked m/z values identified by MALDI MSI showed significantly higher predictive accuracy than the model using immunohistochemistry data. In summary, using publicly available data and complementary proteomics approaches, we were able to improve the prediction model for lymph node metastasis in EC.
  7. Fulltext Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague-Dawley Rats
    Al Zarzour RH, Ahmad M, Asmawi MZ, Kaur G, Saeed MAA, Al-Mansoub MA, et al.
    Nutrients, 2017 Jul 18;9(7).
    PMID: 28718838 DOI: 10.3390/nu9070766
    Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague-Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC-HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.
  8. Fulltext Apocynin and catalase prevent hypertension and kidney injury in Cyclosporine A-induced nephrotoxicity in rats
    Tan YC, Abdul Sattar M, Ahmeda AF, Abdul Karim Khan N, Murugaiyah V, Ahmad A, et al.
    PLoS One, 2020;15(4):e0231472.
    PMID: 32298299 DOI: 10.1371/journal.pone.0231472
    Oxidative stress is involved in the pathogenesis of a number of diseases including hypertension and renal failure. There is enhanced expression of nicotinamide adenine dinucleotide (NADPH oxidase) and therefore production of hydrogen peroxide (H2O2) during renal disease progression. This study investigated the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on Cyclosporine A (CsA) nephrotoxicity in Wistar-Kyoto rats. Rats received CsA (25mg/kg/day via gavage) and were assigned to vehicle, apocynin (2.5mmol/L p.o.), catalase (10,000U/kg/day i.p.) or apocynin plus catalase for 14 days. Renal functional and hemodynamic parameters were measured every week, and kidneys were harvested at the end of the study for histological and NADPH oxidase 4 (NOX4) assessment. Oxidative stress markers and blood urea nitrogen (BUN) were measured. CsA rats had higher plasma malondialdehyde (by 340%) and BUN (by 125%), but lower superoxide dismutase and total antioxidant capacity (by 40%, all P<0.05) compared to control. CsA increased blood pressure (by 46mmHg) and decreased creatinine clearance (by 49%, all P<0.05). Treatment of CsA rats with apocynin, catalase, and their combination decreased blood pressure to near control values (all P<0.05). NOX4 mRNA activity was higher in the renal tissue of CsA rats by approximately 63% (P<0.05) compared to controls but was reduced in apocynin (by 64%), catalase (by 33%) and combined treatment with apocynin and catalase (by 84%) compared to untreated CsA rats. Treatment of CsA rats with apocynin, catalase, and their combination prevented hypertension and restored renal functional parameters and tissue Nox4 expression in this model. NADPH inhibition and H2O2 scavenging is an important therapeutic strategy during CsA nephrotoxicity and hypertension.
  9. Characterization of renal hemodynamic and structural alterations in rat models of renal impairment: role of renal sympathoexcitation
    Salman IM, Ameer OZ, Sattar MA, Abdullah NA, Yam MF, Najim HS, et al.
    J Nephrol, 2010 5 4;24(1):68-77.
    PMID: 20437405 DOI: 10.5301/jn.2010.6
    BACKGROUND: Renal sympathetic innervation plays an important role in the control of renal hemodynamics and may therefore contribute to the pathophysiology of many disease states affecting the kidney. Thus, the present study aimed to investigate the role of the renal sympathetic nervous system in the early deteriorations of renal hemodynamics and structure in rats with pathophysiological states of renal impairment.

    METHODS: Anesthetized Sprague Dawley (SD) rats with cisplatin-induced acute renal failure (ARF) or streptozotocin (STZ)-induced diabetes mellitus (DM) were subjected to a renal hemodynamic study 7 days after cisplatin and STZ administration. During the acute study, renal nerves were electrically stimulated, and responses in renal blood flow (RBF) and renal vascular resistance (RVR) were recorded in the presence and absence of renal denervation. Post mortem kidney collection was performed for histopathological assessment.

    RESULTS: In innervated ARF or DM rats, renal nerve stimulation produced significantly lower (all p<0.05, vs. innervated control) renal vasoconstrictor responses. These responses were markedly abolished when renal denervation was performed (all p<0.05); however, they appeared significantly higher compared with denervated controls (all p<0.05). Kidney injury was suppressed in denervated ARF, while, irrespective of renal denervation, renal specimens from DM rats were comparable to controls.

    CONCLUSIONS: Renal sympathoexcitation is involved in the pathogenesis of the renal impairment accompanying ARF and DM, and may even precede the establishment of an observable renal injury. There is a possible enhancement in the renal sensitivity to intrarenal norepinephrine following renal denervation in ARF and DM rats.
  10. Fulltext Cancer Tissue Classification Using Supervised Machine Learning Applied to MALDI Mass Spectrometry Imaging
    Mittal P, Condina MR, Klingler-Hoffmann M, Kaur G, Oehler MK, Sieber OM, et al.
    Cancers (Basel), 2021 Oct 27;13(21).
    PMID: 34771551 DOI: 10.3390/cancers13215388
    Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) can determine the spatial distribution of analytes such as protein distributions in a tissue section according to their mass-to-charge ratio. Here, we explored the clinical potential of machine learning (ML) applied to MALDI MSI data for cancer diagnostic classification using tissue microarrays (TMAs) on 302 colorectal (CRC) and 257 endometrial cancer (EC)) patients. ML based on deep neural networks discriminated colorectal tumour from normal tissue with an overall accuracy of 98% in balanced cross-validation (98.2% sensitivity and 98.6% specificity). Moreover, our machine learning approach predicted the presence of lymph node metastasis (LNM) for primary tumours of EC with an accuracy of 80% (90% sensitivity and 69% specificity). Our results demonstrate the capability of MALDI MSI for complementing classic histopathological examination for cancer diagnostic applications.
  11. Fulltext Adipocytokine Regulation and Antiangiogenic Activity Underlie the Molecular Mechanisms of Therapeutic Effects of Phyllanthus niruri against Non-Alcoholic Fatty Liver Disease
    Zarzour RHA, Alshawsh MA, Asif M, Al-Mansoub MA, Mohamed Z, Ahmad M, et al.
    Nutrients, 2018 Aug 09;10(8).
    PMID: 30096951 DOI: 10.3390/nu10081057
    The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague⁻Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes.
  12. Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases
    Li CMY, Briggs MT, Lee YR, Tin T, Young C, Pierides J, et al.
    Clin Exp Med, 2024 Mar 16;24(1):53.
    PMID: 38492056 DOI: 10.1007/s10238-024-01311-5
    Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5'-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.
  13. Fulltext Epidemiology of smoking among Malaysian adult males: prevalence and associated factors
    Lim HK, Ghazali SM, Kee CC, Lim KK, Chan YY, Teh HC, et al.
    BMC Public Health, 2013 Jan 07;13:8.
    PMID: 23294728 DOI: 10.1186/1471-2458-13-8
    BACKGROUND: Three National Health and Morbidity Surveys (NHMSs) had been conducted in Malaysia in 10-year intervals from 1986-2006. Based on the latest NHMS survey in 2006, we describe the prevalence of smoking and identify the social and demographic factors associated with smoking among adult males in Malaysia.

    METHODS: A cross-sectional study among 15,639 Malaysian adult males aged 18 years and above was conducted using proportional to size stratified sampling method. The socio-demographic variables examined were level of education, occupation, marital status, residential area, age group and monthly household income.

    RESULTS: The prevalence of smoking among adult males in Malaysia was 46.5% (95% CI: 45.5-47.4%), which was 3% lower than a decade ago. Mean age of smoking initiation was 18.3 years, and mean number of cigarettes smoked daily was 11.3. Prevalence of smoking was highest among the Malays (55.9%) and those aged 21-30 years (59.3%). Smoking was significantly associated with level of education (no education OR 2.09 95% CI (1.67-2.60), primary school OR 1.95, 95% CI (1.65-2.30), secondary school OR 1.88, 95% CI (1.63-2.11), with tertiary education as the reference group). Marital status (divorce OR 1.67, 95% CI (1.22-2.28), with married as the reference group), ethnicity (Malay, OR 2.29, 95% CI ( 1.98-2.66; Chinese OR 1.23 95% CI (1.05-1.91), Other Bumis OR 1.75, 95% CI (1.46-2.10, others OR 1.48 95% CI (1.15-1.91), with Indian as the reference group), age group (18-20 years OR 2.36, 95% CI (1.90-2.94); 20-29 years OR 3.31 , 95% CI 2.82-3.89; 31-40 years OR 2.85 , 95% CI ( 2.47-3.28); 41-50 years OR 1.93, 95% CI (1.69-2.20) ; 51-60 years OR 1.32, 95% CI (1.15-1.51), with 60 year-old and above as the reference group) and residential area (rural OR 1.12 , 95% CI ( 1.03-1.22)) urban as reference.

    CONCLUSION: The prevalence of smoking among Malaysian males remained high in spite of several population interventions over the past decade. Tobacco will likely remain a primary cause of premature mortality and morbidity in Malaysia. Continuous and more comprehensive anti-smoking policy measures are needed in order to further prevent the increasing prevalence of smoking among Malaysian men, particularly those who are younger, of Malay ethnicity, less educated, reside in rural residential area and with lower socio-economic status.

  14. Prevalence and correlates of depression among adolescents in Malaysia
    Kaur J, Cheong SM, Mahadir Naidu B, Kaur G, Manickam MA, Mat Noor M, et al.
    Asia Pac J Public Health, 2014 Sep;26(5 Suppl):53S-62S.
    PMID: 25070697 DOI: 10.1177/1010539514544356
    Depression among adolescents has been recognized as a major public health issue. The objective of this study was to determine the prevalence and correlates of depression among school-going adolescents in Malaysia. Data from the Malaysia Global School-based Health Survey (GSHS) 2012 were analyzed with additional data from the validated DASS21 (Depression, Anxiety, and Stress) questionnaire. The study revealed that 17.7% of respondents had depressive symptoms. Multivariate analysis further showed that feeling lonely (adjusted odds ratio [aOR] = 2.99; 95% CI = 2.57-3.47), Indian ethnicity (aOR = 2.00; 95% CI = 1.63-2.44), using drugs (aOR = 1.85; 95% CI = 1.21-2.82), and being bullied (aOR = 1.79; 95% CI = 1.60-1.99) were significantly associated with depressive symptoms. Lack of parental supervision, alcohol use, and tobacco use were also significant risk factors. Addressing depressive symptoms among adolescents may have implications for managing their risks of being bullied and substance use. This study also highlights the need to further investigate depressive symptoms among adolescents of Indian ethnicity.
    Study name: Global School-Based Student Health Survey (GSHS)
  15. The effects of tempol on renal function and hemodynamics in cyclosporine-induced renal insufficiency rats
    Chia TY, Sattar MA, Abdulla MH, Rathore HA, Ahmad Fu, Kaur G, et al.
    Ren Fail, 2013 Aug;35(7):978-88.
    PMID: 23822648 DOI: 10.3109/0886022X.2013.809563
    This study investigated the effects of tempol, a superoxide dismutase (SOD) mimetic and L-NAME, a nitric oxide (NO) synthase inhibitor on the renal function and hemodynamics in cyclosporine A (CsA) induced renal insufficiency rats. Male Sprague-Dawley rats were treated with either vehicle (C), tempol (T, 1 mmol/L in drinking fluid), L-NAME (L, 1 mmol/L in drinking fluid), CsA (Cs, 25 mg/kg/day via gavage), CsA plus tempol (TCs), CsA plus L-NAME (LCs) or CsA plus a combination of tempol and L-NAME (TLCs) for 21 consecutive days. At the end of treatment regimen, the renal responses to noradrenaline (NA), phenylephrine (PE), methoxamine and angiotensin II (Ang II) were determined. Cs and LCs rats had lower creatinine clearance (0.7 ± 0.1 and 0.6 ± 0.5 vs. 1.3 ± 0.2 mL/min/kg) and fractional excretion of sodium (0.12 ± 0.02 and 0.17 ± 0.01 vs. 0.67 ± 0.04%) but higher systolic blood pressure (145 ± 2 and 178 ± 4 vs. 116 ± 2) compared to the control (all p 
  16. Contribution of the MLH1 -93G>a promoter polymorphism in modulating susceptibility risk in Malaysian colorectal cancer patients
    Nizam ZM, Abdul Aziz AA, Kaur G, Abu Hassan MR, Mohd Sidek AS, Yeh LY, et al.
    Asian Pac J Cancer Prev, 2013;14(2):619-24.
    PMID: 23621208
    BACKGROUND: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable.

    AIM: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk.

    METHODS: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs).

    RESULTS: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253).

    CONCLUSION: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.

  17. Renal ischemic injury affects renal hemodynamics and excretory functions in Sprague Dawley rats: involvement of renal sympathetic tone
    Salman IM, Sattar MA, Abdullah NA, Ameer OZ, Yam MF, Kaur G, et al.
    Ren Fail, 2010 Jan;32(1):96-102.
    PMID: 20113274 DOI: 10.3109/08860220903389196
    The role of renal sympathetic nerves in the pathogenesis of ischemic acute renal failure (ARF) and the immediate changes in the renal excretory functions following renal ischemia were investigated. Two groups of male Sprague Dawley (SD) rats were anesthetized (pentobarbitone sodium, 60 mg kg(-1) i.p.) and subjected to unilateral renal ischemia by clamping the left renal artery for 30 min followed by reperfusion. In group 1, the renal nerves were electrically stimulated and the responses in the renal blood flow (RBF) and renal vascular resistance (RVR) were recorded, while group 2 was used to study the early changes in the renal functions following renal ischemia. In post-ischemic animals, basal RBF and the renal vasoconstrictor reperfusion to renal nerve stimulation (RNS) were significantly lower (all p < 0.05 vs. control). Mean arterial pressure (MAP), basal RVR, urine flow rate (UFR), absolute and fractional excretions of sodium (U(Na)V and FE(Na)), and potassium (U(K)V and FE(K)) were higher in ARF rats (all p < 0.05 vs. control). Post-ischemic animals showed markedly lower glomerular filtration rate (GFR) (p < 0.05 vs. control). No appreciable differences were observed in urinary sodium to potassium ratio (U(Na)/U(K)) during the early reperfusion phase of renal ischemia (p > 0.05 vs. control). The data suggest an immediate involvement of renal sympathetic nerve action in the pathogenesis of ischemic ARF primarily through altered renal hemodynamics. Diuresis, natriuresis, and kaliuresis due to impaired renal tubular functions are typical responses to renal ischemia and of comparable magnitudes.
  18. Fulltext Systematic review on international practices in controlling waterpipe tobacco smoking
    Tee GH, Hairi NN, Nordin F, Choo WY, Chan YY, Kaur G, et al.
    Asian Pac J Cancer Prev, 2015;16(9):3659-65.
    PMID: 25987018
    BACKGROUND: Waterpipe tobacco smoking has becoming popular especially among young people worldwide. Smokers are attracted by its sweeter, smoother smoke, social ambience and the misconception of reduced harm. The objective of this study was to systematically review the effects of waterpipe tobacco policies and practices in reducing its prevalence.

    MATERIALS AND METHODS: A systematic review was conducted electronically using the PubMed, OVID, Science Direct, Proquest and Embase databases. All possible studies from 1980 to 2013 were initially screened based on titles and abstracts. The selected articles were subjected to data extraction and quality rating.

    RESULTS: Three studies met the inclusion criteria and were eligible for this review. Almost all of the waterpipe tobacco products and its accessories did not comply with the regulations on health warning labelling practices as stipulated under Article 11 of WHO FCTC. In addition, the grisly new warning labels for cigarettes introduced by Food and Drug Administration did not affect hookah tobacco smoking generally. Indoor air quality in smoking lounges was found to be poor and some hookah lounges were operated without smoke shop certification.

    CONCLUSIONS: Our findings revealed the availability of minimal information on the practices in controlling waterpipe smoking in reducing its prevalence. The lack of comprehensive legislations or practices in controlling waterpipe smoking warrants further research and policy initiatives to curb this burgeoning global epidemic, especially among the vulnerable younger population.
  19. MALDI Mass Spectrometry Imaging of Early- and Late-Stage Serous Ovarian Cancer Tissue Reveals Stage-Specific N-Glycans
    Briggs MT, Condina MR, Ho YY, Everest-Dass AV, Mittal P, Kaur G, et al.
    Proteomics, 2019 11;19(21-22):e1800482.
    PMID: 31364262 DOI: 10.1002/pmic.201800482
    Epithelial ovarian cancer is one of the most fatal gynecological malignancies in adult women. As studies on protein N-glycosylation have extensively reported aberrant patterns in the ovarian cancer tumor microenvironment, obtaining spatial information will uncover tumor-specific N-glycan alterations in ovarian cancer development and progression. matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is employed to investigate N-glycan distribution on formalin-fixed paraffin-embedded ovarian cancer tissue sections from early- and late-stage patients. Tumor-specific N-glycans are identified and structurally characterized by porous graphitized carbon-liquid chromatography-electrospray ionization-tandem mass spectrometry (PGC-LC-ESI-MS/MS), and then assigned to high-resolution images obtained from MALDI-MSI. Spatial distribution of 14 N-glycans is obtained by MALDI-MSI and 42 N-glycans (including structural and compositional isomers) identified and structurally characterized by LC-MS. The spatial distribution of oligomannose, complex neutral, bisecting, and sialylated N-glycan families are localized to the tumor regions of late-stage ovarian cancer patients relative to early-stage patients. Potential N-glycan diagnostic markers that emerge include the oligomannose structure, (Hex)6 + (Man)3 (GlcNAc)2 , and the complex neutral structure, (Hex)2 (HexNAc)2 (Deoxyhexose)1 + (Man)3 (GlcNAc)2 . The distribution of these markers is evaluated using a tissue microarray of early- and late-stage patients.
  20. Functional contribution of α1D-adrenoceptors in the renal vasculature of left ventricular hypertrophy induced with isoprenaline and caffeine in Wistar-Kyoto rats
    Ahmad A, Sattar MA, Rathore HA, Abdulla MH, Khan SA, Abdullah NA, et al.
    Can J Physiol Pharmacol, 2014 Dec;92(12):1029-35.
    PMID: 25403946 DOI: 10.1139/cjpp-2014-0236
    This study investigated the role of α1D-adrenoceptor in the modulation of renal haemodynamics in rats with left ventricular hypertrophy (LVH). LVH was established in Wistar-Kyoto (WKY) rats with isoprenaline (5.0 mg · (kg body mass)(-1), by subcutaneous injection every 72 h) and caffeine (62 mg · L(-1) in drinking water, daily for 14 days). Renal vasoconstrictor responses were measured for noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) before and immediately after low or high dose intrarenal infusions of BMY 7378, a selective α1D-adrenoceptor blocker. The rats with LVH had higher mean arterial blood pressure and circulating NA levels, but lower renal cortical blood perfusion compared with the control group (all P < 0.05). In the LVH group, the magnitude of the renal vasoconstrictor response to ME was blunted, but not the response to NA or PE (P < 0.05), compared with the control group (LVH vs. C, 38% vs. 50%). The magnitude of the drop in the vasoconstrictor responses to NA, PE, and ME in the presence of a higher dose of BMY 7378 was significantly greater in the LVH group compared with the control group (LVH vs. C, 45% vs. 25% for NA, 52% vs. 33% for PE, 66% vs. 53% for ME, all P < 0.05). These findings indicate an impaired renal vasoconstrictor response to adrenergic agonists during LVH. In addition, the α1D-adrenoceptor subtype plays a key role in the modulation of vascular responses in this diseased state.
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