Displaying publications 61 - 80 of 92 in total

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  1. Awang K, Mukhtar MR, Mustafa MR, Litaudon M, Shaari K, Mohamad K, et al.
    Nat Prod Res, 2007 Jul 10;21(8):704-9.
    PMID: 17616898
    The leaves of the Phoebe scortechinii (Gamb.) Kochummen Comb. Nov. (Lauraceae), afforded one new proaporphine-tryptamine dimer; (-)-phoebescortechiniine (1), along with two known ones; phoebegrandine A and phoebegrandine B. The proaporphine, tetrahydropronuciferine (2), was isolated for the first time as a natural product. The alkaloids were elucidated primarily by means of high field NMR and HRMS.
  2. Hasanpourghadi M, Abdul Majid N, Rais Mustafa M
    PeerJ, 2018;6:e5577.
    PMID: 30245930 DOI: 10.7717/peerj.5577
    Combination Index (CI) analysis suggested that MBIC and doxorubicin synergistically inhibited up to 97% of cell proliferation in ER+/PR+MCF-7 and triple negative MDA-MB-231 breast cancer cell lines. Moreover, treatment of the breast cancer cells with the combined drugs resulted in lower IC50 values in contrast to the individual drug treatment. Small noncoding microRNAs (miRNA) may function as non-mutational gene regulators at post-transcriptional level of protein synthesis. In the present study, the effect of the combined treatment of MBIC and doxorubicin on the expression level of several miRNAs including miR-34a, miR-146a, miR-320a and miR-542 were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. These miRNAs have the potential to alter the protein level of survivin, the anti-apoptotic protein and reduce the metastatic activity in human breast cancer cell lines by interfering with the nuclear accumulation of NF-κB. Our results demonstrated the several fold changes in expression of miRNAs, which is drug and cell line dependent. This finding demonstrated a functional synergistic network between miR-34a, miR-320a and miR-542 that are negatively involved in post-transcriptional regulation of survivin in MCF-7 cells. While in MDA-MB-231 cells, changes in expression level of miR-146a was correlated with inhibition of the nuclear translocation of NF-κB. The overall result suggested that alteration in protein level and location of survivin and NF-κB by miR-34a, miR-320a, miR-146a and miR-542, remarkably influenced the synergistic enhancement of combined MBIC and doxorubicin in treatment of aggressive and less aggressive human breast cancer cell lines.
  3. Mustafa MG, Rajaee AH, Hamli H, A Rahim KA
    PeerJ, 2021;9:e12183.
    PMID: 34721960 DOI: 10.7717/peerj.12183
    The length-weight relationships (LWRs), condition factor (Kn), growth, mortality and exploitation status of three polynemid fishes, i.e., Filimanus xanthonema (Valenciennes, 1831), Polynemus melanochir (Valenciennes, 1831) and Polynemus paradiseus (Linnaeus, 1758) from Batang Lassa River estuary were estimated. Fish samples were caught during April 2019 to September 2020 using the ESBN (locally called Gnian) having 1.25 to 4.00 cm mesh size. The total length (TL) and body weight of each individual fish was measured to the nearest 0.1 cm and 0.01 g respectively. The growth coefficients (b) for F. xanthonema, P. melanochir and P. paradiseus, were 2.880, 2.717 and 2.724 with the R 2 values 0.956, 0.972 and 0.936 respectively. Estimated growth coefficients indicated a negative allometric growth pattern for all three threadfin fishes. To date, information regarding length-weight relationships for F. xanthonema and P. melanochir is insufficient whereas the information is available for P. paradiseus. About 40-48% of fishes exhibited flat or thin body shape (Kn < 1), 48-50% were rounded or fat (Kn > 1) and only 1-3% of fishes showed proportional body shape (Kn = 1). The growth parameters L∞ , K and ϕ' were estimated at 15.75 cm, 0.95 yr-1 and 2.37 for F. xanthonema; 27.61 cm 0.87 yr-1 and 2.82 for P. melanochir; and 27.30 cm, 0.58 yr-1 and 2.64 for P. paradiseus; respectively. The estimated natural mortality (M) included 2.10, 1.69 and 1.30 yr-1; the fishing mortality (F) 0.57, 0.67 and 0.60 yr-1; and exploitation ratio (E) 0.21, 0.28 and 0.31 for F. xanthonema, P. melanochir and P. paradiseus respectively. The study concluded that the stocks are still under exploitation (E < 0.5) condition. However, the studied Batang Lassa estuary could be a potential nursery ground considering the minimum lengths of 5.0, 3.8 and 4.0 cm for F. xanthonema, P. melanochir and P. paradiseus respectively. Therefore, management initiatives are needed to escape juvenile catches.
  4. Dharmani M, Mustafa MR, Achike FI, Sim MK
    Peptides, 2008 Oct;29(10):1773-80.
    PMID: 18603328 DOI: 10.1016/j.peptides.2008.05.017
    Angiotensin II is known to act primarily on the angiotensin AT(1) receptors to mediate its physiological and pathological actions. Des-aspartate-angiotensin I (DAA-I) is a bioactive angiotensin peptide and have been shown to have contrasting vascular actions to angiotensin II. Previous work in this laboratory has demonstrated an overwhelming vasodepressor modulation on angiotensin II-induced vasoconstriction by DAA-I. The present study investigated the involvement of the AT(1) receptor in the actions of DAA-I on angiotensin II-induced vascular actions in the renal vasculature of normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and streptozotocin (STZ)-induced diabetic rats. The findings revealed that the angiotensin receptor in rat kidney homogenate was mainly of the AT(1) subtype. The AT(1) receptor density was significantly higher in the kidney of the SHR. The increase in AT(1) receptor density was also confirmed by RT-PCR and Western blot analysis. In contrast, AT(1) receptor density was significantly reduced in the kidney of the streptozotocin-induced diabetic rat. Perfusion with 10(-9)M DAA-I reduced the AT(1) receptor density in the kidneys of WKY and SHR rats suggesting that the previously observed vasodepressor modulation of the nonapeptide could be due to down-regulation or internalization of AT(1) receptors. RT-PCR and Western blot analysis showed no significant changes in the content of AT(1) receptor mRNA and protein. This supports the suggestion that DAA-I causes internalization of AT(1) receptors. In the streptozotocin-induced diabetic rat, no significant changes in renal AT(1) receptor density and expression were seen when its kidneys were similarly perfused with DAA-I.
  5. Tan PJ, Appleton DR, Mustafa MR, Lee HB
    Phytochem Anal, 2012 Jan-Feb;23(1):52-9.
    PMID: 21692117 DOI: 10.1002/pca.1324
    Photodynamic therapy is a treatment modality that involves site-directed generation of cytotoxic reactive oxygen species by light-activated photosensitisers.
  6. Chung LY, Yap KF, Goh SH, Mustafa MR, Imiyabir Z
    Phytochemistry, 2008 May;69(7):1548-54.
    PMID: 18334259 DOI: 10.1016/j.phytochem.2008.01.024
    The bark extract of Melicope subunifoliolata (Stapf) T.G. Hartley showed competitive muscarinic receptor binding activity. Six polymethoxyflavones [melibentin (1); melisimplexin (3); 3,3',4',5,7-pentamethoxyflavone (4); meliternatin (5); 3,5,8-trimethoxy-3',4',6,7-bismethylenedioxyflavone (6); and isokanugin (7)] and one furanocoumarin [5-methoxy-8-geranyloxypsoralen (2)] were isolated from the bark extract. Compounds 2 and 6 were isolated for the first time from M. subunifoliolata. The methoxyflavones (compounds 1, 3, 4, 5, 6, and 7) show moderate inhibition in a muscarinic receptor binding assay, while the furanocoumarin (compound 2) is inactive. The potency of the methoxyflavones to inhibit [(3)H]NMS-muscarinic receptor binding is influenced by the position and number of methoxy substitution. The results suggest these compounds are probably muscarinic modulators, agonists or partial agonists/antagonists.
  7. Othman R, Ibrahim H, Mohd MA, Mustafa MR, Awang K
    Phytomedicine, 2006 Jan;13(1-2):61-6.
    PMID: 16360934
    Bioassay-guided fractionation was performed on a crude dichloromethane extract of Kaempferia galanga L. using chromatography techniques. Screening of the extract for biological activity started with the brine shrimp lethality bioassay, followed by the study of its antihypertensive activity on anaesthetized rats, which involved monitoring of the extract's effect on mean arterial blood pressure. The components of the fractions obtained from the separation procedures were analyzed using gas chromatography (GC). The yield of the CH(2)Cl(2) extract was 0.29% of the crude plant extract. Analysis of the data for brine shrimp lethality test using the Finney computer program showed that this extract exhibited potent bioactivity with an ED(50) value of 7.92+/-0.13 microgml(-1). Intravenous administration of the extract induced a dose-related reduction of basal mean arterial pressure (MAP) (130+/-5 mmHg) in the anaesthetized rat, with maximal effects seen after 5-10 min of injection. The gas chromatogram showed that the common compound in the active fractions obtained from the bioassay-guided fractionation of the CH(2)Cl(2) extract was ethyl cinnamate. This vasorelaxant active compound, ethyl cinnamate, was isolated as a colorless oil. Ethyl p-methoxycinnamic acid was also isolated as white needles but did not exhibit any relaxant effect on the precontracted thoracic rat aorta.
  8. Dharmani M, Kamarulzaman K, Giribabu N, Choy KW, Zuhaida MZ, Aladdin NA, et al.
    Phytomedicine, 2019 Dec;65:153101.
    PMID: 31648126 DOI: 10.1016/j.phymed.2019.153101
    BACKGROUND: Oestrogen deficiency leads to metabolic disturbances such as insulin resistance and impairment of adipose tissue or lipid metabolism. Marantodes pumilum (Blume) Kuntze (Primulaceae) is believed to have phytoestrogenic properties and is claimed to have beneficial effects in the treatment of diabetes mellitus (DM), but the mechanism behind its phytoestrogenic effects on estrogen-deficient diabetic condition have not been fully examined.

    PURPOSE: The present study investigated the effects of oral treatment with M. pumilum var. alata (MPA) extracts on the estrogen receptor, metabolic characteristics and insulin signaling pathway in pancreas and liver of ovariectomised nicotidamide streptozotocin-induced diabetes in female rats.

    MATERIALS AND METHODS: Ovariectomised diabetic (OVXS) Sprague-Dawley rats were orally administered with either aqueous leaf extract and ethanol (50%) stem-root extract of MPA (50 or 100 mg/kg) respectively for 28 days. Metabolic parameters were evaluated by measuring fasting blood glucose, serum insulin, oral glucose and insulin tolerance test. Distribution and expression level of insulin, oxidative stress and inflammatory marker in the pancreatic islets and liver were evaluated by immunohistochemistry and western blot, respectively.

    RESULTS: Oral treatment with aqueous leaf and ethanol (50%) stem-root extracts of MPA (100 mg/kg) significantly reversed the elevated fasting blood glucose, impaired glucose and insulin tolerance. The protein expression of insulin, glucose transporter (GLUT-2 and GLUT-4) increased in the pancreatic islets and liver. Furthermore, marked improvement in the tissue morphology following treatment with MPA was observed. Similarly, the western blots analysis denotes improved insulin signaling in the liver and decreased reactive oxygen species producing enzymes, inflammatory and pro-apoptotic molecules with MPA treatment.

    CONCLUSIONS: Taken together, this work demonstrate that 100 mg/kg of aqueous leaf extract and ethanol (50%) stem-root extract of MPA improves β-cell function and insulin signaling in postmenopausal diabetes through attenuation of oxidative stress and partially mediated by oestrogen receptor stimulation.

  9. Abdul Manaf MR, Mustafa M, Abdul Rahman MR, Yusof KH, Abd Aziz NA
    PLoS One, 2016;11(6):e0156937.
    PMID: 27280529 DOI: 10.1371/journal.pone.0156937
    BACKGROUND AND PURPOSE: Mental health problems are common in old age, but frequently remain undetected and untreated. Mental health problems in the elderly are the result of a complex interaction of social, psychological and biological factors. The aim of this study is to determine the prevalence of mental health problems (depression, anxiety, and emotional stress) and their associated factors among the Malay elderly in a rural community of Perak, Malaysia.

    METHODS: It was a cross-sectional study. The Malay elderly aged 60 years and above were selected through convenient sampling to give a total of 230 respondents. The Depression, Anxiety, and Stress Scale (DASS-21) was used to assess the symptoms of depression, anxiety, and stress. Bivariate analyses were performed using chi-square tests and multiple logistic regression analyses were conducted to determine the association between the factors and each of the mental health statuses assessed.

    RESULTS: The results showed that the prevalence of depression, anxiety, and stress among the elderly respondents was 27.8%, 22.6%, and 8.7%, respectively. The significant factors for depression were single elderly (Adjusted OR = 3.27, 95%CI 1.66, 6.44), living with family (Adjusted OR = 4.98, 95%CI 2.05, 12.10), and poor general health status (Adjusted OR = 2.28, 95%CI 1.20, 4.36). Living with family was the only significant factor for anxiety (Adjusted OR = 2.68, 95%CI 1.09, 6.57). There was no significant factor for stress.

    CONCLUSIONS: Depression and anxiety among the Malay elderly in the rural community were very worrying. More equity in health should be created or strengthened in order to intensify the opportunity to identify, diagnose, and treat those with mental health problems. Living arrangement in the rural community was an important factor that had influenced depression and anxiety. Therefore, further research is recommended for more comprehensive information, as a result of which appropriate intervention can be made.

  10. Haridan US, Mokhtar U, Machado LR, Abdul Aziz AT, Shueb RH, Zaid M, et al.
    PLoS One, 2015;10(1):e0116791.
    PMID: 25594501 DOI: 10.1371/journal.pone.0116791
    The FCGR3 locus encoding the low affinity activating receptor FcγRIII, plays a vital role in immunity triggered by cellular effector and regulatory functions. Copy number of the genes FCGR3A and FCGR3B has previously been reported to affect susceptibility to several autoimmune diseases and chronic inflammatory conditions. However, such genetic association studies often yield inconsistent results; hence require assays that are robust with low error rate. We investigated the accuracy and efficiency in estimating FCGR3 CNV by comparing Sequenom MassARRAY and paralogue ratio test-restriction enzyme digest variant ratio (PRT-REDVR). In addition, since many genetic association studies of FCGR3B CNV were carried out using real-time quantitative PCR, we have also included the evaluation of that method's performance in estimating the multi-allelic CNV of FCGR3B. The qPCR assay exhibited a considerably broader distribution of signal intensity, potentially introducing error in estimation of copy number and higher false positive rates. Both Sequenom and PRT-REDVR showed lesser systematic bias, but Sequenom skewed towards copy number normal (CN = 2). The discrepancy between Sequenom and PRT-REDVR might be attributed either to batch effects noise in individual measurements. Our study suggests that PRT-REDVR is more robust and accurate in genotyping the CNV of FCGR3, but highlights the needs of multiple independent assays for extensive validation when performing a genetic association study with multi-allelic CNVs.
  11. Boettiger DC, Kerr S, Ditangco R, Merati TP, Pham TT, Chaiwarith R, et al.
    PLoS One, 2014;9(9):e106525.
    PMID: 25184314 DOI: 10.1371/journal.pone.0106525
    Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes.
  12. Chen M, Wong WW, Law MG, Kiertiburanakul S, Yunihastuti E, Merati TP, et al.
    PLoS One, 2016;11(3):e0150512.
    PMID: 26933963 DOI: 10.1371/journal.pone.0150512
    BACKGROUND: We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region.

    METHODS: Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.

    RESULTS: A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.

    CONCLUSION: In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.

  13. Alomar MK, Khaleel F, Aljumaily MM, Masood A, Razali SFM, AlSaadi MA, et al.
    PLoS One, 2022;17(11):e0277079.
    PMID: 36327280 DOI: 10.1371/journal.pone.0277079
    Atmospheric air temperature is the most crucial metrological parameter. Despite its influence on multiple fields such as hydrology, the environment, irrigation, and agriculture, this parameter describes climate change and global warming quite well. Thus, accurate and timely air temperature forecasting is essential because it provides more important information that can be relied on for future planning. In this study, four Data-Driven Approaches, Support Vector Regression (SVR), Regression Tree (RT), Quantile Regression Tree (QRT), ARIMA, Random Forest (RF), and Gradient Boosting Regression (GBR), have been applied to forecast short-, and mid-term air temperature (daily, and weekly) over North America under continental climatic conditions. The time-series data is relatively long (2000 to 2021), 70% of the data are used for model calibration (2000 to 2015), and the rest are used for validation. The autocorrelation and partial autocorrelation functions have been used to select the best input combination for the forecasting models. The quality of predicting models is evaluated using several statistical measures and graphical comparisons. For daily scale, the SVR has generated more accurate estimates than other models, Root Mean Square Error (RMSE = 3.592°C), Correlation Coefficient (R = 0.964), Mean Absolute Error (MAE = 2.745°C), and Thiels' U-statistics (U = 0.127). Besides, the study found that both RT and SVR performed very well in predicting weekly temperature. This study discovered that the duration of the employed data and its dispersion and volatility from month to month substantially influence the predictive models' efficacy. Furthermore, the second scenario is conducted using the randomization method to divide the data into training and testing phases. The study found the performance of the models in the second scenario to be much better than the first one, indicating that climate change affects the temperature pattern of the studied station. The findings offered technical support for generating high-resolution daily and weekly temperature forecasts using Data-Driven Methodologies.
  14. Memon A, Wazir Bin Mustafa M, Anjum W, Ahmed A, Ullah S, Altbawi SMA, et al.
    PLoS One, 2022;17(5):e0265611.
    PMID: 35551274 DOI: 10.1371/journal.pone.0265611
    A brushless double-fed induction generator (BDFIG) has shown tremendous success in wind turbines due to its robust brushless design, smooth operation, and variable speed characteristics. However, the research regarding controlling of machine during low voltage ride through (LVRT) need greater attention as it may cause total disconnection of machine. In addition, the BDFIG based wind turbines must be capable of providing controlled amount of reactive power to the grid as per modern grid code requirements. Also, a suitable dynamic response of machine during both normal and fault conditions needs to be ensured. This paper, as such, attempts to provide reactive power to the grid by analytically calculating the decaying flux and developing a rotor side converter control scheme accordingly. Furthermore, the dynamic response and LVRT capability of the BDFIG is enhanced by using one of the very intelligent optimization algorithms called the Salp Swarm Algorithm (SSA). To prove the efficacy of the proposed control scheme, its performance is compared with that of the particle swan optimization (PSO) based controller in terms of limiting the fault current, regulating active and reactive power, and maintaining the stable operation of the power system under identical operating conditions. The simulation results show that the proposed control scheme significantly improves the dynamic response and LVRT capability of the developed BDFIG based wind energy conversion system; thus proves its essence and efficacy.
  15. Tanuma J, Jiamsakul A, Makane A, Avihingsanon A, Ng OT, Kiertiburanakul S, et al.
    PLoS One, 2016;11(8):e0161562.
    PMID: 27560968 DOI: 10.1371/journal.pone.0161562
    BACKGROUND: In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use.

    METHODS: We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression.

    RESULTS: Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018).

    CONCLUSIONS: Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.

  16. Bilgrami A, Alam MK, Qazi FUR, Maqsood A, Basha S, Ahmed N, et al.
    Polymers (Basel), 2022 Jan 24;14(3).
    PMID: 35160456 DOI: 10.3390/polym14030466
    A vital feature of conservative dentistry is the adhesion of the restorative material to the tooth structure for restoration of the tooth substance lost due to dental decay, trauma, or dental imperfections. In a perfect world, a restorative material should generate a lasting adhesion by bonding the restoration with tooth tissues. The ingress of micro-organisms, oral fluids, molecules, and ions through microscopic spaces due to faulty adhesion between restoration and tooth structure is known as microleakage. This study is focuses on the evaluation of adhesive failures between the restorative materials. In the past, studies have focused more on the bonding potential of a restorative material with the tooth surface. Therefore, there is need to carry out a study that compares the microleakage between resin-based restorative materials in a sandwich manner with and without the intermediate bonding layer after immersion in 2% methylene blue dye at different time intervals. The restorative materials used were composite Ceram X Mono plus (DENTSPLY) and Z350 (3M ESPE), Vitremer resin modified glass ionomer cement (RMGIC) (3M ESPE), smart dentine replacement SDR (3M ESPE), Bond NT (DENTSPLY), and Universal Bond (3M ESPE). A light emitting diode (LED) was used to cure the specimens. Artificial saliva was used as a storage medium for the specimens. Thermocycling of specimens was carried out at 500 cycles/30 s and 1000 cycles/30 s. The world health organization (WHO) grading tool for microleakage was used to analyze fluid ingress in the specimens through disclosing by 2% methylene blue dye. The statistical analysis was carried out with one-way analysis of variance (ANOVA) and Tukey post hoc test, keeping the level of significance at p ≤ 0.05. In Grade 0 = 85 samples, Grade 1 = 10 samples, Grade 2 = 7 samples, Grade 3 = 16 samples, and in Grade 4 = 2 samples were identified. This study describes that no microleakage was observed in SDR and resin composite groups as compared to Vitremer and resin composite groups.
  17. Dharmani M, Mustafa MR, Achike FI, Sim MK
    Regul. Pept., 2005 Jul 15;129(1-3):213-9.
    PMID: 15927718
    The present study investigated the action of des-aspartate-angiotensin I (DAA-I) on the pressor action of angiotensin II in the renal and mesenteric vasculature of WKY, SHR and streptozotocin (STZ)-induced diabetic rats. Angiotensin II-induced a dose-dependent pressor response in the renal vasculature. Compared to the WKY, the pressor response was enhanced in the SHR and reduced in the STZ-induced diabetic rat. DAA-I attenuated the angiotensin II pressor action in renal vasculature of WKY and SHR. The attenuation was observed for DAA-I concentration as low as 10(-18) M and was more prominent in SHR. However, the ability of DAA-I to reduce angiotensin II response was lost in the STZ-induced diabetic kidney. Instead, enhancement of angiotensin II pressor response was seen at the lower doses of the octapeptide. The effect of DAA-I was not inhibited by PD123319, an AT2 receptor antagonist, and indomethacin, a cyclo-oxygenase inhibitor in both WKY and SHR, indicating that its action was not mediated by angiotensin AT2 receptor and prostaglandins. The pressor responses to angiotensin II in mesenteric vascular bed were also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses were significantly smaller in SHR but no significant difference was observed between STZ-induced diabetic and WKY rat. Similarly, PD123319 and indomethacin had no effect on the action of DAA-I. The findings reiterate a regulatory role for DAA-I in vascular bed of the kidney and mesentery. By being active at circulating level, DAA-I subserves a physiological role. This function appears to be present in animals with diseased state of hypertension and diabetes. It is likely that DAA-I functions are modified to accommodate the ongoing vascular remodeling.
  18. Mustafa MR, Dharmani M, Kunheen NK, Sim MK
    Regul. Pept., 2004 Aug 15;120(1-3):15-22.
    PMID: 15177916
    An earlier study showed that des-aspartate-angiotensin I (DAA-I) attenuated the pressor action of angiotensin III in aortic rings of the spontaneously hypertensive rat (SHR) but not the normotensive Wistar Kyoto (WKY) rat. The present study investigated similar properties of DAA-I in isolated perfused kidneys and mesenteric beds of WKY and SHR. In the renal vasculature, angiotensin III induced a dose-dependent pressor response, which was more marked in the SHR than WKY in terms of significant greater magnitude of response and lower threshold. DAA-I attenuated the pressor action of angiotensin III in both the WKY and SHR. The attenuation in SHR was much more marked, occurring at doses as low as 10(-15) M DAA-I, while effective attenuation was only seen with 10(-9) M in WKY. The effects of DAA-I was not inhibited by PD123319 and indomethacin, indicating that its action was not mediated by angiotensin AT2 receptors and prostaglandins. However, the direct pressor action of angiotensin III in the SHR but not the WKY was attenuated by indomethacin suggesting that this notable difference could be due to known decreased response of renal vasculature to vasodilator prostaglandins in the SHR. Pressor responses to angiotensin III in the mesenteric vascular bed was also dose dependent, but smaller in magnitude compared to the renal response. The responses in the SHR, though generally smaller, were not significantly different from those of the WKY. This trend is in line with the similar observations with angiotensin III and II by other investigators. In terms of the effect of DAA-I, indomethacin and PD123319 on angiotensin III action, similar patterns to those of the renal vasculature were observed. This reaffirms that in the perfused kidney and mesenteric bed, where the majority of the vessels are contractile, femtomolar concentrations of DAA-I attenuates the pressor action of angiotensin III. The attenuation is not indomethacin sensitive and does not involve the angiotensin AT2 receptor. The findings suggest that DAA-I possesses protective vascular actions and is involved in the pathophysiology of hypertension.
  19. Mustafa M, Hatah E, Makmor-Bakry M
    Res Social Adm Pharm, 2023 Apr;19(4):673-680.
    PMID: 36529621 DOI: 10.1016/j.sapharm.2022.12.005
    BACKGROUND: Pharmacists' roles have been evolving to include more patient-centered care services such as medication reviews that help patients receive the most benefits from their medication. In Malaysia, medication review is yet to be widely implemented in the community pharmacy setting for several reasons, including the non-dispensing separation healthcare system. To establish and implement a feasible medication review service model in Malaysia, it is important to gather community pharmacists' perspectives on such services.

    AIM: To explore community pharmacists' perceptions of barriers, facilitators, and strategies for the implementation of a medication review service in Malaysia.

    METHODS: A focus group discussion followed by semi-structured interviews were conducted among purposively sampled community pharmacists with an interest in medication review service. A framework analysis approach using the consolidated framework for implementation research (CFIR) was utilized to generate and analyze the data. After data mapping, the CFIR-ERIC (expert recommendations for implementing change) matching tool was used to generate the strategies according to the barriers identified.

    RESULTS: Twenty community pharmacists participated in this study. Several barriers and facilitators to service implementation were identified based on the respondent's input. The CFIR-ERIC strategies matching tool analysis reported potential plans that can mitigate the barriers such as: identify and prepare champions, conduct local consensus discussions, conduct educational meetings, alter incentive/allowance structures, and develop a formal implementation blueprint.

    CONCLUSION: Multifaceted strategies are required to ensure the successful implementation of medication review services in Malaysia. The findings of this study will assist in the development of a sustainable medication review service blueprint for the Malaysian community pharmacy setting.

  20. Lee SH, Yeoh ZX, Sachlin IS, Gazali N, Soelar SA, Foo CY, et al.
    Sci Rep, 2022 02 08;12(1):2111.
    PMID: 35136124 DOI: 10.1038/s41598-022-06029-6
    Alterations in the three chemosensory modalities-smell, taste, and chemesthesis-have been implicated in Coronavirus Disease 2019 (COVID-19), yet emerging data suggest a wide geographic and ethnic variation in the prevalence of these symptoms. Studies on chemosensory disorders in COVID-19 have predominantly focused on Caucasian populations whereas Asians remain understudied. We conducted a nationwide, multicentre cross-sectional study using an online questionnaire on a cohort of RT-PCR-confirmed adult COVID-19 patients in Malaysia between 6 June and 30 November 2020. The aim of our study was to investigate their presenting symptoms and assess their chemosensory function using self-ratings of perceived smell, taste, chemesthesis, and nasal blockage. In this cohort of 498 patients, 41.4% reported smell and/or taste loss when diagnosed with COVID-19, which was the commonest symptom. Blocked nose, loss of appetite, and gastrointestinal disturbances were independent predictors of smell and/or taste loss on multivariate analysis. Self-ratings of chemosensory function revealed a reduction in smell, taste, and chemesthesis across the entire cohort of patients that was more profound among those reporting smell and/or taste loss as their presenting symptom. Perceived nasal obstruction accounted for only a small proportion of changes in smell and taste, but not for chemesthesis, supporting viral disruption of sensorineural mechanisms as the dominant aetiology of chemosensory dysfunction. Our study suggests that chemosensory dysfunction in COVID-19 is more widespread than previously reported among Asians and may be related to the infectivity of viral strains.Study Registration: NMRR-20-934-54803 and NCT04390165.
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