Displaying publications 361 - 380 of 382 in total

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  1. Hong YH, Frugier T, Zhang X, Murphy RM, Lynch GS, Betik AC, et al.
    J Appl Physiol (1985), 2015 May 1;118(9):1113-21.
    PMID: 25749441 DOI: 10.1152/japplphysiol.00056.2015
    Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSμ (nNOSμ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum longus muscles were isolated from nNOSμ(-/-) and nNOSμ(+/+) mice. Muscles were contracted ex vivo in a temperature-controlled (30°C) organ bath with or without the presence of the NOS inhibitor N(G)-monomethyl-l-arginine (L-NMMA) and the NOS substrate L-arginine. Glucose uptake was determined by radioactive tracers. Skeletal muscle glucose uptake increased approximately fourfold during contraction in muscles from both nNOSμ(-/-) and nNOSμ(+/+) mice. L-NMMA significantly attenuated the increase in muscle glucose uptake during contraction in both genotypes. This attenuation was reversed by L-arginine, suggesting that L-NMMA attenuated the increase in muscle glucose uptake during contraction by inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of NOS activity (~4%) were detected in muscles from nNOSμ(-/-) mice, and there was no evidence of compensation from other NOS isoform or AMP-activated protein kinase which is also involved in mediating muscle glucose uptake during contraction. These results indicate that NO regulates skeletal muscle glucose uptake during ex vivo contraction independently of nNOSμ.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  2. Hwong WY, Bots ML, Selvarajah S, Abdul Aziz Z, Sidek NN, Spiering W, et al.
    PLoS One, 2016;11(11):e0166524.
    PMID: 27846309 DOI: 10.1371/journal.pone.0166524
    BACKGROUND: The increase in angiotensin II (Ang II) formation by selected antihypertensive drugs is said to exhibit neuroprotective properties, but this translation into improvement in clinical outcomes has been inconclusive. We undertook a study to investigate the relationship between types of antihypertensive drugs used prior to a stroke event and ischemic stroke severity. We hypothesized that use of antihypertensive drugs that increase Ang II formation (Ang II increasers) would reduce ischemic stroke severity when compared to antihypertensive drugs that suppress Ang II formation (Ang II suppressors).

    METHODS: From the Malaysian National Neurology Registry, we included hypertensive patients with first ischemic stroke who presented within 48 hours from ictus. Antihypertensive drugs were divided into Ang II increasers (angiotensin-I receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics) and Ang II suppressors (angiotensin-converting-enzyme inhibitors (ACEIs) and beta blockers). We evaluated stroke severity during admission with the National Institute of Health Stroke Scale (NIHSS). We performed a multivariable logistic regression with the score being dichotomized at 15. Scores of less than 15 were categorized as less severe stroke.

    RESULTS: A total of 710 patients were included. ACEIs was the most commonly prescribed antihypertensive drug in patients using Ang II suppressors (74%) and CCBs, in patients prescribed with Ang II increasers at 77%. There was no significant difference in the severity of ischemic stroke between patients who were using Ang II increasers in comparison to patients with Ang II suppressors (OR: 1.32, 95%CI: 0.83-2.10, p = 0.24).

    CONCLUSION: In our study, we found that use of antihypertensive drugs that increase Ang II formation was not associated with less severe ischemic stroke as compared to use of antihypertensive drugs that suppress Ang II formation.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  3. Malami I, Abdul AB, Abdullah R, Kassim NK, Rosli R, Yeap SK, et al.
    PLoS One, 2017;12(1):e0170233.
    PMID: 28103302 DOI: 10.1371/journal.pone.0170233
    Uridine-cytidine kinase 2 is an enzyme that is overexpressed in abnormal cell growth and its implication is considered a hallmark of cancer. Due to the selective expression of UCK2 in cancer cells, a selective inhibition of this key enzyme necessitates the discovery of its potential inhibitors for cancer chemotherapy. The present study was carried out to demonstrate the potentials of natural phytochemicals from the rhizome of Alpinia mutica to inhibit UCK2 useful for colorectal cancer. Here, we employed the used of in vitro to investigate the effectiveness of natural UCK2 inhibitors to cause HT-29 cell death. Extracts, flavokawain B, and alpinetin compound from the rhizome of Alpinia mutica was used in the study. The study demonstrated that the expression of UCK2 mRNA were substantially reduced in treated HT-29 cells. In addition, downregulation in expression of 18S ribosomal RNA was also observed in all treated HT-29 cells. This was confirmed by fluorescence imaging to measure the level of expression of 18S ribosomal RNA in live cell images. The study suggests the possibility of MDM2 protein was downregulated and its suppression subsequently activates the expression of p53 during inhibition of UCK2 enzyme. The expression of p53 is directly linked to a blockage of cell cycle progression at G0/G1 phase and upregulates Bax, cytochrome c, and caspase 3 while Bcl2 was deregulated. In this respect, apoptosis induction and DNA fragmentation were observed in treated HT-29 cells. Initial results from in vitro studies have shown the ability of the bioactive compounds of flavokawain B and alpinetin to target UCK2 enzyme specifically, inducing cell cycle arrest and subsequently leading to cancer cell death, possibly through interfering the MDM2-p53 signalling pathway. These phenomena have proven that the bioactive compounds could be useful for future therapeutic use in colon cancer.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  4. Subramanian R, Asmawi MZ, Sadikun A
    Acta Biochim. Pol., 2008;55(2):391-8.
    PMID: 18511986
    There has been an enormous interest in the development of alternative medicines for type 2 diabetes, specifically screening for phytochemicals with the ability to delay or prevent glucose absorption. The goal of the present study was to provide in vitro evidence for potential inhibition of alpha-glucosidase and alpha-amylase enzymes, followed by a confirmatory in vivo study on rats to generate a stronger biochemical rationale for further studies on the ethanolic extract of Andrographis paniculata and andrographolide. The extract showed appreciable alpha-glucosidase inhibitory effect in a concentration-dependent manner (IC(50)=17.2+/-0.15 mg/ml) and a weak alpha-amylase inhibitory activity (IC(50)=50.9+/-0.17 mg/ml). Andrographolide demonstrated a similar (IC(50)=11.0+/-0.28 mg/ml) alpha-glucosidase and alpha-amylase inhibitory activity (IC(50)=11.3+/-0.29 mg/ml). The positive in vitro enzyme inhibition tests paved way for confirmatory in vivo studies. The in vivo studies demonstrated that A. paniculata extract significantly (P<0.05) reduced peak blood glucose and area under curve in diabetic rats when challenged with oral administration of starch and sucrose. Further, andrographolide also caused a significant (P<0.05) reduction in peak blood glucose and area under the curve in diabetic rats. Hence alpha-glucosidase inhibition may possibly be one of the mechanisms for the A. paniculata extract to exert antidiabetic activity and indicates that AP extract can be considered as a potential candidate for the management of type 2 diabetes mellitus.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  5. Kamisah Y, Zuhair JSF, Juliana AH, Jaarin K
    Biomed Pharmacother, 2017 Dec;96:291-298.
    PMID: 28992471 DOI: 10.1016/j.biopha.2017.09.095
    Parkia speciosa Hassk is a plant found abundantly in Southeast Asia region. Its seeds with or without pods and roots have been used in traditional medicine in this region to treat hypertension. Therefore, we aimed to investigate the potential effect of the plant empty pod extract on hypertension development and changes in heart induced by N(G)-nitro-l-arginine methyl ester (l-NAME) administration in rats. Twenty-four male Sprague Dawley rats were divided into four groups. Groups 1 to 3 were given l-NAME (25mg/kg, intraperitoneally) for 8 weeks. Groups 2 and 3 were also given Parkia speciosa empty pods methanolic extract (800mg/kg, orally) and nicardipine (3mg/kg, orally), concurrently with l-NAME. The last group served as the control. l-NAME reduced plasma nitric oxide level and therefore, increased systolic blood pressure, angiotensin-converting enzyme and NADPH oxidase activities as well as lipid peroxidation in the heart. Parkia speciosa extract and nicardipine treatments had significantly prevented the elevations of blood pressure, angiotensin-converting enzyme, NADPH oxidase activities and lipid peroxidation in the heart induced by the l-NAME. Parkia speciosa extract but not nicardipine prevented the reduction in plasma nitric oxide level caused by l-NAME. In conclusion, Parkia speciosa empty pods methanolic extract has a potential to prevent the development of hypertension possibly by preventing the loss of plasma nitric oxide, as well as has cardioprotective effects by reducing angiotensin-converting enzyme activity and oxidative stress in the heart in rats administered l-NAME.
    Matched MeSH terms: Enzyme Inhibitors/toxicity
  6. Sosroseno W, Musa M, Ravichandran M, Fikri Ibrahim M, Bird PS, Seymour GJ
    J Periodontal Res, 2007 Apr;42(2):124-30.
    PMID: 17305870
    Inducible nitric oxide synthase (iNOS) activity is known to regulate the immune response. The present study was carried out to determine the effect of L-N6-(1-iminoethyl)-lysine (L-NIL), an iNOS inhibitor, on the induction of immune response to Actinobacillus actinomycetemcomitans lipopolysaccharide in mice.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*
  7. Lim KK, Sivasampu S, Khoo EM
    Singapore Med J, 2015 May;56(5):291-7.
    PMID: 25597751 DOI: 10.11622/smedj.2015019
    As the population ages, the prevalence of hypertension also increases. Although primary care is usually the patient's first point of contact for healthcare, little is known about the management of hypertension among elderly patients at the primary care level. This study aimed to determine the antihypertensive prescription trend for elderly patients, the predictors of antihypertensive use and any inappropriate prescribing practices in both public and private primary care settings.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  8. Joseph P, Pais P, Dans AL, Bosch J, Xavier D, Lopez-Jaramillo P, et al.
    Am Heart J, 2018 Dec;206:72-79.
    PMID: 30342297 DOI: 10.1016/j.ahj.2018.07.012
    BACKGROUND: It is hypothesized that in individuals without clinical cardiovascular disease (CVD), but at increased CVD risk, a 50% to 60% reduction in CVD risk could be achieved using fixed dose combination (FDC) therapy (usually comprised of multiple blood-pressure agents and a statin [with or without aspirin]) in a single "polypill". However, the impact of a polypill in preventing clinical CV events has not been evaluated in a large randomized controlled trial.

    METHODS: TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. Additional interventions in the factorial design of the study will compare the effect of (1) aspirin versus placebo on CV events (and cancer), (2) vitamin D versus placebo on the risk of fractures, and (3) the combined effect of aspirin and the Polycap on CV events.

    RESULTS: The study has randomized 5713 participants across 9 countries. Mean age of the study population is 63.9 years, and 53% are female. Mean INTERHEART risk score is 16.8, which is consistent with a study population at intermediate CVD risk.

    CONCLUSION: Results of the TIP-3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/administration & dosage
  9. Sosroseno W, Sugiatno E, Samsudin AR, Ibrahim F
    J Oral Implantol, 2008;34(4):196-202.
    PMID: 18780564 DOI: 10.1563/0.910.1
    The aim of the present study was to test the hypothesis that the proliferation of a human osteoblast cell line (HOS cells) stimulated with hydroxyapatite (HA) may be regulated by nitric oxide (NO). The cells were cultured on the surface of HA. Medium or cells alone were used as controls. L-arginine, D-arginine, 7-NI (an nNOS inhibitor), L-NIL (an iNOS inhibitor), L-NIO (an eNOS inhibitor) or carboxy PTIO, a NO scavenger, was added in the HA-exposed cell cultures. The cells were also precoated with anti-human integrin alphaV antibody. The levels of nitrite were determined spectrophotometrically. Cell proliferation was assessed by colorimetric assay. The results showed increased nitrite production and cell proliferation by HA-stimulated HOS cells up to day 3 of cultures. Anti-integrin alphaV antibody, L-NIO, or carboxy PTIO suppressed, but L-arginine enhanced, nitrite production and cell proliferation of HA-stimulated HOS cells. The results of the present study suggest, therefore, that interaction between HA and HOS cell surface integrin alphaV molecule may activate eNOS to catalyze NO production which, in turn, may regulate the cell proliferation in an autocrine fashion.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  10. Venkatason P, Zubairi YZ, Hafidz I, Wan WA, Zuhdi AS
    Ann Saudi Med, 2016 5 30;36(3):184-9.
    PMID: 27236389 DOI: 10.5144/0256-4947.2016.184
    BACKGROUND: The administration of evidence-based pharmacotherapy and timely primary percutaneous coronary intervention have been shown to improve outcome in ST elevation myocardial infarction (STEMI). However, implementation remains a challenge due to the limitations in facilities, expertise and funding.

    OBJECTIVES: To investigate adherence to guideline-based management and mortality of STEMI patients in Malaysia.

    DESIGN: Retrospective analysis.

    SETTINGS: STEMI patients from 18 participating hospital across Malaysia included in the National Cardiovascular Database-Acute Coronary Syndrome (NCVD-ACS) registry year 2006 to 2013.

    PATIENTS AND METHODS: Patients were categorized into four subgroups based on the year of admission (2006 to 2007, 2008 to 2009, 2010 to 2011 and 2012 to 2013). Baseline characteristics and clinical presentation, in-hospital pharmacotherapy, invasive revascularization and in-hospital/30-day mortality were analysed and compared between the subgroups.

    MAIN OUTCOME MEASURE(S): Rate of in-hospital catheterization/percutaneous coronary intervention.

    RESULTS: The registry contained data on 19483 patients. Intravenous thrombolysis was the main reperfusion therapy. Although the overall rate of in-hospital catheterisation/PCI more than doubled over the study period, while the use of primary PCI only slowly increased from 7.6% in 2006/2007 to 13.6% in 2012/2013. The use of evidence-based oral therapies increased steadily over the years except for ACe-inhibitors and angiotensin-receptor blockers. The adjusted risk ratios (RR) for in-hospital mortality for the four sub-groups have not shown any significant improvement. The 30-day adjusted risk ratios however showed a significant albeit gradual risk reduction (RR 0.773 95% CI 0.679-0.881, P < .001).

    CONCLUSION: Adherence to evidence-based treatment in STEMI in Malaysia is still poor especially in terms of the rate of primary PCI. Although there is a general trend toward reduced 30-day mortality, the reduction was only slight over the study period. Drastic effort is needed to improve adherence and clinical outcomes.

    LIMITATION: Retrospective registry data with inter-hospital variation.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  11. Er JL, Goh PN, Lee CY, Tan YJ, Hii LW, Mai CW, et al.
    Apoptosis, 2018 Jun;23(5-6):343-355.
    PMID: 29740790 DOI: 10.1007/s10495-018-1459-6
    Pancreatic adenocarcinoma (PDAC) is a highly aggressive cancer with a high chance of recurrence, limited treatment options, and poor prognosis. A recent study has classified pancreatic cancers into four molecular subtypes: (1) squamous, (2) immunogenic, (3) pancreatic progenitor and (4) aberrantly differentiated endocrine exocrine. Among all the subtypes, the squamous subtype has the worst prognosis. This study aims to utilize large scale genomic datasets and computational systems biology to identify potential drugs targeting the squamous subtype of PDAC through combination therapy. Using the transcriptomic data available from the International Cancer Genome Consortium, Cancer Cell Line Encyclopedia and Connectivity Map, we identified 26 small molecules that could target the squamous subtype of PDAC. Among them include inhibitors targeting the SRC proto-oncogene (SRC) and the mitogen-activated protein kinase kinase 1/2 (MEK1/2). Further analyses demonstrated that the SRC inhibitors (dasatinib and PP2) and MEK1/2 inhibitor (pimasertib) synergized gemcitabine sensitivity specifically in the squamous subtype of PDAC cells (SW1990 and BxPC3), but not in the PDAC progenitor cells (AsPC1). Further analysis revealed that the synergistic effects are dependent on SRC or MEK1/2 activities, as overexpression of SRC or MEK1/2 completely abrogated the synergistic effects SRC inhibitors (dasatinib and PP2) and MEK1/2 inhibitor (pimasertib). In contrast, no significant toxicity was observed in the MRC5 human lung fibroblast and ARPE-19 human retinal pigment epithelial cells. Together, our findings suggest that combinations of SRC or MEK inhibitors with gemcitabine possess synergistic effects on the squamous subtype of PDAC cells and warrant further investigation.
    Matched MeSH terms: Enzyme Inhibitors/therapeutic use
  12. Chin LC, Achike FI, Mustafa MR
    Vascul Pharmacol, 2007 Mar;46(3):223-8.
    PMID: 17126611 DOI: 10.1016/j.vph.2006.10.005
    Hydrogen peroxide (H(2)O(2)) contributes in the regulation of vascular tone, especially in pathological states. The role of H(2)O(2) and superoxide anion free radicals in angiotensin II (Ang II)-induced contraction of diabetic tissues was examined with the aim of elucidating the underlying mechanisms. Isometric tension in response to various drug treatments was measured in isolated superior mesenteric arteries of streptozotocin (STZ)-induced diabetic WKY rats using the Mulvany wire myograph. Compared to the normal (euglycaemic) arteries, the Ang II-induced contraction was significantly reduced in diabetic arteries. Superoxide dismutase (SOD; converts superoxide to H(2)O(2)) significantly reduced the contraction in both types of arteries -- an effect abolished by catalase (H(2)O(2) scavenger), suggesting that the SOD effect was mediated by H(2)O(2). Treatment with catalase had no effect on the Ang II contraction in euglycaemic arteries, but it raised the contraction in diabetic arteries to euglycaemic levels. This increase was similar to that observed with diabetic arteries incubated with L-NAME. Combined catalase and L-NAME treatment further enhanced the contraction in diabetic arteries, suggesting that the catalase effect was not mediated by nitric oxide (NO). The catalase effect was abolished by indomethacin treatment. These results suggest that attenuation of Ang II-induced contraction in diabetic tissues is modulated by endogenous H(2)O(2), the scavenging of which unmasks an indomethacin-sensitive (and therefore cyclooxygenase product-mediated) Ang II-induced contraction.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  13. Hassan Y, Aziz NA, Al-Jabi SW, Looi I, Zyoud SH
    J Cardiovasc Pharmacol Ther, 2010 Sep;15(3):282-8.
    PMID: 20472813 DOI: 10.1177/1074248410368049
    BACKGROUND: Hypertension and ischemic heart disease (IHD) are among the most prevalent modifiable risk factors for stroke. Clinical trial evidence suggests that antihypertensive medications are recommended for prevention of recurrent ischemic stroke in hypertensive and normotensive patients.
    OBJECTIVES: The objectives of this study were to analyze and evaluate the utilization of antihypertensive medication for acute ischemic stroke (AIS) or transient ischemic attack (TIA) survivors in relation to recent recommendations and guidelines and to compare their use among patients with or without IHD.
    METHODS: This was a retrospective cohort study of all patients with AIS/TIA attending the hospital from July 1, 2008 to December 31, 2008. Demographic data, clinical characteristics, different classes of antihypertensive medications, and different antihypertensive combinations prescribed to AIS/TIA survivors were analyzed among patients with and without IHD. Statistical Package for Social Sciences (SPSS) program version 15 was used for data analysis.
    RESULTS: In all, 383 AIS/TIA survivors were studied, of which 66 (19.5%) had a documented history of IHD. Three quarters (n = 260; 76.9%) of AIS or TIA survivors received antihypertensive medication, mostly as monotherapy, at discharge. The majority of patients (n = 201, 59.5%) were prescribed angiotensin-converting enzyme inhibitors (ACEIs). Patients with IHD were significantly prescribed more β-blockers than patients without IHD (P = .003). A history of hypertension, a history of diabetes mellitus, and age were significantly associated with prescription of antihypertensive medications at discharge (P < .001, P < .001, and P < .001, respectively).
    CONCLUSION: Patterns of antihypertensive therapy were commonly but not adequately consistent with international guidelines. Screening stroke survivors for blood pressure control, initiating appropriate antihypertensive medications, and decreasing the number of untreated patients might help reduce the risk of recurrent strokes and increase survival.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  14. Mohd SM, Abdul Manan MJ
    Malays J Nutr, 2012 Apr;18(1):125-36.
    PMID: 23713236 MyJurnal
    The haruan (Channa striatus) is an indigenous, predatory freshwater fish of Malaysia. It is a common food fish among the local populace with traditionally identified pharmacological benefits in treating wound and pain and in boosting energy of the sick. Channa striatus is also a subject of renewed interest in Malaysian folk medicine in the search for a better cure for diseases and ailments. Amino acids and fatty acids, found in high concentrations in the fish, might have contributed to its pharmacological properties. Important amino acids of the fish include glycine, lysine and arginine, while its fatty acids are arachidonic acid, palmitic acid and docosahexaenoic acid. They appear to effect their influence through the formation of several types of bioactive molecules. Extracts of the fish are produced from whole fish, roe, mucus and skin of the fish. This review updates research findings on potential uses of Channa striatus, beyond the traditional prescription as a wound healer, pain reliever and energy booster to include its properties as a ACE-inhibitor, anti-depressant and neuroregenerative agent. The fish appears to have wide-ranging medical uses and should be studied more intensively to unearth its other properties and mechanisms of action.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
  15. Venkatason P, Zaharan NL, Ismail MD, Wan Ahmad WA, Mahmood Zuhdi AS
    Eur J Clin Pharmacol, 2018 Jul;74(7):953-960.
    PMID: 29582106 DOI: 10.1007/s00228-018-2451-3
    PURPOSE: Information is lacking on prescribing of preventative cardiovascular pharmacotherapies for patients with non-ST elevation myocardial infarction (NSTEMI) in the Asian region. This study examined the prescribing rate of these pharmacotherapies, comparing NSTEMI to STEMI, and variations across demographics and clinical factors within the NSTEMI group in the multi-ethnic Malaysian population.

    METHODS: This is a retrospective analysis of the Malaysian National Cardiovascular Disease Database-Acute Coronary Syndrome registry from year 2006 to 2013 (n = 30,873). On-discharge pharmacotherapies examined were aspirin, ADP-antagonists, statins, ACE-inhibitors, angiotensin-II-receptor blockers, and beta-blockers. Multivariate logistic regression was used to calculate adjusted odds ratio of receiving individual pharmacotherapies according to patients' characteristics in NSTEMI patients (n = 11,390).

    RESULTS: Prescribing rates for cardiovascular pharmacotherapies had significantly increased especially for ADP-antagonists (76%) in NSTEMI patients. More than 85% were prescribed statins and antiplatelets but rates remained significantly lower compared to STEMI. Women and those over 65 years old were less likely to be prescribed these pharmacotherapies compared to men and younger NSTEMI patients. Chinese and Indians were more likely to receive selected pharmacotherapies compared to Malays (main ethnicity). Geographical variations were observed; East Malaysian (Malaysian Borneo) patients were less likely to receive these compared to Western region of Malaysian Peninsular. Underprescribing in patients with risk factors such as diabetes were observed with other co-morbidities influencing prescribing selectively.

    CONCLUSION: This study uncovers demographic and clinical variations in cardiovascular pharmacotherapies prescribing for NSTEMI. Concerted efforts by policy makers, specialty societies, and physicians are required focusing on elderly, women, Malays, East Malaysians, and high-risk patients.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
  16. Lim WY, Chia YY, Liong SY, Ton SH, Kadir KA, Husain SN
    Lipids Health Dis, 2009;8:31.
    PMID: 19638239 DOI: 10.1186/1476-511X-8-31
    The metabolic syndrome (MetS) is a cluster of metabolic abnormalities comprising visceral obesity, dyslipidaemia and insulin resistance (IR). With the onset of IR, the expression of lipoprotein lipase (LPL), a key regulator of lipoprotein metabolism, is reduced. Increased activation of glucocorticoid receptors results in MetS symptoms and is thus speculated to have a role in the pathophysiology of the MetS. Glycyrrhizic acid (GA), the bioactive constituent of licorice roots (Glycyrrhiza glabra) inhibits 11beta-hydroxysteroid dehydrogenase type 1 that catalyzes the activation of glucocorticoids. Thus, oral administration of GA is postulated to ameliorate the MetS.
    Matched MeSH terms: Enzyme Inhibitors/administration & dosage; Enzyme Inhibitors/pharmacology*
  17. Ajay M, Achike FI, Mustafa MR
    Pharmacol Res, 2007 May;55(5):385-91.
    PMID: 17317209
    In this study, we report the effects of a non-antioxidant flavonoid flavone on vascular reactivity in Wistar-Kyoto (WKY) rat isolated aortae. Whether flavone directly modulates vascular reactivity in spontaneously hypertensive rat (SHR) and streptozotocin-induced diabetic-WKY rat isolated aortae was also determined. Thoracic aortic rings were mounted in organ chambers and exposed to various drug treatments in the presence of flavone (10 microM) or its vehicle (DMSO), which served as control. Pretreatment with flavone enhanced relaxant effects to endothelium-dependent vasodilator acetylcholine (ACh) and attenuated contractile effects to alpha(1)-receptor agonist phenylephrine (PE) in WKY aortae compared to those observed in control aortic rings. Flavone had no effect on relaxations to ACh in WKY aortae incubated with either L-NAME or methylene blue, but enhanced relaxations to ACh in WKY aortae incubated with indomethacin or partially depolarized with KCl. Relaxations to ACh are totally abolished in both control or flavone pretreated endothelium-denuded WKY aortae. Flavone attenuated the inhibition by beta-NADH of ACh-induced relaxation in WKY aortae, but it had no significant effect on the transient contractions induced by beta-NADH nor the pyrogallol-induced abolishment of ACh-induced relaxation in WKY aortae. Flavone enhanced endothelium-independent relaxation to sodium nitroprusside (SNP) in both endothelium-intact and -denuded WKY aortae. Flavone enhanced relaxation to ACh and SNP as well as attenuated contractile effects to PE in SHR and diabetic aortae, a finding similar to that observed in normal WKY aortae. From these results, we conclude that flavone modulates vascular reactivity in normal as well as hypertensive and diabetic aortae. These effects of flavone results probably through enhanced bioactivity of nitric oxide released from the endothelium.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  18. Sosroseno W, Barid I, Herminajeng E, Susilowati H
    Oral Microbiol. Immunol., 2002 Apr;17(2):72-8.
    PMID: 11929552
    The aim of this study was to determine whether Actinobacillus actinomycetemcomitans lipopolysaccharide (LPS-A. actinomycetemcomitans) could stimulate a murine macrophage cell line (RAW264.7 cells) to produce nitric oxide (NO). The cells were treated with LPS-A. actinomycetemcomitans or Escherichia coli LPS (LPS-Ec) for 24 h. The effects of N(G)-monomethyl-L-arginine (NMMA), polymyxin B and cytokines (IFN-gamma, TNF-alpha, IL-4 and IL-12) on the production of NO were also determined. The role of protein tyrosine kinase, protein kinase C and microtubulin organization on NO production were assessed by incubating RAW264.7 cells with genistein, bisindolylmaleide and colchicine prior to LPS-A. actinomycetemcomitans stimulation, respectively. NO levels from the culture supernatants were determined by the Griess reaction. The results showed that LPS-A. actinomycetemcomitans stimulated NO production by RAW264.7 cells in a dose-dependent manner, but was slightly less potent than LPS-Ec. NMMA and polymyxin B blocked the production of NO. IFN-gamma and IL-12 potentiated but IL-4 depressed NO production by LPS-A. actinomycetemcomitans-stimulated RAW264.7 cells. TNF-alpha had no effects on NO production. Genistein and bisindolylmalemaide, but not colchicine, reduced the production of NO in a dose-dependent mechanism. The results of the present study suggest that A. actinomycetemcomitans LPS, via the activation of protein tyrosine kinase and protein kinase C and the regulatory control of cytokines, stimulates NO production by murine macrophages.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  19. Freestone B, Rajaratnam R, Hussain N, Lip GY
    Int J Cardiol, 2003 Oct;91(2-3):233-8.
    PMID: 14559136
    BACKGROUND: There are established differences in cardiovascular disease in different racial groups. Worldwide, the literature regarding the clinical epidemiology of atrial fibrillation in non-white populations is scarce.

    OBJECTIVES: To document the prevalence of atrial fibrillation (AF) in the multiracial population of Malaysia, and to describe the clinical features and management of these patients.

    SETTING: Busy city centre general hospital in Kuala Lumpur, Malaysia, over a 1-month period.

    SUBJECTS: One-thousand four hundred and thirty-five acute medical admissions, of whom 40 patients (2.8%) had AF.

    RESULTS: Of 1435 acute medical admissions to Kuala Lumpur General Hospital over the 4-week study period, 40 had AF (21 male, 19 female; mean age 65 years). Of these, 18 were Malay, 16 Chinese and six Indian. Nineteen patients had previously known AF (seven with paroxysmal AF) and 21 were newly diagnosed cases. The principal associated medical conditions were ischaemic heart disease (42.5%), hypertension (40%) and heart failure (40%). Dyspnoea was the commonest presentation, whilst stroke was the cause of presentation in only two patients. Investigations were under-utilised, with chest X-ray and echocardiography in only 62.5% of patients and thyroid function checked in 15%. Only 16% of those with previously diagnosed AF were on warfarin, with a further three on aspirin. Anticoagulant therapy was started in 13.5% of patients previously not on warfarin, and aspirin in 8%. Records of contraindications to warfarin were unreliable, being identified in only 25%. For those with known AF, 58% were on digoxin. For new onset AF, digoxin was again the most common rate-limiting treatment, initiated in 38%, whilst five patients with new onset AF were commenced on amiodarone. DC cardioversion was not used in any of the patients with new onset AF.

    CONCLUSION: Amongst acute medical admissions to a single centre in Malaysia the prevalence of AF was 2.8%. Consistent with previous similar surveys in mainly western (caucasian) populations, standard investigations in this Malaysian cohort were also inadequate and there was underuse of anticoagulation, medication for ventricular rate control and cardioversion to sinus rhythm.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  20. Sosroseno W, Bird PS, Seymour GJ
    J Periodontal Res, 2009 Aug;44(4):529-36.
    PMID: 18973550 DOI: 10.1111/j.1600-0765.2008.01157.x
    Elevated nitric oxide (NO) has been associated with destructive periodontal disease. The aim of the present study was to test the hypothesis that exogenous NO may inhibit a protective immune response to Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) in a murine model.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
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