Displaying publications 261 - 280 of 382 in total

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  1. Fulltext Optimization of an Extraction Solvent for Angiotensin-Converting Enzyme Inhibitors from Hibiscus sabdariffa L. Based on Its UPLC-MS/MS Metabolic Profiling
    Salem MA, Michel HE, Ezzat MI, Okba MM, El-Desoky AM, Mohamed SO, et al.
    Molecules, 2020 May 14;25(10).
    PMID: 32422967 DOI: 10.3390/molecules25102307
    Hibiscus species (Malvaceae) have been long used as an antihypertensive folk remedy. The aim of our study was to specify the optimum solvent for extraction of the angiotensin-converting enzyme inhibiting (ACEI) constituents from Hibiscus sabdariffa L. The 80% methanol extract (H2) showed the highest ACEI activity, which exceeds that of the standard captopril (IC50 0.01255 ± 0.00343 and 0.210 ± 0.005 µg/mL, respectively). Additionally, in a comprehensive metabolomics approach, an ultra-performance liquid chromatography (UPLC) coupled to the high resolution tandem mass spectrometry (HRMS) method was used to trace the metabolites from each extraction method. Interestingly, our comprehensive analysis showed that the 80% methanol extract was predominated with secondary metabolites from all classes including flavonoids, anthocyanins, phenolic and organic acids. Among the detected metabolites, phenolic acids such as ferulic and chlorogenic acids, organic acids such as citrate derivatives and flavonoids such as kaempferol have been positively correlated to the antihypertensive potential. These results indicates that these compounds may significantly contribute synergistically to the ACE inhibitory activity of the 80% methanol extract.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/isolation & purification; Angiotensin-Converting Enzyme Inhibitors/chemistry*
  2. Fulltext In vitro inhibitory potential of selected Malaysian plants against key enzymes involved in hyperglycemia and hypertension
    Loh SP, Hadira O
    Malays J Nutr, 2011 Apr;17(1):77-86.
    PMID: 22135867 MyJurnal
    This study was conducted to determine the inhibitory potential of selected Malaysian plants against key enzymes related to type 2 diabetes and hypertension.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/pharmacology; Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  3. Mechanisms of Antimicrobial Resistance (AMR) and Alternative Approaches to Overcome AMR
    Moo CL, Yang SK, Yusoff K, Ajat M, Thomas W, Abushelaibi A, et al.
    Curr Drug Discov Technol, 2020;17(4):430-447.
    PMID: 30836923 DOI: 10.2174/1570163816666190304122219
    Antimicrobials are useful compounds intended to eradicate or stop the growth of harmful microorganisms. The sustained increase in the rates of antimicrobial resistance (AMR) worldwide is worrying and poses a major public health threat. The development of new antimicrobial agents is one of the critical approaches to overcome AMR. However, in the race towards developing alternative approaches to combat AMR, it appears that the scientific community is falling behind when pitched against the evolutionary capacity of multi-drug resistant (MDR) bacteria. Although the "pioneering strategy" of discovering completely new drugs is a rational approach, the time and effort taken are considerable, the process of drug development could instead be expedited if efforts were concentrated on enhancing the efficacy of existing antimicrobials through: combination therapies; bacteriophage therapy; antimicrobial adjuvants therapy or the application of nanotechnology. This review will briefly detail the causes and mechanisms of AMR as background, and then provide insights into a novel, future emerging or evolving strategies that are currently being evaluated and which may be developed in the future to tackle the progression of AMR.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology; Enzyme Inhibitors/therapeutic use
  4. Synthesis, Antioxidant and In-Silico Studies of Potent Urease Inhibitors: N-(4-{[(4-Methoxyphenethyl)-(substituted)amino]sulfonyl}phenyl)acetamides
    Abbasi MA, Raza H, Rehman AU, Siddiqui SZ, Nazir M, Mumtaz A, et al.
    Drug Res (Stuttg), 2019 Feb;69(2):111-120.
    PMID: 30086567 DOI: 10.1055/a-0654-5074
    In this study, a new series of sulfonamides derivatives was synthesized and their inhibitory effects on DPPH and jack bean urease were evaluated. The in silico studies were also applied to ascertain the interactions of these molecules with active site of the enzyme. Synthesis was initiated by the nucleophilic substitution reaction of 2-(4-methoxyphenyl)-1-ethanamine (1: ) with 4-(acetylamino)benzenesulfonyl chloride (2): in aqueous sodium carbonate at pH 9. Precipitates collected were washed and dried to obtain the parent molecule, N-(4-{[(4-methoxyphenethyl)amino]sulfonyl}phenyl)acetamide (3): . Then, this parent was reacted with different alkyl/aralkyl halides, (4A-M: ), using dimethylformamide (DMF) as solvent and LiH as an activator to produce a series of new N-(4-{[(4-methoxyphenethyl)-(substituted)amino]sulfonyl}phenyl)acetamides (5A-M: ). All the synthesized compounds were characterized by IR, EI-MS, 1H-NMR, 13C-NMR and CHN analysis data. All of the synthesized compounds showed higher urease inhibitory activity than the standard thiourea. The compound 5 F: exhibited very excellent enzyme inhibitory activity with IC50 value of 0.0171±0.0070 µM relative to standard thiourea having IC50 value of 4.7455±0.0546 µM. Molecular docking studies suggested that ligands have good binding energy values and bind within the active region of taget protein. Chemo-informatics properties were evaluated by computational approaches and it was found that synthesized compounds mostly obeyed the Lipinski' rule.
    Matched MeSH terms: Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacology*
  5. Fulltext COVID-19 and hypertension-evidence and practical management: Guidance from the HOPE Asia Network
    Kario K, Morisawa Y, Sukonthasarn A, Turana Y, Chia YC, Park S, et al.
    J Clin Hypertens (Greenwich), 2020 Jul;22(7):1109-1119.
    PMID: 32643874 DOI: 10.1111/jch.13917
    There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID-19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin-angiotensin system (RAS) inhibitors due to a key role of angiotensin-converting enzyme 2 receptors in the entry of the SARS-CoV-2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS-CoV-2 virus infection or worsens the course of COVID-19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID-19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N-terminal pro-B-type natriuretic peptide, D-dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID-19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well-being. For the ongoing management of patients with hypertension, telemedicine-based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID-19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects*; Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  6. Impact of angiotensin-converting enzyme inhibitors administration prior to acute ischemic stroke onset on in-hospital mortality
    Hassan Y, Aziz NA, Al-Jabi SW, Looi I, Zyoud SH
    J Cardiovasc Pharmacol Ther, 2010 Sep;15(3):274-81.
    PMID: 20624923 DOI: 10.1177/1074248410373751
    Angiotensin-converting enzyme inhibitors (ACEIs) have shown promising results in decreasing the incidence and the severity of ischemic stroke in populations at risk and in improving ischemic stroke outcomes.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/administration & dosage; Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
  7. Fulltext BACE1 inhibitory activity of fungal endophytic extracts from Malaysian medicinal plants
    Harun A, James RM, Lim SM, Abdul Majeed AB, Cole AL, Ramasamy K
    BMC Complement Altern Med, 2011 Sep 24;11:79.
    PMID: 21943123 DOI: 10.1186/1472-6882-11-79
    BACKGROUND: BACE1 was found to be the major β-secretase in neurons and its appearance and activity were found to be elevated in the brains of AD patients. Fungal endophytic extracts for BACE1 inhibitory activity and cytotoxicity against PC-12 (a rat pheochromocytoma with neuronal properties) and WRL68 (a non-tumorigenic human hepatic) were investigated.

    METHODS: Endophytes were isolated from plants collected from Kuala Pilah, Negeri Sembilan and the National Park, Pahang and the extracts were tested for BACE1 inhibition. For investigation of biological activity, the pure endophytic cultures were cultivated for 14 days on PDA plates at 28°C and underwent semipolar extraction with ethyl acetate.

    RESULTS: Of 212 endophytic extracts (1000 μg/ml), 29 exhibited more than 90% inhibition of BACE1 in the preliminary screening. Four extracts from isolates HAB16R13, HAB16R14, HAB16R18 and HAB8R24 identified as Cytospora rhizophorae were the most active with IC(50(BACE1)) values of less than 3.0 μg/ml. The most active extract HAB16R13 was shown to non-competitively inhibit BACE1 with K(i) value of 10.0 μg/ml. HAB16R13 was considered non-potent against PC-12 and WRL68 (IC(50(CT))) of 60.0 and 40.0 μg/ml, respectively).

    CONCLUSIONS: This first report on endophytic fungal extract with good BACE1 inhibitory activity demonstrates that more extensive study is required to uncover the potential of endophytes.

    Matched MeSH terms: Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry
  8. Inhibitory effects of Sargassum polycystum on tyrosinase activity and melanin formation in B16F10 murine melanoma cells
    Chan YY, Kim KH, Cheah SH
    J Ethnopharmacol, 2011 Oct 11;137(3):1183-8.
    PMID: 21810462 DOI: 10.1016/j.jep.2011.07.050
    ETHNOPHARMACOLOGICAL RELEVANCE: Sargassum polycystum, a type of brown seaweed, has been used for the treatment of skin-related disorders in traditional medicine.

    AIM OF THE STUDY: The aim of the present study is to investigate the antimelanogenesis effect of Sargassum polycystum extracts by cell-free mushroom tyrosinase assay followed by cell viability assay, cellular tyrosinase assay and melanin content assay using B16F10 murine melanoma cells.

    MATERIALS AND METHODS: Sargassum polycystum was extracted with 95% ethanol and further fractionated with hexane, ethyl acetate and water. The ethanolic crude extract and its fractionated extracts were tested for their potential to act as antimelanogenesis or skin-whitening agents by their abilities to inhibit tyrosinase activity in the cell-free mushroom tyrosinase assay and cellular tyrosinase derived from melanin-forming B16F10 murine melanoma cells. The tyrosinase inhibitory activity was correlated to the inhibition of melanin production in α-MSH-stimulated and unstimulated B16F10 cells.

    RESULTS: Sargassum polycystum ethanolic extract and its fractions had little or no inhibitory effect on mushroom tyrosinase activity. However, when tested on cellular tyrosinase, the ethanolic extract and its non-polar fraction, hexane fraction (SPHF), showed significant inhibition of cellular tyrosinase activity. In parallel to its cellular tyrosinase inhibitory activity, SPHF was also able to inhibit basal and α-MSH-stimulated melanin production in B16F10 cells.

    CONCLUSIONS: Our findings showed that (i) cellular tyrosinase assay is more reliable than mushroom tyrosinase assay in the initial testing of potential antimelanogenesis agents and, (ii) SPHF inhibited melanogenesis by inhibiting cellular tyrosinase activity. SPHF may be useful for treating hyperpigmentation and as a skin-whitening agent in cosmetics industry.

    Matched MeSH terms: Enzyme Inhibitors/isolation & purification; Enzyme Inhibitors/pharmacology*
  9. Glycyrrhizic acid (GCA) as 11β-hydroxysteroid dehydrogenase inhibitor exerts protective effect against glucocorticoid-induced osteoporosis
    Ramli ES, Suhaimi F, Asri SF, Ahmad F, Soelaiman IN
    J Bone Miner Metab, 2013 May;31(3):262-73.
    PMID: 23274351 DOI: 10.1007/s00774-012-0413-x
    Rapid onset of bone loss is a frequent complication of systemic glucocorticoid therapy which may lead to fragility fractures. Glucocorticoid action in bone depends upon the activity of 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). Regulations of 11β-HSD1 activity may protect the bone against bone loss due to excess glucocorticoids. Glycyrrhizic acid (GCA) is a potent inhibitor of 11β-HSD. Treatment with GCA led to significant reduction in bone resorption markers. In this study we determined the effect of GCA on 11β-HSD1 activity in bones of glucocorticoid-induced osteoporotic rats. Thirty-six male Sprague-Dawley rats (aged 3 months and weighing 250-300 g) were divided randomly into groups of ten. (1) G1, sham operated group; (2) G2, adrenalectomized rats administered with intramuscular dexamethasone 120 μg/kg/day and oral vehicle normal saline vehicle; and (3) G3, adrenalectomized rats administered with intramuscular dexamethasone 120 μg/kg/day and oral GCA 120 mg/kg/day The results showed that GCA reduced plasma corticosterone concentration. GCA also reduced serum concentration of the bone resorption marker, pyridinoline and induced 11β-HSD1 dehydrogenase activity in the bone. GCA improved bone structure, which contributed to stronger bone. Therefore, GCA has the potential to be used as an agent to protect the bone against glucocorticoid induced osteoporosis.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/therapeutic use
  10. Fulltext Anti-inflammatory effects of Polygonum minus (Huds) extract (Lineminus™) in in-vitro enzyme assays and carrageenan induced paw edema
    George A, Chinnappan S, Chintamaneni M, Kotak C V, Choudhary Y, Kueper T, et al.
    BMC Complement Altern Med, 2014;14:355.
    PMID: 25252832 DOI: 10.1186/1472-6882-14-355
    The study was aimed to evaluate the anti-inflammatory activity of ethanolic and aqueous extracts of Polygonum minus (Huds) using in vitro and in vivo approaches.
    Matched MeSH terms: Enzyme Inhibitors/administration & dosage*
  11. Fulltext Effect of the antihypertensive drug enalapril on oxidative stress markers and antioxidant enzymes in kidney of spontaneously hypertensive rat
    Chandran G, Sirajudeen KN, Yusoff NS, Swamy M, Samarendra MS
    Oxid Med Cell Longev, 2014;2014:608512.
    PMID: 25254079 DOI: 10.1155/2014/608512
    Oxidative stress has been suggested to play a role in hypertension and hypertension induced organ damage. This study examined the effect of enalapril, an antihypertensive drug, on oxidative stress markers and antioxidant enzymes in kidney of spontaneously hypertensive rat (SHR) and Nω -nitro-L-arginine methyl ester (L-NAME) administered SHR. Male rats were divided into four groups (SHR, SHR+enalapril, SHR+L-NAME, and SHR+enalapril+L-NAME). Enalapril (30 mg kg(-1) day(-1)) was administered from week 4 to week 28 and L-NAME (25 mg kg(-1) day(-1)) was administered from week 16 to week 28 in drinking water. Systolic blood pressure (SBP) was measured during the experimental period. At the end of experimental periods, rats were sacrificed; urine, blood, and kidneys were collected for the assessment of creatinine clearance, total protein, total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and catalase (CAT), as well as histopathological examination. Enalapril treatment significantly enhanced the renal TAS level (P < 0.001) and SOD activity (P < 0.001), reduced the TBARS levels (P < 0.001), and also prevented the renal dysfunction and histopathological changes. The results indicate that, besides its hypotensive and renoprotective effects, enalapril treatment also diminishes oxidative stress in the kidneys of both the SHR and SHR+L-NAME groups.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  12. Fulltext Molecular characterization of a recombinant manganese superoxide dismutase from Lactococcus lactis M4
    Tan BH, Chor Leow T, Foo HL, Abdul Rahim R
    Biomed Res Int, 2014;2014:469298.
    PMID: 24592392 DOI: 10.1155/2014/469298
    A superoxide dismutase (SOD) gene of Lactococcus lactis M4 was cloned and expressed in a prokaryotic system. Sequence analysis revealed an open reading frame of 621 bp which codes for 206 amino acid residues. Expression of sodA under T7 promoter exhibited a specific activity of 4967 U/mg when induced with 1 mM of isopropyl-β-D-thiogalactopyranoside. The recombinant SOD was purified to homogeneity by immobilised metal affinity chromatography and Superose 12 gel filtration chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analyses of the recombinant SOD detected a molecular mass of approximately 27 kDa. However, the SOD was in dimer form as revealed by gel filtration chromatography. The purified recombinant enzyme had a pI of 4.5 and exhibited maximal activity at 25°C and pH 7.2. It was stable up to 45°C. The insensitivity of this lactococcal SOD to cyanide and hydrogen peroxide established that it was a MnSOD. Although it has 98% homology to SOD of L. lactis IL1403, this is the first elucidated structure of lactococcal SOD revealing active sites containing the catalytic manganese coordinated by four ligands (H-27, H-82, D-168, and H-172).
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  13. Molecular basis for resistance to ACCase-inhibiting fluazifop in Eleusine indica from Malaysia
    Cha TS, Najihah MG, Sahid IB, Chuah TS
    Pestic Biochem Physiol, 2014 May;111:7-13.
    PMID: 24861927 DOI: 10.1016/j.pestbp.2014.04.011
    Eleusine indica (goosegrass) populations resistant to fluazifop, an acetyl-CoA carboxylase (ACCase: EC6.4.1.2)-inhibiting herbicide, were found in several states in Malaysia. Dose-response assay indicated a resistance factor of 87.5, 62.5 and 150 for biotypes P2, P3 and P4, respectively. DNA sequencing and allele-specific PCR revealed that both biotypes P2 and P3 exhibit a single non-synonymous point mutation from TGG to TGC that leads to a well known Trp-2027-Cys mutation. Interestingly, the highly resistant biotype, P4, did not contain any of the known mutation except the newly discovered target point Asn-2097-Asp, which resulted from a nucleotide change in the codon AAT to GAT. ACCase gene expression was found differentially regulated in the susceptible biotype (P1) and highly resistant biotype P4 from 24 to 72h after treatment (HAT) when being treated with the recommended field rate (198gha(-1)) of fluazifop. However, the small and erratic differences of ACCase gene expression between biotype P1 and P4 does not support the 150-fold resistance in biotype P4. Therefore, the involvement of the target point Asn-2097-Asp and other non-target-site-based resistance mechanisms in the biotype P4 could not be ruled out.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  14. Pancreatic gene variants potentially associated with dipeptidyl peptidase-4 inhibitor treatment response in Type 2 diabetes
    Jamaluddin JL, Huri HZ, Vethakkan SR, Mustafa N
    Pharmacogenomics, 2014 Feb;15(2):235-49.
    PMID: 24444412 DOI: 10.2217/pgs.13.234
    In the adult pancreas, the expression of the genes PAX4, KCNQ1, TCF7L2, KCNJ11, ABCC8, MTNR1B and WFS1 are mainly restricted to β cells to maintain glucose homeostasis. We have identified these genes as the main regulators of incretin-mediated actions, and therefore they may potentially influence the response of DPP-4 inhibitors. This review represents the first detailed exploration of pancreatic β-cell genes and their variant mechanisms, which could potentially affect the response of DPP-4 inhibitors in Type 2 diabetes. We have focused on the signaling pathways of these genes to understand their roles in gastrointestinal incretin-mediated effects; and finally, we sought to associate gene mechanisms with their Type 2 diabetes risk variants to predict the responses of DPP-4 inhibitors for this disease.
    Matched MeSH terms: Enzyme Inhibitors/administration & dosage
  15. Fulltext Effectiveness of antihypertensive drugs in hypertensive patients with end stage renal failure
    Kumolosasi E, Ng WB, Abdul Aziz SA
    Med J Malaysia, 2012 Aug;67(4):379-85.
    PMID: 23082445 MyJurnal
    Hypertension has been identified as one of the causes for end stage renal failure (ESRF) and is likely to worsen kidney function. This retrospective study was carried out at a tertiary hospital in Malaysia with the objective of determining the effectiveness of combination antihypertensive drugs in hypertensive patients with ESRF admitted between 2006 and 2008. Patients with incomplete data and who were on monotherapy were excluded from this study. Although six different combinations gave significant reductions in systolic blood pressure (SBP) (13.38 +/- 9.11 mmHg, p < 0.05) and diastolic blood pressure (DBP) (6.03 +/- 11.39 mmHg, p < 0.05), 69.16% patients did not achieve target blood pressure (BP) (< or = 130/80 mmHg). Combination of beta blocker (BB) with calcium channel blocker (CCB) was the most commonly used. The CCB-diuretic regimen achieved highest percentage of BP control compared to others (40%). Comparison of blood pressure reduction between different combinations of antihypertensive drugs were not significant (p > 0.05) except for CCB-diuretics and BB-CCB-alpha blocker. The findings suggested better BP control with CCB-diuretic relative to other combinations used.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  16. Fulltext Hypertension control in chronic kidney disease: don't miss the forest for the trees
    Ong HT, Ong LM, Ho JJ
    Med J Malaysia, 2012 Aug;67(4):359-62.
    PMID: 23082441 MyJurnal
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  17. Effect of prestroke use of angiotensin-converting enzyme inhibitors alone versus combination with antiplatelets and statin on ischemic stroke outcome
    Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH
    Clin Neuropharmacol, 2011 Nov-Dec;34(6):234-40.
    PMID: 21996648 DOI: 10.1097/WNF.0b013e3182348abe
    BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs), antiplatelets (APs), and statin are increasingly being prescribed for ischemic stroke prevention.
    OBJECTIVES: The objective of the study was to examine whether previous combination therapy of ACEI with AP and/or statin has additive effect compared with ACEI alone on functional outcome after ischemic stroke. Furthermore, factors associated with improving functional outcome were investigated.
    METHODS: Ischemic stroke patients attending a Malaysian hospital in 2008 were categorized according to Barthel Index at discharge. Favorable outcome was defined as Barthel Index of 75 or greater. Data included demographic information, clinical characteristics, and previous medications with particular attention to ACEI, AP, and statin.
    RESULTS: Overall, 505 patients were included. Variables associated with good functional outcome were younger age (P = 0.002), first-ever attack (P = 0.016), lacunar (P = 0.015) or posterior circulation infarct stroke subtype (P = 0.034), minor Glasgow Coma Scale (P < 0.001), and previous use of ACEI alone or combined with AP and/or statin (P = 0.002). Using ACEI alone as the reference for ACEI + AP, ACEI + statin, or ACEI + AP + statin combinations, there was no significant difference among combinations on improving functional outcome (P = 0.852).
    CONCLUSIONS: Prestroke use of ACEI either alone or combined with AP and/or statin was associated with better functional outcome. Previous use of ACEI in combination with AP and/or statin did not significantly differ from ACEI alone in their effect on outcome. Our study provides a potential rationale for optimizing the use of ACEI among individuals at risk of developing ischemic stroke.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/administration & dosage*
  18. Screening and characterization of microbial inhibitors against eukaryotic protein phosphatases (PP1 and PP2A)
    Ong SM, Voo LY, Lai NS, Stark MJ, Ho CC
    J Appl Microbiol, 2007 Mar;102(3):680-92.
    PMID: 17309617
    To identify novel microbial inhibitors of protein phosphatase 1 (PP1).
    Matched MeSH terms: Enzyme Inhibitors/analysis*
  19. Reduction in arterial stiffness with angiotensin II antagonism and converting enzyme inhibition. A comparative study among malay hypertensive subjects with a known genetic profile
    Rehman A, Ismail SB, Naing L, Roshan TM, Abdul Rahman AR
    Am J Hypertens, 2007 Feb;20(2):184-9.
    PMID: 17261465 DOI: 10.1016/j.amjhyper.2006.07.015
    BACKGROUND: Data comparing the effect of losartan and perindopril on aortic stiffness among hypertensive subjects without A(1166)C polymorphism was not available.
    METHODS: The short-term and long-term effects of losartan (50 mg) and perindopril (4 mg) on aortic stiffness measured as carotid femoral pulse wave velocity (PWV) were compared in 39 middle-aged Malay subjects with mild-to-moderate hypertension in a 4-month, double-blind, randomized, controlled, parallel-design study.
    RESULTS: Four-month treatment with both drugs showed a significant reduction in blood pressure (BP) (P < .005) and PWV (P < .05) as compared to the baseline. On the other hand 1-month treatment showed a significant reduction in BP only in perindopril group (P < .05) but not in the losartan group. There was no significant reduction in pulse pressure and PWV after 1 month treatment by both drugs. No significant difference was seen in reduction in BP after 1 month and 4 months treatment between the two drugs. Similarly no significant difference was seen in reduction in PWV between the two drugs after 1 month (P = .613) and 4 months (P = .521) of treatment. Reduction in PWV by losartan (r = 0.470) and perindopril (r = 0.457) correlated significantly only with reduction in DBP (P < .05) and remained significant even after controlling for reduction in DBP (P < .05). Reduction in PWV by both losartan and perindopril was independent of reduction in BP by these drugs.
    CONCLUSIONS: These results showed that long-term treatment with losartan shows similar pressure independent reduction in PWV as perindopril among Malay hypertensive subjects with a homogenous "AA" genotype for angiotensin II type 1 receptor and may serve as a suitable alternative to perindopril.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
  20. Involvement of phenobarbital and SKF 525A in the hepatotoxicity of antifungal drugs itraconazole and fluconazole in rats
    Somchit N, Wong CW, Zuraini A, Ahmad Bustamam A, Hasiah AH, Khairi HM, et al.
    Drug Chem Toxicol, 2006;29(3):237-53.
    PMID: 16777703
    Itraconazole and fluconazole are potent wide spectrum antifungal drugs. Both of these drugs induce hepatotoxicity clinically. The mechanism underlying the hepatotoxicity is unknown. The purpose of this study was to investigate the role of phenobarbital (PB), an inducer of cytochrome P450 (CYP), and SKF 525A, an inhibitor of CYP, in the mechanism of hepatotoxicity induced by these two drugs in vivo. Rats were pretreated with PB (75 mg/kg for 4 days) prior to itraconazole or fluconazole dosing (20 and 200 mg/kg for 4 days). In the inhibition study, for 4 consecutive days, rats were pretreated with SKF 525A (50 mg/kg) or saline followed by itraconazole or fluconazole (20 and 200 mg/kg) Dose-dependent increases in plasma alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma-GT), and alkaline phosphatase (ALP) activities and in liver weight were detected in rats receiving itraconazole treatment. Interestingly, pretreatment with PB prior to itraconazole reduced the ALT and gamma-GT activities and the liver weight of rats. No changes were observed in rats treated with fluconazole. Pretreatment with SKF 525A induced more severe hepatotoxicity for both itraconazole and fluconazole. CYP 3A activity was inhibited dose-dependently by itraconazole treatment. Itraconazole had no effects on the activity of CYP 1A and 2E. Fluconazole potently inhibited all three isoenzymes of CYP. PB plays a role in hepatoprotection to itraconazole-induced but not fluconazole-induced hepatotoxicity. SKF 525A enhanced the hepatotoxicity of both antifungal drugs in vivo. Therefore, it can be concluded that inhibition of CYP may play a key role in the mechanism of hepatotoxicity induced by itraconazole and fluconazole.
    Matched MeSH terms: Enzyme Inhibitors/toxicity*
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