Displaying publications 281 - 300 of 382 in total

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  1. Hurt AC, Selleck P, Komadina N, Shaw R, Brown L, Barr IG
    Antiviral Res, 2007 Mar;73(3):228-31.
    PMID: 17112602
    Since 2003, highly pathogenic A(H5N1) influenza viruses have been the cause of large-scale death in poultry and the subsequent infection and death of over 140 humans. A group of 55 influenza A(H5N1) viruses isolated from various regions of South East Asia between 2004 and 2006 were tested for their susceptibility to the anti-influenza drugs the neuraminidase inhibitors and adamantanes. The majority of strains were found to be fully sensitive to the neuraminidase inhibitors oseltamivir carboxylate, zanamivir and peramivir; however two strains demonstrated increased IC50 values. Sequence analysis of these strains revealed mutations in the normally highly conserved residues 116 and 117 of the N1 neuraminidase. Sequence analysis of the M2 gene showed that all of the A(H5N1) viruses from Vietnam, Malaysia and Cambodia contained mutations (L26I and S31N) associated with resistance to the adamantane drugs (rimantadine and amantadine), while strains from Indonesia were found to be a mix of both adamantane resistant (S31N) and sensitive viruses. None of the A(H5N1) viruses from Myanmar contained mutations known to confer adamantane resistance. These results support the use of neuraminidase inhibitors as the most appropriate class of antiviral drug to prevent or treat human A(H5N1) virus infections.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*
  2. Selim K, Hüseyin C, Ibrahim KH, Hasan BU, Kazim U, Hüseyin K
    Med J Malaysia, 2004 Aug;59(3):391-4.
    PMID: 15727386
    Several pharmacological agents have been found to alter systemic concentrations and/or the activity of different cytokines via a variety of mechanisms, including changes in biosynthesis, secretion, and/or stability. Pentoxifylline (PTX), which is a methylxanthine derivative for example, has multiple effects on the immune system, but inhibition of pro-inflammatory cytokine release predominates. In this study we aimed to evaluate the influence of PTX on plasma levels of tumor necrosis factor (TNF) alpha and interleukin (IL)-6 in newborn infants with sepsis. The study included 20 infants with neonatal sepsis. In all subjects blood samples for serum C-reactive protein, TNF alpha and IL-6 determinations were received before giving PTX and at the 12th and 24th hours following PTX. In addition, white blood cell was counted before giving PTX and on the 3rd and 7th day following PTX. The infants were randomly divided into two groups. Firstly, PTX was used in infants who were successively admitted to the clinic and the subsequent infants were accepted as a control group. Of 20 infants, 13 infants received PTX and seven infants did not. We did not find any difference in the leukocyte count, serum C-reactive protein level, TNF alpha and IL-6 levels between the two groups of patients (P>0.05). While three infants died in the group of receiving PTX, death was not recorded in the group of non-receiving PTX (P>0.05). Our findings showed that PTX treatment did not affect leukocyte counts, serum CRP levels, TNF alpha and IL-6 levels and death ratio in newborn infants with sepsis. The last result may be due to the fact that the number of patients in the study was very small. We think that more extensive and controlled studies should be performed about this subject.
    Matched MeSH terms: Enzyme Inhibitors/therapeutic use
  3. Hassan Y, Kassab Y, Abd Aziz N, Akram H, Ismail O
    J Clin Pharm Ther, 2013 Apr;38(2):97-100.
    PMID: 23441979 DOI: 10.1111/jcpt.12027
    Pharmacists have the knowledge regarding optimal use of medications and the ability to influence physician prescribing. Successful interventions by a pharmacist to implement cardioprotective medications to a coronary artery disease patient's regimen would not only improve the patient's quality of care but may also increase his or her likelihood of survival. Therefore, the aim of this study was to (i) evaluate the effectiveness of pharmacist initiated interventions in increasing the prescription rates of acute coronary syndrome (ACS) secondary prevention pharmacotherapy at discharge, and to (ii) evaluate the acceptance rate of these interventions by prescribers.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  4. Lim EL, Seah TC, Koe XF, Wahab HA, Adenan MI, Jamil MF, et al.
    Toxicol In Vitro, 2013 Mar;27(2):812-24.
    PMID: 23274770 DOI: 10.1016/j.tiv.2012.12.014
    CYP450 enzymes are key determinants in drug toxicities, reduced pharmacological effect and adverse drug reactions. Mitragynine, an euphoric compound was evaluated for its effects on the expression of mRNAs encoding CYP1A2, CYP2D6 and CYP3A4 and protein expression and resultant enzymatic activity. The mRNA and protein expression of CYP450 isoforms were carried out using an optimized multiplex qRT-PCR assay and Western blot analysis. CYP1A2 and CYP3A4 enzyme activities were evaluated using P450-Glo™ assays. The effects of mitragynine on human CYP3A4 protein expression were determined using an optimized hCYP3A4-HepG2 cell-based assay. An in silico computational method to predict the binding conformation of mitragynine to the active site of the CYP3A4 enzyme was performed and further validated using in vitro CYP3A4 inhibition assays. Mitragynine was found to induce mRNA and protein expression of CYP1A2. For the highest concentration of 25 μM, induction of mRNA was approximately 70% that of the positive control and was consistent with the increased CYP1A2 enzymatic activity. Thus, mitragynine is a significant in vitro CYP1A2 inducer. However, it appeared to be a weak CYP3A4 inducer at the transcriptional level and a weak CYP3A4 enzyme inhibitor. It is therefore, unlikely to have any significant clinical effects on CYP3A4 activity.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*
  5. Gopinath VK, Musa M, Samsudin AR, Lalitha P, Sosroseno W
    Arch Oral Biol, 2006 Apr;51(4):339-44.
    PMID: 16214104
    The aim of this study was to determine the role of nitric oxide (NO) in hydroxyapatite (HA)-induced phagocytosis by a murine macrophage cell line (RAW264.7). The cells were incubated with HA particles at various incubation time and phagocytosis was assessed using phagocytic index (PI). NO production from the culture supernatants was determined by the Griess reagent. The inducible nitric oxide synthase (iNOS) expression was determined by Western blot. The particles were also incubated with cells pretreated with various concentrations of L-N(6)-(1-iminoethyl) lysine hydrochloride (L-NIL) or L-arginine. Latex beads were used as a control. Our results showed that macrophage phagocytosis induced by HA was higher than that induced by the beads. However, NO production by HA-stimulated cells was lower than that by bead-stimulated cells. iNOS expression in both bead- and HA-stimulated cells was observed expressed at 7, 15, 30, and 60 min. l-Arginine enhanced but l-NIL inhibited both phagocytosis and NO production by HA-stimulated cells. The results of the present study suggest that nitric oxide may play a crucial role in HA-induced phagocytosis by RAW264.7 cells.
    Matched MeSH terms: Enzyme Inhibitors/immunology
  6. Bavanandan S, Morad Z, Ismail O, Chandran A, Thayaparan T, Singaraveloo M
    Med J Malaysia, 2005 Jun;60(2):158-62.
    PMID: 16114156 MyJurnal
    This study was conducted to determine the tolerability and efficacy of valsartan (DIOVAN) compared to perindopril (COVERSYL) in Malaysian patients with mild to moderate hypertension. Two hundred and fifty adult Malaysian patients with a mean sitting diastolic blood pressure of more than 95 mmHg and less than 115 mmHg after a 14 day washout period were randomized to receive either valsartan 80 mg once daily (n=125) or perindopril 4 mg daily (n=125) for eight weeks. The primary end point for efficacy was the change in mean sitting systolic and diastolic blood pressure (SiSBP and SiDBP). The primary criteria for evaluation of tolerability was the incidence of adverse events. There were no significant differences between the two groups with respect to sex, age, weight, baseline sitting and standing systolic and diastolic blood pressure. At 0, 4 and 8 weeks the mean SiDBP in the valsartan group were 101.4, 92.8 and 91.0 mmHg respectively. The corresponding BP for the perindopril treated group was 102.6, 93.8 and 93.2 mmHg. (95% CI -1.39 to +3.27). There were no significant differences in the mean BP measurements between the valsartan and perindopril group at 0, 4 and 8 weeks. In each group there were significant differences between the BP at 4 and 8 weeks compared to baseline. A similar pattern was seen with SiSBP. At 4 weeks 28.7% of the valsartan and 25% of the perindopril group had their BP normalized (SiDBP <90 mmHg) The percentages of patients who responded (SiDBP reduction >10 mmHg but SiDBP >90 mmHg) were 21.3 in the valsartan group and 20.8 in the perindopril group. At 8 weeks, 31.1% of the valsartan group and 30.8% of the perindopril group had their BP normalized. The response rate was 27% and 22.5% for valsartan and perindopril respectively. The major adverse event was cough which occurred in 18 patients (14.4%) in the perindopril and 1 (0.8%) in the valsartan group at 4 weeks. At 8 weeks the figures were 24 (19.2%) and 2 (1.6%) respectively. The results indicate that Valsartan is safe and efficacious in the treatment of mild to moderate hypertension. It is equally efficacious to Perindopril and not associated with any major adverse event. It has a better tolerability profile with respect to dry cough.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
  7. Tang YQ, Jaganath IB, Manikam R, Sekaran SD
    Nutr Cancer, 2015;67(5):783-95.
    PMID: 25996262 DOI: 10.1080/01635581.2015.1040518
    Tumor angiogenesis and metastasis are the major causes for high morbidity and mortality rates in cancer patient. Modulation on tumor angiogenesis and metastasis provides opportunities to halt progression of cancer. From our previous findings, Phyllanthus plant possesses antiproliferative effects on melanoma and prostate cancer cell lines and induction of apoptosis. The main aims of the present work were further investigated on the antimetastatic and antiangiogenic effects on cancer cells (MeWo and PC-3) and human umbilical vein endothelial cells (HUVECs) of 4 Phyllanthus species (P.amarus, P.niruri, P.urinaria and P.watsonii). Phyllanthus extracts significantly inhibited cell adhesion, migration, invasion, and transendothelial migration activities of cancer (MeWo and PC-3) cells in a dose-dependent manner (P < 0.05) by cell-matrix adhesion, Transwell migration, invasion, and transendothelial migration assays. Phyllanthus extracts were exhibited low cytotoxicity on HUVECs up to a concentration of 500.0 μg/ml by MTS reduction assay. Phyllanthus extracts also exhibited antiangiogenic effects through inhibition of migration, invasion, and microcapillary like-tube structure formation in HUVECs. These observations were due to alteration in activities of matrix metalloproteinase (MMP) -2, -7, -9, and -26 in treated-endothelial and cancer cells by zymographies. These findings suggest that Phyllanthus plant has the potential to inhibit tumour metastasis and angiogenesis through the suppression of MMP enzymes.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  8. Mediani A, Abas F, Khatib A, Tan CP, Ismail IS, Shaari K, et al.
    Plant Foods Hum Nutr, 2015 Jun;70(2):184-92.
    PMID: 25800644 DOI: 10.1007/s11130-015-0478-5
    The study investigated the changes in the metabolite, antioxidant and α-glucosidase inhibitory activities of Phyllanthus niruri after three drying treatments: air, freeze and oven dryings. Water extracts and extracts obtained using different solvent ratios of ethanol and methanol (50, 70, 80 and 100%) were compared. The relationships among the antioxidant, α-glucosidase inhibitory activity and metabolite levels of the extracts were evaluated using partial least-square analysis (PLS). The solvent selectivity was assessed based on the phytochemical constituents present in the extract and their concentrations quantitatively analyzed using high performance liquid chromatography. The freeze-dried P. niruri samples that were extracted with the mixture of ethanol or methanol with low ratio of water showed higher biological activity values compared with the other extracts. The PLS results for the ethanolic with different ratio and water extracts demonstrated that phenolic acids (chlorogenic acid and ellagic acid) and flavonoids were highly linked to strong α-glucosidase inhibitory and antioxidant activities.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  9. Sosroseno W
    Asian Pac J Allergy Immunol, 2000 Dec;18(4):209-14.
    PMID: 11316041
    The aim of the present study was to determine whether Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) may stimulate nitric oxide (NO) production by murine spleen cells. Spleen cells derived from Balb/c mice were cultured in the presence of Pg-LPS or LPS from Salmonella Typhosa. The cell were also cultured in the presence of Pg-LPS with or without L-arginine, L-arginine plus NG-monomethyl-L-arginine (NMMA), or IFN-gamma. Furthermore, the plastic non-adherent spleen cells were stimulated with Pg-LPS and L-arginine. The results showed that Pg-LPS failed to stimulate splenic NO production by themselves. Exogenous L-arginine or IFN-gamma up-regulated the NO production of Pg-LPS-stimulated spleen cells, but the stimulatory effects of L-arginine were completely blocked by NMMA. It was also demonstrated that in the presence of Pg-LPS and L-arginine, splenic macrophages were the cellular source of NO. These results suggest, therefore, that P. gingivalis-LPS may induce murine splenic macrophages to produce NO in a L-arginine and an IFN-gamma-dependent mechanism.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  10. Rahman AR, Lang CC, Struthers AD
    Int J Clin Pharmacol Ther, 1995 Jul;33(7):404-9.
    PMID: 7582398
    Increasing animal evidence support an important facilitatory interaction between angiotensin II and norepinephrine within the kidney. This angiotensin II/norepinephrine interaction was investigated in man by examining the effect of enalapril pretreatment (5 mg for 5 days) on the renal response to a low non-pressor dose of intravenous tyramine 4 micrograms/kg/min for 120 min in 8 healthy subjects undergoing water diuresis. Tyramine is an indirect sympathomimetic agent which causes neuronal release of norepinephrine. Enalapril and tyramine, alone and in combination, had no effect on glomerular filtration, effective renal plasma flow or sodium excretion. Tyramine caused a significant increase in urinary flow rate (p < 0.05) but this was not influenced by enalapril pretreatment. The lack of effect of enalapril on the renal response to tyramine contrasts with a previous study which examined the effect of enalapril on the renal response to circulating norepinephrine. This may suggest that enalapril affect renal function only when there is renal vasoconstriction (as with norepinephrine) and not when renal blood flow is unchanged (as with tyramine).
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/pharmacology*
  11. Sosroseno W, Herminajeng E, Bird PS, Seymour GJ
    Oral Microbiol. Immunol., 2004 Apr;19(2):65-70.
    PMID: 14871343
    The aim of this study was to determine nitric oxide (NO) production of a murine macrophage cell line (RAW 264.7 cells) when stimulated with Porphyromonas gingivalis lipopolysaccharides (Pg-LPS). RAW 264.7 cells were incubated with i) various concentrations of Pg-LPS or Salmonella typhosa LPS (St-LPS), ii) Pg-LPS with or without L-arginine and/or NG-monomethyl-L-arginine (NMMA), an arginine analog or iii) Pg-LPS and interferon-gamma (IFN-gamma) with or without anti-IFN-gamma antibodies or interleukin-10 (IL-10). Tissue culture supernatants were assayed for NO levels after 24 h in culture. NO was not observed in tissue culture supernatants of RAW 264.7 cells following stimulation with Pg-LPS, but was observed after stimulation with St-LPS. Exogenous L-arginine restored the ability of Pg-LPS to induce NO production; however, the increase in NO levels of cells stimulated with Pg-LPS with exogenous L-arginine was abolished by NMMA. IFN-gamma induced independent NO production by Pg-LPS-stimulated macrophages and this stimulatory effect of IFN-gamma could be completely suppressed by anti-IFN-gamma antibodies and IL-10. These results suggest that Pg-LPS is able to stimulate NO production in the RAW 264.7 macrophage cell model in an L-arginine-dependent mechanism which is itself independent of the action of IFN-gamma.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  12. Ali MS, Yun CC, Chor AL, Rahman RN, Basri M, Salleh AB
    Protein J, 2012 Mar;31(3):229-37.
    PMID: 22350313 DOI: 10.1007/s10930-012-9395-8
    A mutant of the lipase from Geobacillus sp. strain T1 with a phenylalanine to leucine substitution at position 16 was overexpressed in Escherichia coli strain BL21(De3)pLysS. The crude enzyme was purified by two-step affinity chromatography with a final recovery and specific activity of 47.4 and 6,315.8 U/mg, respectively. The molecular weight of the purified F16L lipase was approximately 43 kDa by 12% SDS-PAGE analysis. The F16L lipase was demonstrated to be a thermophilic enzyme due its optimum temperature at 70 °C and showed stability over a temperature range of 40-60 °C. The enzyme exhibited an optimum pH 7 in phosphate buffer and was relatively stable at an alkaline pH 8-9. Metal ions such as Ca(2+), Mn(2+), Na(+), and K(+) enhanced the lipase activity, but Mg(2+), Zn(2+), and Fe(2+) inhibited the lipase. All surfactants tested, including Tween 20, 40, 60, 80, Triton X-100, and SDS, significantly inhibited the lipolytic action of the lipase. A high hydrolytic rate was observed on long-chain natural oils and triglycerides, with a notable preference for olive oil (C18:1; natural oil) and triolein (C18:1; triglyceride). The F16L lipase was deduced to be a metalloenzyme because it was strongly inhibited by 5 mM EDTA. Moderate inhibition was observed in the presence of PMSF at a similar concentration, indicating that serine residues are involved in its catalytic action. Further, the activity was not impaired by water-miscible solvents, including methanol, ethanol, and acetone.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  13. Heidari F, Vasudevan R, Mohd Ali SZ, Ismail P, Arkani M
    Arch Med Res, 2017 Jan;48(1):88-95.
    PMID: 28577874 DOI: 10.1016/j.arcmed.2017.03.003
    BACKGROUNDS AND AIMS: Essential Hypertension (EH) is a common disorder associated with increased cardiovascular morbidity and mortality in Malaysia. To investigate how genetic polymorphisms of the renin-angiotensin-aldosterone system (RAS) influence EH control with angiotensin-converting enzyme inhibitor drugs (ACEI).

    METHODS: A case-control, cross-sectional population-based nested study (n = 142) included hypertensive subjects treated with ACEI drugs, either lisinopril or enalapril (20 mg, once daily) as monotherapy for 24 weeks. In total seven possible polymorphisms of RAS genes were genotyped. The association between those polymorphisms and the changes in blood pressure were observed in the 24 week treatment.

    RESULTS: Statistically significant associations of I, G, T, M and G alleles of ACE (I/D, G2350A), AGT (M235T, T175M and G-6A) respectively were observed in essential hypertensive subjects. The decrease in systolic blood pressure and diastolic blood pressure after 24 weeks of treatment of the patients carrying II, GG, and TT genotypes were greater than the groups carrying DD, AA, MM, MM and GG of I/D, G2350A, M235T, T174M and G-6A genotypes respectively. In contrast, No significant difference was observed between renin gene polymorphisms (Bg/I and MboI) and hypertensives.

    CONCLUSIONS: Although this study shows a possible association of polymorphisms of RAS genes with the risk of non-control of HT in ACEI-treated patients and indicates the importance of all this system's components in regulating HT, it needs to be replicated in other data sources.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
  14. Sosroseno W, Musa M, Ravichandran M, Ibrahim MF, Bird PS, Seymour GJ
    Eur J Oral Sci, 2008 Feb;116(1):31-6.
    PMID: 18186729 DOI: 10.1111/j.1600-0722.2007.00501.x
    Animal studies suggest that inducible nitric oxide synthase (iNOS) may be associated with destructive periodontal disease. l-N(6)-(1-Iminoethyl)-lysine (L-NIL) has been shown to inhibit iNOS in a selective manner, and hence the aim of the present study was to test the hypothesis that treatment with l-NIL may induce a T-cell helper 1 (Th1)-like immune response by Aggregatibacter (Actinobacillus) actinomycetemcomitans lipopolysaccharide (LPS)-stimulated murine spleen cells in vitro. BALB/c mice were either sham-immunized or immunized with A. actinomycetemcomitans LPS. Spleen cells were stimulated with A. actinomycetemcomitans LPS in the presence or absence of L-NIL. Nitric oxide (NO), iNOS activity, specific IgG subclass antibodies, interferon-gamma (IFN-gamma), and interleukin-4 (IL-4) levels and cell proliferation were determined. The results showed that treatment with L-NIL suppressed both NO production and iNOS activity but enhanced specific IgG2a, IFN-gamma levels, and increased cell proliferation following stimulation with A. actinomycetemcomitans LPS-stimulated cells. The results of the present study suggest that inhibition of iNOS activity by L-NIL may skew the A. actinomycetemcomitans LPS-stimulated murine splenic immune response towards the Th1-like immune profile in vitro.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*
  15. Saleem H, Zengin G, Khan KU, Ahmad I, Waqas M, Mahomoodally FM, et al.
    Nat Prod Res, 2021 Feb;35(4):664-668.
    PMID: 30919661 DOI: 10.1080/14786419.2019.1587427
    This study sets out to probe into total bioactive contents, UHPLC-MS secondary metabolites profiling, antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum and metal chelating) and enzyme inhibitory (acetylcholinesterase- AChE, butyrylcholinesterase- BChE, α-amylase, α glucosidase, and tyrosinase) activities of methanol extract of Aerva javanica, also known as desert cotton or Kapok bush. Aerva javanica contains considerable phenolic (44.79 ± 3.12 mg GAE/g) and flavonoid (28.86 ± 0.12 mg QE/g) contents which tends to correlate with its significant antioxidant potential for ABTS, FRAP and CUPRAC assays with values of 101.41 ± 1.18, 124.10 ± 1.71 and 190.22 ± 5.70 mg TE/g, respectively. The UHPLC-MS analysis identified the presence of 45 phytochemicals belonging to six major groups: phenolic, flavonoids, lignin, terpenes, glycoside and alkaloid. Moreover, the plant extract also showed potent inhibitory action against AChE (3.73 ± 0.22 mg GALAE/g), BChE (3.31 ± 0.19 mg GALAE/g) and tyrosinase (126.05 ± 1.77 mg KAE/g). The observed results suggest A. javanica could be further explored as a natural source of bioactive compounds.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*
  16. Khadijah Ramli NS, Giribabu N, Muniandy S, Salleh N
    Theriogenology, 2018 Mar 01;108:354-361.
    PMID: 29294437 DOI: 10.1016/j.theriogenology.2017.12.035
    Precise regulation of vas deferens fluid pH is essential for sperm. However, the mechanisms underlying effect of testosterone on vas deferens fluid pH have never been identified, which could involve changes in expression and functional activity of vacoular (V)-ATPase.

    METHODS: Orchidectomized, adult male Sprague-Dawley rats were treated subcutaneously with 125 μg/kg/day and 250 μg/kg/day testosterone with or without flutamide (androgen receptor blocker) and finasteride (5α-reductase inhibitor) for seven (7) days. Following treatment completion, in vivo perfusion of vas deferens lumen was performed and changes in fluid secretion rate, pH and HCO3- content were measured with and without bafilomycin, a V-ATPase inhibitor. Rats were then sacrificed and vas deferens were harvested and subjected for V-ATPase A1 and B1/2 protein expression and distribution analysis by western blotting and immunohistochemistry, respectively.

    RESULTS: In sham-operated and testosterone-treated orchidectomized rats, higher fluid secretion rate, which was not antagonized by bafilomycin but lower HCO3- content and pH which were antagonized by bafilomycin were observed when compared to orchidectomized-only and orchidectomized, testosterone-treated rats receiving flutamide or finasteride, respectively. Bafilomycin had no effect on fluid secretion rate, HCO3- content and pH in orchidectomized and testosterone-treated orchidectomized rats receiving flutamide and finasteride. V-ATPase A1 and B1/2 proteins were expressed at high levels in vas deferens and were highly distributed at the apical membrane of luminal epithelium and in muscle layer of this organ, mainly in sham and testosterone-treated orchidectomized rats.

    CONCLUSIONS: V-ATPase is involved in acidification of vas deferens fluid under testosterone influence.

    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  17. Rahman RN, Geok LP, Wong CF, Basri M, Salleh AB
    J Basic Microbiol, 2010 Apr;50(2):143-9.
    PMID: 20082370 DOI: 10.1002/jobm.200900133
    A gene encoding an organic solvent-stable protease was amplified from Pseudomonas aeruginosa strain K by polymerase chain reaction using consensus primers based on multiple sequence alignment of alkaline and metalloprotease genes from Pseudomonas species. The gene, which consisted of 1440 bp nucleotides and deduced 479 amino acid residues, was successfully expressed in pGEX-4T-1 expression system in the presence of 1.0 mM IPTG, after an incubation of 6 h at 37 degrees C. Under these conditions, the recombinant strain K protease was, subsequently, released into the periplasm of E. coli BL21 (DE3) with an optimum proteolytic activity detected at 1.0112 U/ml. To date, this is the first reported expression of alkaline protease (aprA) with such remarkable property in Escherichia coli.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*
  18. Yam MF, Tan CS, Shibao R
    Hypertens Res, 2018 Oct;41(10):787-797.
    PMID: 30111856 DOI: 10.1038/s41440-018-0083-8
    Orthosiphon stamineus Benth. (Lambiaceae) is an important traditional plant for the treatment of hypertension. Previous studies have demonstrated that the sinensetin content in O. stamineus is correlated with its vasorelaxant activity. However, there is still very little information regarding the vasorelaxant effect of sinensetin due to a lack of scientific studies. Therefore, the present study was designed to investigate the underlying mechanism of action of sinensetin in vasorelaxation using an in vitro precontraction aortic ring assay. The changes in the tension of the aortic ring preparations were recorded using a force-displacement transducer and the PowerLab system. The mechanisms of the vasorelaxant effect of sinensetin were determined in the presence of antagonists. Sinensetin caused relaxation of the aortic ring precontracted with PE in the presence and absence of the endothelium and with potassium chloride in endothelium-intact aortic rings. In the presence of Nω-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), methylene blue (cyclic guanosine monophosphate lowering agent), ODQ (selective soluble guanylate cyclase inhibitor), indomethacin (a nonselective cyclooxygenase inhibitor), tetraethylammonium (nonselective calcium activator K+ channel blocker), 4-aminopyridine (voltage-dependent K+ channel blocker), barium chloride (inwardly rectifying Kir channel blocker), glibenclamide (nonspecific ATP-sensitive K+ channel blocker), atropine (muscarinic receptor blocker), or propranolol (β-adrenergic receptor blocker), the relaxation stimulated by sinensetin was significantly reduced. Sinensetin was also active in reducing Ca2+ release from the sarcoplasmic reticulum (via IP3R) and in blocking calcium channels (VOCC). The present study demonstrates the vasorelaxant effect of sinensetin, which involves the NO/sGC/cGMP and indomethacin pathways, calcium and potassium channels, and muscarinic and beta-adrenergic receptors.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  19. Lee CY, Liu KT, Lu HT, Mohd Ali R, Fong AYY, Wan Ahmad WA
    PLoS One, 2021;16(2):e0246474.
    PMID: 33556136 DOI: 10.1371/journal.pone.0246474
    BACKGROUND: Sex and gender differences in acute coronary syndrome (ACS) have been well studied in the western population. However, limited studies have examined the trends of these differences in a multi-ethnic Asian population.

    OBJECTIVES: To study the trends in sex and gender differences in ACS using the Malaysian NCVD-ACS Registry.

    METHODS: Data from 24 hospitals involving 35,232 ACS patients (79.44% men and 20.56% women) from 1st. Jan 2012 to 31st. Dec 2016 were analysed. Data were collected on demographic characteristics, coronary risk factors, anthropometrics, treatments and outcomes. Analyses were done for ACS as a whole and separately for ST-segment elevation myocardial infarction (STEMI), Non-STEMI and unstable angina. These were then compared to published data from March 2006 to February 2010 which included 13,591 ACS patients (75.8% men and 24.2% women).

    RESULTS: Women were older and more likely to have diabetes mellitus, hypertension, dyslipidemia, previous heart failure and renal failure than men. Women remained less likely to receive aspirin, beta-blocker, angiotensin-converting enzyme inhibitor (ACE-I) and statin. Women were less likely to undergo angiography and percutaneous coronary intervention (PCI) despite an overall increase. In the STEMI cohort, despite a marked increase in presentation with Killip class IV, women were less likely to received primary PCI or fibrinolysis and had longer median door-to-needle and door-to-balloon time compared to men, although these had improved. Women had higher unadjusted in-hospital, 30-Day and 1-year mortality rates compared to men for the STEMI and NSTEMI cohorts. After multivariate adjustments, 1-year mortality remained significantly higher for women with STEMI (adjusted OR: 1.31 (1.09-1.57), p<0.003) but were no longer significant for NSTEMI cohort.

    CONCLUSION: Women continued to have longer system delays, receive less aggressive pharmacotherapies and invasive treatments with poorer outcome. There is an urgent need for increased effort from all stakeholders if we are to narrow this gap.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  20. Maniam P, Nurul Aiezzah Z, Mohamed R, Embi N, Hasidah MS
    Trop Biomed, 2015 Mar;32(1):36-48.
    PMID: 25801253
    Increased susceptibility of diabetics to melioidosis, a disease caused by the Burkholderia pseudomallei bacterium is believed to be attributed to dysfunction of the innate immune system. However, the underlying mechanism of the innate susceptibility is not well-understood. Glycogen synthase kinase-3β (GSK3β) plays an important role in the innate inflammatory response caused by bacterial pathogens. The present study was conducted to investigate the effects of GSK3β inhibition by LiCl on levels of pro- and anti-inflammatory cytokines; and the activity of transcription factor NF-κB in B. pseudomallei-infected peripheral blood mononuclear cells (PBMC) derived from diabetic-induced and normal Sprague Dawley rats. In addition, the effects of LiCl on intracellular bacterial counts were also investigated. Infection of PBMC from diabetic and normal rats with B. pseudomallei resulted in elevated levels of cytokines (TNF-α, IL-12 and IL-10) and phosphorylation of NF-κB in both cell types. Intracellular bacterial counts decreased with time in both cell types during infection. However bacterial clearance was less prominent in diabetic PBMC. Burkholderia pseudomallei infection also caused inactivation (Ser9 phosphorylation) of GSK3β in normal PBMC, an effect absent in infected diabetic PBMC. Inhibition of GSK3β by LiCl lowered the levels of pro-inflammatory cytokines (TNF-α and IL-12) in both normal and diabetic PBMC. Similarly, phosphorylated NF- κB (pNF-κB) levels in both cell types were decreased with LiCl treatment. Also, LiCl was able to significantly decrease the intracellular bacterial count in normal as well as diabetic PBMC. Interestingly, the levels of anti-inflammatory cytokine IL-10 in both normal and diabetic PBMC were further elevated with GSK3β inhibition. More importantly, GSK3β in infected diabetic PBMC was inactivated as in their non-diabetic counterparts upon LiCl treatment. Taken together, our results suggest that inhibition of dysregulated GSK3β in diabetic PBMC resulted in the inactivation of NF-κB and modulation of inflammatory cytokine levels. This is evidence that dysregulation of GSK3β is a contributing factor in the molecular basis of innate dysfunction and susceptibility of diabetic host to melioidosis infection.
    Matched MeSH terms: Enzyme Inhibitors/metabolism
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