Displaying publications 301 - 320 of 382 in total

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  1. Ng CT, Fong LY, Low YY, Ban J, Hakim MN, Ahmad Z
    Physiol Res, 2016 12 13;65(6):1053-1058.
    PMID: 27539106
    The endothelial barrier function is tightly controlled by a broad range of signaling cascades including nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. It has been proposed that disturbances in NO and cGMP production could interfere with proper endothelial barrier function. In this study, we assessed the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, on NO and cGMP levels and examined the mechanisms by which NO and cGMP regulate the IFN-gamma-mediated HUVECs hyperpermeability. The flux of fluorescein isothiocyanate-labeled dextran across cell monolayers was used to study the permeability of endothelial cells. Here, we found that IFN-gamma significantly attenuated basal NO concentration and the increased NO levels supplied by a NO donor, sodium nitroprusside (SNP). Besides, application of IFN-gamma also significantly attenuated both the basal cGMP concentration and the increased cGMP production donated by a cell permeable cGMP analogue, 8-bromo-cyclic GMP (8-Br-cGMP). In addition, exposure of the cell monolayer to IFN-gamma significantly increased HUVECs basal permeability. However, L-NAME pretreatment did not suppress IFN-gamma-induced HUVECs hyperpermeability. L-NAME pretreatment followed by SNP or SNP pretreatment partially reduced IFN-gamma-induced HUVECs hyperpermeability. Pretreatment with a guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), led to a further increase in IFN-gamma-induced HUVECs hyperpermeability. The findings suggest that the mechanism underlying IFN-gamma-induced increased HUVECs permeability is partly related to the inhibition of NO production.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  2. Teh CL, Wan SA, Ling GR
    Clin Rheumatol, 2018 Aug;37(8):2081-2086.
    PMID: 29667100 DOI: 10.1007/s10067-018-4102-6
    Infection is a major cause of morbidity and mortality among patients with systemic lupus erythematosus (SLE). To describe the pattern of serious infections in patients with SLE and to identify the predictors of infection-related mortality among SLE patients with serious infections, we prospectively studied all SLE patients who were hospitalized with infections in Sarawak General Hospital during 2011-2015. Demographic data, clinical features, and outcomes were collected. Cox regression analysis was carried out to determine the independent predictors of infection-related mortality. There were a total of 125 patients with 187 episodes of serious infections. Our patients were of multiethnic origins with female predominance (89.6%). Their mean age was 33.4 ± 14.2 years. The patients had a mean disease duration of 66.8 ± 74.0 months. The most common site of infection was pulmonary (37.9%), followed by septicemia (22.5%). Gram-negative organisms (38.2%) were the predominant isolates within the cohort. There were 21 deaths (11.2%) during the study period. Independent predictors of infection-related mortality among our cohort of SLE patients were flare of SLE (HR 3.98, CI 1.30-12.21) and the presence of bacteremia (HR 2.54, CI 0.98-6.59). Hydroxychloroquine was protective of mortality from serious infections (HR 9.26, CI 3.40-25.64). Pneumonia and Gram-negative organisms were the predominant pattern of infection in our SLE cohort. The presence of flare of SLE and bacteremia were independent prognostic predictors of infection-related mortality, whereas hydroxychloroquine was protective of infection-related mortality among SLE patients with serious infections.
    Matched MeSH terms: Enzyme Inhibitors/therapeutic use
  3. Ng YP, Ahmed R, Ooi GS, Lau CY, Balasubramanian GP, Yap CH
    Diabetes Metab Syndr, 2018 Nov;12(6):1025-1030.
    PMID: 30168425 DOI: 10.1016/j.dsx.2018.06.018
    INTRODUCTION: In Malaysia, 61% of dialysis cases are secondary to diabetes. To date, we are still lacking of data on the rate of progression of type 2 diabetes mellitus (T2DM) to end stage renal disease (ESRD) in Malaysia.

    MATERIALS AND METHODS: This was a retrospective study conducted at nephrology unit of a tertiary hospital in Kedah. All diabetic ESRD patients who fulfilled the inclusion criteria were identified and recruited for analysis.

    RESULTS: The mean duration of DM to ESRD was found to be 14.37 ± 4.42 years. Mean duration for the onset of diabetic nephropathy was 8.73 ± 3.37 years. There was a relative short duration from diabetic nephropathy to ESRD noted, which was 5.63 ± 2.06 years. The mean duration of DM to ESRD for patients receiving RAAS blocker was found to be 18.23 ± 2.38 years as compared to 11.41 ± 2.94 years for those who did not (95% CI: -0.64 to -2.46). For different type of RAAS blockers, namely ACE inhibitor and angiotensin receptor blocker (ARB), there was no significant difference observed pertaining to mean duration of DM to ESRD; 17.89 ± 1.97 years for ACEi and 19.00 ± 4.16 years for ARB (95% CI: -4.74 to 2.52).

    DISCUSSION: Time frame from diabetic nephropathy to ESRF among Malaysian population was shorter as compared to findings from other countries with an average period of 15 to 25 years. RAAS blockers should be initiated early in diabetic patients.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  4. Md Mokhtar AH, Malik IA, Abd Aziz NAA, Almabhouh FA, Durairajanayagam D, Singh HJ
    Andrologia, 2019 Apr;51(3):e13196.
    PMID: 30456785 DOI: 10.1111/and.13196
    This study examined the effects of PI3K and AMPK signalling pathway inhibitors on leptin-induced adverse effects on rat spermatozoa. Sprague-Dawley rats, aged 14-16 weeks, were randomised into control, leptin-, leptin + dorsomorphin (AMPK inhibitor)-, and leptin+LY294002 (PI3K inhibitor)-treated groups with six rats per group. Leptin was given once daily for 14 days via the intraperitoneal (i.p.) route at a dose of 60 ug kg-1 body weight. Rats in the leptin and inhibitor-treated groups received concurrently either dorsomorphin (5 mg kg-1  day-1 ) or LY294002 (1.2 mg kg-1  day-1 ) i.p. for 14 days. Controls received 0.1 ml of normal saline. Upon completion, sperm count, sperm morphology, seminiferous tubular epithelial height (STEH), seminiferous tubular diameter (STD), 8-hydroxy-2-deoxyguanosine (8-OHdG) and phospho-Akt/total Akt ratio were estimated. Data were analysed using ANOVA. Sperm count, STEH and STD were significantly lower, while the percentage of spermatozoa with abnormal morphology and the level of 8-OHdG were significantly higher in rats treated with leptin and leptin + dorsomorphin when compared to those in controls and LY294002-treated rats. Testicular phospho-Akt/total Akt ratio was significantly higher in leptin and leptin + LY294002-treated rats. In conclusion, LY294002 prevents leptin-induced changes in rat sperm parameters, suggesting the potential role of the PI3K signalling pathway in the adverse effects of leptin on sperm parameters.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*
  5. Hussein FA, Chay SY, Ghanisma SBM, Zarei M, Auwal SM, Hamid AA, et al.
    J Dairy Sci, 2020 Mar;103(3):2053-2064.
    PMID: 31882211 DOI: 10.3168/jds.2019-17462
    We evaluated the acute (single-dose) and subacute (repeated-dose) oral toxicity of alcalase-hydrolyzed whey protein concentrate. Our acute study revealed no death or treatment-related complications, and the median lethal dose of whey protein concentrate hydrolysate was >2,500 mg/kg. In the subacute study, when the hydrolysate was fed at 3 different concentrations (200, 400, and 800 mg/kg), no groups showed toxicity changes compared with controls. Then, whey protein concentrate hydrolysate was orally administered to spontaneously hypertensive rats. Results revealed significant reductions in blood pressure in a dose-dependent manner, and dosing at 400 mg/kg led to significant blood pressure reduction (-47.8 mm Hg) compared with controls (blood pressure maintained) and the findings of previous work (-21 mm Hg). Eight peptides-RHPEYAVSVLLR, GGAPPAGRL, GPPLPRL, ELKPTPEGDL, VLSELPEP, DAQSAPLRVY, RDMPIQAF, and LEQVLPRD-were sequentially identified and characterized. Of the peptides, VLSELPEP and LEQVLPRD showed the most prominent in vitro angiotensin-I converting enzyme inhibition with half-maximal inhibitory concentrations of 0.049 and 0.043 mM, respectively. These findings establish strong evidence for the in vitro and in vivo potential of whey protein concentrate hydrolysate to act as a safe, natural functional food ingredient that exerts antihypertensive activity.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/chemistry
  6. Gopinath VK, Musa M, Samsudin AR, Sosroseno W
    PMID: 16997796
    The role of protein kinase C (PKC) in hydroxyapatite (HA)-induced phagocytosis by RAW 264.7 cells was investigated. The cells were incubated with HA particles at various incubation time and the levels of PKC activity were determined from the cell lysate. To determine the role of PKC, particles were incubated with the cells pretreated with the various concentrations of bisindolylmaleimide, a PKC inhibitor, and phagocytosis was then assessed at 60 min. Latex beads were used as a control. Our results showed that following incubation with HA particles, the levels of PKC activity in RAW264.7 cells was highest at 7 min and then decreased to reach the baseline levels of the controls at 30 min. Pretreatment of the cells with bisindolylmaleimide significantly reduced phagocytosis of HA particles in a dose-dependent pattern. The results of our present study suggest therefore that ingestion of HA by RAW264.7 cells may depend on PKC activity that may act in the early stages of phagocytosis.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  7. Looi D, Goh BH, Khan SU, Ahemad N, Palanisamy UD
    Int J Food Sci Nutr, 2021 Jun;72(4):470-477.
    PMID: 33032478 DOI: 10.1080/09637486.2020.1830263
    Hypertension is defined as the persistence of elevated blood pressure in the circulation system. The renin-angiotensin-aldosterone system is a major modulator of blood pressure. Among the risk factors of cardiovascular disease, hypertension is the most preventable and treatable, with drugs such as ACE inhibitors. Many ACE inhibitors are known to have undesirable side effects and hence, natural alternatives are being sought. Dietary polyphenols, particularly ellagitannins, are derived from plant products and are known to exhibit a variety of bioactivities. Geraniin, an ellagitannin has been shown to have antihypertensive activity in animal experiments. It is speculated that the metabolites of geraniin are responsible for its ACE inhibitory activity. We have performed in vitro ACE inhibition and in silico studies with geraniin and its metabolites (ellagic acid, urolithins). Our studies confirm that ellagic acid exhibited similar inhibitory potential to ACE as the positive control captopril.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/pharmacology*
  8. Matsuzaki Tada A, Hamezah HS, Pahrudin Arrozi A, Abu Bakar ZH, Yanagisawa D, Tooyama I
    J Alzheimers Dis, 2022;89(3):835-848.
    PMID: 35964178 DOI: 10.3233/JAD-220192
    BACKGROUND: Tripeptide Met-Lys-Pro (MKP), a component of casein hydrolysates, has effective angiotensin-converting enzyme (ACE) inhibitory activity. Brain angiotensin II enzyme activates the NADPH oxidase complex via angiotensin II receptor type 1 (AT1) and enhances oxidative stress injury. ACE inhibitors improved cognitive function in Alzheimer's disease (AD) mouse models and previous clinical trials. Thus, although undetermined, MKP may be effective against pathological amyloid-β (Aβ) accumulation-induced cognitive impairment.

    OBJECTIVE: The current study aimed to investigate the potential of MKP as a pharmaceutical against AD by examining MKP's effect on cognitive function and molecular changes in the brain using double transgenic (APP/PS1) mice.

    METHODS: Experimental procedures were conducted in APP/PS1 mice (n = 38) with a C57BL/6 background. A novel object recognition test was used to evaluate recognition memory. ELISA was used to measure insoluble Aβ40, Aβ42, and TNF-α levels in brain tissue. Immunohistochemical analysis allowed the assessment of glial cell activation in MKP-treated APP/PS1 mice.

    RESULTS: The novel object recognition test revealed that MKP-treated APP/PS1 mice showed significant improvement in recognition memory. ELISA of brain tissue showed that MKP significantly reduced insoluble Aβ40, Aβ42, and TNF-α levels. Immunohistochemical analysis indicated the suppression of the marker for microglia and reactive astrocytes in MKP-treated APP/PS1 mice.

    CONCLUSION: Based on these results, we consider that MKP could ameliorate pathological Aβ accumulation-induced cognitive impairment in APP/PS1 mice. Furthermore, our findings suggest that MKP potentially contributes to preventing cognitive decline in AD.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  9. Masiran R, Abdul Aziz MF
    BMJ Case Rep, 2017 Aug 28;2017.
    PMID: 28847993 DOI: 10.1136/bcr-2017-220631
    A patient with bipolar I disorder has been treated with lithium and haloperidol for the last 20 years and received an ACE inhibitor for his hypertension since 9 years ago. Despite regular clinic follow-ups and blood monitoring, he recently developed tremors and delirium. On hospital admission, serum level of lithium was far above toxic level. Mental state examination revealed an anxious and disorientated man with irrelevant speech. Immediate discontinuation of lithium resulted in slow reduction of serum lithium levels and gradual resolution of tremor but his delirium persisted for 2 weeks. His condition took a turn for the worse when he developed acute renal failure and arm abscess. We discussed about lithium toxicity and the vulnerability factors which have induced delirium and renal failure in this patient.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
  10. Ng YP, Balasubramanian GP, Heng YP, Kalaiselvan M, Teh YW, Cheong KM, et al.
    Diabetes Metab Syndr, 2018 May;12(3):305-308.
    PMID: 29279269 DOI: 10.1016/j.dsx.2017.12.005
    AIMS: Recent data showed an alarming rise of new dialysis cases secondary to diabetic nephropathy despite the growing usage of RAAS blockers. Primary objective of this study is to explore the prevalence of RAAS blockers usage among type II diabetic patients, secondary objectives are to compare the prescribing pattern of RAAS blocker between primary and tertiary care center and to explore if the dose of RAAS blocker prescribed was at optimal dose as suggested by trials.

    MATERIALS AND METHODS: This is a retrospective study conducted at one public tertiary referral hospital and one public health clinic in Sungai Petani, Kedah, Malaysia.

    RESULTS: RAAS blockers in T2DM patients was found to be 65%. In primary care, 14.3% of the RAAS blockers prescribed was ARB. Tertiary care had higher utilization of ARB, which was 42.9%. In primary care setting, the most commonly used ACEI were perindopril (92.4%) followed by enalapril (7.6%), meanwhile perindopril was the only ACEI being prescribed in tertiary care. The most prescribed ARB was irbesartan (63.6%) and telmisartan (54.2%) respectively in primary and tertiary care. Overall, 64.9% of RAAS blockers prescribed by both levels of care were found to be achieving the target dose as recommended in landmark trials. Crude odd ratio of prescribing RAAS blocker in primary care versus tertiary care was reported as 2.70 (95% CI: 1.49 to 4.91).

    CONCLUSION: RAAS blockers usage among T2DM patients was higher in primary care versus tertiary care settings. Majority of the patients did not receive optimal dose of RAAS blockers.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
  11. Tan F, Mukherjee JJ, Lee KO, Lim P, Liew CF
    Singapore Med J, 2010 Feb;51(2):151-6.
    PMID: 20358155
    INTRODUCTION: Blockade of the renin-angiotensin-aldosterone system (RAAS) by either the angiotensin converting enzyme inhibitor (ACE-I) or the angiotensin II receptor blocker (ARB) has been shown to reduce albuminuria and delay the progression of diabetic nephropathy. This study evaluated the effect of dual blockade of the RAAS by adding an ACEI or an ARB to the administration of either drug alone on albuminuria in Asian type 2 diabetic patients with nephropathy.
    METHODS: 34 patients were randomly assigned to receive either enalapril 20 mg or losartan 100 mg once daily for eight weeks. Following this, all patients received a combination of enalapril 10 mg and losartan 50 mg daily for eight weeks, followed by enalapril 20 mg and losartan 100 mg daily for another eight weeks. The blood pressure and 24-hour urinary albumin excretion (UAE) were monitored.
    RESULTS: Following monotherapy with enalapril, there was a mean and standard error (SE) reduction in the UAE and mean arterial pressure (MAP) of 9.8 (SE 6.8) percent (p-value is 0.061) and 5.3 (SE 2.2) mmHg (p-value is 0.026), respectively; the reduction in UAE and MAP following monotherapy with losartan was by 10.9 (SE 14.1) percent (p-value is 0.053) and 4.5 (SE 1.9) mmHg (p-value is 0.034), respectively. Combination therapy with enalapril and losartan further reduced the UAE (11.2 [SE 8.7] percent, p-value is 0.009] despite there being no significant change in the MAP (-1.2 [SE 1.47] mmHg, p-value is 0.42). The adverse effects included dry cough (seven [19.4 percent] patients, resulting in the withdrawal of medication in two patients), and transient hyperkalaemia (two [six percent] patients).
    CONCLUSION: Dual blockade of the RAAS is safe and effective in reducing albuminuria in Asian type 2 diabetic patients with nephropathy.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
  12. Sabri S, Rahman RN, Leow TC, Basri M, Salleh AB
    Protein Expr Purif, 2009 Dec;68(2):161-6.
    PMID: 19679187 DOI: 10.1016/j.pep.2009.08.002
    Thermostable lipases are important biocatalysts, showing many interesting properties with industrial applications. Previously, a thermophilic Bacillus sp. strain L2 that produces a thermostable lipase was isolated. In this study, the gene encoding for mature thermostable L2 lipase was cloned into a Pichia pastoris expression vector. Under the control of the methanol-inducible alcohol oxidase (AOX) promoter, the recombinant L2 lipase was secreted into the culture medium driven by the Saccharomyces cerevisiae alpha-factor signal sequence. After optimization the maximum recombinant lipase activity achieved in shake flasks was 125 U/ml. The recombinant 44.5 kDa L2 lipase was purified 1.8-fold using affinity chromatography with 63.2% yield and a specific activity of 458.1 U/mg. Its activity was maximal at 70 degrees C and pH 8.0. Lipase activity increased 5-fold in the presence of Ca2+. L2 lipase showed a preference for medium to long chain triacylglycerols (C(10)-C(16)), corn oil, olive oil, soybean oil, and palm oil. Stabilization at high temperature and alkaline pH as well as its broad substrate specificity offer great potential for application in various industries that require high temperature operations.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  13. Amin M, Anwar F, Janjua MRSA, Iqbal MA, Rashid U
    Int J Mol Sci, 2012;13(8):9923-9941.
    PMID: 22949839 DOI: 10.3390/ijms13089923
    A green synthesis route for the production of silver nanoparticles using methanol extract from Solanum xanthocarpum berry (SXE) is reported in the present investigation. Silver nanoparticles (AgNps), having a surface plasmon resonance (SPR) band centered at 406 nm, were synthesized by reacting SXE (as capping as well as reducing agent) with AgNO(3) during a 25 min process at 45 °C. The synthesized AgNps were characterized using UV-Visible spectrophotometry, powdered X-ray diffraction, and transmission electron microscopy (TEM). The results showed that the time of reaction, temperature and volume ratio of SXE to AgNO(3) could accelerate the reduction rate of Ag(+) and affect the AgNps size and shape. The nanoparticles were found to be about 10 nm in size, mono-dispersed in nature, and spherical in shape. In vitro anti-Helicobacter pylori activity of synthesized AgNps was tested against 34 clinical isolates and two reference strains of Helicobacter pylori by the agar dilution method and compared with AgNO(3) and four standard drugs, namely amoxicillin (AMX), clarithromycin (CLA), metronidazole (MNZ) and tetracycline (TET), being used in anti-H. pylori therapy. Typical AgNps sample (S1) effectively inhibited the growth of H. pylori, indicating a stronger anti-H. pylori activity than that of AgNO(3) or MNZ, being almost equally potent to TET and less potent than AMX and CLA. AgNps under study were found to be equally efficient against the antibiotic-resistant and antibiotic-susceptible strains of H. pylori. Besides, in the H. pylori urease inhibitory assay, S1 also exhibited a significant inhibition. Lineweaver-Burk plots revealed that the mechanism of inhibition was noncompetitive.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  14. Mphahlele MJ, Agbo EN, Choong YS
    Molecules, 2021 May 04;26(9).
    PMID: 34064448 DOI: 10.3390/molecules26092692
    The 2-amino-5-(3/4-fluorostyryl)acetophenones were prepared and reacted with benzaldehyde derivatives to afford the corresponding 5-styryl-2-aminochalcone hybrids. The trans geometry of the styryl and α,β-unsaturated carbonyl arms, and the presence of NH…O intramolecular hydrogen bond were validated using 1H-NMR and X-ray data. The 2-amino-5-styrylacetophenones and their 5-styryl-2-aminochalcone derivatives were screened in vitro for their capability to inhibit α-glucosidase and/or α-amylase activities. Their antioxidant properties were evaluated in vitro through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) free radical scavenging assays. Kinetic studies of the most active derivatives from each series against α-glucosidase and/or α-amylase activities have been performed supported by molecular docking studies to determine plausible protein-ligand interactions on a molecular level. The key aspects of the pharmacokinetics of these compounds, i.e., absorption, distribution, metabolism, and excretion have also been simulated at theoretical level. The most active compounds from each series, namely, 2a and 3e, were evaluated for cytotoxicity against the normal monkey kidney cells (Vero cells) and the adenocarcinomic human epithelial (A549) cell line to establish their safety profile at least in vitro.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*
  15. Chong AY, Rajaratnam R, Hussein NR, Lip GY
    Eur J Heart Fail, 2003 Aug;5(4):569-74.
    PMID: 12921820
    BACKGROUND: There are established differences in cardiovascular disease in different racial groups. Worldwide, the literature regarding the clinical epidemiology of congestive heart failure (CHF) in non-white populations is scarce.

    OBJECTIVES: To document the prevalence of CHF 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.

    RESULTS: Of 1435 acute medical admissions to Kuala Lumpur General Hospital over the 4-week study period, 97 patients (6.7%) were admitted with the primary diagnosis of CHF. Coronary artery disease was the main aetiology of CHF, accounting for almost half (49.5%) the patients, followed by hypertension (18.6%). However, there were variations in associated aetiological factors between ethnic groups, with diabetes mellitus affecting the majority of Indians-as well as underutilisation of standard drugs for CHF, such as the angiotensin converting enzyme (ACE) inhibitors, which were only used in 43.3%.

    CONCLUSION: Amongst acute medical admissions to a single centre in Malaysia the prevalence of CHF was 6.7%. Coronary artery disease was the major aetiological factor in heart failure accounting for almost half the admissions. The under-prescription of ACE inhibitors was similar to other clinical surveys carried out amongst Caucasian populations in the West.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/therapeutic use
  16. Zhou Q, Cheung YB, Jada SR, Lim WT, Kuo WL, Gray JW, et al.
    Cancer Biol Ther, 2006 Nov;5(11):1445-9.
    PMID: 17102595
    AIM: The purpose of this study was to test the hypothesis if longer CA dinucleotide repeats are more common in the Asian population and also to gain insights into the interplay between the CA dinucleotide repeats and the frequencies of EGFR gene expression and amplifications as this might have therapeutic implications with regards to treatment with tyrosine kinase inhibitors.

    MATERIALS AND METHODS: The EGFR intron 1 polymorphism was analysed in three distinct healthy Asian subjects, namely, Chinese (N = 96), Malays (N = 98) and Indians (N = 100). Comparative genomic hybridisation was performed to investigate for changes in DNA copy number in relation to the polymorphic CA dinucleotide repeats in breast tumor tissues (N = 22).

    RESULTS: The frequency of short alleles with 14 and 15 CA repeats were most common in the Asian populations and significantly higher than those reported for Caucasians. The frequency of 20 CA repeats was 5%, almost 13-fold lower than previous reports. EGFR amplifications were detected in 23% and 11% of breast tumor tissues harboring short and long CA repeats, respectively.

    CONCLUSION: Our results show that the frequency of alleles encoding for short CA dinucleotide repeats is common in Asian populations. EGFR expression and amplification levels were also higher in Asian breast tumor tissues with short CA dinucleotide repeats. These findings suggest that the EGFR intron 1 polymorphism may influence response to treatment with tyrosine kinase inhibitors in breast cancer patients and further studies are warranted.

    Matched MeSH terms: Enzyme Inhibitors/therapeutic use*
  17. Quah CC, Kim KH, Lau MS, Kim WR, Cheah SH, Gundamaraju R
    PMID: 25392585
    BACKGROUND: The preference for a fairer skin-tone has become a common trend among both men and women around the world. In this study, seaweeds Sargassum polycystum and Padina tenuis were investigated for their in vitro and in vivo potentials in working as skin whitening agents. Seaweed has been used as a revolutionary skin repairing agent in both traditional and modern preparations. The high antioxidant content is one of the prime reasons for its potent action. It has been employed in traditional Chinese and Japanese medicine. For centuries, most medical practitioners in the Asian cultures have known seaweed as an organic source of vitamins, minerals, fatty acids like omega-3 and omega-6 and antioxidants. The present objective of the study was to evaluate the potent dermal protective effect of the two seaweeds Sargassum polycystum and Padina tenuis on human cell lines and guinea pigs.

    MATERIAL AND METHODS: Seaweeds were extracted with ethanol and further fractionated with hexane, ethyl acetate and water. The extracts were tested for mushroom tyrosinase inhibitory activity, cytotoxicity in human epidermal melanocyte (HEM), and Chang cells. Extracts with potent melanocytotoxicity were formulated into cosmetic cream and tested on guinea pigs in dermal irritation tests and de-pigmentation assessments.

    RESULTS: Both Sargassum polycystum and Padina tenuis seaweeds showed significant inhibitory effect on mushroom tyrosinase in the concentration tested. SPEt showed most potent cytotoxicity on HEM (IC50 of 36µg/ml), followed by SPHF (65µg/ml), and PTHF (78.5µg/ml). SPHF and SPEt reduced melanin content in skin of guinea pigs when assessed histologically.

    CONCLUSION: SPEt, SPHF and PTHF were able to inhibit HEM proliferation in vitro, with SPHF being most potent and did not cause any dermal irritation in guinea pigs. The results obtained indicate that SPHF is a promising pharmacological or cosmetic agent.

    Matched MeSH terms: Enzyme Inhibitors/pharmacology
  18. Kow CS, Zaidi STR, Hasan SS
    Am J Cardiovasc Drugs, 2020 Jun;20(3):217-221.
    PMID: 32281055 DOI: 10.1007/s40256-020-00406-0
    There is ongoing debate on the safety of renin-angiotensin system (RAS) inhibitors in COVID-19. Recently published studies highlight a potential relationship between cardiovascular disease (CVD) and COVID-19. This article aims to summarize the evidence on the use of RAS inhibitors in CVD patients with COVID-19, focusing on safety issues of the RAS inhibitors and their relationship with COVID-19.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/pharmacology*
  19. Saidin S, Othman N, Noordin R
    Am J Trop Med Hyg, 2017 Oct;97(4):1204-1213.
    PMID: 28820699 DOI: 10.4269/ajtmh.17-0132
    Adverse effects and resistance to metronidazole have motivated the search for new antiamoebic agents against Entamoeba histolytica. Control of amoeba growth may be achieved by inhibiting the function of the glycolytic enzyme and pyruvate phosphate dikinase (PPDK). In this study, we screened 10 compounds using an in vitro PPDK enzyme assay. These compounds were selected from a virtual screening of compounds in the National Cancer Institute database. The antiamoebic activity of the selected compounds was also evaluated by determining minimal inhibitory concentrations (MICs) and IC50 values using the nitro-blue tetrazolium reduction assay. Seven of the 10 compounds showed inhibitory activities against the adenosine triphosphate (ATP)/inorganic phosphate binding site of the ATP-grasp domain. Two compounds, NSC349156 (pancratistatin) and NSC228137 (7-ethoxy-4-[4-methylphenyl] sulfonyl-3-oxido-2, 1, 3-benzoxadiazol-3-ium), exhibited inhibitory effects on the growth of E. histolytica trophozoites with MIC values of 25 and 50 μM, and IC50 values of 14 and 20.7 μM, respectively.
    Matched MeSH terms: Enzyme Inhibitors/pharmacology*
  20. Mahmoodani F, Ghassem M, Babji AS, Yusop SM, Khosrokhavar R
    J Food Sci Technol, 2014 Sep;51(9):1847-56.
    PMID: 25190839 DOI: 10.1007/s13197-012-0742-8
    Skin and bone gelatins of pangasius catfish (Pangasius sutchi) were hydrolyzed with alcalase to isolate Angiotensin Converting Enzyme (ACE) inhibitory peptides. Samples with the highest degree of hydrolysis (DH) were separated into different fractions with molecular weight cut-off (MWCO) sizes of 10, 3 and 1 kDa, respectively and assayed for ACE inhibitory activity. Skin and bone gelatins had highest DH of 64.87 and 68.48 % after 2 and 1 h incubation, respectively. Results from this study indicated that by decreasing the molecular weight of fractions, ACE inhibitory activity was increased. Therefore, F3 permeates (MWCO 
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
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