Displaying publications 201 - 220 of 382 in total

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  1. Fulltext Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2
    Muchtaridi M, Fauzi M, Khairul Ikram NK, Mohd Gazzali A, Wahab HA
    Molecules, 2020 Sep 01;25(17).
    PMID: 32882868 DOI: 10.3390/molecules25173980
    Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/pharmacology*; Angiotensin-Converting Enzyme Inhibitors/chemistry
  2. Malaysian brown seaweeds Sargassum siliquosum and Sargassum polycystum: Low density lipoprotein (LDL) oxidation, angiotensin converting enzyme (ACE), α-amylase, and α-glucosidase inhibition activities
    Nagappan H, Pee PP, Kee SHY, Ow JT, Yan SW, Chew LY, et al.
    Food Res Int, 2017 Sep;99(Pt 2):950-958.
    PMID: 28847432 DOI: 10.1016/j.foodres.2017.01.023
    Two Malaysian brown seaweeds, Sargassum siliquosum and Sargassum polycystum were first extracted using methanol to get the crude extract (CE) and further fractionated to obtain fucoxanthin-rich fraction (FRF). Samples were evaluated for their phenolic, flavonoid, and fucoxanthin contents, as well as their inhibitory activities towards low density lipoprotein (LDL) oxidation, angiotensin converting enzyme (ACE), α-amylase, and α-glucosidase. In LDL oxidation assay, an increasing trend in antioxidant activity was observed as the concentration of FRF (0.04-0.2mg/mL) and CE (0.2-1.0mg/mL) increased, though not statistically significant. As for serum oxidation assay, significant decrease in antioxidant activity was observed as concentration of FRF increased, while CE showed no significant difference in inhibitory activity across the concentrations used. The IC50 values for ACE inhibitory activity of CE (0.03-0.42mg/mL) were lower than that of FRF (0.94-1.53mg/mL). When compared to reference drug Voglibose (IC50 value of 0.61mg/mL) in the effectiveness in inhibiting α-amylase, CE (0.58mg/mL) gave significantly lower IC50 values while FRF (0.68-0.71mg/mL) had significantly higher IC50 values. The α-glucosidase inhibitory activity of CE (IC50 value of 0.57-0.69mg/mL) and FRF (IC50 value of 0.50-0.53mg/mL) were comparable to that of reference drug (IC50 value of 0.54mg/mL). Results had shown the potential of S. siliquosum and S. polycystum in reducing cardiovascular diseases related risk factors following their inhibitory activities on ACE, α-amylase and α-glucosidase. In addition, it is likelihood that FRF possessed antioxidant activity at low concentration level.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/isolation & purification; Angiotensin-Converting Enzyme Inhibitors/pharmacology*
  3. Fulltext Therapeutic-diagnostic evaluation of chronic cough amongst adults: causes, symptoms and management at the primary care level, Malaysia
    Nantha YS
    J Family Med Prim Care, 2014 Jul;3(3):207-12.
    PMID: 25374855 DOI: 10.4103/2249-4863.141611
    BACKGROUND: Patients presenting with chronic cough pose a common diagnostic dilemma during routine consultations at public primary care clinics in Malaysia. To date, there has been little attempt at designing a standardized model or algorithm to facilitate an accurate diagnosis of chronic cough. This study proposes a clinical method to detect the causes of chronic cough in a primary care setting in Malaysia.
    MATERIALS AND METHODS: A total of 117 patients aged above 18 at an urban primary care clinic were tracked over a span of 5 months to diagnose the cause of chronic cough. A therapeutic-diagnostic method was employed to help identify the causes of chronic cough. Subsequently, the demographic details of patients, the prevalence of the different causes of chronic cough and the relationship between history and diagnosis were analyzed statistically.
    RESULTS: Chronic cough had a slightly higher male preponderance (51.3% vs. 48.7%). Patients within the 'above 60' age category had the highest frequency of chronic cough. The most common cause of chronic cough was post-infectious cough (n = 42, 35.9%), followed closely by angiotensin-converting enzyme-inhibitor related cough (n = 14, 12%). Majority of patients had the symptom of phlegm production (n = 41, 54%). 33 patients (29.2%) had recent upper respiratory tract infection (<2 weeks ago) prior to the diagnosis of chronic cough. There were poor association between symptoms and the various entities comprising chronic cough. The exceptions were the following associations: (1) Bronchial asthma and itchiness of throat (P = 0021), (2) gastroesophageal reflux disease and heartburn (P < 0.001), (3) upper airway cough syndrome and running nose (P = 0.016) and (4) pulmonary tuberculosis and absence of weight loss (P = 0.004).
    CONCLUSION: This study demonstrates that the effectiveness of a therapeutic-diagnostic technique in the diagnosis of chronic cough. Consistent with previous studies, there was poor association between most symptoms and the causes of chronic cough. A study involving a larger primary care population is required to confirm the findings found in this analysis.
    KEYWORDS: Angiotensin-converting enzyme-I related cough; chronic cough; post-infectious cough; primary care; therapeutic-diagnostic evaluation
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
  4. Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II
    Bera H, Ojha Pk, Tan BJ, Sun L, Dolzhenko AV, Chui WK, et al.
    Eur J Med Chem, 2014 May 6;78:294-303.
    PMID: 24686016 DOI: 10.1016/j.ejmech.2014.03.063
    In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones were designed, synthesized and evaluated for their TP inhibitory potential. All the synthesized analogues conferred a varying degree of TP inhibitory activity, comparable or better than positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 μM). A systematic approach to the lead optimization identified compounds 3c and 4a as the most promising TP inhibitors, exhibiting mixed mode of enzyme inhibition. Moreover, selected compounds demonstrated the ability to attenuate the expression of the angiogenic markers (viz. MMP-9 and VEGF) in MDA-MB-231 cells at sublethal concentrations. In addition, molecular docking studies revealed the plausible binding orientation of these inhibitors towards TP, which was in accordance with the experimental results. Taken as a whole, these compounds would constitute a new direction for the design of novel TP inhibitors with promising antiangiogenic properties.
    Matched MeSH terms: Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry
  5. Fulltext Comparative study of Mg/Al- and Zn/Al-layered double hydroxide-perindopril erbumine nanocomposites for inhibition of angiotensin-converting enzyme
    Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Zainal Z, Hakim MN
    Int J Nanomedicine, 2012;7:4251-62.
    PMID: 22904631 DOI: 10.2147/IJN.S32267
    The intercalation of a drug active, perindopril, into Mg/Al-layered double hydroxide for the formation of a new nanocomposite, PMAE, was accomplished using a simple ion exchange technique. A relatively high loading percentage of perindopril of about 36.5% (w/w) indicates that intercalation of the active took place in the Mg/Al inorganic interlayer. Intercalation was further supported by Fourier transform infrared spectroscopy, and thermal analysis shows markedly enhanced thermal stability of the active. The release of perindopril from the nanocomposite occurred in a controlled manner governed by pseudo-second order kinetics. MTT assay showed no cytotoxicity effects from either Mg/Al-layered double hydroxide or its nanocomposite, PMAE. Mg/Al-layered double hydroxide showed angiotensin-converting enzyme inhibitory activity, with 5.6% inhibition after 90 minutes of incubation. On incubation of angiotensin-converting enzyme with 0.5 μg/mL of the PMAE nanocomposite, inhibition of the enzyme increased from 56.6% to 70.6% at 30 and 90 minutes, respectively. These results are comparable with data reported in the literature for Zn/Al-perindopril.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/pharmacokinetics; Angiotensin-Converting Enzyme Inhibitors/pharmacology*; Angiotensin-Converting Enzyme Inhibitors/chemistry
  6. Fulltext Anti-snake venom and methanolic extract of Andrographis paniculata: a multipronged strategy to neutralize Naja naja venom acetylcholinesterase and hyaluronidase
    Nayak AG, Kumar N, Shenoy S, Roche M
    3 Biotech, 2020 Nov;10(11):476.
    PMID: 33083200 DOI: 10.1007/s13205-020-02462-4
    The study investigates the ability of methanolic extract of Andrographis paniculata (MAP) to supplement polyvalent anti-snake venom (ASV) in inhibiting neurotoxic enzyme acetylcholinesterase (AChE) and 'spreading factor' hyaluronidase from Naja naja (N.N) venom. AChE and hyaluronidase activity were measured in 100 or 200 µg of crude venom, respectively, and designated as 'control'. In Test Group I, enzyme assays were performed immediately after the addition of ASV/MAP/ASV + MAP to the venom. Inhibition of AChE by ASV (100-367 µg) was 12-17%, and of hyaluronidase (22-660 µg) was 33-41%. Under the same conditions, MAP (100-400 µg) inhibited AChE and hyaluronidase to the extent of 17-33% and 17-52%, respectively. When ASV (220 µg) and MAP (100-200 µg) were added together, AChE and hyaluronidase were inhibited to a greater extent from 39-63 to 36-44%, than when either of them was used alone. In Test Group 2, the venom was incubated with ASV/MAP/ASV + MAP for 10-30 min at 37 °C prior to the assay which enhanced AChE inhibition by 6%, 82% and 18% respectively, when compared to Test Group I. Though there was no change in inhibition of hyaluronidase in the presence of ASV, MAP could further increase the extent of inhibition by 27% and ASV + MAP upto 4%. In Test Group III, venom and substrate were incubated for 90 min and hyaluronidase activity was measured after the addition of inhibitors. Here, ASV + MAP caused increased inhibition by 69% compared to ASV alone. The study confirms the ability of phytochemicals in MAP to contribute to a multipronged strategy by supplementing, thereby augmenting the efficacy of ASV.
    Matched MeSH terms: Enzyme Inhibitors
  7. Fulltext The impact of four processing methods on trypsin-, chymotrypsin- and alpha-amylase inhibitors present in underutilised legumes
    Choi WC, Parr T, Lim YS
    J Food Sci Technol, 2019 Jan;56(1):281-289.
    PMID: 30728570 DOI: 10.1007/s13197-018-3488-0
    The global trend in increasing plant-based protein diets due to health and ideological reasons, has created an increased demand for food legumes that exceeds current production. To meet this demand, it is timely to reduce relying solely on soybean, and explore the potential of the underutilised legumes that are cultivated regionally. Underutilised legumes are rich in protein, carbohydrates and other nutrients that are essential for consumer. However, relatively little is known about their anti-nutritional properties and processing methods. Anti-nutritional factors (ANFs) such as enzyme inhibitors are prevalent in legumes and may interfere with digestibility and nutrient absorption. Nevertheless, an optimised food processing method will overcome this challenge and warrant a safe inclusion of legume in plant-based protein diets. Hence current study aimed to optimise the food processing methods (soaking, wet heating, autoclaving and freezing) and evaluate their efficiency in eliminating the enzyme inhibitors [trypsin, chymotrypsin (CIA) and α-amylase (AIA) inhibitors] present in seven underutilised legumes. Current study showed that autoclaving at 121 °C for 15 min reduced the AIA in all underutilised legumes tested. The AIA and CIA of bambara groundnut were successfully inactivated by wet heating at 50 °C for 60 min, and by autoclaving at 121 °C for 15 min. While the CIA of chickpea was successfully inactivated by freezing at - 80 °C for 24 h.
    Matched MeSH terms: Enzyme Inhibitors
  8. Fulltext QSAR Studies on Neuraminidase Inhibitors as Anti-influenza Agents
    Veerasamy R, Rajak H
    Turk J Pharm Sci, 2021 04 20;18(2):151-156.
    PMID: 33900700 DOI: 10.4274/tjps.galenos.2020.45556
    Objectives: The present study aimed to establish significant and validated quantitative structure-activity relationship (QSAR) models for neuraminidase inhibitors and correlate their physicochemical, steric, and electrostatic properties with their anti-influenza activity.

    Materials and Methods: We have developed and validated 2D and 3D QSAR models by using multiple linear regression, partial least square regression, and k-nearest neighbor-molecular field analysis methods.

    Results: 2D QSAR models had q2: 0.950 and pred_r2: 0.877 and 3D QSAR models had q2: 0.899 and pred_r2: 0.957. These results showed that the models werere predictive.

    Conclusion: Parameters such as hydrogen count and hydrophilicity were involved in 2D QSAR models. The 3D QSAR study revealed that steric and hydrophobic descriptors were negatively contributed to neuraminidase inhibitory activity. The results of this study could be used as platform for design of better anti-influenza drugs.

    Matched MeSH terms: Enzyme Inhibitors
  9. Fulltext COVID-19 in adult patients with pre-existing chronic cardiac, respiratory and metabolic disease: a critical literature review with clinical recommendations
    Flaherty GT, Hession P, Liew CH, Lim BCW, Leong TK, Lim V, et al.
    Trop Dis Travel Med Vaccines, 2020;6:16.
    PMID: 32868984 DOI: 10.1186/s40794-020-00118-y
    Background: A high burden of severe disease and death from the coronavirus disease 2019 (COVID-19) has been consistently observed in older patients, especially those with pre-existing medical co-morbidities. The global pandemic lockdown has isolated many patients with chronic illnesses from their routine medical care. This narrative review article analyses the multitude of issues faced by individuals with underlying medical conditions during the COVID-19 pandemic.

    Methods: Sources for this publication were identified through searches of PubMed for articles published between 31st December 2019 and 4th June 2020, using combinations of search terms. Guidelines and updates from reputable agencies were also consulted. Only articles published in the English language were included.

    Results: The volume of literature on COVID-19 continues to expand, with 17,845 articles indexed on PubMed by 4th June 2020, 130 of which were deemed particularly relevant to the subject matter of this review. Older patients are more likely to progress to severe COVID-19 disease requiring intensive care unit (ICU) admission. Patients with pre-existing cardiovascular disease, especially hypertension and coronary heart disease, are at greatly increased risk of developing severe and fatal COVID-19 disease. A controversial aspect of the management of COVID-19 disease has been the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Obese COVID-19 patients are more likely to require complex ICU management. Putative mechanisms of increased COVID-19 disease severity in diabetes include hyperglycaemia, altered immune function, sub-optimal glycaemic control during hospitalisation, a pro-thrombotic and pro-inflammatory state. Patients with mental health disorders are particularly vulnerable to social isolation, and this has been compounded by the suspension of non-emergency care in hospitals around the world, making it difficult for patients with chronic mental illness to attend outpatient appointments.

    Conclusions: The global pandemic of COVID-19 disease has had a disproportionately negative impact on patients living with chronic medical illness. Future research should be directed at efforts to protect vulnerable patients from possible further waves of COVID-19 and minimising the negative impact of pandemic mitigation strategies on these individuals.

    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
  10. Gynura procumbens causes vasodilation by inhibiting angiotensin II and enhancing bradykinin actions
    Poh TF, Ng HK, Hoe SZ, Lam SK
    J Cardiovasc Pharmacol, 2013 May;61(5):378-84.
    PMID: 23328388 DOI: 10.1097/FJC.0b013e31828685b3
    Previous studies showed that Gynura procumbens reduced blood pressure by blocking calcium channels and inhibiting the angiotensin-converting enzyme activity. The present experiments were to further explore the effects and mechanisms of a purer aqueous fraction (FA-I) of G. procumbens on angiotensin I (Ang I)-induced and angiotensin II (Ang II)-induced contraction of aortic rings and also on the bradykinin (BK) effect on cardiovascular system. Rat aortic rings suspended in organ chambers were used to investigate the vascular reactivity of FA-I. Effect of FA-I on BK was studied by in vitro and in vivo methods. Results show that FA-I significantly (P < 0.05) decreased the contraction evoked by Ang I and Ang II. In the presence of indomethacin (10 µM) or N-nitro-L-arginine methyl ester (0.1 µM), the inhibitory effect of FA-I on Ang II-induced contraction of aortic rings was reduced. Besides, FA-I potentiated the vasorelaxant effect and enhanced the blood pressure-lowering effect of BK. In conclusion, FA-I reduced the contraction evoked by Ang II probably via the endothelium-dependent pathways, which involve activation of the release of nitric oxide and prostaglandins. The inhibition of angiotensin-converting enzyme activity by FA-I may contribute to the potentiation of the effects of BK on cardiovascular system.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/pharmacology; Enzyme Inhibitors/pharmacology
  11. Fulltext Alternative RNA Extraction Method in Vibrio vulnificus Infected BrownMarbled Grouper, Epinephelus fuscoguttatus
    Fahmeeda Mohamad Jazamuddin, Wan Mohd Aizat, Hoe-Han Goh, Chen-Fei Low, Syarul Nataqain Baharum
    Trop Life Sci Res, 2019;30(2):2012-209.
    MyJurnal
    Vibriosis is a prevalent aquatic disease caused by Vibrio species and has led to massive loss of brown-marbled grouper, Epinephelus fuscoguttatus. The complexity of molecular mechanisms associated with immune defence can be studied through transcriptomics analysis. High quality and quantity of total RNAs are crucial for the veracity of RNA sequencing and gene expression analysis. A low quality RNA will compromise downstream analysis, resulting in loss of time and revenue to re-acquire the data again. Thus, a reliable and an efficient RNA isolation method is the first and most important step to obtain high quality RNA for gene expression studies. There are many aspects need to be considered when deciding an extraction method, such as the cost-effectiveness of the protocol, the duration of chemical exposure, the duration required for a complete extraction and the number of sample-transferring. A good RNA extraction protocol must be able to produce high yield and purity of RNA free from enzyme inhibitors, such as nucleases (RNase), phenols, alcohols or other chemicals carryover, apart from protein and genomic DNA contamination, to maintain isolated RNA integrity in storage condition. In this study, TransZolTM Up produced clean and pure RNA samples from control gills only but not from the infected gill and whole-body tissues. Modified conventional CTAB (conventional hexadecyltrimethylammonium bromide) method was then used as an alternative method to isolate RNA from gill and whole-body tissues of Vibrio-infected E. fuscoguttatus. Modified CTAB method produced intact RNA on gel electrophoresis with higher RIN number (>6.5) for infected gill and whole-body tissues, suggesting that this method could also be used to isolate high quality RNA from fish samples. Therefore, this method is potentially suitable to be used to extract RNA from other fish species especially those that have been infected.
    Matched MeSH terms: Enzyme Inhibitors
  12. Fulltext Evaluation of anti-hypertensive drug utilisation and cost in Hospital Tengku Ampuan Afzan, Kuantan.
    Azarisman S.M.S., Aszrin A., Sahimi M.S., Ngow, Harris, Marzuki A.O., Jamalludin A.R., et al.
    International Medical Journal Malaysia, 2009;8(2):29-36.
    MyJurnal
    Introduction: Hypertension is one of the most important risk factors for cardiovascular disease in Malaysia. The prevalence of hypertension nearly doubled over a ten-year period (1986 – 1996). This has resulted in a significant rise in its attendant cost. We aim to review the institutional anti-hypertensive use, the cost incurred and the implications on management in our local setting. Materials and Methods: A retrospective review of the annual cost (2006) of anti-hypertensive medications was undertaken at the Department of Pharmacy, Hospital Tengku Ampuan Afzan, a 600-bed major regional hospital on the east-coast of Malaysia. The total number of prescriptions given out and the total cost per drug is then factored to give the annual cost per drug per person in a percentage of the total annual expenditure.Results: The majority of patients were on either 2 (46.5%) or 3 (25.9%) anti-hypertensives. The most frequently prescribed medications were ACE Inhibitors (33.45%), Calcium channel blockers (29.63%), diuretics (16.67%) and β-blockers (13.64%). In terms of cost however, the Calcium channel blockers constituted the greatest percentage of the annual anti-hypertensive budget (63.67%) compared to ACE Inhibitors at just 20.04% of the annual expenditure. The least costly group of drugs is the diuretic making up 16.67% of the total annual prescriptions but only constituting 1.23% of the annual cost. Conclusion: The majority of patients were on ACE Inhibitors and/or Calcium channel blockers. This has huge monetary implications as they represent a large proportion of the annual antihypertensive allocation. There may be a need to reverse the trend in the developing world due to cost restrictions.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
  13. Fulltext Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay
    Hariono M, Abdullah N, Damodaran KV, Kamarulzaman EE, Mohamed N, Hassan SS, et al.
    Sci Rep, 2016 12 20;6:38692.
    PMID: 27995961 DOI: 10.1038/srep38692
    We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ~0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.
    Matched MeSH terms: Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacology; Enzyme Inhibitors/chemistry
  14. Fulltext The use of febuxostat for gout in Hospital Tengku Ampuan Afzan (HTAA) Kuantan. [Abstract]
    Abdullah H
    International Medical Journal Malaysia, 2017;16(11):50.
    MyJurnal
    Introduction: Febuxostat is a non-purine-selective oral xanthine oxidase inhibitor drug, and is an alternative to Allopurinol to lower serum uric acid in gout patients. It is probably more effective than Allopurinol, however, its use is limited because of its cost and availability. Allopurinol has been the mainstay treatment for gout for about 50 years. However, its use has been associated with allergic reactions especially in patients with renal impairment.The objective of this study was to describe HTAA Rheumatology Unit experiences with Febuxostat in the management of gout.
    Materials and method: Case records belonging to 6 patients who had been started on Febuxostat between January 2012 and January 2017 were analysed.
    Results: The majority of patients on Febuxostat were males (83.3%) as well as Malays (83.3%). About 66.7% of patients had already developed mild to moderate chronic kidney disease (GFR between 30-89 mL/min) due to multifactorial causes by the time they were started on Febuxostat. Also 33% of patients had mild liver impairment (ALT & AST < 1.5 ULN) due to fatty liver prior to Febuxostat. All patients had been started on Febuxostat due to allergic reactions to Allopurinol. All patients were on Febuxostat 40 mg once a day. Following Febuxostat, a significant decrease in the uric acid levels much closer to the target level i.e. less than 360 µmol/L were achieved in all patients. Only 1 patient (16.7%) developed a side effect i.e. ALT > 1.5 ULN while the rest tolerated the drug very well.
    Conclusion: Although the number of patients analysed was small, Febuxostat was shown to be very effective and safe for use in patients with gout even with concomitant mild to moderate renal impairment. Serum uric acid levels reduced significantly while on the lowest dose of 40 mg once a day.
    Matched MeSH terms: Enzyme Inhibitors
  15. Antioxidant, α-amylase and α-glucosidase activity of various solvent fractions of I. obliquus and the preventive role of active fraction against H2 O2 induced damage in hepatic L02 cells as fungisome
    Gao X, Santhanam RK, Xue Z, Jia Y, Wang Y, Lu Y, et al.
    J Food Sci, 2020 Apr;85(4):1060-1069.
    PMID: 32147838 DOI: 10.1111/1750-3841.15084
    Inonotus obliquus is a traditional mushroom well known for its therapeutic value. In this study, various solvent fractions of I. obliquus were preliminarily screened for their antioxidant, α-amylase and α-glucosidase inhibition properties. To improve the drug delivery, the active fraction (ethyl acetate fraction) of I. obliquus was synthesized into fungisome (ethyl acetate phophotidyl choline complex, EAPC) and its physical parameters were assessed using Fourier transform infrared spectroscopy (FTIR), High performance liquid chromatography (HPLC), Scanning electron microscope (SEM), and ς potential analysis. Then normal human hepatic L02 cells was used to evaluate the cytotoxicity of EAPC. The results showed that EA fraction possesses significant free radical scavenging, α-amylase and α-glucosidase inhibition properties. FTIR, SEM, and HPLC analysis confirmed the fungisome formation. The particle size of EAPC was 102.80 ± 0.42 nm and the ς potential was -54.30 ± 0.61 mV. The percentage of drug entrapment efficiency was 97.13% and the drug release rates of EAPC in simulated gastric fluid and simulated intestinal fluid were 75.04 ± 0.29% and 93.03 ± 0.36%, respectively. EAPC was nontoxic to L02 cells, however it could selectively fight against the H2 O2 induced oxidative damage in L02 cells. This is the first study to provide scientific information to utilize the active fraction of I. obliquus as fungisome. PRACTICAL APPLICATIONS: Inonotus obliquus (IO) is a traditional medicinal fungus. The extracts of IO have obvious antioxidant and hypoglycemic activities. Ethyl acetate (EA) fraction of IO was encapsulated in liposomes to form EAPC. EAPC has a sustained-release effect. It has nontoxic to L02 cells and could protect L02 cells from oxidative damage caused by hydrogen peroxide. This study could provide new ideas for the treatment of diabetes.
    Matched MeSH terms: Enzyme Inhibitors/isolation & purification; Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry
  16. Fulltext Synthesis and evaluation of anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities of some 3H-quinazolin-4-one derivatives
    El-Sayed NNE, Almaneai NM, Ben Bacha A, Al-Obeed O, Ahmad R, Abdulla M, et al.
    J Enzyme Inhib Med Chem, 2019 Dec;34(1):672-683.
    PMID: 30821525 DOI: 10.1080/14756366.2019.1574780
    Some new 3H-quinazolin-4-one derivatives were synthesised and screened for anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities. Compound 15d was more potent in reducing the cell viabilities of HT-29 and SW620 cells lines to 38%, 36.7%, compared to 5-FU which demonstrated cell viabilities of 65.9 and 42.7% respectively. The IC50 values of 15d were ∼20 µg/ml. Assessment of apoptotic activity revealed that 15d decreased the cell viability by down regulating Bcl2 and BclxL. Moreover, compounds, 8j, 8d/15a/15e, 5b, and 8f displayed lowered IC50 values than oleanolic acid against proinflammatory isoforms of hGV, hG-X, NmPLA2, and AmPLA2. In addition, 8d, 8h, 8j, 15a, 15b, 15e, and 15f showed better anti-α-amylase than quercetin, whereas 8g, 8h, and 8i showed higher anti-α-glucosidase activity than allopurinol. Thus, these compounds can be considered as potential antidiabetic agents. Finally, none of the compounds showed higher antiproteases or xanthine oxidase activities than the used reference drugs.
    Matched MeSH terms: Enzyme Inhibitors/chemical synthesis; Enzyme Inhibitors/pharmacology*; Enzyme Inhibitors/chemistry
  17. Effect of rosiglitazone/ramipril on preclinical vasculopathy in newly diagnosed, untreated diabetes and IGT patients: 1-year randomised, double-blind, placebo-controlled study
    Rahman S, Ismail AA, Ismail SB, Naing NN, Abdul Rahman AR
    Eur J Clin Pharmacol, 2007 Aug;63(8):733-41.
    PMID: 17565489 DOI: 10.1007/s00228-007-0315-3
    OBJECTIVE: To investigate whether pharmacological interventions with rosiglitazone/ramipril can reverse preclinical vasculopathy in newly diagnosed untreated patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT).

    METHODS: In this randomised, double-blind, placebo-controlled study, 33 T2DM and 33 IGT patients were randomised to 4 mg rosiglitazone or 5 mg ramipril or placebo for 1 year. The subjects were newly diagnosed, untreated, normotensive, nonobese, nonsmoker, and nonhyperlipidaemic. Haemodynamic variables were measured at three treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period.

    RESULTS: Rosiglitazone showed a significant reduction in PWV (p=0.039) and AI (p=0.031) and ramipril demonstrated a significant reduction of AI (p=0.025) in IGT in comparison to placebo on the 12th month of treatment. No significant difference was observed in PWV and AI in T2DM with rosiglitazone/ramipril in comparison to placebo during overall treatment period.

    CONCLUSIONS: Rosiglitazone significantly reversed preclinical vasculopathy in IGT as evident by significant decrease in PWV and AI after 1 year of treatment. Ramipril also reduced large artery stiffness as shown by significant decrease of AI after 1 year of treatment in IGT. Further trials are needed for a longer period of time, maybe with higher doses, to show whether rosiglitazone/ramipril can reverse preclinical vasculopathy in T2DM.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/administration & dosage; Angiotensin-Converting Enzyme Inhibitors/pharmacology; Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
  18. Blood-pressure lowering efficacy of winged bean seed hydrolysate in spontaneously hypertensive rats, peptide characterization and a toxicity study in Sprague-Dawley rats
    Chay SY, Salleh A, Sulaiman NF, Zainal Abidin N, Hanafi MA, Zarei M, et al.
    Food Funct, 2018 Mar 01;9(3):1657-1671.
    PMID: 29469915 DOI: 10.1039/c7fo01769c
    Winged bean seed (WBS) is an underutilized tropical crop. The current study evaluates its potential to reduce blood pressure (BP) in spontaneously hypertensive rats and finds that it reduces BP significantly, in a dose-dependent manner. Five peptides with the sequences, RGVFPCLK, TQLDLPTQ, EPALVP, MRSVVT and DMKP, have been characterized in terms of their stability against ACE via in vitro and in silico modelling. All peptides exhibited IC50 values between 0.019 and 6.885 mM and various inhibitory modes, including substrate, prodrug and true inhibitor modes. The toxicity status of non-Current Good Manufacturing Practice (non-CGMP) peptides is evaluated and the results show that such peptides are toxic, and thus are not suitable to be tested in animals, particularly in repeated-dose studies. In short, WBS hydrolysate demonstrated in vitro ACE inhibitory properties and in vivo blood pressure lowering efficacy in rat models, fostering its potential as a functional food ingredient. Non-CGMP grade peptides are toxic and unfit for testing in animal models.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/administration & dosage; Angiotensin-Converting Enzyme Inhibitors/adverse effects; Angiotensin-Converting Enzyme Inhibitors/chemistry
  19. Fulltext Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma
    Ahmad M, Suhaimi SN, Chu TL, Abdul Aziz N, Mohd Kornain NK, Samiulla DS, et al.
    PLoS One, 2018;13(1):e0191295.
    PMID: 29329342 DOI: 10.1371/journal.pone.0191295
    Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.
    Matched MeSH terms: Cytochrome P-450 Enzyme Inhibitors/pharmacology; Cytochrome P-450 Enzyme Inhibitors/toxicity; Cytochrome P-450 Enzyme Inhibitors/chemistry
  20. Antimicrobial resistance in aquaculture: Occurrence and strategies in Southeast Asia
    Suyamud B, Chen Y, Quyen DTT, Dong Z, Zhao C, Hu J
    Sci Total Environ, 2024 Jan 10;907:167942.
    PMID: 37863226 DOI: 10.1016/j.scitotenv.2023.167942
    Aquaculture is a highly important and expanding industry in Southeast Asia (SEA). An upcoming problem is the emergence of antibiotic resistant pathogens due to the unchecked use of antibiotics and human clinical practices. This review focused insight into the occurrence of antimicrobial resistance (AMR) and strategies from SEA aquaculture based on the original research publication over the period 2002 to 2023. Amongst the 11 SEA countries, the most AMR report has come from Vietnam, Malaysia, and Thailand, respectively. The AMR found in SEA aquaculture were classified into 17 drug classes. The most reported AMR are aminoglycosides, beta-lactams, (fluoro)quinolones, tetracycline, sulpha group and multi-drug. Beta-lactams, tetracycline, sulpha group are reported in each country with the reported frequencies higher than 40 %. Escherichia coli, Aeromonas and Vibrio are the most widely and frequently reported ARB in SEA aquaculture. Multiple antibiotic resistance (MAR) indexes for the sample containing multiple bacterial isolates were generally low, while the medium numbers of MAR indexes for the typical bacteria species were higher than 0.2 and showed higher MAR levels than the global mean. Most of the detected ARGs are related to beta-lactams, tetracycline, sulpha group, and aminoglycosides. Amongst the beta-lactam resistance genes, blaTEM, and blaSHV are the most frequently detected. Almost all the available information of antibiotics, ARB and ARGs in SEA aquaculture was consistent with the global scale analysis. In addition, factors that contribute to the development and spread of AMR in SEA aquaculture were discussed. Moreover, the national action plan to combat AMR in SEA countries and the available technologies that already applied in the SEA aquaculture are also included in this review. Such findings underline the need for synergistic efforts from scientists, engineers, policy makers, government managers, entrepreneurs, and communities to manage and reduce the burden of AMR in aquaculture of SEA countries.
    Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors
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