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  1. Fulltext Evaluation of the effect of andrographolide on atherosclerotic rabbits induced by Porphyromonas gingivalis
    Al Batran R, Al-Bayaty F, Al-Obaidi MM, Hussain SF, Mulok TZ
    Biomed Res Int, 2014;2014:724718.
    PMID: 25215291 DOI: 10.1155/2014/724718
    Epidemiologic evidence has demonstrated significant associations between atherosclerosis and Porphyromonas gingivalis (Pg). We had investigated the effect of andrographolide (AND) on atherosclerosis induced by Pg in rabbits. For experimental purpose, we separated thirty male white New Zealand rabbits into 5 groups. Group 1 received standard food pellets; Groups 2-5 were orally challenged with Pg; Group 3 received atorvastatin (AV, 5 mg/kg), and Groups 4-5 received 10 and 20 mg/kg of AND, respectively, over 12 weeks. Groups treated with AND showed significant decrease in TC, TG, and LDL levels (P<0.05) and significant increase in HDL level in the serum of rabbits. Furthermore, the treated groups (G3-G5) exhibited reductions in interleukins (IL-1β and IL-6) and C-reactive protein (CRP) as compared to atherogenicgroup (G2). The histological results showed that the thickening of atherosclerotic plaques were less significant in treated groups (G3-G5) compared with atherogenicgroup (G2). Also, alpha-smooth muscle actin (α-SMA) staining decreased within the plaques of atherogenicgroup (G2), while it was increased in treated groups (G3-G5). Lastly, groups treated with AV and AND (G3-G5) showed significant reduction of CD36 expression (P<0.05) compared to atherogenicgroup (G2). These results substantially proved that AND contain antiatherogenic activity.
    Matched MeSH terms: Heptanoic Acids/administration & dosage; Heptanoic Acids/pharmacology; Heptanoic Acids/toxicity
  2. Effects of even and odd number fatty acids cofeeding on PHA production and composition in Pseudomonas putida Bet001 isolated from palm oil mill effluent
    Mohd Razaif-Mazinah MR, Mohamad Annuar MS, Sharifuddin Y
    Biotechnol Appl Biochem, 2016 Jan-Feb;63(1):92-100.
    PMID: 25643814 DOI: 10.1002/bab.1354
    The biosynthesis of medium-chain-length poly-3-hydroxyalkanoates by Pseudomonas putida Bet001 cultivated on mixed carbon sources was investigated. The mixed carbon sources consisted of heptanoic acid (HA) and oleic acid (OA). A relatively low PHA content at 1.2% (w/w) and 11.4% (w/w) was obtained when HA or OA was used as the sole carbon source. When these fatty acids were supplied as a mixture, PHA content increased threefold. Interestingly, the mixture-derived PHA composed of both odd and even monomer units, namely. 3-hydroxyheptanoate, 3-hydroxyoctanoate, 3-hydroxydecanoate, and 3-hydroxydodecanoate and no unsaturated monomer was detected. It is hypothesized that the even-numbered monomers were derived primarily from OA, whereas the odd-numbered monomer was derived from HA. This also points out to an efficient and yet distinct fatty acids metabolism that fed the PHA biosynthesis machinery of this particular microorganism. PHA obtained was elastomeric because melting temperature (Tm ) and crystallinity were absent. It showed good thermal stability with degradation temperature (Td ) ranging from 275.96 to 283.05 °C.
    Matched MeSH terms: Heptanoic Acids/metabolism
  3. Fulltext Long-term efficacy and safety of a generic atorvastatin in usual clinical care setting
    Ong LM, Punithavathi N, Lena YLL, Mahanim O, Leekha S, Storvas Clinical Trial Study Group
    Med J Malaysia, 2011 Aug;66(3):214-9.
    PMID: 22111443
    A multicentre study was conducted to assess the long term efficacy and safety of a generic atorvastatin in the treatment of primary hypercholesterolaemia. Eighty five patients who received 10mg or 20 mg of atorvastatin for 8 weeks depending on target cholesterol goal were followed up by their own physicians and had final evaluation at 52 weeks. Reduction in mean low density Lipoprotein (LDL-C) was 36.5%, 37.9% and 32.2% at weeks 4, 8 and 52 respectively. LDL-C target was maintained in 81% and 69% of patients at week 8 and 52 respectively without drug related serious adverse events. Generic atorvastatin is safe and effective in usual clinical care setting.
    Matched MeSH terms: Heptanoic Acids/therapeutic use*
  4. Treat the graft to improve the regenerative ability of the host
    Mamidi MK, Pal R, Govindasamy V, Zakaria Z, Bhonde R
    Med Hypotheses, 2011 Apr;76(4):599-601.
    PMID: 21277690 DOI: 10.1016/j.mehy.2011.01.010
    The staggering number of publications featuring the use of stem cells has revolutionized regenerative medicine research. Preclinical studies indicate that allogeneic human mesenchymal stem cells (MSCs) may be useful for the treatment of several clinical disorders, including sepsis, acute renal failure, acute myocardial infarction, and more recently, acute lung injury (ALI). However, considerable success would not be obtained in clinical trials due to poor survival of transplanted cells under the influence of inflammatory conditions. Despite robust approaches like cellular reprogramming, scaffolds and conditioned media have been tested to overcome this problem; however the success rate of these approaches remain questionable. Recently, pretreatment of bioactive compounds in vitro have been shown to suppress cell apoptosis and promote cell survival. Quite likely a similar phenomenon can take place in vivo. Based on such studies, we hypothesize that MSCs derived from human post-natal tissues could be conditioned and prepared for targeted disease therapy. Depending on the disease condition, the MSCs could be treated prior to delivery with appropriate bioactive compounds to allow them survive longer and perform a better role as biocatalyst. The advantage of this approach could be the tailor made availability of MSCs preconditioned with appropriate bioactive compounds for disease specific therapy. Therefore, the choice of suitable bioactive molecule is likely to enhance the efficacy of targeted stem cell therapy and preconditioning may provide a novel strategy in maximizing biological and functional properties of MSCs.
    Matched MeSH terms: Heptanoic Acids/pharmacology
  5. Short-term effect of atorvastatin on endothelial function in healthy offspring of parents with type 2 diabetes mellitus
    Amudha K, Choy AM, Mustafa MR, Lang CC
    Cardiovasc Ther, 2008;26(4):253-61.
    PMID: 19035876 DOI: 10.1111/j.1755-5922.2008.00064.x
    Endothelial function is impaired in healthy subjects at risk of type 2 diabetes mellitus (DM). We investigated whether endothelial dysfunction can be normalized by statin therapy in this potentially predisposed population. Flow-mediated dilation (FMD) was measured in 56 first-degree relatives (FDRs) (normotensive, normal glucose tolerance) and 20 age-, sex-, and BMI-matched controls with no family history of DM. Other measurements included insulin resistance index using the homeostasis model of insulin resistance (HOMA(IR)), plasma lipids, and markers of inflammation. The FDRs were then randomized and treated with atorvastatin (80 mg) or placebo daily in a 4-week double-blind, placebo-controlled trial. The FDRs had significantly impaired FMD (4.4 +/- 8.1% vs. 13.0 +/- 4.2%; P < 0.001), higher HOMA(IR) (1.72 +/- 1.45 vs. 1.25 +/- 0.43; P = 0.002), and elevated levels of plasma markers of inflammation-highly sensitive C-reactive protein (hsCRP) (2.6 +/- 3.8 mg/L vs. 0.7 +/- 1.0 mg/L; P = 0.06), interleukin (IL)-6 (0.07 +/- 0.13 ng/mL vs. 0.03 +/- 0.01 ng/mL; P < 0.001), and soluble intercellular adhesion molecule (sICAM) (267.7 +/- 30.7 ng/mL vs. 238.2 +/- 20.4 ng/mL; P < 0.001). FMD improved in the atorvastatin-treated subjects when compared with the placebo-treated subjects (atorvastatin, from 3.7 +/- 8.5% to 9.8 +/- 7.3%; placebo, from 3.9 +/- 5.6% to 4.7 +/- 4.2%; P = 0.001). There were also reductions in the levels of IL-6 (0.08 +/- 0.02 ng/mL vs. 0.04 +/- 0.01 ng/mL; P < 0.001) and hsCRP (3.0 +/- 3.9 mg/L vs. 1.0 +/- 1.3 mg/L; P = 0.006). Our study suggests that treatment with atorvastatin may improve endothelial function and decrease levels of inflammatory markers in FDRs of type 2 DM patients.
    Matched MeSH terms: Heptanoic Acids/pharmacology*; Heptanoic Acids/therapeutic use*
  6. A randomised study comparing the efficacy and safety of rosuvastatin with atorvastatin for achieving lipid goals in clinical practice in Asian patients at high risk of cardiovascular disease (DISCOVERY-Asia study)
    Zhu JR, Tomlinson B, Ro YM, Sim KH, Lee YT, Sriratanasathavorn C
    Curr Med Res Opin, 2007 Dec;23(12):3055-68.
    PMID: 18196620
    BACKGROUND: Most studies investigating the benefits of statins have focused on North American and European populations. This study focuses on evaluating the lipid-lowering effects of rosuvastatin and atorvastatin in Asian patients.

    OBJECTIVES: The DIrect Statin COmparison of LDL-C Values: an Evaluation of Rosuvastatin therapY (DISCOVERY)-Asia study is one of nine independently powered studies assessing the efficacy of starting doses of statins in achieving target lipid levels in different countries worldwide. DISCOVERY-Asia was a 12-week, randomised, open-label, parallel-group study conducted in China, Hong Kong, Korea, Malaysia, Taiwan, and Thailand.

    RESULTS: A total of 1482 adults with primary hypercholesterolaemia and high cardiovascular risk (> 20%/10 years, type 2 diabetes, or a history of coronary heart disease) were randomised in a 2 : 1 ratio to receive rosuvastatin 10 mg once daily (o.d.) or atorvastatin 10 mg o.d. The percentage of patients achieving the 1998 European Joint Task Force low-density lipoprotein cholesterol (LDL-C) goal of < 3.0 mmol/L at 12 weeks was significantly higher in the rosuvastatin group (n = 950) compared with the atorvastatin group (n = 471) (79.5 vs. 69.4%, respectively; p < 0.0001). Similar results were observed for 1998 European goals for total cholesterol (TC), and the 2003 European goals for LDL-C and TC. LDL-C and TC levels were reduced significantly more with rosuvastatin compared with atorvastatin. Both drugs were well-tolerated and the incidence and type of adverse events were similar in each group.

    TRIALS REGISTRATION: The trial registry summary is available at http://www.clinicaltrials.gov/; ClinicalTrials.gov Identifier: NCT00241488

    CONCLUSIONS: This 12-week study showed that the starting dose of rosuvastatin 10 mg o.d. was significantly more effective than the starting dose of natorvastatin 10 mg o.d. at enabling patients with primary hypercholesterolaemia to achieve European goals for LDL-C and TC in a largely Asian population in real-life clinical practice. The safety profile of rosuvastatin 10 mg is similar to that of atorvastatin 10 mg in the Asian population studied here, and is consistent with the known safety profile of rosuvastatin in the white population.

    Matched MeSH terms: Heptanoic Acids/adverse effects; Heptanoic Acids/therapeutic use*
  7. Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin
    Nawawi H, Osman NS, Annuar R, Khalid BA, Yusoff K
    Atherosclerosis, 2003 Aug;169(2):283-91.
    PMID: 12921980
    Adhesion molecules and cytokines are involved in the pathogenesis of intimal injury in atherosclerosis but their relationship with endothelial function remains unclear. The objectives of this study were to examine the effects of atorvastatin on soluble adhesion molecules, interleukin-6 (IL-6) and brachial artery endothelial-dependent flow mediated dilatation (FMD) in patients with familial (FH) and non-familial hypercholesterolaemia (NFH). A total of 74 patients (27 FH and 47 NFH) were recruited. Fasting lipid profiles, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular-cellular adhesion molecule-1 (sVCAM-1), E-selectin, IL-6 and FMD were measured at baseline, 2 weeks, 3 and 9 months post-atorvastatin treatment (FH--80 mg/day, NFH--10 mg/day). In both groups, compared to baseline, sICAM-1 levels were significantly reduced at 2 weeks, further reduced at 3 months and maintained at 9 months (P<0.0001). The IL-6 levels were significantly reduced at 3 months and 9 months compared to baseline for FH (P<0.005) and NFH (P<0.0001). In both groups, the FMD at 2 weeks was higher than baseline (P<0.005), with progressive improvement up to 9 months. FMD was negatively correlated with sICAM-1 and IL-6. In conclusion, both low and high doses of atorvastatin lead to early progressive improvement in endothelial function in patients with primary hypercholesterolaemia. sICAM-1 and IL-6 levels reflect endothelial dysfunction in these patients.
    Matched MeSH terms: Heptanoic Acids/administration & dosage; Heptanoic Acids/therapeutic use*
  8. Effect of extraction solvents and plant parts used on the antihyperlipidemic and antioxidant effects of Garcinia atroviridis: a comparative study
    Al-Mansoub MA, Asmawi MZ, Murugaiyah V
    J Sci Food Agric, 2014 Jun;94(8):1552-8.
    PMID: 24166055 DOI: 10.1002/jsfa.6456
    Garcinia atroviridis is a seasonal fruit plant found in many parts of South East Asia. The fruit rind is used in cooking and traditionally consumed for various reasons, including to lower blood cholesterol. A comparative study was undertaken to investigate the influence of extraction solvents and plant parts used on the lipid-lowering and antioxidant activities of Garcinia atroviridis.
    Matched MeSH terms: Heptanoic Acids/therapeutic use
  9. Fulltext Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study
    Hing Ling PK, Civeira F, Dan AG, Hanson ME, Massaad R, De Tilleghem Cle B, et al.
    Lipids Health Dis, 2012;11:18.
    PMID: 22293030 DOI: 10.1186/1476-511X-11-18
    A considerable number of patients with severely elevated LDL-C do not achieve recommended treatment targets, despite treatment with statins. Adults at high cardiovascular risk with hypercholesterolemia and LDL-C ≥ 2.59 and ≤ 4.14 mmol/L (N = 250), pretreated with atorvastatin 20 mg were randomized to ezetimibe/simvastatin 10/40 mg or atorvastatin 40 mg for 6 weeks. The percent change in LDL-C and other lipids was assessed using a constrained longitudinal data analysis method with terms for treatment, time, time-by-treatment interaction, stratum, and time-by-stratum interaction. Percentage of subjects achieving LDL-C < 1.81 mmol/L, < 2.00 mmol/L, or < 2.59 mmol/L was assessed using a logistic regression model with terms for treatment and stratum. Tolerability was assessed.
    Matched MeSH terms: Heptanoic Acids/therapeutic use*
  10. Fulltext Low-density lipoprotein cholesterol goal attainment among Malaysian dyslipidemic patients
    Al-Khateeb A, Mohamed MS, Imran K, Ibrahim S, Zilfalill BA, Yusof Z
    Southeast Asian J Trop Med Public Health, 2011 Mar;42(2):388-94.
    PMID: 21710862
    The aim of the present study was to evaluate Malaysian dyslipidemic patient treatment practices and outcomes. Factors contributing to success in reaching treatment goal were determined. A retrospective review of the records of dyslipidemic patients who attended the Universiti Sains Malaysia Hospital in 2007 was conducted. All the patients were receiving standard recommended doses of statins. Records were analysed for 890 patients. Patients were divided into three categories: 384 patients (43.1%) had coronary heart disease or coronary heart disease risk equivalents, 216 patients (24.3%) had moderate risk for coronary heart disease and 290 patients (32.6%) had low risk. Statins were the most commonly prescribed drug group (92%), of which atorvastatin was the most commonly prescribed drug (50.6%). The overall success rate for reaching goal was 64.2%. The percentages of patients achieving low-density lipoprotein cholesterol targets in the coronary heart disease and coronary heart disease risk equivalents, moderate, and low-risk groups were 50.5, 66.7, and 80.3%, respectively (p < 0.001). Multiple logistic regression showed achievement of therapeutic goal declined with increasing risk group. The baseline low-density lipoprotein cholesterol value was inversely related to therapeutic goal attainment. An inadequate proportion of dyslipidemic patients achieved the National Cholesterol Education Program therapeutic goals for low-density lipoprotein cholesterol, especially those in the coronary heart disease and coronary heart disease risk equivalent group. The achievement of this goal was dependent on baseline low-density lipoprotein cholesterol levels.
    Matched MeSH terms: Heptanoic Acids/therapeutic use
  11. Insights into the antiatherogenic molecular mechanisms of andrographolide against Porphyromonas gingivalis-induced atherosclerosis in rabbits
    Al Batran R, Al-Bayaty F, Al-Obaidi MM, Ashrafi A
    Naunyn Schmiedebergs Arch Pharmacol, 2014 Dec;387(12):1141-52.
    PMID: 25172523 DOI: 10.1007/s00210-014-1041-x
    Atherosclerosis is the commonest and most important vascular disease. Andrographolide (AND) is the main bioactive component of the medicinal plant Andrographis paniculata and is used in traditional medicine. This study was aimed to evaluate the antiatherogenic effect of AND against atherosclerosis induced by Porphyromonas gingivalis in White New Zealand rabbits. Thirty rabbits were divided into five groups as follows: G1, normal group; G2-5, were orally challenged with P. gingivalis five times a week over 12 weeks; G2, atherogenic control group; G3, standard group treated with atorvastatin (AV) 5 mg/kg; and G4 and G5, treatment groups treated with AND 10 and 20 mg/kg, respectively over 12 weeks. Serums were subjected to antioxidant enzymatic and anti-inflammatory activities, and the aorta was subjected to histological analyses. Groups treated with AND showed a significant reversal of liver and renal biochemical changes, compared with the atherogenic control group. In the same groups, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total glutathione (GSH) levels in serum were significantly increased (P < 0.05), and lipid peroxidation (malondialdehyde (MDA)) levels were significantly decreased (P < 0.05), respectively. Furthermore, treated groups with AV and AND showed significant decrease in the level of VCAM-1 and ICAM-1 compared with the atherogenic control group. In aortic homogenate, the level of nitrotyrosine was significantly increased, while the level of MCP1 was significantly decreased in AV and AND groups compared with the atherogenic control group. In addition, staining the aorta with Sudan IV showed a reduction in intimal thickening plaque in AV and AND groups compared with the atherogenic control group. AND has showed an antiatherogenic property as well as the capability to reduce lipid, liver, and kidney biomarkers in atherogenic serum that prevents atherosclerosis complications caused by P. gingivalis.
    Matched MeSH terms: Heptanoic Acids/pharmacology
  12. Reduction in serum levels of adhesion molecules, interleukin-6 and C-reactive protein following short-term low-dose atorvastatin treatment in patients with non-familial hypercholesterolemia
    Nawawi H, Osman NS, Yusoff K, Khalid BA
    Horm. Metab. Res., 2003 Aug;35(8):479-85.
    PMID: 12953165 DOI: 10.1055/s-2003-41805
    Hypercholesterolemia causes endothelial dysfunction, an early feature of atherosclerosis, leading to increased production of adhesion molecules and cytokines. The aim of this study was to investigate the effects of three months of treatment with low dose atorvastatin on serum levels of adhesion molecules, interleukin-6 (IL-6) and highly sensitive C-reactive protein (hs-CRP) in patients with non-familial hypercholesterolemia. Fifty-five patients with non-familial hypercholesterolemia were randomized to treatment with atorvastatin 10 mg/day or placebo for 3 months. Soluble intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, IL-6 and hs-CRP levels were measured to assess the inflammatory activity of the endothelium. There was a significant reduction in ICAM-1 at 2 weeks (p<0.0001) with further reduction at 3 months (p<0.0001). At 3 months, there were significant reductions in VCAM-1 (p<0.02), IL-6 (p<0.0001) and hs-CRP (p<0.01), but an increase in E-selectin levels (p<0.002). Treatment with statin was an independent determinant of change in ICAM-1 (p<0.05) and IL-6 levels (p<0.05) after correcting for anthropometric indices, blood pressure and lipid profile. Low-dose atorvastatin treatment leads to reduction in proinflammatory markers of endothelial function, suggesting an attenuation of endothelial activation and improvement in endothelial function, independent of lipid lowering. This may lead to a reduction in the progression of atherosclerosis.
    Matched MeSH terms: Heptanoic Acids/administration & dosage*
  13. Fulltext A multicenter study in Malaysia to determine the efficacy and safety of a generic atorvastatin
    Punithavathi N, Ong LM, Lena YL, Leekha S, Storvas Clinical Trial Study Group
    Med J Malaysia, 2009 Jun;64(2):150-4.
    PMID: 20058576 MyJurnal
    A multicenter study was conducted to assess the efficacy of a generic form of Atorvastatin (Ranbaxy's Storvas) in the treatment of Primary Hypercholesterolemia. One hundred and nineteen patients were given 10 mg of Storvas for four weeks and increased to 20 mg if target LDL-Cholesterol was not achieved. LDL-Cholesterol was reduced by 36.6% at four weeks and 37.5% at eight weeks from baseline. Total cholesterol and triglycerides were significantly reduced. There were no drug-related serious adverse events. We conclude that the generic atorvastatin is safe and effective in the treatment of primary hypercholesterolaemia and the results are comparable to published data on innovator atorvastatin.
    Matched MeSH terms: Heptanoic Acids
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