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1.  Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with metabolic syndrome parameters in Malaysian subjects 
The plasminogen activator inhibitor-1 4G/5G and tissue plasminogen activator Alu-repeat insertion/deletion polymorphisms might be genetic determinations of increased or decreased of their plasma activities. The aim of this study was to investigate the association of plasminogen activator inhibitor-1 4G/5G and tissue plasminogen activator Alu-repeat I/D polymorphisms with metabolic syndrome parameters in normal Malaysian subjects and to assess the impact of these polymorphisms on their plasma activities and antigens. The genetic polymorphisms were genotyped in 130 normal subjects. In addition, the plasma activities and antigens of plasminogen activator inhibitor-1 and tissue plasminogen activator as well as levels of insulin, glucose, and lipid profile at fasting state were investigated. The subjects with homozygous 4G/4G showed association with an increased triglyceride (p = 0.007), body mass index (p = 0.01) and diastolic blood pressure (p = 0.03). In addition, the plasminogen activator inhibitor-1 4G/5G polymorphism modulates plasma plasminogen activator inhibitor-1 activity and antigen and tissue plasminogen activator activity (p = 0.002, 0.014, 0.003) respectively. These results showed that, the plasminogen activator inhibitor-1 4G/5G polymorphism is associated with metabolic syndrome parameters, plasminogen activator inhibitor-1 and tissue plasminogen activator activities in Malaysian subjects, and may serve to increase the risk of type 2 diabetes and cardiovascular disease in Malaysian subjects.
PMCID: PMC3334369  PMID: 22573918
plasminogen activator inhibitor-1; tissue plasminogen activator; type 2 diabetes; metabolic syndrome; cardiovascular disease
2.  Wound Healing Activities of Rafflesia Hasseltii Extract in Rats 
The effects of topical application of Rafflesia hasseltii buds and flowers extract on the rate of wound healing and histology of healed wound were assessed. Four groups of adult male Sprague Dawley rats were experimentally wounded in the posterior neck area. A thin layer of blank placebo was applied topically to wounds of Group 1 rats. Wounds of experimental animals (Group 2 and 3) were treated with placebo containing 5% and 10% R. hasseltii buds extract, respectively. A thin layer of Intrasite gel was applied topically to wounds of Group 4 animals as reference. Macroscopically, wounds treated with placebo containing 5% and 10% R. hasseltii buds extract or Intrasite gel have been significantly accelerated the rate of wound healing compared to placebo-treated wounds. Histological analysis of healed wounds has confirmed this effect. Wounds treated with placebo containing 5%, 10% R. hasseltii buds extract or Intrasite gel showed markedly less scar width at wound enclosure and granulating tissue contained markedly more collagen and proliferating fibroblasts, but with the absence of inflammatory cells compared to wounds treated with blank placebo. In conclusion, the findings of increased rate of wound closure and contraction together with the histological findingssuggest that Rafflesia hasseltii buds extract is very effective in accelerating the wound healing process.
PMCID: PMC2771251  PMID: 19902020
Wounds healing; Rafflesia hasseltii extract; Intrasite gel; placebo
3.  F2-Isoprostanes as Novel Biomarkers for Type 2 Diabetes: a Review 
Oxidative stress (OS) has been implicated as one of the major underlying mechanisms behind many acute and chronic diseases. However, the measurement of free radicals or their end products is complicated. Isoprostanes, derived from the non-enzymatic peroxidation of arachidonic acid are now considered to be reliable biomarkers of oxidant stress in the human body. Isoprostanes are involved in many of the human diseases such as type 2 diabetes. In type 2 diabetes elevated levels of F2-Isoprostanes (F2-IsoPs) have been observed. The measurement of bioactive F2-IsoPs levels offers a unique noninvasive analytical tool to study the role of free radicals in physiology, oxidative stress-related diseases, and acute or chronic inflammatory conditions. Measurement of oxidative stress by various other methods lacks specificity and sensitivity. This review aims to shed light on the implemention of F2-IsoPs measurement as a gold-standard biomarker of oxidative stress in type 2 diabetics.
PMCID: PMC2704321  PMID: 19590700
oxidative stress; lipid peroxidation; isoprostanes; type 2 diabetes
4.  Nε-(Carboxymethyl)lysine and Coronary Atherosclerosis-Associated Low Density Lipoprotein Abnormalities in Type 2 Diabetes: Current Status 
In comparison to the general population, individuals with diabetes suffer a 3- to 4-fold increased risk for developing complications of atherosclerosis and vascular insufficiency. This fact should be taken into account to develop a suitable determinant for the early detection of these complications and subsequently reduce the adverse effect of type 2 diabetes. In vitro experiments have shown that the products of glucose auto-oxidation and Amadori adducts are both potential sources of Nε-(carboxymethyl)lysine (CML). Excessive formation of CML on low density lipoprotein (LDL) has been proposed to be an important mechanism for the dyslipidemia and accelerated atherogenesis observed in patients with type 2 diabetes. It has been postulated that the uptake of CML-LDL by LDL receptors is impaired, thereby decreasing its clearance from the blood circulation. Alternatively, the uptake of these modified LDL particles by scavenger receptors on macrophages and vascular smooth muscle cells (SMCs) and by AGE receptors on endothelial cells, SMCs, and monocytes is highly enhanced and this, in turn, is centrally positioned to contribute to the pathogenesis of diabetic vascular complications especially coronary artery disease. The present review summarizes the up-to-date information on effects and mechanism of type 2 diabetes-associated coronary atherosclerosis induced by CML-LDL modification.
PMCID: PMC2613495  PMID: 19177184
Nε-(carboxymethyl)lysine; low density lipoprotein; atherosclerosis; type 2 diabetes
5.  Role of Nε-(Carboxymethyl)Lysine in the Development of Ischemic Heart Disease in Type 2 Diabetes Mellitus 
This study aims to determine the levels of Nε-(carboxymethyl)lysine (CML) in patients with Type 2 diabetic patients with and without ischemic heart disease (IHD) and to find for a possible association between circulating CML and a number of clinical parameters including lipids, hemoglobin A1c (HbA1c) and malondialdehyde (MDA) in Type 2 diabetic IHD patients. Serum CML levels were measured by enzyme-linked immunosorbent assay using polyclonal anti-CML antibodies. Serum levels of CML and MDA were assessed in 60 IHD patients with Type 2 diabetes, 43 IHD patients without Type 2 diabetes, 64 Type 2 diabetics without IHD, and 80 sex- and age-matched healthy subjects. Correlations studies between CML levels and lipids, HbA1c, and lipid peroxidation were performed in Type 2 diabetes patients with and without IHD. A statistical significance was observed in the levels of serum glucose, lipids (triglyceride, total cholesterol, HDL-cholesterol), MDA, HbA1c, CML and LDL-cholesterol (p<0.05) between the groups of the study. CML levels were significantly increased in diabetic IHD patients compared with Type 2 diabetes patients but without IHD (537.1 ± 86.1 vs 449.7 ± 54.9, p<0.001). A positive correlation was observed between serum levels of CML and MDA, r = 0.338 (p = 0.008) in Type 2 diabetes patients with IHD. However, age, HbA1c and lipids had no significant influence on CML levels among diabetics (p>0.05). In conclusion, this study demonstrates the effect of both diabetes and oxidative stress on the higher levels of circulating CML. These results showed that increased serum levels of CML are associated with the development of IHD in Type 2 diabetes mellitus.
PMCID: PMC2170948  PMID: 18193103
advanced glycation end products; Nε-(carboxymethyl)lysine; Type 2 diabetes mellitus; ischemic heart disease; oxidative stress

Results 1-5 (5)