Angiotensin Converting Enzyme Insertion/Deletion Gene Polymorphism: An Observational Study among Diabetic Hypertensive Subjects in Malaysia

Purpose: This study investigated the influence of angiotensin-1 converting enzyme (ACE) insertiondeletion (ID) gene polymorphism on the treatment responses of type 2 diabetic subjects at varying stages of nephropathy to ACE inhibitors (ACEI) with regard to blood pressure (MAP) and renal response (GFR). Methods: The pharmacological effect of ACE inhibition on mean arterial pressure (MAP) and glomerular filtration rate (GFR) were observed among a total of 62 subjects for a short-term duration of 15 months. MAP and GFR were calculated by standard mathematical formulae while the ACE ID genotype was determined using triple primer PCR. The general linear model repeated measures were applied to study the modulation of ACE inhibition on these parameters. Results: ACE ID genotyping of the 62 subjects showed that 19 (30.6 %) subjects had the II genotype, while 35 (56.4 %) subjects showed ID genotype and 8 (12.9 %) subjects had the DD genotype. Significant mean MAP reduction (p 0.05) from baseline values were observed among the subjects following antihypertensive treatment. However, when stratified according to ACE genotypes, no significant mean MAP and GFR changes were observed between genotypes following antihypertensive treatment (p > 0.05).Conclusion: ACE ID gene polymorphism does not determine the treatment efficacy of ACE inhibitors in the Malaysian population.Keywords: ACE genotype, ACE inhibitor, Type 2 diabetes mellitus, Diabetic nephropath

Green synthesis of ag nanoparticles and their performance towards antimicrobial properties

Green synthesis is a forthcoming trend in the nanotechnology field where classical methods of synthesis are now replaced by inexpensive and eco-friendly methods. In this study, a green method has been developed for the synthesis of silver nanoparticles (AgNPs) where AgNPs were synthesised using water-based facile hydrothermal method. Silver nitrate (AgNO3) and polyvinylpyrrolidone (PVP) were used as precursor and reducing agents to produce AgNPs. The molar ratio effect of the precursor and stabiliser, its reaction temperature and reaction time were investigated. X-ray Powder Diffraction (XRD), Field-Emission Scanning Electron Microscope (FESEM) and UV-Vis Spectrometry were used to characterise the AgNPs. The as-synthesized AgNPs with different molar ratios of the precursor to stabiliser were tested for antibacterial activities using Gram-positive bacteria (Bacillus subtilis) and Gram-negative bacteria (Escherichia coli). All the AgNPs samples exhibited antibacterial activities that were stronger against Gram-negative bacteria, as compared with Gram-positive bacteria. The diameter of the zone of inhibition (ZOI) increased with the increase of the AgNO3: PVP molar ratios. The results obtained proved that uniform AgNPs synthesized via green techniques have a high potential of influencing applications involving antimicrobial properties

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

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

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

Green Synthesis Of Tio2 – Ag Nanocomposites For Self-Cleaning And Antimicrobial Properties On Cotton Fabric

Green chemistry approach is an emerging interdisciplinary area that is expected to have wide ranging implications in all fields of science and technology. Although green chemistry is still in its infancy, it is already proving to be a useful tool in improving the performance of nanomaterial and generating worldwide interest. Titanium (IV) dioxide nanoparticles (TiO2 NPs), silver nanoparticles (AgNPs) and titanium dioxide – silver nanocomposites (TiO2 – NCs) have been successfully synthesised using hydrothermal green chemistry approaches

A Prototype Expert System for the Selection of Road Construction Materials

A prototype for an expert system in road construction material selection system, which is based on the outcomes of Friedman and multiple comparisons statistical methods was developed. The outcomes were acquired through questionnaires from selected pavement experts. The factors affecting pavement materials under each particular site condition were incorporated into the specific rules of the system. The system knowledge-base was extracted from the statistical testing outcomes and then rearranged and compiled prior to the development of the system. Visual Basic 6.0 was adopted as the programming tool for development of the system, while the knowledge-base of the separate system was kept in Microsoft Access 2000. The prototype expert system can be used to emulate part of the professional reasoning capabilities based on the knowledge of a pavement expert or a specialist to solve problems on materials selection. The system can help road designers to improve their professional ability to evaluate all available materials even before carrying out any laboratory tests

Paraoxonase 1 activity as a predictor of cardiovascular disease in type 2 diabetes

The role of paraoxonase 1 in cardiovascular disease complications in type 2 diabetes mellitus is not fully understood. We studied paraoxonase activity towards paraoxon in 188 non-diabetic and 140 diabetic subjects using general linear models and univariate analysis. Adjusting for age revealed a reduction in activity towards paraoxon was associated with a significant increase in risk (p=0.023) for cardiovascular disease complications in diabetic patients. Multivariate analysis of two plasma measures of paraoxonase activity using paraoxon and diazoxon also showed reduced paraoxonase activity towards paraoxon was associated with a significant increase in risk (p=0.045) for cardiovascular disease complications in diabetic patients. These analyses showed that a reduced paraoxonase activity towards paraoxon was associated with ethnicity. Based on multivariate analysis, subjects of Malay ethnic origin have significantly higher than expected activity (p=0.008, compared to Indians), towards paraoxon than subjects of Chinese origin who in turn had higher than expected paraoxonase activity (p=0.028, compared to Indians) Indian subjects

Association of plasminogen activator inhibitor-1 and tissue plasminogen activator with type 2 diabetes and metabolic syndrome in Malaysian subjects

<p>Abstract</p> <p>Background</p> <p>Increased plasma plasminogen activator inhibitor-1 (PAI-1) activity and decreased tissue plasminogen activator (tPA) activity could be considered a true component of the metabolic syndrome (MetS) associated with an increased risk of developing cardiovascular diseases (CVD) and fibrinolytic abnormalities. The aim of this study was to investigate the association of tPA and its inhibitor PAI-1 with type 2 diabetes (T2D) and MetS and interrelationship between PAI-1and tPA activities and antigens in Malaysian T2D and normal subjects.</p> <p>Methods</p> <p>The plasma activities and antigens of PAI-1 and tPA and the levels of the tPA/PAI-1 complex as well as serum insulin, parameter of the coronary risk panel and plasma glucose at fasting state were studied in 303 T2D subjects (227 with MetS and 76 without MetS), 131 normal non-diabetic non-metabolic subjects and 101 non-diabetic MetS subjects.</p> <p>Results</p> <p>The PAI-1 activity was higher in subjects with T2D with MetS (P = 9.8 × 10^-19) and non-diabetic subjects with MetS (P = 3.0 × 10^-15), whereas the tPA activity was lower in T2D with MetS (P = 0.003) as compare to normal subjects. Plasma tPA antigen levels were higher in subjects with T2D with MetS (P = 8.9 × 10^-24), T2D without MetS (P = 1.3 × 10^-13) and non-diabetic MetS subjects (P = 0.002). The activity and antigen of PAI-1 in normal subjects were related to insulin resistance (P = 2.2 × 10^-4; 0.007). Additionally, the PAI-1 activity was associated with an increased waist circumference (P = 2.2 × 10^-4) and decreased HDL-c (P = 0.005), whereas the tPA activity was associated with decreased FBG (P = 0.028). The highest correlation was between PAI-1 activity and its antigen (R²= 0.695, P = 1.1 × 10^-36) in diabetic subjects. The tPA activity negatively correlated with its antigen (R²= -0.444, P = 7.7 × 10^-13) in normal subjects and with the PAI-1 activity and antigen (R²= -0.319, P = 9.9 × 10^-12; R2 = -0.228, P = 3.4 × 10^-6) in diabetic subjects.</p> <p>Conclusions</p> <p>PAI-1 and tPA activities and antigens were associated with diabetes and MetS parameters in Malaysian subjects.</p

Effect of Plasminogen Activator Inhibitor-1 and Tissue Plasminogen Activator Polymorphisms on Susceptibility to Type 2 Diabetes in Malaysian Subjects

Elevated activity of plasminogen activator inhibitor-1 (PAI-1) and decreased tissue plasminogen activator (tPA) activity are considered to be important risk factors for type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). The aim of this study was to investigate the association of the PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms with T2DM in Malaysian subjects. Serum insulin, coronary risk panel, plasma glucose, and PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms were studied in 303 T2DM subjects (227 with MetS and 76 without MetS) and 131 normal subjects without diabetes and MetS. Statistical analysis showed that the dominant and additive models of PAI-1 4G/5G polymorphism showed a weak association with T2DM without MetS (OR = 2.35, P = 0.045; OR = 1.67, P = 0.058). On the other hand, the recessive model of the tPA Alu-repeat I/D polymorphism showed an association with T2DM with MetS (OR = 3.32, P = 0.013) whereas the dominant and additive models of the tPA Alu-repeat I/D polymorphism were not associated with T2DM either with or without MetS