Perbezaan Respon Terhadap Halangan Reseptor Beta Di Kalangan Kaum-kaum Di Malaysia

Tidak banyak diketahui tentang perbezaan etnik dalam respon terhadap drug antara kaum-kaum di Malaysia. Not much is known regarding racial differences in response to drugs amorig racial groups m Malaysia

Understanding the mechanism of actions of 1A calcidol on arterial stiffness, microvascular endothelial function, inflammation and proteinuria in Type 2 Diabetic patients with nephropathy

Introduction: Low vitamin D levels correlate with presence of cardiovascular diseases (CVD) in diabetics. Mechanism for the beneficial effects of vitamin D on CVD has not been fully explained. This study aimed to evaluate possible mechanisms for vitamin D effects on markers linked to CVD progression. The effects of vitamin D (as 1-alfacalcidol) in diabetic nephropathy patients on i) arterial stiffness ii) microvascular endothelial function iii) inflammation iv) proteinuria were evaluated. Methodology: A prospective randomized controlled study was conducted in diabetic nephropathy patients. Vitamin D treated group (n=28) were given la calcidol 0.25 meg daily for 6 months, while control patients (n=32) received standard treatment. Baseline measurements for vitamin D levels, hsCRP, arterial stiffness, blood pressure (BP), microvascular endothelial function, renal function and albuminuria were performed and repeated after 6 months. Results and conclusion: After 6 months treatment with vitamin D, there was significant improvement in arterial stiffness in vitamin D deficient patients. Significant reductions in central SBP, central pulse pressure and peripheral SBP were also observed. Microvascular endothelial function was impaired in vitamin D deficient diabetic nephropathy patients, however, 6 months treatment with 0.25 meg alfacalcidol did not improve this parameter. Systemic inflammation increased after 6 months in controls patients but was not seen in vitamin D treated patients. It appears that the effects of vitamin D on CV markers were more apparent in vitamin D deficient diabetic nephropathy patients. Thus, vitamin D may be beneficial for CVD via its effect of improving BP, arterial stiffness, microvascular function and delaying progression of inflammation in diabetic nephropathy patients

Role of endothelial contracting and relaxing factors in the mechanism of endothelial dysfunction in subcutaneous arteries (microvasculature) of diabetic patients.

This study aims to examine the signalling pathways underlying endothelium-dependent responses in subcutaneous arteries of humans with Type 2 diabetes mellitus (T2DM) by assessing the relative contributions of nitric oxide (NO), prostacyclin and endothelium derived hyperpolarising factor (EDH) to responses to endothelium-dependent and independent agonists. This study was approved by the Human Ethical Committee of Universiti Sains Malaysia (USM); work conducted in this study conformed to the provisions of the Declaration of Helsinki. Written informed consent was obtained from patients undergoing lower limb surgical procedures. Sixteen healthy controls and twenty diabetic patients between the ages of 18 to 65 years old were recruited among those undergoing lower limb surgical procedures. Acetylcholine hydrochloride, phenylephrine and sodium nitroprusside were purchased from Sigma Chemical Co. (St. Louis, MO). l-[(2- Chlorophenyl) diphenylmethyl]-1Hpyrazole (TRAM 34), 6,12,19,20,25,26-hexahydro-5,27:13,18:21,24-trietheno-l 1,7-metheno- 7H-dibenzo \b,n\ [l,5,12,16]tetraazacyclotricosine-5,13-diium dibromide (UCL 1684) and salbutamol were purchased from Tocris Bioscience (Bristol, UK). Indomethacin, L-NAME and prostacyclin were obtained from Cayman Chemical Company (Ann Arbor, MI). Distilled water was used to prepare the drug solutions, except for indomethacin, TRAM-34 and UCL 1684, which were dissolved in dimethyl sulphoxide (DMSO). Concentrations are given as final molar concentration in the bath solution. Primary antibodies against endothelial nitric oxide synthase (eNOS; AB5589), cyclooxygenase-1 (COX-1; AB53766), cyclooxygenase-2 (COX-2; AB15191), prostacyclin synthase (PGIS; AB23668), prostacyclin (IP; AB123419) receptor and horseradish peroxidase (HRP)-conjugated secondary antibodies (AB 6721) were purchased from Abeam (Cambridge, UK). A rabbit polyclonal antibody to 0-actin was purchased from Sigma Chemical Co. Subcutaneous tissues from lower limb surgical procedures were transported to Pharmacology Vascular laboratory in ice cold physiological salt solution. Subcutaneous arteries were dissected free of connective tissue and fat, and then cut into rings. Care wa

Obesity intervention outcome: i)the effect of pharmacological intervention in failed lifestyle intervention ii)weight loss maintenance with cessation of pharmacological intervention

This study aimed to determine the effect of anti-obesity drug treatment in overweight and obese subjects who had failed to achieve satisfactory weight loss after a 9 months' weight loss intervention programme involving education on lifestyle modification. 25 subjects had originally undergone a 9 months' intervention programme aimed to reduce weight involving education on lifestyle modification. 11 (8 females and 3 males) subjects who had failed to reduce their weight satisfactorily (defined as still having body mass index (BMI) 2: 27 kg/m2 after intervention) were offered anti-obesity drugs for a period of 4 months. Anthropometric measurements, body composition (body and visceral fat percentages), metabolic and cardiovascular (CVS) profiles were measured at 9 months after completing lifestyle modification, and repeated at the end of 4 months with anti-obesity drugs. Anti-obesity drugs used in this study were orlistat 120 mg three times daily or sibutramine 10- 15 mg daily. subjects were on orlistat while 4 were on sibutrarnine. These 11 subjects did not significantly reduce weight when they were on 9 months education on lifestyle modification, mean weight before and after intervention was 75.7 (18.8) vs 76.5 (21.0) kg; p=0.452. Weight reduced significantly after 4 months drug treatment by 2.06 kg (p=0.041). Visceral fat significantly reduced from 13.7 (6.5)% to 12.9 (6.9)% (p=0.036) after drug treatment. A borderline reduction in waist circumference was seen (87.2 (10.2) em vs 85.9 (11.0) em, (p = 0.073). No difference was seen in lipid profile, fasting blood sugar, insulin level and resistance, blood pressure and arterial stiffuess with 4 months anti-obesity agents. Or!istat and Sibutramine reduced weight significantly in subjects who had failed to reduce weight with education on lifestyle medication. The weight reduction was however modest at 2.7% and was not associated with improvements in other CVS and metabolic risk markers

Effect Of Commercially Available Vitamin E Preparations On Arterial Compliance And Selected Cardiovascular Parameters [QP772.T6 A288 2006 f rb].

Vitamin E adalah antioksidan larut lemak yang dilaporkan mempunyai sifat antioksidan yang kuat. Ia adalah antioksidan pemecah rantai utama pada tisu manusia, membran dan plasma. Vitamin E boleh dibahagikan kepada dua famili iaitu tokoferol dan tokotrienol, setiap famili pula boleh dibahagikan kepada empat isomer yang berbeza iaitu alfa, gama, delta dan beta tokotrienol dan tokoferol. Matlamat tesis PhD ini adalah untuk menyiasat dengan lebih lanjut beberapa isu yang masih tidak diketahui tentang penggunaan vitamin E bagi kesihatan vaskular. Vitamin E is a potent lipid soluble antioxidant. It is the principal chain breaking antioxidant in human tissues, membrane and plasma. Vitamin E comprised of two families, the tocopherols and tocotrienols, each family is further divided into the alpha, gamma, delta and beta isomers. This PhD thesis aimed to address some of the unresolved issues on vitamin E use in vascular health

Anomalous right pulmonary artery from the aorta

Anomalous origin of the right pulmonary artery is a rare form of congenital heart disease. It usually presents in early infancy with heart failure and rapid development of pulmonary hypertension. There are about 131 cases reported in the literature and we report one such case.peer-reviewe

Method optimisation and validation study on use of laser doppler flowmetery to assess microvascular endothelial function

Introduction: Human postocclusive forearm skin reactive hyperemia is not only a potential means of identifying early signs of cardiovascular diseases, it can also be used in the assessment of local microvascular response to topically applied compounds on skin. The method is not fully characterized. In this study, we investigated the influence of occlusion time on postocclusive forearm skin reactive hyperemia using laser Doppler fluximetly (LDF). Methods: Twenty healthy male volunteers were studied on three separate days (at least 24 lti h apart) via a randomized design. Volunteers were studied in a supine position while fasted. Laser Doppler probes were placed on the volar surface of the antebrachium. In preliminary studies, 3 min of upper arm blood flow occlusion at suprasystolic pressure was found to be the upper limit of tolerability. Subsequently, volunteers were randomized to receive 1, 2, or 3 min occlusion on 3 different days. Skin blood flux 1~ was measured before, during, and after occlusion using LDF. The primary outcome calculated was maximal change in ski11 blood flux before and after occlusion, expressed in arbitrary units (AU). Results: Skin blood flux changes (mean ± S.E.M.) after 1, 2, and 3 min occlusion period were 15.39 ± 1.27 AU, 24.84 ± 1.62 AU, and 32.14 ± 1.73 AU, respectively. Using repeated-measures analysis of variance (ANOVA), significant difference (P<.OS) in skin blood flux changes were revealed between these three occlusion durations, where 3 min occlusion produced significantly greater in skin blood flux occlusion change compared to I and 2 min occlusion. Conclusion: Three minutes of occlusion produces the greater postocclusive reactive hyperemia. It is recommended that studies using postocclusive forearm skin reactive hyperemia should occlude the forearm for at least 3 min

Vitamin D associated inflammation and atherosclerosis

Vitamin D is known to play a crucial role in mineral homeostasis and bone metabolism. Recent discoveries showed that the vitamin also regulate the inflammatory mediators. A number of studies have reported on the association of low vitamin D levels with increased level of inflammatory parameters; which predisposes to atherosclerosis and development of cardiovascular diseases (CVD). Since inflammation is implicated in the pathogenesis of CVD, measurement of inflammatory marker levels has been proposed as a method to improve the prediction of these events. In this review, the mechanism of inflammation and role of vitamin D in combating inflammation are discusse

Metabolic, inflammatory, and oxidative stress markers in women exposed to secondhand smoke

Background Secondhand smoke (SHS) exposure has adverse effects on the cardiovascular system. This study aimed to determine the effects of SHS on the cardiovascular disease biomarkers, namely the metabolic, inflammatory, and oxidative stress markers in healthy adult women. Methods This comparative cross-sectional study was conducted among healthy women. The cases included those women exposed to SHS, and the controls included those women not exposed to SHS. SHS exposure was defined as being exposed to SHS for at least 15 min for 2 days per week. Venous blood was taken to measure the metabolic markers (high molecular weight adiponectin, insulin level, insulin resistance, and nonesterified fatty acids), oxidative stress markers (oxidized low density lipoprotein cholesterol and 8-isoprostane), and inflammatory markers (high-sensitivity C-reactive protein and interleukin-6). A hair nicotine analysis was also performed. An analysis of covariance and a simple linear regression analysis were conducted. Results There were 101 women in the SHS exposure group and 91 women in the non-SHS exposure group. The mean (with standard deviation) of the hair nicotine levels was significantly higher in the SHS exposure group when compared to the non-SHS exposure group [0.22 (0.62) vs. 0.04 (0.11) ng/mg; P = 0.009]. No significant differences were observed in the high molecular weight adiponectin, insulin and insulin resistance, nonesterified fatty acids, 8-isoprostane, oxidized low density lipoprotein cholesterol, interleukin-6, and high-sensitivity C-reactive protein between the two groups. The serum high molecular weight adiponectin was negatively associated with the insulin level and insulin resistance in the women exposed to SHS. However, no significant relationships were seen between the high molecular weight adiponectin and nonesterified fatty acids, 8-isoprostane, oxidized low density lipoprotein cholesterol, high-sensitivity C-reactive protein in the SHS group. Discussion There were no significant differences in the metabolic, oxidative stress, and inflammatory markers between the SHS exposure and non-SHS exposure healthy women. A low serum level of high molecular weight adiponectin was associated with an increased insulin level and resistance in the women exposed to SHS

Understanding development of vasculopathy in diabetic microcirculation - role of endothelial prostanoids, prostacyclin and nitric oxide

This study aims to elucidate how endothelial dysfunction develops in diabetic • microcirculation. The roles of endothelial derived factors that regulate blood vessel tone and homeostasis: prostacyclin, nitric oxide (NO), endothelium derived hyperpolarizing factors (EDHF) and endothelial prostanoids were studied in streptozotocin induced diabetic rats. The first part of the project involved In-vitro vascular response studies to determine relative contributions of each endothelial NO, EDHF, prostacyclin and prostanoids mediated relaxation /contraction in normal and diabetic vessels. The second part were biochemical studies (western blot and immunohistochemistry) to determine presence and protein expression of the enzymes and receptors involved in synthesis and action of these factors. These experiments were conducted durin'!l early and late phases of diabetes