The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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    YKL-40 Correlates with Soluble CD 40 Ligand in Old Myocardial Infarction with Hypertension

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    BACKGROUND: Myocardial infarction is one of the coronary artery diseases caused by plaque rupture, plaque erosion or calcified nodules, with the occurence of thrombus formation and artery occlusion. YKL-40 has a functional role in plaque fibrous formation because of its high expression during fibrosis development, vascular smooth muscle cells differentiation, elevated matrix turnover and tissue remodelling in old myocardial infarction, whereas CD40 ligand, which is stored in the cytoplasm of resting platelets, rapidly presents on the surface. After cleavage, a soluble functional CD40 ligand (sCD4OL) is generated. The aim of this study was to assess the association between YKL-40 and sCD4OL in old myocardial infarction.METHODS: This study used the cross sectional study design. Fifty six patients with old myocardial infarction were selected based on their electrocardiographical results. Among these patients, 23 subjects had hypertension and 15 subjects had hsCRP >3-l0 mg/L. YKL-40 and sCD40L were measured by ELISA method.RESULTS: There was no significant correlation between YKL-40 and sCD40L (r=0.078; p=0.569) in old myocardial infarction and in subjects with hsCRP >3-10 mg/L (r=0.524; p=0.045). However, significant positive correlations Were found in subjects with hypertension (r=0.447; p=0.029).CONCLUSIONS: Our findings showed that YKL 40 correlated significantly with sCD4OL in subjects with hypertension.KEYWORDS: myocardial infarction, ruptured plaque, coronary artery disease, YKL-40, soluble CD40 ligan

    GFAP and S100B Protein are Associated with Discharged NIHSS of Anterior Circulation Ischemic Stroke

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    BACKGROUND: Patient with larger ischemic lesion will suffer more severe neurogical deficit. The utility of MRI for lesion size measurement is still limited, therefore additional approach was pursued through examination of markers released by damaged brain cell, GFAP and S100B protein. The aim of this study is to know whether both markers are associated with the neurological deficit of anterior circulation ischemic stroke. METHODS: This observational prospective study enrolled 74 patients with anterior circulation ischemic stroke diagnosis. GFAP and S100B protein were measured with ELISA using blood collected at 48 to 72 hours after onset. The neurological deficit was assessed with NIHSS ad discharged.RESULTS: There was a significant association between GFAP level and discharged NIHSS (p=0.008) with 100% sensitivity and 100% negative predictive value. S100B protein also showed a significant correlation with discharged NIHSS (r=0.488; p=0.000) and this correlation could be described with an equation (OR=1.009; 95% CI=1.0003-1.0188; p=0.044). S100B protein at 78.3215 ng/L would give true prediction as 73.9% (95% CI=62.7%-85.2%, p=0.001). CONCLUSIONS: GFAP and S100B protein that were measured at 48 to 72 hours after onset were significantly associated with NIHSS at discharge. KEYWORDS: GFAP, S100B protein, discharged NIHSS, ischemic strok

    Waist Circumference was Positively Correlated with Chemerin, Retinol-Binding Protein 4 and hsCRP

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    BACKGROUND: Central obesity is associated with various chronic metabolic disorders characterized by abnormal cytokine production, increased acute phase reactants, and activation of inflammatory signaling pathways. This study was aimed to investigate the association of waist circumference, chemerin, and retinol binding protein (RBP)-4 with inflammation in men with central obesity.METHODS: The research was conducted with a crosssectional design involving 68 centrally obese male subjects aged 30 to 60 years old, with waist circumference (WC) >90 cm. All subjects fulfilled the inclusion and exclusion criteria. Anthropometric parameters, fasting glucose, creatinine, SGOT, SGPT and hsCRP were measured. Serum concentrations of chemerin and RBP4 were measured by ELISA.RESULTS: The trend lines showed that chemerin, RBP4, and hsCRP increased with WC. Pearson correlation test showed a positively significant correlation between WC and hsCRP (r=0.242, p<0.05); and also between chemerin and hsCRP (r=0.244, p<0.05) and RBP4 (r=0.321, p<0.01). Subjects were stratified into four groups based on their chemerin and RBP4 levels (high chemerin/high RBP4, high chemerin/low RBP4, low chemerin/high RBP4, or low chemerin/low RBP4). Subjects who were in the high chemerin/low RBP4 group were more likely to have high level of inflammation (47.6%), but subjects with high chemerin/high RBP4 showed low level of inflammation (42.9%) as compared with the other three groups.CONCLUSIONS: We concluded that increased WC was correlated with elevated levels of chemerin, RBP4, and hsCRP. High chemerin was correlated with increased level of RBP4 as well as with high level of inflammation.KEYWORDS: waist circumference, chemerin, RBP4, hsCRP, inflammatio

    Phosphorylated-Survivin at Ser81 Induced Protein Kinase A (PKA): A Back Loop

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    BACKGROUND: Survivin, a bifunctional protein, acts as suppressor of apoptosis and has an essential role in mitosis. Survivin is physically phosphorylated on Thr34, and other important sites such as Thr117, Ser20, Thr48 and Ser81. Our previous report has shown that Ser81 of survivin plays role in cytoprotection. In order to investigate the underlying mechanism, all motifs with medium stringency were scanned. We found that site of survivin at Ser81 was correlated to PKA, which is well reported to many cell signal machineries, including cell survival. Therefore, we focused our current investigation in finding possible correlation and interaction between survivin’s Ser81 site and PKA.METHODS: Wild-type survivin (Survivin), antisense survivin (Survivin-AS), mutated-survivin and mutated-survivin Ser81Ala (Survivin-S81A) were constructed. Each retroviral product was produced. Some cell lysates were prepared and immunoprecipitated. For analysis, we performed immunoblotting and PKA’s activity assays.RESULTS: In our current results, phosphorylated-PKA was correlated with survivin. Infection of survivin could lead to acceleration of PKA’s activity in a viral particle dependent manner. This positive back loop induction by survivin was shown to be correlated to Ser81 site, since survivin-mediated PKA activity was not resulted by mutated form of survivin at Ser81 to nonphosphorylatable Ala (S81A).CONCLUSIONS: Our results suggested a possible back loop of survivin to activate PKA, and Ser81 could be an important site to mediate the survivin-PKA back loop signaling. Survivin-induced activation of PKA might be related to cytoprotection.KEYWORDS: survivin, S81A, L929, PK

    Lipoprotein (a) and Lipoprotein-associated Phospholipase A2 as Atherosclerosis Risk Factors (oxLDL) in Men with Central Obesity

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    BACKGROUND: The increasing prevalence of obesity in Indonesia triggers a lot of research interest to overcome it. Obesity has a very important role as atherosclerosis and cardiovascular risk factors. The presence of oxidized LDL (oxLDL) on the vascular wall is a marker of atherosclerosis. The increase of Lipoprotein(a) (Lp(a)) and Lipoprotein associate phospholipase A2 (LpPLA2) occurs in patients with coronary artery disease (CAD), myocardial infarction, and unstable angina. It is well accepted that obesity is closely related to atherosclerosis and cardiovascular risk factors. However, correlation between Lp(a), LpPLA2 and oxLDL in central obesity has not yet been investigated. The aim of this study was to observing the correlation between Lp(a), LpPLA2 and oxLDL in early central obesity.METHODS: An observational study with cross-sectional design on 76 men with central obesity, aged 30-67 years, was conducted. Central obesity was characterized by waist circumference >90 cm. Test of Lp(a) was performed by turbidimetric method and that of LpPLA2 was performed by sandwich enzyme immunoassay. Test of oxLDL was performed by ELISA. All statistical analyses were carried out using SPSS for Windows v.11.5 at a significance level of p 10 mg/L), renal failure (Creatinine >1.5 mg/dL) and consumed antiinflammation were excluded from this study.RESULTS: The concentration of LpPLA2 had a linear correlation (r=-0.340, p=0.003) with the increase of oxLDL concentration. However, concentration of Lp(a) did not have linear correlation (r = 0.025) with increase of oxLDL concentration. This finding indicates that concentration of LpPLA2 had a negative correlation with increase of concentration of oxLDL. In addition, Lp(a) appears not to correlate with oxLDL significantly.CONCLUSION: The study showed there was a significant correlation between concentration of LpPLA2 and concentration of oxLDL in men with central obesity. Higher concentration of LpPLA2 correlated with lower concentration of oxLDL.KEYWORDS: Lp(a), LpPLA2, oxLDL, atherosclerosis, central obesit

    Correlation between Inflammation and Fibrinolysis Impairment on Central Obesity: A Study for hsCRP, PAI-1, PAP and TAFI

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    BACKGROUND: Inflammation in the vascular wall plays an important role in the pathogenesis of atherosclerosis. Current studies have shown that increase of systemic inflammatory marker like the acute phase component C-reactive protein (CRP) are associated with an unfavorable progression of disease and an increased risk for acute cardiovascular events. Recently, a close association of Metabolic Syndrome (MetS) with hemostatic abnormalities has been reported. Among hemostatic abnormalities, an increase in plasminogen activator inhibitor (PAI)-1, a strong inhibitor of fibrinolysis, is considered a core feature of MetS. High PAI-1 concentrations may be associated with thrombus formation, also causing cardiovascular events. Therefore, we investigated the association between markers for chronic inflammation (CRP) and the markers of fibrinolytic impairment (PAI-1, PAP, TAFI) in subjects with central obesity.METHODS: This was a cross-sectional study in 80 male Indonesian subjects, aged 30-60 years old with central obesity, conducted from January to March 2008 in Bandung.RESULTS: The study results showed that there was a difference of PAI-1 levels between MetS and Non-MetS group. There were significant correlations between hsCRP and PAI-1 (r=0.252, p=0.024 ), hsCRP and PAP (r=0.253, p=0.024), and also between PAI-1 and PAP (r=-0.239, p=0.033 ) respectively. But, no correlation found between hsCRP and TAFI.CONCLUSIONS: There was correlation between inflammation and fibrinolysis impairment on central obesity. Concentrations oh hsCRP, PAI-1 and TAFI were significantly higher in MetS.KEYWORDS: inflammation, fibrinolysis impairment, hsCRP, PAI-1, PAP, TAF

    Association of Aldosterone, Plasma Renin Activity (PRA) and Superoxide Dismutase (SOD) with Inflammation and Insulin Resistance in Adult Men with Central Obesity

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    BACKGROUND: Visceral Obesity is related with chronic low grade inflammation, and is the main component of metabolic syndrome (MetS). MetS is associated with increased cardiovascular disease (CVD). Furthermore, superoxide dismutase (SOD) is correlated with insulin resistance. Several studies have reported a strong correlation between Renin Angiotensin Aldosterone System (RAAS) and CVD, but the association of Aldosterone, Plasma Renin Activity (PRA) and SOD with inflammation, insulin resistance and MetS have not been fully elucidated. The aim of this study was to investigate the correlation of Aldosterone, PRA, and SOD with inflammation (high sensitivity c-reactive protein/hsCRP) and insulin resistance (homeostasis model assessment-insulin resistance/HOMA-IR) in adult men with central obesity.METHODS: This was a cross-sectional study, which was carried out on 80 male subjects with central obesity who were divided into 2 groups: the group of subjects who had fulfilled the MetS criteria and the other group of subjects who did not. After an overnight fasting, blood pressure (BP) was measured on all subjects and laboratory examinations were done for measurement of the concentration of fasting glucose, high density lipoprotein cholesterol (HDL-C), triglyceride, hsCRP, insulin, aldosterone, PRA, and SOD.RESULTS: We found aldosterone had positive correlation with PRA (r = 0.389; p < 0.001) and triglycerides (r =0.234; p=0.036). PRA had positive correlation with SOD (r=0.220; p=0.05) and HDL-C (r=0.273; p=0.014), but not with hsCRP (r=-0.044; p=0.696) and HOMA-IR (r=0.168 p=0.136). PRA correlated with HOMA-IR in MetS (r=0.471; p=0.01). Aldosterone and PRA were correlated with diastolic pressure in those with hypertension (r=0.680; p=0.003 and r=0.608; p=0.01).CONCLUSIONS: There is no direct correlation between aldosterone or SOD and Insulin resistance, and inflammation in men with central obesity. The correlation between PRA and MetS might be through insulin resistance mechanism. We found significant correlation between PRA, HDL-C and SOD. Increased aldosterone was ccorrelated with elevated triglycerides, thus possibly increasing the risk of MetS.KEYWORDS: central obesity, aldosterone, plasma renin activity, superoxide dismutase, inflammation, insulin resistanc

    Correlation of Urine Albumin/Creatinine Ratio (UACR), High Sensitivity C-Reactive Protein (hsCRP) and N-Terminal Pro Brain Natriuretic Peptide (NT-proBNP) with Atherosclerosis (OxLDL) in Centrally Obese Men

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    BACKGROUND: Obesity is closely associated with atherosclerosis risk and cardiovascular disease. Novel cardiovascular risk biomarkers such as Urine Albumin/Creatinine Ratio (UACR), High Sensitivity C-Reactive Protein (hsCRP) and N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) have been observed to predict cardiovascular disease in the general population. The aim of this study was to observe the correlation of UACR, hsCRP and NT-proBNP with atherosclerosis (OxLDL) in centrally obese men.METHODS: The study was observational with a cross sectional design done on 76 male subjects aged 30–50 years with central obesity and mean of age of 37 years. Urine albumin was determined by PEG enhanced immunoturbidimetric assay, urine creatinine by Jaffe without deproteinase, hsCRP by chemiluminescent immunometric assay, NT-proBNP by electrochemiluminescence (ECLIA) and OxLDL by ELISA.RESULTS: There was significant correlation between hsCRP and OxLDL (r=0.230, p=0.046). There was no significant correlation between UACR and OxLDL (r=-0.138, p=0.236), neither between Log NT-proBNP and OxLDL (r=-0.173, p=0.136).CONCLUSIONS: Atherosclerosis was significantly correlated with hsCRP (low grade inflammation).KEYWORDS: NT-proBNP, UACR, hsCRP, OxLDL, atherosclerosi

    Progress and Future Challenges of Human Induced Pluripotents Stem Cell in Regenerative Medicine

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    BACKGROUND: Less than a decade ago the prospect for reprogramming the human somatic cell looked bleak at best. It seemed that the only methods at our disposal for the generation of human isogenic pluripotent cells would have to involve somatic cell nuclear transfer (SCNT). Shinya Yamanaka in August 2006 in his publication (Cell) promised to change everything by showing that it was apparently very simple to revert the phenotype of a differentiated cell to a pluripotent one by overexpressing four transcription factors in murine fibroblasts.CONTENT: Mouse and human somatic cells can be genetically reprogrammed into induced pluripotent stem cells (iPSCs) by the expression of a defined set of factors (Oct4, Sox2, c-Myc, and Klf4, as well as Nanog and LIN28). iPSCs could be generated from mouse and human fibroblasts as well as from mouse liver, stomach, pancreatic, neural stem cells, and keratinocytes. Similarity of iPSCs and embryonic stem cells (ESCs) has been demonstrated in their morphology, global expression profiles, epigenetic status, as well as in vitro and in vivo differentiation potential for both mouse and human cells. Many techniques for human iPSCs (hiPSCs) derivation have been developed in recent years, utilizing different starting cell types, vector delivery systems, and culture conditions. A refined or perfected combination of these techniques might prove to be the key to generating clinically applicable hiPSCs.SUMMARY: iPSCs are a revolutionary tool for generating in vitro models of human diseases and may help us to understand the molecular basis of epigenetic reprogramming. Progress of the last four years has been truly amazing, almost verging on science fiction, but if we can learn to produce such cells cheaply and easily, and control their differentiation, our efforts to understand and fight disease will become more accessible, controllable and tailored. Ability to safely and efficiently derive hiPSCs may be of decisive importance to the future of regenerative medicine.KEYWORDS: iPSCs, ESC, reprogramming factor, reprogramming efficiency, somatic cel

    Correlation between Interleukin-6 (IL-6), High Sensitivity C-Reactive Protein (hsCRP), Endothelin-1 (ET-1), Asymmetric Dimethylarginine (ADMA) and Insulin Resistance (HOMA-IR) in Central Obese Men

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    BACKGROUND: Many studies have shown that obesity was closely related to insulin resistance via several pathways such as inflammation, oxidative stress, lipolysis, and endothelial dysfunction. This study was carried out to observe the correlation between inflammation (IL-6 and hsCRP), lipolysis process (ET-1), and endothelial dysfunction (ADMA) and insulin resistance (HOMA-IR) in centrally obese men.METHODS: This was a cross sectional study on 62 male subjects aged 30–60 years old with waist circumference (WC) >90 cm. IL-6, ET-1 and ADMA levels were measured using ELISA method, while hsCRP and insulin were measured using chemiluminescence method. All blood testings were conducted in Prodia Clinical Laboratory.RESULTS: The results showed that WC was significantly correlated with hsCRP (r=0.294, p=0.022 ), ET-1 (r=0.257, p=0.047 ) and ADMA (r=0.338, p=0.009). We also found a significant correlation between hsCRP with HOMA-IR (r=0.324, p=0.021), ADMA with HOMA-IR (r=0.280, p=0.045), and IL-6 with hsCRP (r=0.437, p=0.003).CONCLUSIONS: hsCRP and ADMA have significant correlation with HOMA-IR in centrally obese men. HOMA-IR significantly increases in subjects with ADMA above median and either IL-6 or hsCRP above median, as compared to those in the other groups. Inflammation and endothelial dysfunction are important causal pathways of insulin resistance state in centrally obese men.KEYWORDS: obesity, IL-6, hsCRP, ET-1, ADMA, HOMA-I

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