The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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Relations Between Atherogenic Index of Plasma, Ratio of Small Dense Low Density Lipoprotein/Lecithin Cholesterol Acyl Transferase and Ratio of Small Dense Low Density Lipoprotein/Cholesteryl Ester Transfer Protein of Controlled and Uncontrolled Type 2 DM
BACKGROUND: Patients with Diabetes Melitus are proven to be prone to atherosclerosis and coronary heart disease, especially type 2 Diabetes Melitus (T2DM) patient who have higher risk and mortality for cardiovascular risk factor. The Dyslipidemia condition is very common in T2DM as one of the risk factors. Diabetic dyslipidemia is marked by the increased triglyceride (TG), low HDL cholesterol (HDL-C), and increased small dense LDL and apolipoprotein B. Therefore the aim of this study is to assess the differential and correlation between Atherogenic Index of Plasma (AIP), ratio of small dense low density lipoprotein (sdLDL)/lecithin cholesterol acyl transferase (LCAT) and ratio of sdLDL/cholesteryl ester transfer protein (CETP) of controlled and uncontrolled T2DM.METHODS: This study was observational with cross sectional design. In total of 72 patients with T2DM consist of 36 controlled and 36 uncontrolled, participated in this study. The serum TG, HDL-C, sdLDL, LCAT and CETP were examined in their relationship with to T2DM risk.RESULTS: The results of the study indicate that the AIP (p<0.001) increase controlled and uncontrolled T2DM and the ratio of sdLDL/CETP (p=0.004), odds ratio of AIP was 4 (95% CI : 1.501-10.658) and odds ratio of sdLDL/CETP ratio was 4 (95% CI : 1.501-10.658) in uncontrolled T2DM.CONCLUSION: This study showed that the AIP and ratio of small dense LDL/CETP had a significant correlation with the uncontrolled T2DM. The AIP and ratio of small dense LDL/CETP increase was found at the uncontrolled T2DM to be 4 times greater than the controlled T2DM.KEYWORDS: T2DM, atherosclerosis, atherogenic index of plasma, small dense LDL, LCAT, CETP, ratio of sdLDL/LCAT, ratio of sdLDL/CET
Adipose Tissue Biology: An Update Review
BACKGROUND: Obesity is a major health problem in most countries in the world today. It increases the risk of diabetes, heart disease, fatty liver and some form of cancer. Adipose tissue biology is currently one of the “hot” areas of biomedical science, as fundamental for the development of novel therapeutics for obesity and its related disorders.CONTENT: Adipose tissue consist predominantly of adipocytes, adipose-derived stromal cells (ASCs), vascular endothelial cells, pericytes, fibroblast, macrophages, and extracellular matrix. Adipose tissue metabolism is extremely dynamic, and the supply of and removal of substrates in the blood is acutely regulated according to the nutritional state. Adipose tissue possesses the ability to a very large extent to modulate its own metabolic activities including differentiation of new adipocytes and production of blood vessels as necessary to accommodate increasing fat stores. At the same time, adipocytes signal to other tissue to regulate their energy metabolism in accordance with the body's nutritional state. Ultimately adipocyte fat stores have to match the body's overall surplus or deficit of energy. Obesity causes adipose tissue dysfunction and results in obesity-related disorders.SUMMARY: It is now clear that adipose tissue is a complex and highly active metabolic and endocrine organ. Undestanding the molecular mechanisms underlying obesity and its associated disease cluster is also of great significance as the need for new and more effective therapeutic strategies is more urgent than ever. KEYWORDS: Obesity, Adipocyte, Adipose, Tissue, Adipogenesis, Angiogenesis, Lipid Droplet, Lipolysis, Plasticity, Dysfunction
Lipopolysaccharide Binding Protein, Soluble-Intercellular Adhesion Molecule-1, Procalcitonin, and Protein C Activity and Clinical Outcome in Systemic Inflammatory Response Syndrome (SIRS) or Sepsis Patients
BACKGROUND: Biochemical markers may be used in diagnosis, prognostic and monitoring treatment and therapy for sepsis patients. In this study we used Lipopolysacharide Binding Protein (LBP), serum-Intercellular Adhesion Molecule-1 (ICAM-1), Procalcitonin (PCT) and protein C activity. LBP is related to lipopolysachharide or gram-negative bacterial endotoxin which bound to LBP and induced inflammatory response. ICAM-1 is associated with endothelial dysfunction in response to systemic inflammatory and septic condition. PCT increased in bacterial infection and in severe systemic inflammatory. Role of Protein C is protecting the intravascular system to systemic inflammation, sepsis and the concomitant intravascular coagulopathy. The aim of this study was to examine the associations between levels of serum LBP, sICAM-1, PCT, and protein C activity with the clinical outcome of SIRS or sepsis patients.METHODS: We included 19 post surgery patients with SIRS criteria from intensive care unit (ICU) and evaluated the level of LBP serum with Chemiliuminescent Enzyme Immunoassay (Diagnostic Product Co.), ICAM-1 with ELISA (R&D System), PCT with immunochromatography (BRAHMS), protein C activity with chromogenic method (Dade Behring). We performed the samples serially at the first admission of patients and after 72 hours. Data were analysed by non-parametric with Wilcoxon test and Mann-Whitney test. Correlation study between biomarkers calculated by Kendall’s tau and Spearman’s rho.RESULTS: Of 19 patients, 9 (47,4%) died and 10 (52,6%) surviving. The level of LBP serum decreased after 72 hours in surviving-sepsis patients, and increased in nonsurviving sepsis patients with significant different levels at 72 hours examination (P0.05). In all patients were found high level of PCT serum since the first admission examination, decreasing levels were occurred significantly in surviving patients after 72 hours (P0.05) both in surviving and non-surviving patients.CONCLUSIONS: Increasing level of LBP and PCT in sepsis patients showed that those biomarkers useful for predict the clinical outcome in sepsis patients. Decreasing protein C activity level was not a good predictor in worsening clinical outcomes. Soluble ICAM-1 level was not a good marker for predict risk of sepsis severity. LBP and PCT tests were more useful in serially testing from the first admission of sepsis patients, those tests are more faster than bacterial culture.KEYWORDS: Sepsis, SIRS, Lipopolysachharide Binding Protein, soluble- Intercellular Adhesion Molecule-1, Procalcitonin, Protein
Endothelial Progenitor Cells in Diabetic Vasculopathy
BACKGROUND: The discovery of endothelial progenitor cell (EPC) a decade ago by Asahara, et al has refuted the previous belief that vasculogenesis only occurs during embryogenesis. The reduced circulating concentration of EPCs is a surrogate marker of endothelial function and has been implicated in the pathogenesis of many vascular diseases.CONTENT: Diabetes is linked to impaired vascular function, including alterations in both endothelial cells and EPCs. A number of studies have shown that individuals with diabetes have decreased level of circulating EPCs and that the severity of disease is inversely proportional to EPC levels. In vitro, hyperglycemia increases the rate of EPC senescence and the angiogenic function of EPCs from patients with either type 1 or type 2 diabetes is impaired such that they are poorly proliferative and fail to incorporate into forming vessel-like structures. Given the comprehensive role of EPC alterations in diabetes complications, modulation of the levels and/or function of EPCs may be considered a potential therapeutic strategy.SUMMARY: The available data demonstrating that decrease or dysfunction of EPCs may have a prominent role in the pathogenesis of all diabetes complications. Further approaches, such as EPC administration, may represent novel treatments for diabetic vasculopathy in the future. To date, many barriers remain to such a therapeutic approach. Firstly, there is no specific marker for EPC at present. Secondly, techniques of EPC isolation are not standardized, preventing direct comparison between various studies. The long-term effects of transplanted EPCs are currently unknown
Elevated Serum Neopterin is Associated with Increased Risk of Cardiovascular Events in Acute Coronary Syndromes
BACKGROUND: Neopterin is a soluble biomarker of monocyte activation and its increased concentration might be expressed in atherosclerosis. Until recently, there has been lacking of information on the prognostic role of neopterin in acute coronary syndromes (ACS). The study was aimed at measuring the associations between elevated serum neopterin and increased risk of cardiovascular (CV) events in ACS.METHODS: This was a prospective cohort study, recruited 71 ACS patients from January 31 through August 31, 2007 in Sanglah Hospital of Udayana School of Medicine, Denpasar – Bali. Cardiovascular events, such as: CV death, recurrent myocardial infarction, stroke and recurrent myocardial ischemia were previously defined. Relative risk and survival rate were measured successively by Cox proportional model and Kaplan-Meier curve.RESULTS: Of 71 ACS patients aged 56.8 ± 9.5 years, 21 (29.5%) subjects underwent CV events. Overall mean followup was 151.6 (95% CI: 129.7 – 173.5) days. Baseline characteristic were similarly distributed between groups with the highest quartile neopterin level (≥ 14.7 nmol/L) than those with lowest quartile (≤ 6.2 nmol/L). Patients with the highest quartile had the worst survival curve than those with the lowest quartile (log-rank test; P = 0.047). On Cox proportional model, relative risk of highest quartile group was 5.84 (95% CI: 1.19 – 28.47; P = 0.029) compared to lowest quartile, after being adjusted with other predictors.CONCLUSIONS: Elevated serum neopterin is associated with increased risk of CV events in acute coronary syndromes.KEYWORDS: neopterin, cardiovascular events, acute coronary syndrome
Association of Obesity and Breast Cancer Risk: The Role of Estrogen, Tumor Necrosis Factor-alpha, and Adiponectin as Risk factors (preliminary study)
BACKGROUND: Breast cancer is the most frequent cancer diagnosed among women. Many factors influence the carcinogenesis of breast cancer. The aim of this study to analyze the role of obesity (waist circumference and body mass index), serum Estradiol levels, TNF-α, and Adiponectin in the occurrence of breast cancer.METHODS: This was observational study with casecontrol design. Eleven breast cancer patients as cases and twelve Fibroadenoma Mammae (FAM) patients as controls were analyzed. The serum Estrogen, TNF-α and Adiponectin were examined in their association with breast cancer risk.RESULTS: Women with breast tumor and waist circumference > 80 cm have significantly higher breast cancer risk than women with breast tumor and waist circumference 2.30 pg/ml) have higher breast cancer risk (19.25 times) than women with breast tumor and have lower serum TNF-α levels (95% CI=1.77-209.55, p=0.015). Whereas, women with breast tumor and lower Adiponectin/TNF-α ratio (80 cm and low Adiponectin/TNF-α ratio in women with breast tumor are significantly associated with an increased risk for breast cancer.KEYWORDS: Obesity, breast cancer, adiponectin/TNF-α rati
Association of Free Fatty Acid (FFA), Fatty Acid Binding Protein (FABP) and Adiponectin with Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-6 (IL-6) Among Obese Non Diabetic Males
BACKGROUND: The prevalence of obesity has increased dramatically in recent years. It is commonly associated with type 2 diabetes, coronary artery disease, and hypertension. White adipose tissue (WAT) is a major site of energy storage and is important for energy homeostasis. WAT has been increasingly recognized as an important endocrine organ that secretes a number of biologically active “adipokines”. The resultant higher FFA, FABP4, FABP5 concentration; and lower concentration of adiponectin is known to be correlated with inflammation. The aim of this study was to observe the correlation between FFA, FABP4, FABP5 and adiponectin with TNF-α and Interleukin-6 as markers of inflammation.METHOD: The study was observational with a cross sectional design. The analysis was done on 69 male subjects aged 30-60 years with non diabetic abdominal obesity which is characterized by waist circumference (WC) 98.7±6.5 cm and fasting blood glucose 87.1±9.7 mg/dL. FFA testing was performed by enzymatic colorimetric assay; whereas FABP4, FABP5, TNF-α, adiponectin and IL-6 were performed by ELISA. All statistical calculations were performed with the SPSS 11.5 statistical software package. We used the Pearson or Spearman’s rho correlation coefficient to assess the correlation between various anthropometric and biochemical measures. We also used path analysis Lisrel 8.30 for Windows.RESULT: This study revealed that there was no correlation between FFA, FABP4 and adiponectin with TNF-α and Interleukin-6, whereas there was correlation between FABP5 with TNF- and Interleukin-6. This study also showed there were correlations between WC and hsCRP (r=0.314, p=0.000), WC and IL-6 (r=0.276, p=0.022), FFA and FABP4 (r=0.263, p=0.029), FABP4 and WC (r=0.249, p =0.039), FABP4 and BMI (r=0.311, p=0.009), FABP5 and TNF- (r=0.408, p=0.000), FABP5 and FABP4 (r=0.296, p=0.014), FABP5 and Interleukin-6 (r=0.248, p=0.04), Adiponectin and HDL-Cholesterol (r=0.301, p=0.012).CONCLUSION: Abdominal obesity might contribute to inflammation in obese nondiabetic males. This study indicated that in abdominal obesity, FFA may induce inflammation through FABP4 and FABP5. Advancing our understanding of the function and measurement of FABP4 and FABP5 serum concentration will give insight into the clinical diagnosis of obesity-related metabolic disorders.KEYWORDS: Obesity, Waist Circumference, Free Fatty Acid (FFA), Fatty Acid Binding Protein (FABP), Adiponectin, TNF-α, Interleukin-6, Inflammatio
Porphyromonas gingivalis Induced Fragmentation of Type IV Collagen Through Macrophage-Activated MMP-9: (In Vitro Study of Collagenolytic Mechanism in Pathogenesis of Atherosclerotic Plaque Rupture)
BACKGROUND: Periodontitis is caused mostly by Porphyromonas gingivalis (P.gingivalis) and it is related to acute coronary syndrome. P.gingivalis readily invades blood circulation and potentially induces collagenolytic activity of inflammatory cells that results in collagen vascular degradation leading to atherosclerotic plague rupture (APR). APR is responsible for the occurence of fatal cardiovascular events such as acute myocardial infraction (AMI).AIMS: To show that P.gingivalis potentially induces fragmentation of the type IV vascular collagen due to macrophage-activated MMP-9.MATERIAL AND METHODS: The ability of P.gingivalis to induce the type IV collagen fragmentation, shown by digesting type IV collagen with the supernatant of monocyte-derived macrophage activated by exposure to P.gingivalis suspension for 18 hours, 37oC, 5%CO2. The type IV collagen fragments were analyzed by SDS-PAGE and confirmed by Western-blotting. Antibody of type IV collagen produced and confirmed by dot-blotting prior to its being used as primary antibody of Western-blotting. The existence of MMP-9 was detected by Dot-blot and Western-blot technique, while the MMP-9 activity was assessed by SDS-PAGE and zymograms.RESULTS: Our data showed that P.gingivalis induced macrophage to produce MMP-9 as one of collagenolytic components, and interaction with P.gingivalis proteases enhanced the proteolytic activity and resulted in degradation of type IV collagen with molecular weight of 88 kDa into two smaller fragments with molecular weight of 80 kDa and 60 kDa. CONCLUSION: P.gingivalis induced macrophage to activate its MMP-9 that led to fragmentation of vascular type IV collagen in the pathogenesis of atherosclerotic plaque rupture. KEYWORDS: P.gingivalis, macrophage, type IV collagen fragmentation, atherosclerotic plaque rupture, AM
Relationship of Endothelin-1, Tumor Necrosis Factor-alpha and Interleukin-6 with the Progression of Heart Failure
BACKGROUNDS: Heart failure, a new epidemic of cardiovascular disease, has become an important issue and its prognosis is poor. Heart failure is the condition where the impaired heart cannot pump enough blood to provide the needs of metabolic tissues and organs. Early diagnosis of heart failure is really crucial to determine the success of treatment and to prevent further myocardial dysfunction and worsening clinical symptoms. This condition can be worsened by ET-1, which triggers the secretion of IL-6 and TNF-α as pro inflammation factors. In Systolic Heart Failure, systolic function changes are accompanied by changes in diastolic function. Thus, the condition of systolic heart failure is worse than Diastolic Heart Failure. The purpose of this study is to assess the relationship of ET-1 with diastolic and systolic heart failure groups and the relationship of ET-1 with TNF-α and IL-6 as pro inflammation factors.METHODS: The design of this study was cross-sectional analysis on 62 patients with heart failure, grouped according to the classification of diastolic and systolic heart failure.RESULTS: A significant positive correlation of ET-1 with diastolic and systolic heart failure was found (p=0.008; r=0.324). A significant positive correlation was also found between ET-1 and IL-6 (p=0.001; r=0.393), but a less significant correlation was noted between ET-1 and TNF-α (p=0.201; r=-0.158).CONCLUSIONS: ET-1 has the strongest correlation (p=0.033) with prevalence ratio 3.930 and can differentiate between Diastolic and Systolic Heart Failure.KEYWORDS: Endothelin-1 (ET-1), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), heart failur
Visfatin and Adiponectin Have an Opposite Correlation with Inflammation and Metabolic Syndrome in Non-Diabetic Obese Indonesian Men
BACKGROUND: Along with the increase in obesity is a parallel increase in the prevalence of metabolic complications of obesity, often referred to as the metabolic syndrome (MetS). The role of adipose tissue in MetS has continued to evolve with the description of numerous secretory peptides from adipocytes named adipocytokines or adipokines. Recent studies have found visfatin as the regulation of inflammatory and immunomodulating prosesses, meanwhile adiponectin was known to have a potent anti-inflammatory properties. Here we try to assess the correlation between those two adipokines to MetS, via an inflammatory pathway.METHODS: This was a cross-sectional study on 128 non diabetic obese male subject (waist circumferences ≥90 cm). Visfatin and adiponectin were assessed by ELISA. Statistical analysis was performed using SPSS for Windows v.16.00 with signifcantly p<0.05. The correlations among biomarkers were assessed using Spearman's Rho test.RESULTS: This study showed a significant positive correlation between levels of visfatin and inflammatory markers TNF-α (r=0.22, p<0.005), and hsCRP (r=0.12, p=0.19), significant negative correlation between levels of adiponectin and TNF-α (r=-0.22-8, p<0.005-1), adiponectin and hsCRP (r=-0.14, p=0.11) and visfatin (r=-0.029, p<0.01). Plasma visfatin levels were increased along with the number MetS components, white plasma adiponectin showed inversely relation.CONCLUSION: Our present study has shown that visfatin has a proinflammatory properties and adiponectin has an anti-inflammatory properties, and how they have an opposite effects on MetS. Visfatin was found to have a positive correlaton while adiponectin was found to have a negative correlation with the number of MetS components.KEYWORDS: Obesity, Inflammation, Metabolic Syndrome, Adipocytokines, Visfatin, Adiponectin, TNF-α, hsCR