The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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The Relationship of Proinflammatory and Antiinflammatory Adipokines in the Development of Metabolic Syndrome in Centrally Obese Men
No full textBACKGROUND: The increased prevalence of obesity worldwide is correlated with increasing prevalence of metabolic syndrome. Studies of adipose tissue have been improved from an inert energy storage to a metabolic active endocrine organ. Adipokines secreted by this tissue play a role in maintaining metabolic homeostasis. The large mass of visceral fat tissue causing the imbalance of these adipokines leading to metabolic abnormality known as the metabolic syndrome (MetS). This study was performed to understand relationship of proinflammatory adipokines (resistin, TNF-α, RBP4 and visfatin) and anti-inflammatory adipokines (adiponectin and vaspin) in the development of MetS.METHODS: This was a cross-sectional study using 122 central obesity men with waist circumference >90 cm, age from 30–60 years old. Proinflammatory adipokines (resistin, TNF-α, RBP4 and visfatin) and anti-inflammatory adipokines (adiponectin and vaspin) was measured by ELISA method.RESULTS: The crosstab study showed that subjects who have >2 high proinflammatory adipokines (17.3%) has higher MetS prevalence (OR = 1.16; p = 0.72) compare to subjects with <2 high proinflammatory adipokines (14.8%), subjects with low anti-inflammatory adipokines profile (18.9%) has higher prevalence of MetS (OR=1.38; p=0.22) compare to subjects with high anti-inflammatory adipokines (13.7%) and the prevalence of MetS became 1.49 times higher (p=0.24) when we combine the high RBP4 and low adiponectin profile (21.1%) compare to subjects with low RBP4 and high adiponectin (14%).CONCLUSIONS: This study showed that each adipokine was not strong enough to induce MetS, so the interaction between proinflammatory and antiinflammatory adipokines were needed to induce a systemic metabolic abnormality. Thus, the adipokines equilibrium was important to prevent MetS especially in centrally obese subjects.KEYWORDS: obesity, metabolic syndrome, adipokines, resistin, TNF-α, RBP4, visfatin, adiponectin, vaspi
Correlation Between Visfatin, Insulin Resistance (Homeostasis Model Assesment of Insulin Resistance), Inflammation (High Sensitivity C-Reactive Protein) and HDL Cholesterol Concentration in Individuals with Visceral Obesity
No full textBACKGROUND: Visfatin is a novel adipokine secreted from visceral adipose tissue and has insulinomimetic properties. Visceral obesity is a risk factor for metabolic syndrome. Insulin resistance and inflammation are linked to visceral obesity and metabolic syndrome. Dysregulation of visfatin as an adipokine could play an important role in metabolic syndrome through insulin resistance and inflammation, or lower HDL cholesterol concentration. However, this need more evidence.METHOD: This was a crossectional study in 40 Indonesian obese men and 40 Indonesian obese women. Age: 30-60 years in men and 50-60 years for women, from February to March 2008 in Jakarta.RESULTS: No correlation between visfatin and hs-CRP as a marker of inflammation (r=0.190, p=0,101), or HOMA-IR as a marker of insulin resistance (r=-0.020, p=0.246). Suprisingly visfatin concentration is correlated with HDL Cholesterol (r=0.416, p=0.000).CONCLUSIONS: Visfatin plays an important role in metabolic syndrome through lipid metabolism. Positive correlation between visfatin and HDL cholesterol, was assumed that visfatin had a protective effect. Visfatin also known as as nicotinamide phosphoribosyltransferase (NAMPT) links Nicotinamide Adenine Dinucleotide (NAD) metabolism and raising of HDL Cholesterol. But the exact mechanisms need to be further studied.KEYWORDS: visceral obesity, metabolic syndrome, NAMPT, visfatin, HD
The Search for Biomarkers in Alzheimer's Disease
No full textBACKGROUND: As population demographic shift and the number of individuals with Alzheimer Disease (AD) continue to increase, the challenge is to develop targeted, effective treatments and our ability to recognize early symptoms. In view of this, the need for specific AD biomarker is crucial.CONTENT: In recent years it has become evident that CSF concentrations of some brain-specific proteins are related to underlying disease pathogenesis and may therefore aid clinical investigation. Among several, we have focused on three candidates that have been suggested to fulfil the requirements for biomarkers of AD: β-amyloid 42 (Aβ42), total Tau (T-tau) and tau phosphorylated at various epitopes (P-tau). An increasing number of studies suggest that supplementary use of these CSF markers, preferably in combination, adds to the accuracy of an AD diagnosis. More recently visinin – like protein (VLP-1), a marker for neuronal cell injury has been studied. CSF VLP-1 concentrations were 50% higher in AD patients than in the control population.SUMMARY: The number of studies aimed at the identification of new biomarkers for AD is expected to increase rapidly, not only because of the increasing insights into the pathological mechanisms underlying this disease, but also because new therapies have been developed or are under consideration now, which warrant an early and specific diagnosis for effective treatment of the patients.KEYWORDS: dementia, amyloid plaque, neurofibrillary tangels, amyloid β-peptide 42 (Aβ42), total tau (T-tau), phosphorylated tau (P-tau), visinin–like protein 1 (VLP-1)
Pro-inflammatory Profiles of Indonesian Adult Men with Central Obesity: A Preliminary Study on TNF-alpha, sTNFR-2 and IL-1beta
No full textBACKGROUND: Central obesity is closely associated with chronic inflammation, characterized by abnormal cytokine production such as IL-1β, tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor-2 (TNFR-2). Central obesity and chronic inflammation form a complex link with insulin resistance, leading to the development of type-2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Knowing the coinciding occurrence of chronic inflammation and central obesity, this study aimed to examine pro-inflammatory cytokine profiles of Indonesian adult men with central obesity.METHODS: This cross-sectional study recruited 80 apparently healthy Indonesian adult men, aged 23-53 years with waist circumference of 64-125 cm. This study was done in Jakarta. Measurements included clinical parameters like systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), aspartate amino transferase (AST), alanine amino transferase (ALT), creatinine, high sensitivity C-reactive protein (hsCRP), anthropometric parameters, namely weight, height and waist circumference; and pro-inflammatory cytokines TNF-α, soluble TNFR-2 (sTNFR-2) and IL-1β.RESULTS: Basic characteristics of the subjects showed linear increase in values of SBP, DBP and the serum concentrations of AST, ALT, FBG, GFR, hsCRP (p<0.005, respectively) with the degree of obesity. sTNFR-2 and IL-1 β positively correlated with hsCRP (r=0.277, p=0.013 and r= 0.257, p=0.022, respectively), WC (r=0.380, p=0.001 and r=0.400, p<0.001, respectively) and body mass index (BMI) (r=0.364, p=0.001 and r=0.399, p<0.001, respectively). Moreover, TNF-α did not show correlations with hsCRP, WC and BMI.CONCLUSION: There was a linear increase in the serum concentrations of sTNFR-2 and IL-1β in subjects with central obesity. Both pro-inflammatory markers, correlated with hsCRP, WC and BMI, but TNF-α did not. sTNFR-2 and IL-1β were, therefore, considered as valid biomarkers to indicate chronic inflammation in Indonesian adult men with central obesity.KEYWORDS: central obesity, TNF-α, soluble TNFR-2 (sTNFR-2), IL-1
Novel Biomarkers in Cardiovascular Disease: A Review
No full textBACKGROUND: The investigation of novel circulating serum and plasma biomarkers in patients with cardiovascular disease has been accelerating at a remarkable pace. New markers or tests are often presented too early to the medical profession, potentially leading to overuse and, thus, extra burden and costs to patients, the healthcare industry, and the economy. The challenge for clinicians and medical researchers is how to optimally apply existing and new markers/tests.CONTENT: Biomarkers are biological parameters that can be objectively measured and quantified as indicators of normal biologic processes, pathogenic processes, or responses to a therapeutic intervention. Typically thought of as disease process screening, diagnosing, or monitoring tools, biomarkers may also be used to determine disease susceptibility and eligibility for specific therapies. Cardiac biomarkers are protein components of cell structures that are released into circulation when myocardial injury occurs. They play a pivotal role in the diagnosis, risk stratification, and treatment of patients with chest pain and suspected acute coronary syndrome (ACS) as well as those with acute exacerbations of heart failure.SUMMARY: Active investigation has brought forward an increasingly large number of novel candidate markers but few have withstood the test of time and become integrated into contemporary clinical care because of their readily apparent diagnostic, prognostic, and/or therapeutic utility. With regard to the more novel biomarkers, careful thought is needed with regard to the appropriate target populations for discovery and validation, as well as the criteria used to sort out the contenders from the pretenders.KEYWORDS: biomarker, cardiovascular disease, atherosclerosis, acute myocardial infarction, heart failure, risk stratification, diagnosis, prognosi
Survivin S81A Enhanced TRAIL's Activity in Inducing Apoptosis
No full textBACKGROUND: Survivin is rarely expressed in normal healthy adult tissues, however, it is upregulated in the majority of cancers. Survivin, which belongs to IAPs family, has been widely reported to protect cells from apoptosis by inhibiting caspases pathway. Survivin’s mitotic activity is modulated by many kinases, and its phosphor status can also influence its ability to inhibit apoptosis. There are several important survivin’s phosphorylation sites, such as S20 and T34. We have continued our investigation on other potential survivin’s phosphorylation sites that could be important site for regulating survivin’s cyto-protection.METHODS: By assuming that S81 could be a potential target to modify activity of survivin, wild-type survivin (Survivin), antisense survivin (Survivin-AS), mutated-survivin Thr34Ala (Survivin-T34A) and mutated-survivin Ser81Ala (Survivin-S81A) were constructed and inserted into pMSCV-IRES-GFP vector with cytomegalovirus (CMV) promoter. Each retroviral product was produced in BOSC23 cells. LY294002 pretreatment and TRAIL treatment along with infection of retroviral products were performed in murine fibrosarcoma L929 cells. For analysis, flow cytometric apoptosis assay and western blot were performed.RESULTS: In our present study, survivin for providing cytoprotection was regulated by PI3K. The results showed that LY294002, an inhibitor of PI3K, effectively suppressed survivin-modulated cytoprotection in a TRAIL-induced apoptotic model. In addition, mutated survivin S81A showed marked suppression on survivin’s cytoprotection. Along with that, TRAIL’s apoptotic activity was enhanced for inducing apoptosis.CONCLUSION: We suggested that survivin could inhibit apoptosis through PI3K and S81A could be another potential target in order to inhibit Survivin-modulated cytoprotection as well as to sensitize efficacy of TRAIL or other related apoptotic inducers.KEYWORDS: apoptosis, survivin, TRAIL, S81A, L929, LY29400
Correlation of Ferritin and Transferrin Serum with hsCRP and F2-Isoprostane in Metabolic Syndrome
No full textBACKGROUND: The low inflammatory state that accompanies the Metabolic Syndrome (MetS) associates with the overexpression of oxidative stress. Ferritin and Transferrin serum are often used to measure iron status and their concentrations are altered in several metabolic conditions. We hypothesized that concentration of Ferritin and Transferrin serum increase in Metabolic Syndrome (MetS) and correlate with the inflammation and oxidative stress.METHODS: We studied 65 male MetS patients, aged 43.26±7.16 years. Iron metabolism was measured by concentration of Ferritin and Transferrin serums, while inflammatory and oxidative stress by high sensitivity C-reactive Protein (hsCRP) and F2-Isoprostane.RESULTS: Concentration of Ferritin 315.70±188.63 ng/L and Transferrin 2.36±0.31 g/L increased along with increasing components of MetS. Concentration of Ferritin serum had a positive correlation with hsCRP (r=0.220) and F2-Isoprostane (r=0.023).CONCLUSION: Serum concentration of Ferritin increased in the MetS and correlates with hsCRP and F2-Isoprostane.KEYWORDS: metabolic syndrome, ferritin, transferrin, hsCRP, F2-isoprostan
The Stem Cell Hypothesis of Aging
Get PDFBACKGROUND: There is probably no single way to age. Indeed, so far there is no single accepted explanation or mechanisms of aging (although more than 300 theories have been proposed). There is an overall decline in tissue regenerative potential with age, and the question arises as to whether this is due to the intrinsic aging of stem cells or rather to the impairment of stem cell function in the aged tissue environment.CONTENT: Recent data suggest that we age, in part, because our self-renewing stem cells grow old as a result of heritable intrinsic events, such as DNA damage, as well as extrinsic forces, such as changes in their supporting niches. Mechanisms that suppress the development of cancer, such as senescence and apoptosis, which rely on telomere shortening and the activities of p53 and p16INK4a may also induce an unwanted consequence: a decline in the replicative function of certain stem cells types with advancing age. This decrease regenerative capacity appears to pointing to the stem cell hypothesis of aging.SUMMARY: Recent evidence suggested that we grow old partly because of our stem cells grow old as a result of mechanisms that suppress the development of cancer over a lifetime. We believe that a further, more precise mechanistic understanding of this process will be required before this knowledge can be translated into human anti-aging therapies.KEYWORDS: stem cells, senescence, telomere, DNA damage, epigenetic, agin
The Differences of Food Compositions in Adolescent Metabolic Syndrome in Malang
No full textBACKGROUND: Obesity, especially obesity in adolescent, is a worldwide health problem needing much of our attention because it can continue to be obesity in adulthood. About 50% obese adolescents grew up to be obese adults. It was a concern since it is one of risk factor associated with cardiovascular events including hypertension, dyslipidemia, insulin resistance and stroke. Visceral obesity is correlated with diabetogenic, atherogenic, prothrombotic, pro-inflammation, and abnormal metabolism. The objective of this study was to assess the prevalence of obese adolescents in Malang and to identitfy the differences in food compositions between metabolic syndrome and non-metabolic adolescents.METHODS: Prevalence of obesity was determined by assessing BMI in 20 Senior and Junior High Schools. Metabolic syndrome was diagnosed using IDF criteria; waist circumference of >80cm and >90cm for female and male, respectively, and increased triglyceride and decreased HDL concentration levels. The food composition was assessed using food recalls, and then regression linier test was done to define the correlation between food intake and the components of metabolic syndrome.RESULTS: The prevalence of adolescent obesity in Malang had reached 3.32%, with the prevalence of obesity in male subjects higher than in female subjects, i.e. 54.1% compared to 45.9%. The boys had higher mean for height and weight than the girls did, however, the BMI was higher in girls rather than boys. The difference of fat in food composition was significantly higher for the metabolic groups (p=0.031), but the carbohydrate did not significantly differ between the two groups (p=0.407).CONCLUSIONS: The prevalence of adolescent obesity in Malang had reached 3.32%, with the prevalence of 54.1% in male and 45.9% in female. From the statistics test, fat intake showed a significant difference between metabolic syndrome and non-metabolic syndrome groups, but other food compositions didn’t.KEYWORDS: obesity, metabolic syndrome, adolescen
Brown Adipose Tissue: A New Target for Antiobesity Therapy
No full textBACKGROUND: Human fat consist of white and brown adipose tissue (WAT and BAT). Though most fat is energy-storing WAT, the thermogenic capacity of even small amounts of BAT makes it an attractive therapeutic target for inducing weight loss through energy expenditure.CONTENT: Over the past year, several independent research teams used a combination of positron-emission tomography and computed tomography (PET/CT) imaging, immunohistochemistry and gene and protein expression assays to prove conclusively that adult humans have functional BAT. BAT is important for thermogenesis and energy balance in small mammals and its induction in mice promotes energy expenditure, reduces adiposity and protects mice from diet-induced obesity. The thermogenic capacity of BAT is impressive. In humans, it has been estimated that as little as 50g of BAT could utilize up to 20% of basal caloric needs if maximally stimulated.SUMMARY: The obesity pandemic requires new and novel treatments. The past few years have witnessed multiple studies conclusively showing that adult humans have functional BAT, a tissue that has a tremendous capacity for obesity-reducing thermogenesis. Novel therapies targeting BAT thermogenesis may be available in the near future as therapeutic options for obesity and diabetes. Thermogenic ingredients may be considered as functional agents that could help in preventing a positive energy balance and obesity.KEYWORDS: brown adipose tissue, thermogenesis, energy expenditure, antiobesity therap