The Indonesian Biomedical Journal (Prodia Education and Research Institute)
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    431 research outputs found

    Vascular Endothelial Growth Factor Level as A Predictor of Hepatocellular Carcinoma in Liver Cirrhosis Patients

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    BACKGROUND: Alpha-fetoprotein (AFP) has been used for hepatocellular carcinoma (HCC) diagnosis and screening, however, AFP has poor specificity. The extensive hypervascularity associated with HCC could be driven in part by the pro-angiogenic factor known as vascular endothelial growth factor (VEGF). Furthermore, invasiveness of certain HCC lesions has recently been linked to high levels of VEGF. Therefore, circulating VEGF levels of patients with liver cirrhosis (LC) and HCC were investigated and analysed.METHODS: An analytical cross sectional study was designed. Diagnosis of HCC and LC was performed using clinical criteria and findings obtained from B-mode ultrasonography (USG), computed tomography (CT) angiography, or magnetic resonance imaging (MRI). Blood were collected intravenously from all subjects. Obtained serum and plasma were stored in -80°C for following analyses: hepatitis B surface antigen (HBSAg), hepatitis C virus (HCV), alanine aminotransferase (ALT), total bilirubin, albumin, VEGF and AFP.RESULTS: Levels of VEGF and AFP were significantly higher in HCC group compared with LC group with p = 3.05 x 10-6 and p = 8.74 x 10-5, respectively. There was a significant positive correlation (p=0.029, r=0.309) between VEGF level and tumor size in HCC group. The area under curve (AUC) for VEGF level in HCC and LC groups was 0.771. In the level of median 435.6 pg/mL VEGF, the sensitivity was 50% and specificity was 86%. In the level of 199.99 pg/mL VEGF the sensitivity was 74% and specificity was 76%.CONCLUSION: The present findings suggested that VEGF level could be a useful marker for the presence of HCC in patients with LC.KEYWORDS: hepatocellular carcinoma, HCC, liver cirrhosis, LC, vascular endothelial growth factor, VEGF, alpha-fetoprotein, AFP

    Brown and Beige Fat: Therapeutic Potential in Obesity

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    BACKGROUND: The epidemic of obesity and type 2 diabetes presents a serious challenge to scientific and biomedical communities worldwide. There has been an upsurge of interest in the adipocyte coincident with the onset of the obesity epidemic and the realization that adipose tissue plays a major role in the regulation of metabolic function.CONTENT: Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible ‘brown-like’ adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.SUMMARY: The complexity of adipose tissue presents numerous challenges but also several opportunities for therapeutic intervention. There is persuasive evidence from animal models that enhancement of the function of brown adipocytes, beige adipocytes or both in humans could be very effective for treating type 2 diabetes and obesity. Moreover, there are now an extensive variety of factors and pathways that could potentially be targeted for therapeutic effects. In particular, the discoveries of circulating factors, such as irisin, fibroblast growth factor (FGF)21 and natriuretic peptides, that enhance brown and beige fat function in mice have garnered tremendous interest. Certainly, the next decade will see massive efforts to use beige and brown fat to ameliorate human metabolic disease.KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, adipose organ, thermogenesis, energy expenditur

    Pathomechanism of Renal Damage in Type 2 Diabetes Mellitus Patients

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    BACKGROUND: Hyperglycemia in diabetic patients cause both chronic inflammation and extracellular matrix accumulation that can lead to progressive renal damage. Albumin, Gammaglutamytransferase (GGT) and clusterin in urine are markers to detect damage in glomerulus, cell of the tubules and proximal tubules, respectively.METHODS: This study aimed to evaluate the pathomechanism of haemoglobin A1c (HbA1c), albumin, GGT, clusterin, type IV collagen in urine, and high sensitivity C-reactive protein (hsCRP) in type 2 diabetes mellitus (DM) patients. The study was a cross sectional study involving 82 subjects consisting of 36 males and 46 females, 35-65 years old, divided into 3 groups: uncontrolled DM, controlled DM and non DM. Data were obtained from interviews, physical examinations (weight, height, blood pressure) and laboratory examinations (HbA1c, serum glutamic oxaloacetic (SGOT), serum glutamic pyruvic (SGPT), creatinine, hsCRP, urinary albumin, urinary GGT, urinary clusterin, and urinary type IV collagen). Statistical analysis was performed for correlation, difference and cross tabulation tests.RESULTS: The study results showed there were significant differences (p<0.05) between uncontrolled DM group compared with controlled DM and non DM groups in HbA1c, ratio of urinary type IV collagen and ratio of urinary albumin. However, there were no significant differences between controlled DM and non DM groups. There were positive significant correlations between HbA1c with hsCRP (r=0.223, p<0.05), HbA1c with ratio of urinary type IV collagen/creatinine (r=0.563, p<0.001), HbA1c with ratio of urinary albumin/creatinine (r=0.263, p<0.05), and ratio of urinary type IV collagen/creatinine with ratio urinary albumin/creatinine (r=0.613, p<0.001).CONCLUSION: Results of this study indicated that albumin and type IV collagen in urine play a role in renal damage caused by uncontrolled glucose level in subjects with type 2 DM. The increased concentration of both HbA1c and urinary type IV collagen indicates increased risk factor of glomerulus damage. Urinary type IV collagen is likely to be future potential marker for early detection of renal damage.KEYWORDS: renal damage, HbA1c, hsCRP, type IV collagen, GGT, clusterin, diabetes mellitu

    Correlation of Oxidized-LDL, Resistin and Interleukin-1 Beta in Centrally Obese Men

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    BACKGROUND: Obesity is one of serious health problems, which increases the risks of cardiovascular disease, type 2 diabetes mellitus, and cancers. It is strongly associated with changes in the physiological function of adipose tissue, leading to altered secretion of adipokines and activation of inflammatory signaling pathways. This study was aimed to investigate the correlation of resistin, interleukin-1 beta (IL-1β), and oxidized low-density lipoprotein (OxLDL) in centrally obese men.METHODS: The research was conducted with a crosssectional design involving 68 centrally obese men aged 31 to 60 years old, with waist circumference (WC) >90 cm. All subjects fulfilled the exclusion criteria. Anthropometric parameters, creatinine, estimated glomerular filtration rate (eGFR), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), and high sensitivity C-reactive protein (hs-CRP) were measured. Serum concentrations of resistin, IL-1β and OxLDL were measured by enzyme-linked immunosorbent assay.RESULTS: The study results showed there was a significant correlation of WC-OxLDL (r=0.235; p=0.030) and some correlation of WC-resistin (r=0.201; p=0.050). However, we observed no significant correlation of IL-1β-OxLDL (r=0.042; p=0.369), resistin-OxLDL (r=-0.072; p=0.285) and WC-IL-1β (r=-0.042; p= 0.367).CONCLUSION: Our data show a relationship between WC and OxLDL, but the mechanism does not appear to be directly related to resistin or IL-1β.KEYWORDS: resistin, IL-1β, OxLDL, atherosclerosi

    Correlation between Extracellular Heat Shock Protein 60 (exHSP60) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in Non Diabetic Men

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    BACKGROUND: Adipose tissue expansion in obesity leads to abnormal adipocyte function, chronic low grade inflammation, primary reticulum stress, and mitochondrial stress. This induces mitochondrial unfolded protein response (UPRmt) that selectively upregulates mitochondrial chaperone protein. Heat shock Protein 60 (HSP60) is the primary chaperone in mitochondrial matrix. Inflammatory stress promotes HSP60 released from adipocytes and induces insulin resistance. In this study we attempted to investigate the correlation between exHSP60 and HOMA-IR in men with different ranges of waist circumference (WC).METHODS: This study was an observational cross sectional study carried out on 141 non diabetic men, aged 30-55 years old, who were divided into three groups based on WC; WC ≤90 cm, 90 cm 100 cm. Fasting plasma glucose, triglyceride, HDL-C, hsCRP, HSP60 serum and anti-HSP60 antibody, serum IL-1β serum, insulin, were examined. For statistical analysis, Kolmogorov-Smirnov and Spearman’s correlation analysis were conducted.RESULTS: There were a significant correlation between exHSP60 and HOMA-IR (r=0.281; p=0.041) in WC ≤ 90 cm group; and a negative significant correlation between exHSP60 and HOMA-IR (r=-0.508; p=0.007) in WC > 100 cm group.CONCLUSION: This study showed that there was a dynamic correlation between exHSP60 and HOMA-IR in WC ≤ 90 cm group compared with WC > 100 cm group. We also found inverse correlation patterns between exHSP60 and HOMA-IR, and between anti-HSP60 antibody and HOMA-IR in non diabetic subjects.KEYWORDS: obesity, insulin resistance, mitochondrial stress, exHSP60, hsCRP, HOMA-I

    The Role of Free Radicals and Antioxidant in Abortion

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    BACKGROUND: Free radicals and antioxidant exist in balance under normal condition. In prooxidant condition, excessive free radicals can initiate a state of oxidative stress (OS) followed by capillary endothelial cell damage, a process involved in the pathophysiology of abortion.CONTENT: Abortion is a common complication of pregnancy and occurs in 25% of women. Many factors can cause abortion including fetal factor, implantation process and hormonal status. Combination those factors with OS influence the entire reproductive life of a woman. Antioxidant can neutralize free radicals and used to reduce OS especially in recurrent abortion.SUMMARY: Antioxidant therapy is a very interesting field in abortion especially used as prevention approach mainly caused by the high cost of infertility treatment methods.KEYWORDS: free radical, antioxidant, abortio

    Correlation of Progranulin, Granulin, Adiponectin and Vaspin with Metaflammation (hs-CRP) in Indonesian Obese Men

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    BACKGROUND: Obesity is closely related to chronic, low grade systemic inflammation (metaflammation) and it leads to further metabolic complications such as hypertension, atherosclerosis, and type 2 diabetes due to the adipocytokine imbalance. This study was carried out to assess the correlation between progranulin, granulin, adiponectin and visceral adipose tissue-derived serine protease inhibitor (Vaspin) with metaflammation (high sensitivity C-reactive protein (hs-CRP)) in centrally obese men.METHODS: This study was observational with a cross sectional design involving 60 men aged 30-60 years, consisted of 43 obese men (waist circumference (WC) ≥90 cm) and 13 non obese men (WC 105 cm.CONCLUSION: We found metaflammation (hs-CRP) was significantly correlated with Vaspin, but not with progranulin, granulin and adiponectin, in obese men. We suggest the possibility of a dynamic expression of adipokines related to WC that are subjected to adipocytes hypertrophy-hyperplasia phenomenon.KEYWORDS: progranulin, granulin, adiponectin, Vaspin, hs-CRP, metaflammation, central obesit

    Altered Level of Soluble fms-like Tyrosine Kinase 1 (sFlt1) and Hypoxia Inducible Factor-1alpha (HIF-1alpha) in Normotensive Pregnancy and Preeclampsia

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    BACKGROUND: Preeclampsia is still a significant problem worldwide. Of the many suggested mechanisms of its pathogenesis, the latest one is the balance of angiogenic factor and its relationship with hypoxia factors. The objective of this study was to observe changes or dynamic process of soluble fms-like tyrosine kinase 1 (sFlt1) as anti-angiogenic factor and hypoxia inducible factor 1-alpha (HIF-1α) as hypoxia marker in normotensive pregnancy and preeclampsia in mid-term and full-term pregnancies.METHODS: A cohort study was conducted on 36 normotensive subjects, first examination was conducted at 20-28 weeks of gestation. Then second examination was conducted at the time of preeclampsia diagnosed or full-term pregnancy. Preeclampsia was characterized by hypertension of systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, with two readings separated in 4-6 hours period, and/or proteinuria with urine dipstick of ≥1+ or ≥300 mg per 24 hours. Examinations of sFlt-1 and HIF-1α were done by enzyme-linked immunosorbent assay method. Statistical analysis was done using a significance level of p<0.05.RESULTS: Concentration of sFlt-1 was elevated in normotensive pregnancy and preeclampsia. Higher sFlt-1 concentration elevation was seen in preeclamptic group comparing to normotensive group, although not significant. This finding was related to the fact that investigated subjects were mostly developing mild preeclampsia merely. Comparing to normotensive group, preeclamptic group had higher HIF-1α concentration-per-week elevation, but not significant. There was a positive correlation between concentrations of sFlt-1 and HIF-1α, but not significant.CONCLUSION: sFlt-1 concentration elevation was correlated with preeclampsia. Therefore comparing to averages, changes of sFlt-1 concentrations were more important. Concentrations of HIF-1α and sFlt-1 were positively correlated.KEYWORDS: sFlt-1, HIF-1α, preeclampsia, normotensio

    Pathomechanism of Insulin Resistance in Men with Central Obesity: Correlation of GGT, GPx, hs-CRP and Plasma Total Cysteine

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    BACKGROUND: Gamma glutamyltransferase (GGT) was reported recently to be associated with inflammation, oxidative stress and increased amino acid. However, role of GGT in insulin resistance pathomechanism is not exactly known. Therefore correlation of GGT with inflammation, oxidative stress and elevated amino acid, in men with central obesity need to be confirmed.METHODS: A cross-sectional study was designed. Men with central obesity were recruited and selected. Anthropometric parameters, creatinine, hs-CRP, fasting glucose, fasting insulin, glutathione peroxidase (GPx) activity, GGT, plasma total cysteine (tCys) and fatty liver were measured. Subjects were then divided in 4 groups based on waist circumference (WC) and fatty liver: Group I: WC ≤100 cm, without fatty liver; Group II: WC ≤100 cm, with fatty liver; Group III: WC >100 cm, without fatty liver; Group IV: WC >100 cm, with fatty liver. All biochemical characteristics in each group were then statistically analyzed.RESULTS: Seventy-two men with central obesity were selected. Numbers of subjects in each group were: Group I: n=33; Group II: n=5; Group III: n=17; Group IV: n=17. We found significant difference of HOMA-IR between Group I and IV, significant correlation between GGT and HOMAIR, and significant negative correlation between tCys with HOMA-IR in Group IV.CONCLUSION: GGT was significantly correlated with HOMA-IR in men with WC >100 cm and fatty liver. Further investigation with more subjects is necessary to determine clear GGT cut-off to distinguish subjects with fatty liver and insulin resistance.KEYWORDS: GGT, hs-CRP, GPx, tCys, HOMA-IR, insulin resistanc

    Macrophage Polarization in Metabolism and Metabolic Disease

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    BACKGROUND: Obesity is now recognized as the main cause of the worldwide epidemic of type 2 diabetes. Obesity-associated chronic inflammation is a contributing key factor for type 2 diabetes and cardiovascular disease. Numbers of studies have clearly demonstrated that the immune system and metabolism are highly integrated.CONTENT: Macrophages are an essential component of innate immunity and play a central role in inflammation and host defense. Moreover, these cells have homeostatic functions beyond defense, including tissue remodeling in ontogenesis and orchestration of metabolic functions. Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to interferons (IFNs), toll-like receptor (TLR), or interleukin (IL)-4/IL-13 signals, macrophages undergo M1 (classical) or M2 (alternative) activation. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1, M2 or M2-like polarized activation.SUMMARY: In response to various signals, macrophages may undergo classical M1 activation (stimulated by TLR ligands and IFN-γ) or alternative M2 activation (stimulated by IL-4/IL-13); these states mirror the T helper (Th)1–Th2 polarization of T cells. Pathology is frequently associated with dynamic changes in macrophage activation, with classically activated M1 cells implicate in initiating and sustaining inflammation, meanwhile M2 or M2-like activated cells associated with resolution or smoldering chronic inflammation. Identification of the mechanisms and molecules that are associated with macrophage plasticity and polarized activation provides a basis for macrophage centered diagnostic and therapeutic strategies.KEYWORDS: obesity, adipose tissue, inflammation, macrophage polarizatio

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