The Indonesian Biomedical Journal

13-24

Authors: Anna Meiliana, Andi Wijaya

BACKGROUND: Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity. CONTENT: Perivascular adipose tissue (PVAT) is a local deposit of adipose tissue surrounding the vasculature. PVAT is present throughout the body and has been shown to have a local effect on blood vessels. The influence of PVAT on the vasculature changes with increasing adiposity. PVAT similarly to other fat depots, is metabolically active, secreting a wide array of bioactive substances, termed ‘adipokines’. Adipokines include cytokines, chemokines and hormones that can act in a paracrine, autocrine or endocrine fashion. Many of the proinflammatory adipokines upregulated in obesity are known to influence vascular function, including endothelial function, oxidative stress, vascular stiffness and smooth muscle migration. Adipokines also stimulate immune cell migration into the vascular wall, potentially contributing to the inflammation found in atherosclerosis. Finally, adipokines modulate the effect of insulin on the vasculature, thereby decreasing insulin-mediated muscle glucose uptake. This leads to alterations in nitric oxide signaling, insulin resistance and potentially atherogenesis. SUMMARY: PVAT surrounds blood vessels. PVAT and the adventitial layer of blood vessels are in direct contact with each other. Healthy PVAT secretes adipokines and regulates vascular function. Obesity is associated with changes in adipokine secretion and the resultant inflammation of PVAT. The dysregulation of adipokines changes the effect of PVAT on the vasculature. Changes in perivascular adipokines secretion in obesity appear to contribute to the development of obesity-mediated vascular disease.

31-6

Authors: Dwi Yuniati Daulay, Suryani As'ad, Ali Aspar Mappahya, Andi Wijaya

BACKGROUND: Advanced glycation end products (AGE) and their receptor (RAGE) system play an important role in the development of diabetic vascular complications. Recently, an endogenous secretory RAGE (esRAGE) has been identified as a novel splice variant, which lacks the transmembrane domain and is secreted in human sera. Interestingly, it was reported that esRAGE binds AGE ligands and neutralizes AGE actions. Many studies have reported that diabetes mellitus correlates with vascular calcification event and increases progressively in uncontrolled diabetes. Matrix Gla Protein (MGP) is known to act as an inhibitor in vascular calcification. The aim of this study was to observe progress of vascular calcification in uncontrolled diabetes patient by biochemical markers MGP as inhibitor in vascular calcification, via mechanism of AGEs. METHODS: This study was an observational study with cross sectional design on adult type 2 diabetic male patients who were defined by the 2011 Indonesian diabetes mellitus consensus criteria. RESULTS: The results of this study showed that there was a positive significant correlation between esRAGE and HbA1C (r=0.651, p=0.009), and negative correlation between MGP and HbA1C (r=-0.465, p=0.081) in controlled diabetes group. In uncontrolled diabetes group there was a positive significant correlation between MGP and HbA1C (r=0.350, p=0.023), despite the fact esRAGE showed no significant correlation with HbA1C. There was no significant difference in level of esRAGE and MGP in controlled and uncontrolled diabetes group, but MGP showed lower level in uncontrolled diabetes group, contrary to esRAGE that had higher concentration. CONCLUSION: In diabetes condition, complications of vascular calcification are caused by the mechanism of increased AGE formation represented by esRAGE. In diabetes control it is very important to keep the blood vessels from complications caused by vascular calcification.

43-50

Authors: Doddy de Queljoe, Amelia Lorensia, Liana Widharta, Sugiarto Widjaja

BACKGROUND: Acute variceal haemorrhage is a complication of cirrhosis that can be life threatening. It is a pharmacist’s duty to ensure therapeutic and pharmaceutical care which is not only safe and effective for the patient but also is cost-effective in order to attain improvement of the patient’s quality of life. Therefore, pharmacoeconomic evaluation especially cost-effectiveness analysis (CEA), which compares costs and consequences of drug therapy, is needed. This study was aimed to evaluate the therapeutic cost-effectiveness of hematemesis-melena treatment in hepatic cirrhotic patients. METHODS: A total of 42 patients receiving vitamin K and vitamin K-transamin were studied retrospectively from patients’ medical records in 2 years and analyzed with cost-effectiveness grid and average cost-effectiveness ratio (ACER) based on Child-Turcotte-Pugh (CTP) Score. RESULTS: Cost-effectiveness grid was dominant for vitamin K in patients with CTP Score A. ACER analysis showed a lower score for vitamin K in all patients included CTP Score classification. There was no significant difference in duration of cessation of bleeding treatment in patients with vitamin K compared with vitamin K-transamin in patients with CTP Score A and B, while significant difference was found in patients with CTP Score C. CONCLUSION: Vitamin K appeared to be more cost effective as compared with vitamin K-transamin in all patients. The use of vitamin K had greater benefit than the combination with transamin in all patients and CTP Score classification, and thus should be considered as a primary therapy. Therefore, transamin addition as an alternative therapy for hepatic cirrhosis patients with hematemesis-melena should be considered.

59-64

Authors: Tri Nevita Margareth Panjaitan, Marita Kaniawati, Ilhamjaya Patellongi

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.