The Indonesian Biomedical Journal

129-42

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Aging per se is a risk factor for reduced cardiac function and heart diseases, even when adjusted for aging-associated cardiovascular risk factors. Accordingly, aging-related biochemical and cell-biological changes lead to pathophysiological conditions, especially reduced heart function and heart disease. CONTENT: Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1a and PGC-1b in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/ metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging. SUMMARY: The aging myocardium with telomere shortening and accumulation of senescent cells restricts the tissue regenerative ability, which contributes to systolic or diastolic heart failure. Moreover, patients with ion channel defects might have genetic imbalance caused by oxidative stress-related accelerated telomere shortening, which may subsequently cause sudden cardiac death. Telomere length can serve as a marker for the biological status of previous cell divisions and DNA damage with inflammation and oxidative stress. It can be integrated into current risk prediction and stratification models for cardiovascular diseases and can be used in precise personalized treatments.

147-52

Authors: Siska Mayasari Lubis, Miswar Fattah, Harun Alrasyid Damanik, Jose Rizal Latief Batubara

BACKGROUND: Childhood obesity is associated with the risk of adult obesity and obesity-related chronic disease. The fat mass and obesity-associated gene (FTO) rs9939609 variant are of particular interest because of its association with body mass index (BMI) and obesity-related phenotypes. This study was conducted to investigate the association between FTO gene rs9939609 variant with early onset obesity among Bataknese and Chinese children in Medan, Sumatera Utara, Indonesia. METHODS: The case-control study was carried out at 10 elementary schools in Medan. There were 212 children recruited; 56 early onset obesity and 61 control Bataknese and 49 early onset obesity and 46 control Chinese children. This study included a questionnaire, anthropometric measurements, and blood test analysis. rs9939609 polymorphism genotyping was performed using RT-PCR. Logistic regression, odds ratio (OR) and 95% confidence interval (CI) were calculated to determine the risk of obesity associated with the risk alleles, p<0.05 was considered as statistically significant. RESULTS: This study found a significant association between rs9939609 and early onset obesity in Chinese children(p=0.01), but not in Bataknese. The frequency of AA genotype was lower in the early onset obesity than in the normal weight children, while an OR of 0.69 showed that this genotype may protect against weight gaining and that the TT genotype may predispose to obesity. CONCLUSION: We concluded that the FTO gene rs9939609 is associated with early onset obesity in Chinese ethnicity but not in Bataknese.

160-4

Authors: Ferry Sandra, Karina Febriani Hudono, Amelia Astriani Putri, Chantika Amardhia Paramita Putri

BACKGROUND: Caffeic acid has been shown to induce apoptosis in MG63 osteosarcoma cells. Along with the apoptotic induction, caffeic acid was shown to activate caspase-8, -9 and -3. However, the role of caspase in mediating caffeic acid-induced apoptosis in MG63 cells are not clear yet. In this study, caspase role was further investigated by inhibiting caspase activity in the caffeic acid-induced apoptosis system in the MG63 cells. METHODS: MG63 cells were cultured, starved, pretreated with/without Z-VAD FMK and treated with/without 10 μg/mL caffeic acid. To quantify the number of apoptotic MG63 cells, Sub-G1 method was performed. The caffeic acid-induced apoptotic morphology was confirmed with 4',6-diamidino-2-phenylindole (DAPI) staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Meanwhile, to detect apoptotic underlying mechanism, immunoblotting was performed to detect caspase-8, -9 and -3. RESULTS: The MG63 cells were significantly induced into apoptosis with the treatment of 10 μg/mL caffeic acid for 48 hours. However, pretreatment of 100 μM Z-VAD-FMK, a pan caspase inhibitor, for 2 hours, the percentage of apoptotic MG63 cells was significantly diminished. The apoptotic phenomenon induced by caffeic acid as well as the inhibition of Z-VAD-FMK were confirmed by DAPI staining and TUNEL assay. Cleaved caspase-8, -9 and -3 were formed markedly upon the treatment of caffeic acid. Pretreatment of 100 μM Z-VAD-FMK could inhibit the cleaved caspase-8, -9 and -3. CONCLUSION: Taken together, caffeic acid has the potential to induce apoptosis in MG63 cells, specifically through the caspase signaling pathway.

73-7

Authors: Asri Hendrawati

BACKGROUND: Increasing free radicals and oxidative stress due to chronic hyperglycemia in type-2 diabetes mellitus (DM) promotes the activity of endogenic antioxidative genes. Nuclear factor erythroid 2-related factor 2 (Nrf2) expression and activity are important to regulate the production of endogenic antioxidative enzymes. CONTENT: Normally, Nrf2 is bound by protein Kelchlike ECH-associated protein-1 (Keap1) in the cytosol. Stimulation from oxidative stress causes the release of Nrf2 from Keap1. When activated, Nrf2 enters the nucleus and activates the antioxidant response element (ARE). This will further increase the production of antioxidative enzymes, such as catalase, nitrite oxydase and heme oxygenase-1. The discovery of oxidative stress, as the cause of complications in DM, gives rise to the idea of developing a treatment which can increase the expression and activity of Nrf2, one of which is a flavonoid antioxidant. SUMMARY: Currently, nuclear factor erythroid 2-related factor 2 is an important target in the therapy of DM.

84-90

Authors: Djaja Rusmana, Roro Wahyudianingsih, Mariska Elisabeth, Balqis, Maesaroh, Wahyu Widowati

BACKGROUND: Normal metabolism of oxygen and exogenous factors constantly generate free radicals which could be harmful to the human body. Human need antioxidants to provide protection against free radicals, thus plants are a good source of natural antioxidants. Phyllanthus niruri (P. niruri) has been known to possess several medicinal properties and contain numerous active phytochemical. In this research, we conducted phytochemical screening and antioxidant assay of P. niruri extract along with the compounds rutin and quercetin, which are flavonoids possessing medicinal properties. This study was conducted to determine P. niruri, rutin and quercetin as antioxidant. METHODS: In this study, qualitative phytochemical screening was performed to detect phenol, flavonoid, saponin, tannin, steroid/triterpenoid, terpenoid and alkaloid in P. niruri extract. Antioxidant analysis of P. niruri, rutin and quercetin was conducted using total measured phenolic content, 2,2-diphenyl-1-picrylhydrazil (DPPH), 2,2’-azinobis-3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) assays. RESULTS: The study revealed that P. niruri extract contained saponin, phenol, flavonoid and tannin based on phytochemical screening. In DPPH and ABTS assays quercetin possessed highest antioxidant activity with IC50 value of 0.55 and 1.17 μg/ml respectively. Meanwhile, P. niruri extract showed the highest FRAP activity which was 373.95 μM Fe(II)/μg extract. Rutin possessed the lowest antioxidant activity in all antioxidant assays. CONCLUSION: This study confirmed that P. niruri extract and quercetin have great potential as a natural antioxidant source.

99-105

Authors: Yenny Surjawan, Hwee Lian Tan, Rahajuningsih Dharma Setiabudy, Wiwik Rositawati

BACKGROUND: The mutation spectrums of hemoglobinopathy are different among populations that yield a different result of erythrocyte indices. Calculation of erythrocyte indices with some formula has been reported to differentiate between hemoglobinopathy and non-hemoglobinopathy, but its cut-off should be recalculated specific for each population to gain a better sensitivity and specificity. We aimed to evaluate red blood cell count (RBC), Mentzer index, red cell distribution width (RDW), RDW index (RDWI), Shine and Lal index (S&L) and Green and King index (G&K) to screen hemoglobinopathy in Indonesia. METHODS: A retrospective cross-sectional study was performed on 202 subjects. The diagnosis of hemoglobinopathy was determined based on the results of complete blood count (CBC) data, high-performance liquid chromatography (HPLC) and Hemoglobin H (HbH) inclusion body. The ferritin concentration was checked to determine the status of iron. The erythrocytes indices were analyzed and calculated to predict hemoglobinopathy. RESULTS: A total 202 subjects who met the criteria were involved in this study. Fifty percent showed pure hemoglobinopathy and 4% showed a combination of thalassemia and hemoglobinopathy. The hemoglobin concentration and RBC were significantly higher, and the mean corpuscular volume (MCV) and RDW were significantly lower in hemoglobinopathy compared to iron deficiency. The difference was not significant if the hemoglobinopathy was combined with iron deficiency. By this study's cut-off, the G&K and RDWI showed the highest accuracy, sensitivity, and specificity. CONCLUSION: The new cut-off of erythrocyte index and its calculation to screen hemoglobinopathy in Indonesia showed a higher sensitivity and specificity, especially for G&K and RDWI with cut-off 73 and 228, respectively. The presence of iron deficiency in hemoglobinopathy could decrease the sensitivity.

17-22

Authors: Djanggan Sargowo, Olivia Handayani

BACKGROUND: The association between elevated triglycerides and cardiovascular risk has been extensively studied. The elevated level of triglycerides occurs through abnormalities in hepatic very low-density lipoprotein (VLDL) production and intestinal chylomicron synthesis, dysfunctional lipoprotein lipase (LPL)-mediated lipolysis or impaired remnant clearance. CONTENT: Hypertriglyceridemia (HTG) commonly leads to a reduction in high-density lipoprotein (HDL) and increase in atherogenic small dense low-density lipoprotein (LDL) cholesterol, called the atherogenic dyslipidemia (AD). Triglycerides may also stimulate atherogenesis by mechanisms, such excessive release of free fatty acids, and production of pro-inflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia (HTG) and high concentration of triglyceride-rich lipoprotein (TRL) as causal risk factors for cardiovascular disease. Therefore, lipid management is crucial in reducing cardiovascular risk. Combination of lipid lowering drug therapy may be needed to achieve both LDL and non-HDL cholesterols treatment goal for cardiovascular disease prevention in patients with elevated triglyceride levels, particularly those with triglyceride ≥500 mg/dL. SUMMARY: LDL and non-HDL cholesterol can be a promising target therapy in HTG. Additional clinical outcomes data are needed to provide a more evidence-based rationale for clinical lipid management of hypertriglyceridemic patients.

29-34

Authors: Idar Mappangara, Magma Purnawan Putra, Khalid Saleh

BACKGROUND: Many studies showed the association between peripheral artery disease (PAD) and coronary artery disease (CAD). The anklebrachial index (ABI) was a simple, noninvasive, and not expensive test that showed high sensitivity and specificity in the diagnosis of PAD. Previous studies showed PAD correlation with the number of coronary artery lesions and higher complexity of the lesions. These correlations might contribute to worse cardiovascular outcomes, especially acute coronary syndrome (ACS) cases. Aim of this study is to evaluate the correlation abnormal ABI with the risk of ACS patients to have multivessel coronary artery lesions. METHODS: This was a retrospective analytical casec ontrol study. The data were taken from Dr. Wahidin Sudirohusodo Hospital medical records from November 2015 to February 2016. The inclusion criteria were (>18 years old) patients with ACS who had underwent ABI examination and coronary angiography. RESULTS: The prevalence of patients with ST-elevation myocardial infarction (STEMI) was lower than non-ST elevation ACS (NSTE-ACS). The prevalence of patients with abnormal ABI was 43.3% and patients with multivessel CAD was 65%. Male patients dominated the ACS population with 73.3%, about half of patients were smoking, and 86.7% had dyslipidemia. Patients with abnormal ABI and multivessel disease had greater number than patients with normal ABI (p=0.025). Analysis with binary logistic regression model showed abnormal ABI (odd ratio [OR] 4.83; p=0.021) and male sex (OR 19.35; p=0.010) were associated with greater risk of multivessel CAD. CONCLUSION: An abnormal ABI is associated with greater risk of multivessel CAD in ACS patients.

43-8

Authors: Octaviani, Agus Rahardjo, Untung Alifianto, Setya Anton

BACKGROUND: Peritoneal adhesion is a side effect of abdominal surgery that often occurs. Many efforts were made in abdominal surgery to prevent or minimize the occurrence of this adhesion. One way to reduce the risk of bowel adhesions is through washing peritoneum method, so the differences in the use of washing solution on the incidence of adhesions after laparotomy surgery need to be investigated. The objective of this study is to determine differences in the effect of using sterile water and normal saline for washing irrigation to peritoneal adhesions after laparotomy in white rats. METHODS: This was an experimental study. Thirty-two sample of white rats were divided into two groups, group A and Group B, each group consists of 16 rats. Group A got washing using normal saline and group B got washing using sterile water for irrigation in laparotomy procedure to assess the peritoneal adhesion microscopically after relaparotomy. RESULTS: This study was conducted in April-May 2016. The founding of peritoneal adhesion after laparotomy in white rats using sterile water for irrigation in grade 1 were seven samples, grade 2 were five samples and grade 3 were four samples. Meanwhile, the founding of peritoneum adhesion after laparotomy using normal saline grade 1 are two samples, grade 2 are five samples, and grade 3 are nine samples. Statistically, significant differences were found (p<0.05). CONCLUSION: Some risk factors can lead to adhesion, such as trauma surgery, tissue ischemia, infection blood and foreign body irritating. Intraperitoneal irrigation with sterile water for irrigation is better than the use of normal saline in preventing peritoneal adhesion.