The Indonesian Biomedical Journal

225-39

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Along with its increased prevalence, in the past decade, cancer had joined the list of chronic debilitating diseases. Nutrition become substantial aspects, due to its time-dependent effect to modulate inflammation thus trigger carcinogenic effects by altering the immune check point. Thus, nutrition contributes to the progression and therapeutic response of cancer, both in human or animal models. CONTENT: Meat is well favored food with appreciable appealing. Due to its high nutritional values it plays a central role in human development. Meat or meat derivate are important sources of proteins, minerals and vitamins. Their nutritional importance is worth compare to their economic impact but recent publication of WHO has set the social alarm about the relationship between red and/or processed meat consumption and cancer. On the other side, some natural or biologic agents may inhibit or reverse tumor growth. Some phytochemical agents including curcumin, resveratrol, lycopene, folates and tea polyphenols clinically proved to tune the signaling pathways regulating cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents. SUMMARY: Recent studies on chemopreventive agents involves a wide range of molecules, natural (plants, fruits and vegetables) or synthetic will provide better insights for cancer early pathogenesis, important end-point biomarker, and finally potential for reducing the burden of cancer.

247-56

Authors: Nasar Alwahaibi, Siti Balkis Budin, Zariyantey Abdul Hamid, Jamaludin Mohamed, Jalifah Latip, Norzamzurina Binti Ismail, Alefee Bin Ayatillah, Fatmah Ali Matough

BACKGROUND: Tocotrienol-rich fraction (TRF) from palm oil has been shown to exhibit potent antioxidative properties in various pathological conditions. This study aimed to determine the antioxidative properties of TRF on the plasma and erythrocyte membrane lipids composition in streptozotocin-induced diabetic rats. METHODS: Male Sprague-Dawley rats (n=40) were divided randomly into four groups of 10, which were a normal group, a normal group with TRF, a diabetic group, and a diabetic group with TRF. Following four weeks of treatment, lipids compositions in the plasma and erythrocyte membrane were investigated. RESULTS: TRF significantly reduced the plasma total cholesterol, to that in the diabetic group. In addition, supplementation of TRF was able to reduce the very low density lipoprotein cholesterol (VLDL-C), triglycerides levels in treated diabetic rat although no significant different was observed when compared with untreated diabetic rats alone. Furthermore, TRF supplementation showed increased the levels of phosphatidylinositol, phosphatidylserine, and total phospholipid levels in diabetic rats. However, the linoleic acid (18:2) levels were reduced in diabetic rats compared to the control group, and the eicosadienoic acid (20:2) levels were significantly increased by TRF supplementation in diabetic rats. CONCLUSION: Supplementation with 200 mg/kg TRF improves dyslipidemia and that TRF, therefore, might have protective effects against oxidative damage of phospholipids. This study also showed the antioxidative properties of TRF on the erythrocyte membrane lipids composition, in particular, its protective effects against peroxidation of unsaturated fatty acids.

262-6

Authors: Miftakh Nur Rahman, Indriyanti Rafi Sukmawati, Irma Melyani Puspitasari, Miswar Fattah

BACKGROUND: Central obesity is known as a risk factor for type 2 diabetes mellitus (T2DM). Its development is influenced by many factors such as a progressive failure of pancreatic beta cell function. The beta cells increase their function to secret insulin along T2DM development to compensate before it becomes exhausted. Zinc (Zn) plays a crucial role in beta cell function and insulin secretion. The majority of Zn in serum are bound to protein which is not readily available interact with cells. The free Zn in serum has been suggested as being more representative than total Zn in beta cell function. This research aimed to investigate the correlation between serum free Zn and homeostasis model assessment for beta cell function (HOMA-B) and to predict the pancreatic beta cell function in the development of T2DM. METHODS: This study was designed as an observational with a cross-sectional approach. The subjects were centrally obese men aged 30-50 years and who had met the inclusion and exclusion criteria from the screening tests. Control subjects were lean men without T2DM. Serum free Zn and serum total Zn were measured by using inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: There was positive correlation between serum free Zn and HOMA-B (R=0.361, p-value<0.001) but there was no correlation between serum total Zn and HOMA-B (R=-0.062, p-value=0.563). This study found that if the concentration of serum free Zn >1.7 ug/dL in central obese men was suggested as an excessive function of pancreatic beta cell and as an early warning before its exhausted. CONCLUSION: This study suggested that serum free Zn had a correlation with beta cell function and had a predictive ability for beta cell excessive function before its exhausted.

273-8

Authors: Aditya Kurniawan, Erika Diana Risanti, Saihas Suhda, Hanggoro Tri Rinonce, Ery Kus Dwianingsih, Jajah Fachiroh

BACKGROUND: Tobacco smoking plays an important role in nasopharyngeal carcinoma (NPC) risk. The Wingless-related integration site (WNT) Inhibitory Factor 1 (WIF1) as one of the tumor suppressor gene (TSG), functions to control cell proliferation through suppression of WNT signaling pathway. WIF1 methylation is one of epigenetic mechanisms which causes overactivated of WNT pathway in NPC development. WIF1 methylation from buffy coat related to smoking status and NPC risk is not known yet. METHODS: This was a nested case-control study involving 39 newly diagnosed NPC patients and 40 healthy controls. All subjects were enrolled at Dr. Sardjito Hospital, Yogyakarta. Subjects were male, with known smoking status, duration, and quantity of cigarette consumed. Parallel DNA isolated from buffy coat was used for WIF1 DNA methylation analysis, by using methylation-specific PCR (MSP) method. Chi-square analysis was used to determine distribution of differences among groups. Two tailed p-value≤0.05 was considered as statistically significant. RESULTS: No significant difference between WIF1 methylation of cases and controls (p=0.30), nor smoking habit among smokers (p=0.51) and non-smokers (p=0.43). CONCLUSION: WIF1 methylation from buffy coat could not be used as an NPC marker nor as a smoking behavior marker.

286-92

Authors: Irianiwati Widodo, Ery Kus Dwianingsih, Teguh Aryandono, Soeripto Soeripto

BACKGROUND: Triple negative breast cancer (TNBC) is a breast cancer subtype with negative expressions of estrogen receptors (ER), progesterone receptors (PR) and Her-2 protein receptors. This subtype exhibits aggressive behavior and poor prognosis since it is unresponsive to hormonal and Her-2 targeted therapy. The identification of clinicopathological characteristics and their prognostic values will provide guidance in developing effective treatment. This study was performed to analyze the clinicopathological characteristics and prognostic significance in Indonesian TNBC. METHODS: Forty paraffin-embedded tissues of TNBC, stage I to IIIA, dating from 2008 to 2010 in Dr. Sardjito Hospital, were enrolled. Survival follow-up was done from January 2008 to June 2013. The samples were immunostained with ER, PR and Her-2 monoclonal antibodies to determine the TNBC subtypes. The clinicopathological characteristics were statistically analyzed. The survival was analyzed using the Kaplan Meier method. The Cox proportional hazards model was used for multivariate analysis. RESULTS: Mean age of TNBC patients was 51.42±11.72 years old, whereas the mean of tumor size was 5.4±2.92 cm. Lymph node metastasis was found in 70% of cases. Number of locally advanced samples (IIIA) was 37.5%, while moderate to high grade samples were 95%. Number of still alive patients at the end of the study was 55%. Number of patients that still alive up to the end of the study was 45.50%. Lymph node was an independent prognostic factor for survival of TNBC patients as positive status of lymph node increases the death risk to 6 times higher (p=0.02, RR=6.6). However, after being adjusted with age and stage, lymph node status was suggested as a modifier effect for the survival of TNBCs patients (RR=0.19). CONCLUSION: Indonesian TNBC patients were mostly found already with large tumor size, lymph node metastasis, high pathological grade and relatively young age. Lymph node status serves as a modifier effect for the survival of Indonesian TNBC.

299-303

Authors: Muhammad Diah, Rahmawati Rahmawati, Aznan Lelo, Zulfikri Muhktar, Dharma Lindarto, Ferry Sandra

BACKGROUND: Tumor necrosis factor (TNF)-α, an important primary pro-inflammatory cytokine, has a crucial role in the pathogenesis of atherosclerosis. Since the pathophysiological mechanism of coronary slow flow (CSF) is not fully understood, we investigated the level of TNF-α in coronary artery disease (CAD), CSF and healthy subjects. METHODS: This study was conducted in cross-sectional design involving 16 CAD, 18 CSF and 18 healthy subjects. Coronary angiography was recorded at the left anterior oblique, cranial, right anterior oblique, caudal, and horizontal positions. The flow in coronary arteries of the subjects were assessed using Thrombolysis in the Myocardial Infarction (TIMI) frame count method. Peripheral blood-derived serum was collected and level of TNF-α was determined by using highly sensitive enzymelinked immunosorbent assay (ELISA). RESULTS: No significant difference in level of TNF-α in CAD, CSF and healthy subjects (2.72±2.64 pg/mL, 1.88±0.8 pg/mL, 1.64±0.35 pg/mL, respectively) (p=0.087). In addition, there was no correlation between the concentration of TNF-α and TIMI frame count (r<0.2, p>0.05). CONCLUSION: There was no significant difference of TNF-α level in CAD, CSF and healthy subjects. In addition, there was no correlation between the TNF-α level with TIMI frame count as well. Nevertheless, further clinical studies with more subjects are needed.

314-9

Authors: Rininta Firdaus, Hege Hartz Jartun, Miriam Khider

BACKGROUND: Rapid and accurate identification of Staphylococcus capitis is required to provide a better prognosis for endocarditis patients and tackle the emergence of multidrug resistant strains of the bacteria in hospitals. The current study was aimed to develop polymerase chain reaction (PCR) assay for specific identification of S. capitis using sodA and gap genes as markers. METHODS: Five sequences of sodA and sixteen sequences of gap registered in GeneBank were analysed using bioinformatic tools. PCR primers were designed based on the conserved and specific regions of sodA and gap. Four clinical isolates of S. capitis (named no. 56-59) and six reference strains of coagulase-negative staphylococci (CoNS) species including S. epidermidis ATCC 35984, S. epidermidis 48951I/09, S. lugdunensis 44987/09, S. sciuri 109645I/08, S. warneri 135612/09, S. hominis 114202/08 were used to validate the conventional PCR system. RESULTS: The current PCR system only amplified the DNA template of S. capitis. Current primers specifically targeted S. capitis as the agarose images only showed bands from S. capitis samples. CONCLUSION: The sodA and gap genes might serve as effective markers for identification of S. capitis using conventional PCR. The PCR assay in the current study was able to identify five clinical isolates of S. capitis accurately without mispriming, misamplification and misidentification. The PCR system was also able to discriminate other CoNS including S. epidermidis, S. lugdunensis, S. sciuri, S. warneri and S. hominis.

327-37

Authors: Adnan Jassim Mohammed Al-Fartosy, Nadhum Abdulnabi Awad, Rsha Abdulradha Mahmood

BACKGROUND: To date, there is no study regarding women with unexplained infertility in the province of Basrah, Iraq. This study was conducted to compare the level of leptin, oxidant/antioxidant status, and some trace element levels in women of healthy control and unexplained infertility. METHODS: From total 96 women subjects, 32 subjects had primary unexplained infertility, 31 had secondary unexplained infertility, while 33 fertile women were taken as controls. The body mass index (BMI) of subjects was calculated with standard procedures. The level of fasting serum leptin, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), thyroid-stimulating hormone (TSH), 4-hydroxynonenal (4-HNE), lipid hydroperoxide (LOOH), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and the total antioxidant capacity (TAC) were determined by enzyme-linked immunosorbent assay (ELISA) methods. Magnesium (Mg) and zinc (Zn) were measured by flame, copper (Cu) by flameless atomic absorption spectrometry, while Selenium (Se) in whole blood was determined using hydride generation method. RESULTS: Non-significant changes (p>0.05) were seen in the level of BMI, leptin, TSH, FSH, LH and LH/FSH ratio. Level of 4-HNE, LOOH and Cu were significantly increased (p<0.01), while level of GSH, SOD, CAT, TAC, Se, Zn and Mg were significantly decreased (p<0.01) in primary and secondary type of unexplained infertility, compared to control. CONCLUSION: Serum leptin hormone is significantly associated with BMI and physical activity in both groups. The significant difference in oxidant/antioxidants status between unexplained infertile and fertile women may suggests a possible additional role of oxidative stress mechanisms in pathophysiology of unexplained infertility.