The Indonesian Biomedical Journal

1-15

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Low back pain (LBP) mostly caused by disc degeneration, reflects to a tremendous of health care system and economy. More knowledge about these underlying pathologies will improve the opportunities that may represent critical therapeutic targets. CONTENT: Basic research is advancing the understanding of the pathogenesis and management of LBP at the molecular and genetic levels. Cytokines such as matrix metalloproteinases, phospholipase A2, nitric oxide, and tumor necrosis factor-α are thought to contribute to the development of LBP. Mesenchymal stem cells (MSCs) transplant to cartilage-like cells and secrete extracellular matrix and encourage nucleus pulposus (NP) cell activity inhibiting NP cell apoptosis, together with some chemical mediators such as cytokines and growth factors become a safe and effective new strategy for intervertebral disc degeneration (IDD) treatment and regeneration. SUMMARY: IDD occurs where there is a loss of homeostatic balance with a predominantly catabolic metabolic profile. A basic understanding of the molecular changes occurring in the degenerating disc is important for practicing clinicians to help them to inform patients to alter lifestyle choices, identify beneficial or harmful supplements, or offer new biologic, genetic, or stem cell therapies.

35-9

Authors: Ferry Sandra

BACKGROUND: Generally ameloblastoma is a locally aggressive, slow growing, non-metastatic epithelial odontogenic benign tumor. However, rarely some ameloblastoma can metastasize in spite of a benign histologic appearance. Targeting ameloblastoma by inducing it into apoptosis could be a beneficial strategy, since many ameloblastoma cases were reported recurrent after surgical therapy. CONTENT: To investigate ameloblastoma in cellular aspect,cytological pattern of ameloblastoma was divided intoouter layer/peripheral and inner layer/central cells. Tumor necrosis factor (TNF)-α, Fas ligand (FasL), TNF receptor (TNFR)1/death receptor (DR)1, TNFR2/DR2, DR4, DR5andFas were highly expressed in central than peripheral cells. Despite inducing apoptosis, TNF-α can induce PI3K leading to Akt and p44/42 mitogen-activated protein kinases (MAPK) activation in AM-1 cells, which later induce cell survival and proliferation. Therefore apoptotic induction in ameloblastoma should be suggested in higher TNF-α concentration. Expression of FasL and Fas are closely associated with squamous metaplasia and granular transformation of the tumor cells, suggesting that apoptosis induced by FasL may play a role in the terminally differentiated or degenerative ameloblastoma cells. TNF-related apoptosis-inducing ligand (TRAIL) has emerged as an apoptotic inducing anticancer agent in tumor cells specifically. TRAIL induced activation of caspases, lowering mitochondrial membrane potential, high number of apoptotic cells in ameloblastoma cells. Therefore, TRAIL could be a potential agent for targeting ameloblastoma, although further study should be explored. SUMMARY: Targeting ameloblastoma by inducing it into apoptosis could be achieved effectively, although some criteria should be considered. Therefore understanding the underlying apoptosis signaling pathways are necessary for inducing ameloblasotma into apoptosis. Investigations on other apoptosis-related molecules, potential apoptosis-inducing natural products, and novel approach in reprogramming, are important in the future for a better anagement of ameloblastoma.

46-50

Authors: Hartanto Bayuaji, Heda Melinda Nazaruddin Nataprawira, Herri Suhari Sastramihardja

BACKGROUND: Polycystic ovary syndrome (PCOS), a common reproductive endocrinologic disorder in woman, was considered to be related to sleep disturbance. This study is aimed to analyze the correlation between excess androgen markers and Athens Insomnia Scale (AIS) in PCOS. METHODS: This observational, cross-sectional study of PCOS was conducted to 31 subjects to evaluate the correlation between serum total testosterone, sex hormone binding globulin (SHBG) and free androgen index with the incidence of sleep disturbance using AIS. Sleep disturbance was present if the score ≥6. The correlation between excess androgen markers and sleep disturbance was analyzed using Pearson’s coefficient of correlation or Spearman’s rho test. Correlation coefficient more than 0.5 with p<0.05 was considered significant. RESULTS: Out of 31 PCOS subjects aged 20-40 years, 39% subjects had AIS score ≥6. Mean serum testosterone in AIS score >6 group was higher than AIS score <6 group but not statistically significant (46.68 vs. 28.49 ng/mL, p>0.05). No significant correlation was found between serum total testosterone, SHBG and free androgen index with AIS score. After adjusting for AIS score, there was the moderate positive correlation between serum total testosterone level although not statistically significant (r=0.54, p=0.07). CONCLUSION: The serum total testosterone level might influence the occurrence of sleep disturbance in PCOS.

56-61

Authors: Edhyana Sahiratmadja, Simeon Penggoam, Ani Melani Maskoen, Alvinsyah Adhityo Pramono, Dias Aryani, Nurul Setia Rahayu, Ramdan Panigoro

BACKGROUND: N-acetyltransferase-2 (NAT2) enzyme, encoded by NAT2 gene, plays a key role in metabolism of anti-tuberculosis (TB) drug isoniazid. Polymorphisms in NAT2 gene may result in different responses to TB therapy. Since TB prevalence in the eastern part of Indonesia is high, the aim of this study is to explore the distribution of NAT2 gene polymorphisms among population from Kupang, Nusa Tenggara Timur. METHODS: A total of 234 respondents were included from Kupang in 2012. Polymorphisms of NAT2 gene were examined using mass screening platform and the genotypes distribution were presented in percentage. To confirm NAT2 gene polymorphisms, polymerase chain reaction (PCR)-sequencing was performed in a subset of population. RESULTS: The polymorphisms of NAT2 gene showed that the distribution of rs1801279 for GG genotype was 100%; whereas the genotype distribution of rs1799930 for GG, GA and AA was 57%, 35.1% and 7.9%, respectively. In a subset of individuals (n13), acetylator status was well determined by PCR-sequencing, resulting in individual with wild type fast acetylator (NAT2*4; n4), intermediate (NAT2*4/*5 or NAT2*4/*6 or NAT2*4/*7; n7) and poor acetylators (NAT2*6/*6 or NAT2*7/*7; n2). CONCLUSION: The amino acid change in rs1799930 result in intermediate and poor acetylator status in Kupang population. This may lead to suboptimal response of TB therapy. Assessing acetylator status before TB therapy is important and may serve as personalized INH therapy.

66-73

Authors: Dwi Ramadhani, Siti Nurhayati, Tur Rahardjo, Mukh Syaifudin

BACKGROUND: Mamuju area in West Sulawesi considered as the high natural background radiation area in Indonesia. Our previous study showed that the mean mitotic index (MI) and nuclear division index (NDI) in lymphocytes of Botteng Village, Mamuju inhabitants was lower compared to control samples. To validate our previous study results, here in this study the evaluation of cell proliferation markers which were MI and NDI in peripheral blood lymphocytes (PBL) of Takandeang Village inhabitants was conducted. METHODS: A total 60 people were enrolled in this study, consisted of 35 samples from Takandeang Sub-Village and 25 from normal background radiation area. MI was calculated manually and automatically using Metafer 3.11.2 imaging system. The NDI defined as proportion of mononucleated, binucleated, trinucleated and tetranucleated cells were conducted using cytokinesis block micronucleus (CBMN) assay. RESULTS: The results of this study showed that the mean manual MI in Takandeang Sub-Village inhabitants was lower compared to control group (4.96±2.25 vs. 5.93±2.14). In contrast, the mean automatic MI (20.37±10.49 vs. 18.87±7.49) and NDI (1.555±0.174 vs. 1.523±0.112) in Takandeang Sub-Village inhabitants was higher compared to the control group. Statistical analysis revealed that the difference of mean manual MI, automatic MI and NDI in Takandeang Sub-Village inhabitants was not significantly different compared to the control group (p>0.05). CONCLUSION: It can be concluded that based on this study the chronic low radiation dose exposure in Takandeang Sub-Village, Mamuju has no significant effect on the lymphocytes proliferation.

79-83

Authors: Hartono Apriliasta Purba, Santi Syafril, Dharma Lindarto

BACKGROUND: Inflammation is one of the factors that associated with insulin resistance which causes type 2 diabetes mellitus (T2DM). Inflammation can be measured by using high sensitivity C-reactive protein (hs-CRP), a quantitative measurement of CRP concentration. Puguntano is a plant that traditionally used for antidiabetic treatment found in North Sumatera. The objective of this study is to know the effect of Puguntano extract on hs-CRP level in newly diagnosed T2DM patient. METHODS: The study was a randomized controlled clinical trial on 24 newly diagnosed T2DM patients. Subjects were divided into 2 groups. The first group was given Puguntano extract with starting doses at 100 mg daily, then the dose was increased in titration up to a maximum dose of 2x100 mg daily depending on blood sugar level monitoring. Meanwhile, the other group (which serves as a control group) was given metformin with starting doses at 500 mg daily, then the dose was increased in titration up to a maximum dose of 3x500 mg per day depending on blood sugar level monitoring. The hs-CRP and HbA1c are assessed at the baseline and after 12 weeks of treatment. RESULTS: The hs-CRP level was decreased in Puguntano group by 1.41 (-7.54-0.52) (p=0.06) and decrease by 0.58 (-7.86-33.41) (p=0.695) in metformin group. There was no difference in hs-CRP level between the two groups (p=0.630). CONCLUSION: Puguntano extract showed the effect of lowering HbA1C and hs-CRP level in T2DM patients, although it was not statistically significant.

113-28

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: The number of elderly population in the world keep increasing. In their advanced ages, many elderly face years of disability because of multiple chronic diseases, frailty, making them lost their independence. Consequently, this could have impacts on social and economic stability. A huge challenge has been sent for biomedical researchers to compress or at least eliminate this period of disability and increase the health span. CONTENT: Over the past decades, many studies of telomere biology have demonstrated that telomeres and telomere-associated proteins are implicated in human diseases. Accelerated telomere erosion was clearly correlated with a pack of metabolic and inflammatory diseases. Critically short telomeres or the unprotected end, are likely to form telomeric fusion, generating genomic instability, the cornerstone for carcinogenesis. Enlightening how telomeres involved in the mechanisms underlying the diseases’ pathogenesis was expected to uncover new molecular targets for any important diagnosis or therapeutic implications. SUMMARY: Telomere shortening was foreseen as an imporant mechanism to supress tumor by limiting cellular proliferative capacity by regulating senescence check point activation. Many human diseases and carcinogenesis are causally related to defective telomeres, asserting the importance of telomeres sustainment. Thus, telomere length assessment might serve as an important tool for clinical prognostic, diagnostic, monitoring and management.

143-6

Authors: Arundina Sanyoto, Ketut Suega, Losen Adnyana, I Made Bakta

BACKGROUND: Diagnosing iron deficiency anemia (IDA) is easy, but also can be complicated in condition with inflammation. A new modality for diagnostic which isn’t influenced with inflammation is needed. The aim of this study is to find the cut-off point and evaluate the accuracy of reticulocyte hemoglobin equivalent (Ret-He) to diagnose IDA using ferritin as the gold standard. METHODS: This study was an observational study with cross-sectional analytical design continued with the diagnostic test conducted in anemic individuals with age 18 years old or above. RESULTS: Eighty-seven patients (41 men and 46 women) were included in this study with mean of hemoglobin 7.42 g/dL, serum iron 42.71 mg/dL, total iron-binding capacity(TIBC) 242.82 mg/dL, ferritin 799 mg/L and Ret-He 23.63 pg. Ret-He with cut-off value 25 pg showed a sensitivity 97.2% (95% CI 83.79-99.85%), specificity 66.67% (95% CI 51.97-78.85%), positive predictive value 67.30% (95% CI 52.77-79.28%) and negative predictive value 97.14% (95% CI 83.38-99.85%). CONCLUSION: Ret-He showed the best sensitivity for detection of IDA and was suggested as the screening test for IDA.

153-9

Authors: Djanggan Sargowo, Titin Andri Wihastuti, Cathrine Theodora Sukotjo, Prasanti Mahesa Anjani, Olivia Handayani, Liemena Harold Adrian

BACKGROUND: Type 2 Diabetes Mellitus (DM) is one of dominant factors in cardiovascular deaths and induces endothelial dysfunction. A definite sign of endothelial dysfunction is foam cells formation derived from oxidized LDL. This study was conducted to determine the effect of Polysaccharides Peptides (PsP) Ganoderma lucidum to foam cell counts and lipid profile in diabetic model rats with high-fat diet. METHODS: Treatment group was categorized to negative control, positive control, DM-50, DM-150, and DM-300. Type 2 DM induced by Streptozotocin. PsP was administered with predetermined doses on each treatment’s group (50, 150 and 300 mg/kgBW) for 12 weeks. Measurements of foam cell count were held after obtaining rat’s aorta. To assess lipid profile, blood sample was taken from the rat's heart. The data were analyzed by One-way ANOVA and Post Hoc Tukey tests. RESULTS: The administration of Ganoderma lucidum PsP to diabetic model rats provided a significant difference in lowering foam cell (p=0.017; CI 95%). It also gave significant difference between levels of each lipid components (Total Cholesterol, Trygliceride, LDL and HDL) in at least two treatment groups (p=0.010; CI 95%). Based on Post Hoc Tukey tests, the relationship between administration of PsP and foam cell is significant (p=0.002). CONCLUSION: PsP has antioxidant and anti-inflammatory effect in type 2 DM model Rattus norvegicus strain Wistar, which can inhibit atherosclerosis and endothelial damage process. Further studies are necessary to evaluate the benefits of PsP as an adjuvant therapy in the management of diabetic dyslipidemia.

165-72

Authors: Samad Javadi, Hojjatallah Alaei, Ebrahim Hosseini, Mohammad Amin Edalatmanesh

BACKGROUND: The prelimbic area (PL) of the prefrontal cortex is susceptible to abnormal developmental stimuli that raises the risk of addiction. Glutamate receptors play a key role in opiate reinforcement and reward functions in this area. Therefore, we examined the effect of the DL-2-amino-5-phosphonopentanoic acid (AP5), as N-methyl-D-aspartate(NMDA) receptor antagonist into the PL on the phases of conditioned place preference (CPP) induced by morphine. METHODS: Male Wistar rats were divided into 12 groups(3 surgical groups for each dose of morphine in any phase of CPP) and anaesthetized with chloral hydrate. Cannula was implanted into the PL and the AP5 was injected into this area and morphine-induced CPP was investigated. Data were processed with the commercially available SPSS 22 software using one-way ANOVA and Tukey's test. p<0.05 were considered statistically significant. RESULTS: Our findings indicated, morphine in doses of 2.5 to 10 mg/kg induced CPP. Microinjection of various doses of the AP5 into the PL before the administration of the effective dose of morphine significantly reduced place preference in the acquisition and the expression phases of the CPP test compared to the sham group (p<0.001). In another set of our experiments was seen that, different doses of the AP5 with the ineffective dose of morphine only reduced the expression phase of the CPP (p<0.001) while, produced neither preference nor aversion effect on the acquisition phase (p=0.147). CONCLUSION: It seems that the glutamate NMDA receptors in the PL through memory formation and morphine-related reward signals play a critical role in addiction process during morphine-induced CPP.

53-72

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: The introduction of mechanism based targeted therapies to treat human cancers has been pledge as one of the results of three decades of remarkable progress of research into the mechanisms of cancer pathogenesis. We ponder how the description of hallmark principles is start to inform therapeutic development currently and may increasingly do so in the future. CONTENT: There are 10 biological capabilities involved as the hallmarks of cancer, during the multistep of human tumors development. These hallmarks simplify the complexities of neoplastic disease into a structured rational principles, includes sustaining proliferative signaling, eluding growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genome instability, inflammation, reprogramming energy metabolism and evading immune destruction. SUMMARY: The 10 hallmarks of cancer, in other words, the tumor’s distinctive and complementary capabilities that enable its growth and metastatic dissemination, continue to provide a solid foundation for understanding the biology of cancer. The acknowledgment of the widespread applicability of these concepts will increasingly influence the development of new manners to treat human cancer.

78-83

Authors: Ferry Sandra, Janti Sudiono, Ciptadhi Tri Oka Binartha, Angliana Chouw, Melanie Sadono Djamil

BACKGROUND: Dental pulp stem cell (DPSC) and periodontal ligament stem cell (PDLSC) have been suggested as valuable seed cells for bone engineering, suggesting that both stem cells are potential osteogenic sources. Since DPSC and PDLSC seem like to have similar potential in bone formation, we conducted a study to compare morphology, immunophenotype and cell growth of DPSC and PDLSC isolated from the same teeth. METHODS: Human dental pulps and periodontal ligaments were obtained from freshly extracted partial impacted third molar teeth. Collected samples were digested with type I collagenase. Resulted cell suspension was washed and cultured. For biomarker identification, the cells were fixed and bound with anti-fluorescein isothiocyanate (FITC)-cluster of differentiation (CD)117 antibody. For cell growth quantification, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used. Meanwhile for osteogenic differentiation, the cells were cultured in osteogenic medium for 1-3 weeks, fixed and stained with alizarin red. RESULTS: Morphology of dental pulps cell (DPC) and periodontal ligament cell (PDLC) in passage 5 was similar. Clear CD117 green fluorescence of DPC and PDLC in passage 5 was observed. Cell growth rate of PDLC was higher than the one of DPC, 0.3858 and 0.3848 respectively. DPC formed bone nodule on the third week culture in osteogenic medium, while PDLC showed bone nodule formation on the second week culture. CONCLUSION: We suggest that DPC and PDLC are potential seed cells for osteogenic regeneration, since they had cell growth capacity and osteogenic differentiation, particularly PDLC that had faster osteogenic differentiation.

91-8

Authors: Sunarno, Yuanita Mulyastuti, Nelly Puspandari, Kambang Sariadji

BACKGROUND: dtxR gene is a global regulator that can be used as a marker for detection of Corynebacterium diphtheriae (C. diphtheriae) and it is also a representative tool for mapping purpose (molecular typing) of this bacteria. The aim of this study was to analyze the DNA sequences of partial dtxR gene of C. diphtheriae causing diphtheria in some region of Indonesia. DNA sequence analysis was used to verify the accuracy of the in-house multiplex polymerase chain reaction (PCR) method that used for detection of C. diphtheriae in the clinical specimen as well as a preliminary study to determine the strain diversity of C. diphtheriae circulating in Indonesia. METHODS:Ten PCR products targeting the dtxR gene that have been detected as positive C. diphtheriae previously by in-house multiplex PCR used as samples in this study. The DNA sequencing carried out by Sanger method and the sequence data was analyzed by Bioedit software offline and basic local alignment sequence typing (BLAST) online. RESULTS: All of DNA sequence analyzed in this study were similar or identical to the dtxR gene sequence data of C. diphtheriae registered in GenBank. Within the 162 nucleotides (base 150-311) of dtxR gene that analyzed, at least 2 clonals were found among 10 samples. Substitutions of 2 nucleotides (base 225 and 273) was detected, both were silent mutation. CONCLUSION:Ten partial DNA sequences of dtxR genes in this study verify the accuracy of in-house multiplex PCR which used to identify the bacteria causing diphtheria in the clinical specimen. The DNA sequences also represent the existing diversity of the bacteria causing diphtheria circulating in Indonesia.

106-12

Authors: Arash Payehdar, Ebrahim Hosseini, Davood Mehrabani, Mohsen Forouzanfar

BACKGROUND: Busulfan, a chemotherapeutic drug, is an alkylating antineoplastic agent that belongs to the class of alkyl sulfonates and has some side effects on fertility. This research was aimed to investigate the effects of busulfan on testicular tissue and serum levels of anti-Mullerian hormone (AMH) and testosterone in adult mice. METHODS: Eighteen adult male Balb/C mice were collected randomly and were assigned in three groups including; control, azoospermia and spontaneous recovery. The groups, except for control group, received two injections of busulfan (10 mg/kg) intraperitoneally with 21-days interval in order to induce azoospermia. Thirty-five and 140 days after the last injection, the effects of busulfan on testicular tissue were evaluated by histologic, histomorphometric and hormonal changes. AMH and testosterone were measured by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) kits, respectively. RESULTS: Hormonal analyses showed no significant differences in AMH and testosterone serum levels. Histologic and histomorphometric evaluation showed disrupted spermatogenesis in azoospermia group, and restoration of spermatogenesis spontaneously in spontaneous recovery group. CONCLUSION: Busulfan at doses was used had no effect on AMH and testosterone serum levels. Busulfan can also induce azoospermia on a temporary basis however, in long term, spontaneous recovery can occur. The results indicated that some side effects are reversible and may depend on the dose applied.

1-16

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Recently established genome editing technologies will open new avenues for biological research and development. Human genome editing is a powerful tool which offers great scientific and therapeutic potential. CONTENT: Genome editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPRassociated protein 9 (Cas9) technology is revolutionizing the gene function studies and possibly will give rise to an entirely new degree of therapeutics for a large range of diseases. Prompt advances in the CRISPR/Cas9 technology, as well as delivery modalities for gene therapy applications, are dismissing the barriers to the clinical translation of this technology. Many studies conducted showed promising results, but as current available technologies for evaluating off-target gene modification, several elements must be addressed to validate the safety of the CRISPR/Cas9 platform for clinical application, as the ethical implication as well. SUMMARY: The CRISPR/Cas9 system is a powerful genome editing technology with the potential to create a variety of novel therapeutics for a range of diseases, many of which are currently untreatable.

23-8

Authors: Ferry Sandra, Janti Sudiono, Pretty Trisfilha, Deviyanti Pratiwi

BACKGROUND: Alpinia galanga (A. galanga) was reported as a potential medicinal source due to its wide effect. A. galanga rhizome crude extract (ARCE) was reported to have high cytotoxic effect in cancer cells, but low in normal cells. However half maximal inhibitory concentration (IC50) of ARCE is not clearly known yet. Hence, current study was conducted to investigate the IC50 of ARCE in normal standard fibroblast cell line, NIH-3T3 cells. METHODS: Rhizomes of A. galanga were collected, peeled, dried, milled and weighed. Extraction was performed using maceration method, then filtered and evaporated. ARCE with various concentrations were applied in NIH-3T3 cells for 24 or 48 hours. Cells were documented and counted with 3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide (MTT) assay. RESULTS: Five hundreds grams of simplicia were macerated with ethanol and evaporated, 1 mg/mL crude extract with total volume of 114 mL was obtained. By addition of ARCE in NIH-3T3 cell culture, number of NIH-3T3 cells were shown less when treated with higher concentration of ARCE. Cell numbers of 0, 3.125, 6.25, 12.5, 25 and 50% ARCE treatment for 24 hours are 11,531, 11,352, 10,920, 10,365, 9,471, 8,360, respectively, meanwhile for 48 hours are 13,219, 12,686, 12,278, 11,390, 10,279, 8,390, respectively. CONCLUSION: IC50 of ARCE in 24 hours treatment was 620.5 mg/mL, while in 48 hours treatment was 666.6 mg/mL. Hence, ARCE is suggested to have low cytotoxic effect in NIH-3T3 cells.

35-42

Authors: Isabelle Deli Lestadi, Nurjati Chaerani Siregar, Puspita Eka Wuyung

BACKGROUND: Plasma cell neoplasm (PCN) is a neoplastic plasma cell proliferation which includes solitary bone plasmacytoma (SBP), extramedullary plasmacytoma (EMP) and multiple myeloma (MM). Bartl classifies the degrees of PCN as low, intermediate and high. The aim of this study is to find the correlation between tumor suppressor gene p53 (TP53) expression and Ki-67 proliferation with Bartl malignancy degree of PCN. Therefore earlier PCN diagnostic method to prevent the development of PCN into MM can be found. METHODS: Thirty-two PCN cases were classified into three groups based on Bartl’s degrees of malignancy. TP53 and Ki-67 immunohistochemical staining were performed on samples and the percentage of positivity was evaluated. RESULTS: The Bartl’s low degree of malignancy was found in 10 MM cases (31.2%), intermediate degree in 5 SBP cases (15.6%) and high in 2 SBP and EMP cases (6.2%). TP53 expression was obtainable at 4% of low, 16% of intermediate and 10% of high degree. There was a significant difference between TP53 expression in low and intermediate degree (p=0.004). Mean proliferation index of Ki-67 was 57% in low, 44.6% in intermediate, and 32.6% in high degree. There was no significant difference of Ki-67 proliferation indexes among the group (p=0.339). CONCLUSION: Increasing expression TP53 was in accord with Bartl’s degrees of malignancy, especially in low and intermediate degree, but there was no significant difference between Ki-67 proliferation index and Bartl’s degrees of malignancy.

49-52

Authors: Yusrawati, Dyka Aidina, Eti Yerizel

BACKGROUND: According to the theory of endothelial dysfunction, the pathogenesis of preeclampsia is associated with the imbalance of angiogenic and anti-angiogenic factors. Transforming growth factor-beta 1 (TGF-β1) has also proposed as a proangiogenic factor that influences preeclampsia. This study was conducted to compare a mean difference of TGF-β1 between preeclampsia and normal pregnancy. METHODS: This study was an observational crosssectional study with 25 subjects of pregnant women with preeclampsia and 25 subjects of normotensive pregnant women. The study was conducted in Dr. Reksodiwiryo Hospital, Bhayangkara Hospital, and Dr. Rasidin Hospital in Padang, Indonesia from October 2015 to January 2016. For the determination of TGF-β1 concentration, peripheral Abstract venous blood samples were taken. The blood samples were analyzed by enzyme-linked immunosorbent assay (ELISA) in Biomedical Laboratory, Faculty of Medicine, Andalas University. The mean difference was statically analyzed by independent samples T-test. RESULTS: The mean difference of TGF-β1 was lower in preeclampsia group than normal pregnancy group (2.02±0.99 ng/mL vs. 3.24±2.67 ng/mL; p<0.05). CONCLUSION: The TGF-β1 concentration was lower in pregnant women with preeclampsia. Thus, it may have a role as a marker in preeclampsia.

127-46

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Most medical treatments have been designed for the “average patients”. As a result of this “one-size-fits-all-approach”, treatments can be very successful for some patients but not for others. The issue is shifting by the new innovation approach in diseases treatment and prevention, precision medicine, which takes into account individual differences in people’s genes, environments, and lifestyles. This review was aimed to describe a new approach of healthcare performance strategy based on individual genetic variants. CONTENT: Researchers have discovered hundreds of genes that harbor variations contributing to human illness, identified genetic variability in patients’ responses to different of treatments, and from there begun to target the genes as molecular causes of diseases. In addition, scientists are developing and using diagnostic tests based on genetics or other molecular mechanisms to better predict patients’ responses to targeted therapy. SUMMARY: Personalized medicine seeks to use advances in knowledge about genetic factors and biological mechanisms of disease coupled with unique considerations of an individual’s patient care needs to make healthcare more safe and effective. As a result of these contributions to improvement in the quality of care, personalized medicine represents a key strategy of healthcare reform.

157-60

Authors: Tugas Ratmono, Andi Wijaya, Cahyono Kaelan, Andi Asadul Islam, Ferry Sandra

BACKGROUND: After stroke, there are dynamic changes of motor evoked potential (MEP), including latency, amplitude, central motoric conduction time(CMCT) and resting motor threshold (RMT) in cerebral. However, latency, CMCT, amplitude and RMT have not been clearly shown in acute ischemic stroke patients with motoric function impairment based on Modified Motoric Research Council Scale (MRCs). METHODS: Patients with motoric function impairment after acute ischemic stroke were recruited, scored based on MRCs and grouped. Latency, amplitude, CMCT and RMT(% intensity) was measured using transcranial magnetic stimulation (TMS). Latency, amplitude, CMCT and RMT of subjects based on affected hemisphere (AH) and unaffected hemisphere (UH); stroke onset; and motoric severity; were analyzed and compared statistically. RESULTS: Thirty-seven subjects with complete assessments were selected. Results of MEP size measurement between AH and UH showed that latency, amplitude, CMCT and RMT of AH and UH were significantly different (p<0.05). In accordance to AH and UH results, latency, amplitude, CMCT and RMT of mild, moderate and severe groups based on motoric severity, showed that latency and CMCT were prolonged, RMT was increased, while amplitude was decreased along with severity increment. The amplitude and RMT among the groups were significantly different with p=0.034 and p=0.029, respectively. CONCLUSION: MEP size measurement including latency, amplitude, CMCT and RMT have significant different in AH and UH. In addition, amplitude and RMT were significantly different in MRCs groups, therefore the MEP size measurement could be suggested as prognostic tool.

167-72

Authors: Dharma Lindarto, Santi Syafril, Dairion Gatot

BACKGROUND: Elevated blood glucose level is a major factor in development of diabetic complications due to unfavorable hyperglycemic induced biochemical as well as hematological indices changes. The aim of this study was to evaluate the correlation between glycemic characteristic and erythrocyte indices in obese subjects with different glycemic status. METHODS: Cross cross-sectional study was designed, and 80 obese subjects were enrolled. The correlations between glycemic characteristic (fasting plasma glucose (FPG), postprandial plasma glucose (PPG), hemoglobin A1c (HbA1c) and homeostasis model assessment of insulin resistance (HOMA-IR)) and erythrocyte indices (Hb, red blood count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC)) were evaluated. RESULTS: Of 80 obese subjects with different glycemic status, there were 48 patients with only obesity (HbA1c <5.7%), 19 patients with pre-diabetes (HbA1c 5.7-6.4%) and 13 patients with diabetes (HbA1c >6.4%). Glycemic characteristic and profile lipid (high-density lipoprotein cholesterol (HDL-C), triglycerides (TG)) were differ significantly in the different HbA1c level. Erythrocyte indices were not differ significantly in the different HbA1c level. Partial Spearman's correlation analysis showed that only MCV was significantly correlated with glycemic characteristic of FPG, PPG, HbA1c and HOMA-IR (r=-0.36, p=0.001; r=-0.29, p=0.007; r=-0.27, p=0.014 and r=-0.236, p=0.035; respectively). CONCLUSION: MCV was significantly correlated with glycemic characteristic (FPG, PPG, HbA1C and HOMAIR). Further investigations are recommended.

179-82

Authors: Tomy Nurtamin, Resty Yulianita Nurman, Indria Hafizah

BACKGROUND: Typhoid fever has become one global health problem. Typhoid fever is caused by a Gram-negative bacterium, Salmonella typhi. Eel (Anguilla spp.) is a fish which lives in the sea or in freshwater. Several previous studies have found that Anguilla spp. mucus has the ability as antibacterial against Gram-positive and negative. Although the antibacterial activity of Anguilla spp. against various pathogens had been reported, very little is known about its activity against Salmonella typhi. The aim of this study was to investigate antibacterial activity of Anguilla spp. mucus against Salmonella typhi bacteria. METHODS: Present study was an experimental in vitro test. Antibacterial activity assays were carried out by the disc diffusion method. Antibacterial activity was determined by the clear zone formed around the paper disc and minimum inhibitory concentration was determined by observing the lowest concentration which could inhibit the growth of Salmonella typhi. RESULTS: Result of the present study showed that the Anguilla spp. mucus has inhibitory effects against Salmonella typhi. Minimum inhibitory concentration from the Anguilla spp. mucus was 12.5%. CONCLUSION: Anguilla spp. mucus has antibacterial activity against the Salmonella typhi bacteria.