The Indonesian Biomedical Journal

1-15

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Mitochondrial dysfunction known to be associated with most of human inherited disorders and diseases, including neurodegenerative disorders, cardiomyopathies, metabolic syndrome, muscle weakness, cancer, also obesity. CONTENT: Mitochondria charges for multiple anabolic and catabolic circuitries, as the main provider for adenosine triphosphate (ATP). Mitochondria also responsible for cellwide stress responses and control non-apoptotic cell death routines, such as autophagy and regulated necrosis. In other words, mitochondria play an extended role in regulating cellular functions, both vital and lethal, from physiological metabolism to stress responses and death to maintain adult tissue homeostasis. Furthermore, mitochondria are crucial for both embryonic and postembryonic development. Therefore, any defect or alteration in mitochondria signaling pathways will lead to a large number of diseases in human, including premature aging, neurodegenerative disorders, muscle weakness, cardiovascular disorders, and cancer. SUMMARY: Mitochondria perform a dynamic, integrated interconnected network, to maintain tissue homeostasis, beyond the cell boundaries and regulating cells and tissues communication. Certainly any mitochondrial dysfunction could direct to neurodegenerative diseases and metabolic disorders.

30-5

Authors: Sri Adi Sumiwi, Ade Zuhrotun, Rini Hendriani, Mochamad Rizal, Jutti Levita, Sandra Megantara

BACKGROUND: Previous works indicated various pharmacology activities of bay plant (Syzygium polyanthum (Wight) Walp.), however only few studies investigated its toxicity. This work was aimed to study the subchronic toxicity of ethanol extract of this plant. METHODS: White Wistar rats were divided into 4 groups and were treated with 2% of Arabic gum (PGA) suspension, 1000 mg/kg of body weight (BW), 400 mg/kg of BW and 100 mg/kg of BW, respectively. The animals were observed on their body weight, hematology, clinical biochemistry parameters, organ index and histopathology. RESULTS: Flavonoids, tannins, polyphenols, saponins, quinones, monoterpenes and sesquiterpenes were detected in dried leaves and ethanol extract of bay plant. An increase of body weight in male and female groups treated with dose 100 and 400 mg/kg BW compared to controls, was observed. Moreover, there was an increase of white blood cell (WBC) in male and female groups treated with S. polyanthum extracts compared to controls, whereas a decrease of red blood cell (RBC) was observed in male groups treated with S. polyanthum extracts in dose-dependent manner compared to control. No significant changes of RBC were seen in female groups, haemoglobin values were not altered by extract treatment. Photomicrographs of liver, kidney, lungs, heart and spleen histopathology of male and female S. polyanthum extract-treated groups showed no significant alteration compared to controls. CONCLUSION: Our study revealed that S. polyanthum extracts does not show toxicity on the body weight, hematology, creatinine and serum glutamic pyruvic transaminase (SGPT), but fatty liver and necrosis are observed in female rats. This result can be beneficial for plant-based drug discovery, particularly this study provides information about the safety of S. polyanthum to be further developed as candidate of phytopharmaceutics.

42-7

Authors: Mona Hmoud AlSheikh, Shayma Ibrahim Almubayadh

BACKGROUND: Vitamin D is an essential nutrient requirement for adults and children for normal metabolism and maintenance of healthy bones. Its deficiency may disrupt homeostasis and contribute to systemic diseases, especially in obese patients. This study aimed to examine the effect of vitamin D on insulin, fasting blood glucose (FBG) and waist-hip ratio (WHR) in young and obese Saudi females with pre-existing hypovitaminosis D. METHODS: The results of this study were based on prospective parallel randomised controlled clinical trial conducted at King Fahd University Hospital in which 30 obese Saudi young females aging 18-23 years with preexisting vitamin D deficiency contributed. Participants were randomly assigned to either vitamin D supplementation group (experimental) or placebo group (control). Subjects of vitamin D group received 50,000 IU/week of cholecalciferol drops and placebo group received 10 mL of normal saline drops for 12 weeks. RESULTS: The results of multivariate repeated measures analysis showed a change in serum 25-Hydroxycholecalciferol levels after vitamin D supplementation (F=296.132, p<0.05). There was also an indication of difference between the vitamin D group and placebo group. The only significant relationship was found between vitamin D and FBG (p<0.05). Supplementation of vitamin D improved FBG but did not contribute to improving insulin level. There was no association between vitamin D supplementation and WHR. CONCLUSION: This study concludes that supplementation of vitamin D improves FBG, but it has no contribution in improving insulin level. No association exists between vitamin D supplementation and WHR. The insignificant correlation of vitamin D intake with WHR and insulin can be attributed to the small sample size, therefore, further research is suggested with large sample size.

52-8

Authors: Supriono Supriono, Asri Nugraheni, Handono Kalim, Mudjiwijono Handaru Eko

BACKGROUND: Transforming growth factor (TGF)-β1 has a pivotal role in liver fibrogenesis. Curcumin effectively prevent the progression of liver fibrosis through inhibition of TGF-β1/Sma and drosophila MAD (Smad) signaling pathway. However, the role of curcumin in the regression of liver fibrosis is still unknown. This study investigated the role of curcumin and TGF-β1 in liver fibrosis regression. METHODS: An experimental Wistar rat model included 6 treatment groups as well as positive and negative control groups. The treatment and positive control groups were injected with carbon tetrachlorid (CCl4) for 9 weeks to induce liver fibrosis. After cessation of injection, 3 of the treatment groups were given curcumin and 3 were given carboxymethylcellulose (CMC) for 2, 5 and 9 weeks, while the positive control was untreated. The negative control was injected with normal saline. TGF-β1 liver tissue levels were analyzed by ELISA, while the TGF-β1 expression in liver cells was analyzed by immunohistochemical assay. The metavir score was used to assess the degree of liver fibrosis. Values of p<0.05 were regarded as statistically significant. RESULTS: Nine weeks of CCl4 injection induced liver fibrosis (metavir F3); and significantly increased TGF-β1 levels and expression in tissues (p=0.00, p=0.021, respectively). Curcumin administration decreased levels and expression of TGF-β1 in the liver and accelerated regression of liver fibrosis. There was a significant correlation between duration of administration of curcumin with an expression of TGF-β1 in the liver tissue (r=0.87; p<0.00). CONCLUSION: Curcumin accelerates regression of liver fibrosis, likely through decreasing of TGF-β1 expression in the liver.

63-9

Authors: Amelia Lorensia, Zullies Ikawati, Tri Murti Andayani, Daniel Maranatha, Mariana Wahyudi

BACKGROUND: Aminophylline (theophylline) is one of the most frequent asthma therapies in Indonesia, although it remains as a narrow therapy. The effects of drugs are individualized and strongly influenced by genetic, one of which is CYP1A2 gene polymorphisms. This study aimed to determine the profile of CYP1A2 polymorphism and theophylline level in asthma exacerbation patients receiving intravenous aminophylline therapy. METHODS: This cross sectional study was conducted in the emergency room (ER), to adults asthma exacerbation patients without complication (n=27), visiting the ER. The gene polymorphism data were compared with theophylline levels in the blood using chi-square test. RESULTS: In the CYP1A2 gene polymorphism profile, the most common heterozygous alleles are T/G genotype of CYP1A2*1E and C/A genotype of CYP1A2*1F. Most homozygote alleles exist in CYP1A2*1D and CYP1A2*1F. There was significant difference between CYP1A2*1D (p<0.005), CYP1A2*1E (p<0.023) and CYP1A2*1F (p<0.000) polymorphisms and theophylline level. CONCLUSION: CYP1A2*1D, CYP1A2*1E and CYP1A2*1F gene polymorphisms had an effect on theophylline levels. However, no one experienced an overdose theophylline, and no correlation between theophylline levels with CYP1A2 gene polymorphism.

78-84

Authors: Arum Kartikadewi, Awal Prasetyo, Lisyani Budipradigdo, Heri Nugroho, Kusmiyati Tjahjono, Arthur Lelono

BACKGROUND: The depletion of glucose transporter 4 (GLUT-4) affects blood glucose level in the type 2 diabetes mellitus (T2DM) patient. Herbals supplementation such as Artemisia annua is known to posses an antidiabetic potency, but its effect on long term glucose control marker, glicated hemoglobin (HbA1C) and muscle GLUT-4 expression still has not been investigated. METHODS: Twenty Wistar rats were divided into four groups (five rats per group). The C1 group was consist of healthy control rats and C2 group was consist of diabetic control rats. Diabetic condition was induced by giving high lard fat diet for 28 days, followed with 30 mg/kgBW of Streptozotocin injection at the 29th day. Meanwhile, T1 and T2 group were consist of diabetic rats, which were supplemented with 50 mg/kgBW and 100 mg/kgBW of Artemisia annua leaf extract, respectively. GLUT-4 expression and HbA1C level were measured at the 14th day post-treatment. RESULTS: The GLUT-4 was expressed 1.8 and two times higher in T1 and T2 group, respectively, compared to C2 group. Meanwhile, HbA1C level in C2 group was two times higher than C1 group (11.95±2.52 compared to 5.61±2.69, p<0.01). Further, the administration of 100 mg/ kgBW Artemisia annua extract caused a slight reduction of HbA1C (11.95±2.52 compared to 8.18±3.53, p>0.05) CONCLUSION: Muscle cell’s GLUT-4 in T1 and T2 group was expressed increasingly and significantly different compared to the C2 group. HbA1C level in T2 was slightly reduced although no significant different compared to C2 group.

91-9

Authors: Mahalul Azam, Susanti Lestari, Sri Ratna Rahayu, Arulita Ika Fibriana, Budhi Setianto, Nyoman Suci Widyastiti, Suhartono Suhartono, Hardhono Susanto, Martha Irene Kartasurya, Udin Bahrudin, Thijs Eijsvogels

BACKGROUND: Inflammation plays an important role in the atherosclerotic process. High-sensitivity C-reactive-protein (hs-CRP) is commonly used as inflammatory biomarker. It is well known that regular physical activity lowers hs-CRP levels, while prolonged exercise induces hs-CRP elevations. However, the relationship of training and exercise characteristics with hs-CRP levels remains not well elucidated. We evaluated baseline and post-exercise hs-CRP levels and its association with training and exercise characteristics. METHODS: Eighty-eight male endurance cyclists were involved. Demographic data, health condition and training characteristics were collected. Baseline and postexercise blood-samples were collected to determine hsCRP concentrations. A hs-CRP cut-off point of 3 mg/L was used. Blood-cell count and biochemical parameters were measured at baseline. Heart rate (HR) was measured during exercise. RESULTS: Cyclists performed 7.3 hours (interquartilerange (IQR) = 5.4-7.5) of endurance exercise at intensity of 81.8 % (IQR = 74.9-85.8). Cyclists with baseline hsCRP ≥ 3 mg/L reported higher body mass, body mass index (BMI), waist-circumference and total-cholesterol. An increase in hs-CRP was following endurance exercise. Cyclists with any elevation of hs-CRP reported a higher BMI, HR during exercise and exercise intensity. Binary logistic regression analysis showed BMI (OR = 1.24, 95% CI = 1.04-1.48) and cycling distance (OR = 0.22, 95% CI = 0.06-0.76) were associated with post-exercise hs-CRP elevations. CONCLUSION: Body mass, BMI, waist-circumference, total- and HDL-cholesterol are associated with baseline hsCRP, whereas BMI and cycling distance were associated with hs-CRP elevations. These findings suggest that anthropometry parameters and lipid levels attributed to baseline hs-CRP, while anthropometry parameters and cycling intensity attributed to post-exercise hs-CRP elevations.

107-12

Authors: Lucky Hartati Moehario, Thomas Robertus, Anis Karuniawati, Rudyanto Sedono, Delly Chipta Lestari, Andi Yasmon

BACKGROUND: Antibiotic resistance has become a worldwide problem. Among Asia countries, Indonesia has high prevalence of multi-drug resistant organisms mainly due to Gram-negative bacilli Enterobacteriaceae. This study aimed to find out whether gene family of AmpC and AmpC/ESBL-producing Enterobacteriaceae were present in the Intensive Care Unit (ICU) of Cipto Mangunkusumo Hospital, Jakarta, Indonesia. METHODS: Specimens were obtained from several body sites of adult patients with infection hospitalised in ICU of Cipto Mangunkusumo Hospital. VITEK®2 was used to identify the microorganisms. Antibiotic susceptibility tests were conducted using VITEK®2 and disc diffusion technique according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Double disc synergy (DDS) test method was employed to detect AmpC activity. Gene families of ampC were identified using multiplex polymerase chain reaction (PCR). RESULTS: Forty five isolates were identified as putative AmpC, extended-Spectrum β-lactamases (ESBL) and AmpC/ESBL-producing Enterobacteriaceae. Klebsiella pneumoniae (n=32) were predominant, followed by Escherichia coli (n=6), Enterobacter cloacae (n=5) and Enterobacter aerogenes (n=2). AmpC activity was detected in 9 isolates, in which 4 isolates were AmpC producing and 5 isolates were AmpC/ESBL. In vitro, AmpC-producing Enterobacteriaceae showed good susceptibility to many antibiotic tested, while those of AmpC/ESBL-producing only to Amikacin. The gene families of ampC were DHA, EBC and CIT identified from 6 isolates. CONCLUSION: DHA, EBC and CIT gene families were identified from AmpC and AmpC/ESBL-producing Enterobacteriaceae in the ICU of Cipto Mangunkusumo Hospital. While the AmpC-producing was still susceptible to almost all antibiotics tested, the AmpC/ESBL-producing showed resistant except for Amikacin.