The Indonesian Biomedical Journal

117-28

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Attempts to understand the causes of obesity and develop new therapeutic strategies have mostly focused on caloric intake and energy expenditure. Recent studies have shown that the circadian clock controls energy homeostasis by regulating circadian expression and/or activity of enzymes, hormones, and transport systems involved in metabolism. Moreover, disruption of circadian rhythms leads to obesity and metabolic disorders. CONTENT:Regularly alternating periods of light and darkness, such as normally occur with the rising and the setting of the sun, are essential for the maintenance of undisturbed circadian rhythms in all organisms including humans. The light-dark environment, as detected by specialized photoreceptors in the retinas, impacts the endogenous circadian clock in the anterior hypothalamus, the suprachiasmatic nuclei. These nuclei, via both neural and humoral signals, communicate with cells throughout the organism to establish regular circadian rhythms. The introduction of artificial sources of light roughly 150 years ago has significantly undermined the naturally occurring light-dark environment and, likewise, has disturbed circadian rhythms since light is now available at unusual times, i.e., at night. Light at night is known to cause circadian disruption and melatonin suppression. Many potentially pathophysiological consequences of these artificial light-mediated changes, include cancer, cardiovascular diseases, insomnia, metabolic syndrome, diabetes, and cognitive disorders may be aggravated by the increased exposure to light at night, which is inevitable in well-developed societies that have undergone extensive electrification. SUMMARY: Therefore, it is plausible that resetting of the circadian clock can be used as a new approach to attenuate obesity. Feeding regimens, such as restricted feeding, calorie restriction and intermittent fasting, provide a time cue and reset the circadian clock and lead to better health. In contrast, high-fat diet leads to disrupted circadian expression of metabolic factors and obesity.

147-52

Authors: Theresia Monica Rahardjo

BACKGROUND: Propofol is an intravenous anesthetic used worldwide as an anesthesia induction and maintenance agent. Propofol also used as sedation agent in Intensive Care Unit (ICU). Despite it’s usual anesthesia properties, propofol has an unique pharmacologic characteristic, especially as antioxidant and stress response reduction. These advantages suggested propofol has positive effects when used as an anesthesia agent in surgery or sedation in ICU in conditions when high stress and free radical level are released. CONTENT:Stress response and free radical can be elevated in various conditions including surgery or during care in ICU, especially critical ill patient. Cortisol is a major stress hormone that influences metabolism, cardiovascular and central nervous system, either in acute or chronic phase. Oxidative stress was marked by free radical elevation called Radical Oxygen Species (ROS). Combination of both elements (cortisol and ROS) can worsen patient condition. Propofol with anti-stress and antioxidant properties could be used to reduce stress response and attenuate free radical level in order to improve patient condition. SUMMARY: The anti-stress and antioxidant properties of Propofol are interesting, because these benefits can be added as adjunctive therapy when propofol was used as an anesthetic agent in surgery and a sedation in ICU.

157-62

Authors: Wahyu Widowati, Maesaroh Maesaroh, Nurul Fauziah, Pande Putu Erawijantari, Ferry Sandra

BACKGROUND: Diabetes mellitus (DM) is associated with oxidative reaction and hyperglycemic condition. Human body has an antioxidant defense system toward free radical, but overproduction of free radical causing imbalance condition between the free radical and the antioxidant defense in the body that lead to several diseases, including DM. Glucosidase is an enzyme that hydrolize carbohydrates causing increase of blood glucose level, so by inhibiting this enzyme blood glucose level in plasma could be effectively decreased. Rambutan (Nephelium lappaceum L.) peel has been reported to have many potential roles, such as antioxidant and anti-glycemia. Therefore our current study was conducted to evaluate possible effectivity of Rambutan peel to scavenge free radical and to inhibit α- and β-glucosidases. METHODS:Rambutan peel extraction (RPE) was performed based on maceration method. Geraniin was used as control. For antioxidant study, 2,2-diphenyl-1- picrylhydrazyl (DPPH) free radical scavenging test was performed. For glucosidase inhibitory activity study, α- and β-glucosidases inhibitory activity tests were performed. Results were analyzed for median of Inhibitory Concentration (IC50). RESULTS: The scavenging activity of RPE was comparable with Geraniin. Meanwhile, the α-glucosidase inhibitory activity of RPE was higher than the one of Geraniin. The α-glucosidase-inhibitory-activity IC50 of RPE and Geraniin were 0.106±0.080 μg/ml and 16.12±0.29 μg/ml, respectively. The β-glucosidase inhibitory activity of RPE was also higher than the one of Geraniin. The β-glucosidase-inhibitory-activity IC50 of RPE and Geraniin were 7.02±0.99 μg/ml and 19.81±0.66 μg/ml, respectively. CONCLUSION: Since RPE showed comparable free radical scavenging activity with Geraniin and higher α- and β-glucosidases inhibitory activities than Geraniin, RPE could be suggested as a promising antioxidant and antiglycemic agent.

57-72

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Recent evidence suggested that we grow old partly because of our stem cells grow old as a result of mechanisms that suppress the development of cancer over a lifetime. We believe that a further, more precise mechanistic understanding of this process will be required before this knowledge can be translated into human anti-aging therapies. CONTENT: A diminished capacity to maintain tissue homeostasis is a central physiological characteristic of aging. As stem cells regulate tissue homeostasis, depletion of stem cell reserves and/or diminished stem cell function have been postulated to contribute to aging. It has further been suggested that accumulated DNA damage could be a principal mechanism underlying age-dependent stem cell decline. It is interesting that many of the rejuvenating interventions act on the stem cell compartments, perhaps reflecting shared genetic and biochemical pathways controlling stem cell function and longevity. Strategy to slow down the aging processes is based on caloric restriction refers to a dietary regimen low in calories but without undernutrition. Sirtuin (SIRT)1 and 3, increases longevity by mimicking the beneficial effects of caloric restriction. SIRT3 regulates stress-responsive mitochondrial homeostasis, and more importantly, SIRT3 upregulation rejuvenates aged stem cells in tissues. Resveratrol (3,5,4’-trihydroxystilbene), a natural polyphenol found in grapes and wine, was the most powerful natural activator of SIRT1. In fact, resveratrol treatment has been demonstrated to rescue adult stem cell decline, slow down bodyweight loss, improve trabecular bone structure and mineral density, and significantly extend lifespan. SUMMARY: Tissue-specific stem cells persist throughout the entire lifespan to repair and maintain tissues, but their self-renewal and differentiation potential become dysregulated with aging. Given that adult stem cells are thought to be central to tissue maintenance and organismal survival, SIRT3 may promote organismal longevity by maintaining the integrity of tissue-speciic stem cells.

87-100

Authors: Anna Meilana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: The skin protects mammals from insults, infection and dehydration and enables thermoregulation and sensory perception. Various skin-resident cells carry out these diverse functions. Constant turnover of cells and healing upon injury necessitate multiple reservoirs of stem cells. The skin is a complex organ harboring several distinct populations of stem cells and a rich array of cell types. Advances in genetic and imaging tools have brought new findings about the lineage relationships between skin stem cells and their progeny. Such knowledge may offer novel avenues for therapeutics and regenerative medicine. CONTENT: In the past years, our view of the mechanisms that govern skin homeostasis and regeneration have markedly changed. New populations of stem cells have been identified that behave spatio-temporally differently in healthy tissues and in situations of damage, indicating that a great level of stem cell heterogeneity is present in the skin. There are believed to be distinct populations of stem cells in different locations. The lineages that they feed are normally constrained by signals from their local environment, but they can give rise to all epidermal lineages in response to appropriate stimuli. Given the richness of structures such as blood vessels, subcutaneous fat, innervation and the accumulation of fibroblasts under the upper parts of the rete ridges (in the case of human skin), it is reasonable to speculate that the microenvironment might be essential for interfollicular epidermal homeostasis. The bloodstream is probably the main source of long-range signals reaching the skin, and cues provided by the vascular niche might be essential for skin homeostasis. SUMMARY: A key function of the interfollicular epidermis is to act as a protective interface between the body and the external environment, and it contains several architectural elements that enable it to fulfill this function. All elements of the epidermis play active roles in regulating skin function, which might not have been anticipated from their role in maintaining skin integrity. Skin cell research benefits from the integration of complementary technologies and disciplines. How skin function is regulated and how it may be possible to intervene to treat a variety of skin conditions. Ultimately also impairing the maintenance of self-renewing satellite cells. Therefore, only anti-aging strategies taking both factors, the stem cell niche and the stem cells per se, into consideration may ultimately be successful.

107-10

Authors: Britanto Dani Wicaksono, Enos Tangkearung, Ferry Sandra

BACKGROUND: Brucea javanica extract has been reported to have anti-proliferative and cell death induction activities. B. javanica extract was reported to induce apoptosis through caspase cascade. Most of investigated B. javanica extracts were derived from seeds and fruits, or commercially available oil emulsion. Therefore we conducted a study on B. javanica leaf extract (BJLE) in oral cancer cells. METHODS: B. javanica leaves were collected, identified, minced, dried, extracted with distilled ethanol at room temperature for 24 hours, filtered and evaporated. Resulted BJLE was stored at 4°C. Human oral squamous cell carcinoma (HSC)-2 cells were fasted for 12 hours and treated with BJLE in various concentrations for 24 hours. Cells were then quantified with 3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide (MTT) assay, demonstrated with 4',6'-diamidino-2-phenylindole (DAPI) staining. To find out mitochondrial membrane permeability (MMP), mitochondrial membrane potential (ΔΨM) was analyzed. RESULTS: BJLE reduced percentage of viable HSC-2 cells in a concentration dependent manner. BJLE induced apoptosis in HSC-2 cells. With treatment of 50 μg/ml BJLE, fragmented nuclei were seen. ΔΨM of HSC-2 cells treated with 50 μg/ml BJLE were shifted to the left, meaning that BJLE induced reduction of ΔΨM and attenuation of MMP. CONCLUSION: Our results suggested that BJLE could induce apoptosis by attenuating MMP.

1-14

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life. CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Resveratrol have been shown to prevent and reduce the severity of age-related diseases such as atherosclerosis, stroke, myocardial infarct, diabetes, neurodegenerative diseases, osteoarthritis, tumors and metabolic syndrome, along with their ability to extend lifespan. SUMMARY: The purpose of aging research is the identification of interventions that may avoid or ameliorate the ravages of time. In other words, the quest is for healthy aging, where improved longevity is coupled to a corresponding healthspan extension. It is only by extending the healthy human lifespan that we will truly meet the premise of the Roman poet Cicero: “No one is so old as to think that he may not live a year.”

31-6

Authors: Djanggan Sargowo, Ferry Sandra

BACKGROUND: Acute myocardial infarction (AMI) is one of cardiovascular diseases with high morbidity and mortality rates. Novel biomarkers that can detect accurately acute coronary syndrome (ACS) at early stage, are necessary to improve current strategies and/or to identify subjects who are at risk. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP) roles in inflammation process could be potential for ACS early detection. This study was conducted to evaluate measurements of fibrinogen and hs-CRP on ACS. METHODS: An analytic observational study with cross sectional approach was conducted on patients with Troponin I positive. After signing informed consent, anamnesis and complete blood count were conducted. Besides that, liver function, renal function, and blood glucose tests were conducted as well. Samples of selected subjects were quantified with enzyme-linked immunosorbent assay (ELISA) for Troponin I, fibrinogen and hs-CRP. Then statistical analyses were performed. RESULTS: There were 76 subjects in each ACS and non-ACS groups. ACS group showed significant higher levels of both fibrinogen and hs-CRP compared to Non-ACS group (p=0.000). Among evaluated risk factors, diabetes mellitus (DM) (p=0.003) and hypertension (p=0.000) were significantly higher in ACS group than in non-ACS group. Among evaluated clinical factors, blood glucose (p=0.001) and age (p=0.000) were significantly higher in ACS group than in non-ACS group. Combination of fibrinogen and hs-CRP measurements showed the highest sensitivity (75.00%), specificity (80.26%), accuracy (77.63%), positive predictive value (79.19%) and negative predictive value (76.25%). CONCLUSION: Since fibrinogen and hs-CRP were increased in ACS group and combination of fibrinogen and hs-CRP measurements showed the highest sensitivity, specificity, accuracy, positive predictive value and negative predictive value, we suggest that combination of fibrinogen and hs-CRP measurements could give added value to identify ACS.

43-8

Authors: Lisa Aditama, Dewi Rahmawati, Nani Parfati, Astrid Pratidina

BACKGROUND: The prevalence of obesity is increasing and tends to be higher in adult population groups who are also more educated and employed as a civil/military/police/oficers. This study aims to analyze cardiovascular disease (CVD) risk, perceptions about physical activity and barriers experienced to perform physical activity, also stage of change to physical activity. METHODS: The study design was an observational study, use qualitative methods with in-depth interviews and quantitative analysis CVD risk also stage of change to physical activity questionnaire. RESULTS: Framingham 10-years CVD risk of obese men in University of Surabaya was 11.97% (1.70 to 29.90) based on lipid profile and 13.90% (2.30 to 30.00) based on body mass index. Perception of obese men in University of Surabaya regarding physical activity had findings several barriers that can be grouped into time constraint, facility constraint, low motivation, and knowledge about physical activities. CONCLUSION: In this study we found that 10-years CVD risk of obese men in University of Surabaya can be categorized as medium risk. There are several barriers regarding life style modification for physical activity and exercise, whereas the subjects included in this study are quite ready to start the program, but improvement for the readiness before starting the program will still be needed.