The Indonesian Biomedical Journal

201-13

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Hypothalamus is the master regulator of body’s systemic homeostasis including energy balance, body temperature, sleep, blood pressure, and circadian rhythms. This review article will highlight the shifting of the old paradigm of obesityinflammation-metabolic syndrome, which was focused on visceral organs and systemic inflammation, into a new model involving microinflammation in the master regulator of endocrine system, i.e., hypothalamus. CONTENT: Since the early stage of over-nutritional conditions and aging process, microinflammation in hypothalamus has started to emerge, due to the activation of several proinflammatory signaling pathways, especially the nuclear factor kappa B (NF-kB) and c-Jun N-terminal kinase (JNK)-mediated nuclear transcriptional programs. Together with intracellular organelle stress signals, these pathways develop a chronic microinflammatory environment in the hypothalamus leading to obesity and metabolic disorders. SUMMARY: Hypothalamic inflammation has been noted not only as an important driver of impaired energy balance, but also contribute in altered neurocircuit functions and promote obesity-associated metabolic impairment.

220-6

Authors: Ronny Lesmana, Setiawan Setiawan, Ferdyan Efza, Yuni Susanti Pratiwi, Gilang Muhamad Nur Iqbal, Hanna Goenawan, Nova Sylviana, Unang Supratman

BACKGROUND: Ethionamide usage as one of the drug regimens still becomes a challenge due to high numbers of patients developing hypothyroid. Ethionamide had been associated with the inhibition of thyroid hormone (TH) synthesis and interestingly, ethionamide (C8H10N2S)-induced hypothyroidism is supported by its similar structure with thioamides, propythiouracil (C7H8N2S). However, hypothyroidism is not solely caused by its production, it could be caused by signaling alteration. Therefore, knowing that important TH action is determined via genomic pathway, alteration of this receptor could bring serious clinical problem. Unfortunately, there is limited study about the regulation of ethionamide and its connection on TH genomic signaling especially thyroid hormone receptor (TR) gene expression in soleus, gastrocnemius and cardiac muscle. METHODS: Thirty-eight rats were divided into control, ethionamide and propylthiouracyl groups. After 12-week treatment, rat were sacrificed, then gastrocnemius, soleus and cardiac muscles were dissected out, snap freezed using liquid nitrogen, and stored in -80oC until use. RNA was extracted and run for reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In soleus muscle, ethionamide stimulated TR mRNA expressions and deiodinase compared to control group. In contrast, TRα1 gene expression was not affected by ethionamide administration. In gastrocnemius muscle, only TRβ1 gene and Dio2 gene expressions that were significantly increased compared to control group. In cardiac muscle, ethionamide significantly stimulated all the thyroid hormone receptor isoform and iodothyronine deiodinase gene expression compared to the control group. CONCLUSION: Long ethionamide treatment upregulates TR gene expressions and deiodinase in soleus and cardiac muscle, there is different expression pattern of soleus, gastrocnemius and cardiac muscle after ethionamide stimulation.

233-8

Authors: Johan Gunadi, Starry Homenta Rampengan, Janry Antonius Pangemanan, Agnes Lucia Panda, Nancy Lampus, Hasjim Hasbullah

BACKGROUND: Heart failure (HF) is a clinical syndrome caused by structural or functional cardiac disorders and is the final stage of every heart disease, marked by decreased functional capacity and patients’ quality of life (QoL). Suppression of tumorigenicity-2 (ST2) is a biomarker depicting heart fibrosis and remodeling that altered left ventricular geometry, which in turn decreases left ventricular contractility, decreases functional capacity, and ultimately affects the QoL of the HF patient. METHODS: An observational study was conducted with a cross-sectional approach involving 60 patients with systolic heart failure. Left ventricular geometry, left ventricular ejection fraction (LVEF), ST2 level, and other biomarkers were examined, continued by QoL assessment. RESULTS: The ST2 level (33.25±23.55 ng/mL) was negatively correlated with LVEF (r=-0.257; p=0.024) and was positively correlated with QoL (r=0.255; p=0.05). The LVEF was negatively correlated with QoL (r=-0.224; p=0.031). However, no significant correlation was found between left ventricular geometry with ST2 level or patients’ QoL. CONCLUSION: Elevated ST2 levels are correlated with decreased LVEF and worse QoL in systolic heart failure subjects. Therefore, ST2 together with LVEF can be used as prognostic tools for patients with HF.

245-50

Authors: Reza Gunadi Ranuh, Andy Darma, Alpha Fardah Athiyyah, Ergia Latifolia, Retno Asih Setyoningrum, Boerhan Hidajat, Siti Nurul Hidayati, Anang Endaryanto, Ferry Sandra, Subijanto Marto Sudarmo

BACKGROUND: Risk of acute respiratory infections in children less than 5 years of age is up to 95%. Zinc deficiency is one of the main risk factors. This study aimed to explore the effect of zinc on the bronchial mucosae inflammatory status expressed by nuclear factor (NF)-κB p105/p50, NF-κB p65, interleukin (IL)-8, and IL-1β. METHODS: Twenty-four Wistar rats were divided into 4 groups: normal zinc diet group without zinc supplementation (Z1), normal zinc diet group with zinc supplementation (Z2), zinc deficient diet group without zinc supplementation (Z3), and zinc deficient diet group with zinc supplementation (Z4). NF-κB p105/p50, p-NF-κB p65, IL-8, and IL-1β were measured by immunohistochemical staining. RESULTS: The inflammatory status of bronchial mucosae between Z1 and Z2 groups showed no difference (p=0.055). However, the inflammatory status of bronchial mucosae between Z3 and Z4 groups showed significant difference (p<0.01). Multivariate factorial design showed that zinc supplementation was beneficial when given to zinc deficient diet group with regard to decrease p-NF-κB p65, IL-8 and IL-1β levels (p<0.001) and increase dendritic cell (p=0.022). CONCLUSION: Zinc administration under conditions of zinc deficiency affects the inflammatory status, as shown by the decrease of p-NF-κB p65, IL-8 and IL-1β and the increase of NF-κB p105/p50.

261-6

Authors: Mas Rizky Anggun Adipurna Syamsunarno, Alif Bagus Rakhimullah, Uni Gamayani, Masahiko Kurabayasi, Tatsuya Iso, Ratu Safitri, Ramdan Panigoro

BACKGROUND: Iron-overload cardiomyopathy (IOC) is a major comorbidity in patients with chronic repetitive blood transfusion due to myocardial iron uptake that facilitated by calcium channels. As cardiac compensatory mechanism to IOC, we hypothesized the cardiac calcium channels expression would be increased and involved in cardiomyopathy progressivity. This study was aimed to investigate the gene expression of calcium channels in the heart of the iron overload mice model. METHODS: Mice were divided into three groups according to iron administration doses 0, 0.1, and 0.3 mg/day. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured for the representation of cardiovascular outcomes. The heart tissues were harvested. Further mRNA levels of L-type calcium channels (LTCCs) and T-type calcium channels (TTCCs) were examined using semi-quantitative PCR. The expressions of cardiac calcium channels and blood pressure among the three groups were compared. RESULTS: The expressions of TTCCs in the two iron-injected groups were higher than the control group (p=0.018). The expressions of LTCCs were not different (p=0.413) among groups. SBP, DBP, and MAP of the iron-injected group were lower than the control group (p=0.025, p=0.011, and p=0.008, respectively). CONCLUSION: Iron administration affects the expression of TTCCs but not the LTCCs, accompanied by decreasing of systolic and diastolic blood pressure.

275-82

Authors: Deddy Satriya Putra, Fadil Oenzil, Eryati Darwin, Hafni Bachtiar, Tofrizal Tofrizal

BACKGROUND: Glutamine, a non-essential amino acid, is the main fuel in the gastrointestinal mucosa. It is thought to protect the intestinal mucosa against local or systemic injury from diarrhea. This study aimed to determine the relationship between glutamine supplementation and ileum histopathology in acute and chronic diarrhea rats induced by enteropathogenic Escherichia coli (EPEC). METHODS: A randomized post-test only control group design was conducted. Thirty Rattus norvegicus Wistar strain were divided into 5 groups: one negative control group, two acute, and two chronic diarrhea groups. All four diarrhea groups were induced by EPEC at a dose of 108 CFU/mL. One acute and one chronic groups were supplemented with glutamine at a dose of 810 mg/200 g body weight for 14 days. While the other two diarrhea groups were not treated. The intestinal histopathology of each group was assessed and the level of inflammation was classified. RESULTS: Significant differences in inflammation levels were found among the groups (p<0.05). The highest inflammation level was observed in the acute diarrhea group without glutamine supplementation. Inflammation levels of both acute and chronic diarrhea with glutamine supplementation groups were significantly lower than the inflammation levels of acute and chronic diarrhea without glutamine supplementation groups. CONCLUSION: Supplementation of glutamine reduces the level of inflammation and leads to the histopathological improvement of the rat’s ileum.