Subijanto Marto Sudarmo
Department Of Child Health, Dr. Soetomo Hospital, Faculty Of Medicine Universitas Airlangga, Surabaya, Indonesia

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Zinc Administration Affects Bronchial Mucosal NF-κB p105/p50, p-NF-κB p65, IL-8, and IL-1β of Zinc-deficient Rats 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
The Indonesian Biomedical Journal Vol 12, No 3 (2020)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v12i3.1041

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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.KEYWORDS: zinc, NF-κB, p105/p50, p65, IL-8, IL-1β, rat
MTHFR C677T and TS 5’-UTR 3R/3R Gene Polymorphism in Methotrexate-Resistant Childhood Acute Lymphoblastic Leukemia I Dewa Gede Ugrasena; Harianto Notopuro; Subijanto Marto Sudarmo; Ketut Sudiana; Djajadiman Gatot; Ponpon Idjradinata
The Indonesian Biomedical Journal Vol 12, No 2 (2020)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v12i2.1109

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BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy in Indonesia and often treated by methotrexate (MTX). Though it can be cured in 30-60% of patients, MTX resistance remains the major cause of treatment failure in childhood ALL. Previous sudies showed that its anti-leukemic property was moderated by MTX ability to inhibitmethylene tetra hydrofolate reductase (MTHFR) and thymidylate synthase (TS) in folate metabolism. This study investigates the correlation between MTHFR and TS polymorphism and MTX resistance in ALL children.METHODS: A total of 155 subjects obtained from all subjects prior to chemotherapy. DNA from blood samples were extracted and underwent polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) to evaluate MTHFR C677T and TS 5’-UTR 3R/3R polymorphism.RESULTS: There was significant correlation between MTHFR C677T and TS 5’-UTR 3R/3R gene polymorphism with MTX resistance. Subjectswith MTHFR C677T and TS 5’-UTR 3R/3R gene polymorphism were 4 times (p=0.007) and 6.4 times (p=0.001) more likely to be MTX resistant than those without gene polymorphisms, respectively.CONCLUSION: MTHFR C677T andTS 5’-UTR 3R/3R represent dominant gene polymorphism related to MTX resistance in childhood ALL.KEYWORDS: gene polymorphism, folate metabolism, acute lymphoblastic leukemia
Lactobacillus plantarum IS-20506 Probiotic Restores Galectin-4 and Myosin-1a Expressions in Duodenum, Jejunum and Ileum of Lipopolysaccharide-induced Rats Reza Gunadi Ranuh; Alpha Fardah Athiyyah; Andy Darma; Wibi Riawan; Ingrid Suryanti Surono; Ferry Sandra; Subijanto Marto Sudarmo
The Indonesian Biomedical Journal Vol 12, No 3 (2020)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v12i3.1098

Abstract

BACKGROUND: Galectin-4 and Myosin-1a are important proteins for normal intestinal brush border structure and composition. Damage of these proteins by inflammation may alter digestion, absorption and barrier function. Probiotic has been widely known in maintaining gut health. However, the molecular mechanism of Lactobacillus plantarum IS-2056 probiotic in repairing intestinal brush border is not well defined. Therefore, current study was conducted by investigating the Galectin-4 and Myosin-1a expressions in a rodent model.METHODS: Male Wistar rats were induced with/without lipopolysaccharide (LPS) and treated with/without L. plantarum IS-2056 probiotic. On the seventh day, duodenum, jejunum, and ileum were collected and analyzed with western blot and immunohistochemistry for Galectin-4 and Myosin-1a expressions.RESULTS: Rats administrated with L. plantarum IS-2056 probiotic showed significant increase of Galectin-4 and Myosin-1a expressions in duodenum, jejunum, and ileum compared to the control group (p<0.05). While in control group, Galectin-4 level tended to increase in more distal of intestinal segment and Myosin-1a level tended to decrease in more distal intestinal segment.CONCLUSION: L. plantarum IS-20506 probiotic may facilitate the repairment of damaged intestinal brush border as demonstrated by significant restoration of Galectin-4 and Myosin-1a expressions in duodenum, jejunum, and ileum of LPS-induced rats.KEYWORDS: Lactobacillus plantarum, IS-20506, probiotic, galectin-4, myosin-1a, duodenum, jejunum, ileum
Zinc Supplementation Effect on the Bronchial Cilia Length, the Number of Cilia, and the Number of Intact Bronchial Cell in Zinc Deficiency Rats Andy Darma; Alpha Fardah Athiyyah; Reza Gunadi Ranuh; Wiweka Merbawani; Retno Asih Setyoningrum; Boerhan Hidajat; Siti Nurul Hidayati; Anang Endaryanto; Subijanto Marto Sudarmo
The Indonesian Biomedical Journal Vol 12, No 1 (2020)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v12i1.998

Abstract

BACKGROUND: Airway epithelium is the first line of defense against a variety of exposures. Inflammatory processes, hyperresponsiveness and zinc deficiency cause epithelial damage. Zinc is involved in apoptosis and microtubule formation. However, its role in the integrity of bronchial mucosa and cilia is unclear.METHODS: To assess the effect of zinc on the integrity of the bronchial epithelium, 24 male Rattus norvegicus strain Wistar rats were randomized into four experimental groups: normal zinc diet group without zinc supplementation, normal zinc diet group with 60 ppm zinc supplementation, zinc deficient diet group without zinc supplementation, and zinc deficient diet group with 120 ppm zinc supplementation. Bronchial mucosal integrity was measured with the number of epithelial cells, and the number and length of cilia.RESULTS: Number of cell in normal zinc diet group was 8.8±1.82, while it was only 8.1±1.08 in zinc deficient diet group (p<0.001). Number of cilia per cell was 4.6±1.08 in normal zinc diet group, compared to 4.0±0.79 in zinc deficient diet group (p<0.001). Ciliary length also differ by 7.68±0.66 μm in normal zinc diet group and only 5.16±0.91 μm in zinc deficient diet group (p<0.001).CONCLUSION: Zinc supplementation of the normal zinc diet group affected the length of bronchial cilia. Zinc supplementation of the zinc deficient diet group affected the integrity of the bronchial epithelium, which was shown by the number and length of cilia, and the number of epithelial cells.KEYWORDS: zinc, bronchial epithelial integrity, cilia length, number of cilia, epithelial cell 
THE CLINICAL EPIDEMIOLOGY OF NOROVIRUS INFECTION IN CHILDREN WITH DIARRHEA AT REGIONAL PUBLIC HOSPITAL DR.SOETOMO Alpha Fardah Athiyyah; Sofia Wardhani; Andy Darma; Reza Gunadi Ranuh; Dadik Raharjo; Toshiro Shirakawa; Subijanto Marto Sudarmo
Jurnal Berkala Epidemiologi Vol. 8 No. 3 (2020): Jurnal Berkala Epidemiologi (Periodic Epidemiology Journal)
Publisher : Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/jbe.V8I32020.200-207

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Background: Norovirus has become a major cause of severe outbreaks of gastroenteritis since the discovery of the rotavirus vaccine, with the main symptom being diarrhea. Until now, research on the epidemiological analysis of norovirus has not been carried out at Regional Public Hospital (RSUD) Dr. Soetomo, Surabaya. Purpose: This study aims to provide clinical epidemiology data and an analysis of norovirus infections in children with diarrhea at Regional Public Hospital (RSUD) Dr. Soetomo, Surabaya, Indonesia, including the prevalence of norovirus infection in each age group and sex, its clinical appearance, and its seasonal variation. Methods: A cross-sectional study was conducted in children aged 1–60 months hospitalized for diarrhea in RSUD Dr. Soetomo between April 2013 and March 2014. Identification of the virus in the stool was done by norovirus enzyme immunoassay Quick NaviTM Noro2. The proportion, age, sex, clinical symptoms, and patterns of the norovirus seasonal data were calculated. Results: Norovirus was detected in 64 samples (19%) of the 340 stool samples, with a mean patient age of 11.75 months; it was mostly found in patients less than 24 months of age (95%), and 64% were male. The monthly pattern of norovirus infection was mostly found in November, followed by May and April. The clinical symptoms were fever (72%), vomiting (66%), bloating (59%), abdominal cramps (34%), perianal inflammation (27%), abdominal distension (16%), and seizures (8%). Conclusion: The prevalence of norovirus was found to be high in patients with diarrhea aged 1–60 months hospitalized in RSUD Dr. Soetomo, with a proportion of 19%. Further research is needed to determine the severity of norovirus infection.
Assessment of the Rapid Immunochromatographic Test as a Diagnostic Tool for Norovirus Related Diarrhea in Children Reza Gunadi Ranuh; Alpha Fardah Athiyyah; Deanty Ayu PA; Andy Darma; Dadik Raharjo; Toshiro Shirakawa; Subijanto Marto Sudarmo
Folia Medica Indonesiana Vol. 55 No. 1 (2019): March
Publisher : Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (158.387 KB) | DOI: 10.20473/fmi.v55i1.24377

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In developing countries, Norovirus is the second-leading cause of acute diarrhea, after rotavirus. The approved gold standard method for diagnosis of norovirus infection is RT-PCR. The rapid immunochromatographic test is a novel and expedient method for diagnosing norovirus that is relatively affordable. However, the use of the rapid immunochromatographic test remains controversial because of its accuracy. This study aimed to explore whether the rapid immunochromatographic test could be used for diagnosing norovirus-related diarrhea in children. Rapid immunochromatographic test (QuickNaviTM-Norovirus2) and RT-PCR on stool samples was used to diagnose norovirus. Stool samples were obtained from pediatric patients aged between 1 and 60 months who had diarrhea and were admitted to the pediatric ward at Dr. Soetomo General Hospital Surabaya, between April 2013 and March 2014. Ninety-four subjects provided stool samples that were tested using QuickNaviTM-Noro2 and RT-PCR. Using the test, 64 samples tested positive for norovirus and 30 tested negatives. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the rapid immunochromatographic test were consecutively 90.3%, 42.9%, 43.8%, 90%, and 58.5%. RT-PCR was used to test all samples to assess the accuracy, which showed that one from 31 samples contained the GI strain (1.1%), while 30 samples (32%) contained the GII strain. This study definitively establishes that the rapid immunochromatography test is not sufficiently accurate for use as a screening or diagnostic tool in norovirus-related diarrhea cases in children.
Analytical study of inflammatory cytokines and immunoglobulin expression following dust mite allergen exposure in pregnant mice Risa Etika; Subijanto Marto Sudarmo; Suwarno Suwarno; Muhammad Pradhika Mapindra; Muhammad Pradhiki Mahindra
Paediatrica Indonesiana Vol 61 No 6 (2021): November 2021
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14238/pi61.6.2021.336-42

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Background Allergen tolerability due to allergic immune reactions could be transferred through the placenta from maternal to fetal circulation. Hence, a further investigation regarding the tolerability following mite allergen exposures is desirable. Objective To evaluate various doses of mite allergens and cytokines associated with Th1, Th2, and Treg cells with regards to possible allergic tolerance in neonatal mice. Methods This study used an experimental design with a post-test only control group, to assess the effect of mite allergens on pregnant BALB/C mice and their newborns. In this study female BALB/C mice aged 10 weeks were mated with male mice, then pregnant BALB/C mice were exposed to allergens at 4 weeks gestation. During pregnancy, pregnant females’ blood specimens were taken to measure cytokines and immunoglobulins. Meanwhile, neonatal blood specimens were taken at 2 weeks postnatally to measure cytokines and immunoglobulins. Blood specimens from pregnant BALB/C mice and their newborns were evaluated using ELISA kits for the following cytokines: interleukin (IL)-2, interferon (IFN)-γ, interleukin (IL)-4, IL-5, IL-10, TGF-β1, as well as immunoglobulins (Ig)G-1, IgG-2a, IgG-2b, IgG3 subclass, IgM, IgA, and IgE. The case group was the group that received high and low doses of exposure, while the control group did not get exposure. Results In response to low dose mite allergen exposure, there were significant increases of IL-2, IFN-y, and IL-4, IL-5, and TGF-β1 in mothers and neonates. Pregnant mices that received high doses of allergens, however, had significant increases in IL-5 and TGF-B1; results were likewise for their offspring. Mothers and neonates, had significantly increased expression of IgG subclasses after a low dose of dust mite allergen. Following a ten-fold increase in allergen dose, the mothers showed significant increases in IgA, IgM, IgE, and IgG subclasses, whereas in neonatal mice, those immunoglobulin levels were not significantly different from control mice. Conclusion Exposure to mite allergens can trigger regulatory functions of Th1, Th2, and Tregs cells to activate their cytokines, except IL-10. The regulatory function of Tregs is dominated by TGFβ in maternal and neonatal mice, at low and high doses. Th1 cytokines express cytokines during exposure only to low-dose allergens and Th2 cells regulate IL-5 levels to both low- and high-dose allergens.
The expression of TLR-2 and NOD-2 in gingival epithelium of rat after probiotic Lactobacillus reuteri supplementation to inhibit Streptococcus mutans growth Tuti Kusumaningsih; Subijanto Marto Sudarmo; Retno Indrawati; Rini Devijanti Ridwan; Sidarningsih Sidarningsih
JURNAL PENELITIAN BIOLOGI BERKALA PENELITIAN HAYATI Vol 21 No 1 (2015): December 2015
Publisher : The East Java Biological Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (574.642 KB) | DOI: 10.23869/91

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Lactobacillus reuteri is probiotic from Gram positive bacteria which has specific molecular structure, consisted of peptidoglycan (PG) and lipotheihoic acid (LTA). These structure have potential in pattern recognition receptors (PRRs) activation, such as TLR-2 and NOD-2 that are the up stream of beta defensin-2 (BD-2) signaling cascade. BD-2 is antimocrobial peptides naturally produced in mouth cavity that can against Streptococcus mutans effectively. This study was aimed to prove that probiotic L. reuteri supplementation can increase the expression of TLR-2 and NOD-2 in gingival epithelium. Experimental design in this study was randomized control group post test only design. Study was carried on 24 white rat (Rattus norvegicus) Wistar strain which divided into 4 groups. Positive control was rats that induced with S. mutans, while rats in negative control group were not induced. Group I was rats that suppelemented with L. reuteri for 14 days (day 1-14) and induced with S. mutans for 7 days (day 8-14). Group II was rats that supplemented with L. reuteri and induced with S. mutans simustaneously for 14 days (day 1-14). Concentration of bacterial suspension was 108 cfu ∕ml for L. reuteri and 1010 cfu/ml for S. mutans. Both of these two bacteria was given orally to rats. TLR-2 and NOD-2 expressions were evaluated with immunohistochemistry technique. Significant differences of protein expression between each treatment groud was analyzed with ANOVA (p=0.001). TLR-2 and NOD-2 expressions were higher than negative control. It can be conclude that L. reuteri supplementation as probiotic could increase the expression of TLR-2 and NOD-2 in gingival epithelium of rat.
Clinical Characteristic of Bloody Diarrhea in Under- Five Pediatric Inpatients Steven Christian Susianto; Alpha Fardah Athiyyah; Anak Agung Putri Nadia Paramitha; Eko Budi Koendhori; Khadijah Rizky Sumitro; Andy Darma; Reza Gunadi Ranuh; Subijanto Marto Sudarmo
Archives of Pediatric Gastroenterology, Hepatology, and Nutrition Vol. 1 No. 1 (2022): APGHN Vol. 1 No. 1 May 2022
Publisher : The Indonesian Society of Pediatric Gastroenterology, Hepatology, and Nutrition

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (325.457 KB) | DOI: 10.58427/apghn.1.1.2022.9-16

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Background: Diarrhea is the most common cause of death in under-five children. Bloody diarrhea comprises around 10% of all cases of diarrhea and may lead to severe complications until death. This study examined the characteristics of bloody diarrhea in children under five years old in Dr. Soetomo General Hospital Surabaya from 2013 to 2017. Material and Methods: A retrospective, cross-sectional study was conducted using secondary data from Dr. Soetomo General Hospital's inpatients with bloody diarrhea from 2013 to 2017. Gender, age, nutritional status, clinical symptoms, degree of dehydration, and laboratory results were assessed, and the data were presented in percentage (%) Results: Fifty-six samples were included in this study. The main demographics were male (58,9%), aged 7-24 months (44,6%), and normal nutritional status (66,1%). Meanwhile, the most notable manifestations were stool mucous (55,3%), mild to moderate degree of dehydration (60,7%), and leukocytosis (62%). Eleven patients (39,2%) had temperatures ≥380C. Leukocytes were positive in 93.7% of the stools. Furthermore, amoeba was found in 46,8% of samples. The serum electrolyte result showed hyponatremia (18%) and hypokalaemia (15%). Conclusion: The primary demographics of bloody diarrhea in under-five children admitted to Dr. Soetomo General Hospital were males, 7-24 months of age, and with normal nutritional status. The most frequent manifestations were mucous in stool, mild to moderate dehydration, leucocytosis, as well as positive leucocytes and amoeba in the stool.