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"Latar Belakang. Kelahiran bayi prematur di Indonesia menempati peringkat ke-5 di dunia. Sebanyak 50% bayi prematur memiliki risiko kematian yang lebih tinggi akibat infeksi, dimana 90% diantaranya disebabkan oleh infeksi saluran cerna. Hal ini dikaitkan dengan imaturitas saluran cerna. Spermin, senyawa poliamin, diketahui berperan penting dalam proliferasi, pertumbuhan, serta diferensiasi sel. Pada saluran cerna, spermin diketahui berinteraksi dengan protein penyusun barier usus dan berperan penting dalam penyembuhan luka serta sistem imun. Belum pernah dilakukan penelitian mengenai efek spermin selama masa gestasi, sehingga efek spermin terhadap maturasi usus in utero menjadi penting untuk diketahui. Tujuan. Untuk mengetahui pengaruh suplementasi spermin dalam diet terhadap maturasi protein tight junction selama masa gestasi yang berbeda pada kelinci. Metode Penelitian. Desain penelitian merupakan studi analitik eksperimental menggunakan hewan coba kelinci New Zealand White (Oryctolagus cuniculus), yang dilakukan di Laboratorium Hewan Coba Puslitbang Biomedis dan Teknologi Dasar Kesehatan Badan Litbangkes Kementrian Kesehatan Republik Indonesia, Departemen Histologi FKUI, Departemen Biokimia dan Biologi Molekuler FKUI, dan Laboratorium Terpadu FKUI mulai dari bulan Oktober 2018 - September 2019. Setelah dilakukan anestesis umum, sampel jaringan usus halus janin kelinci diambil dan dibagi dalam 6 kelompok yang terdiri dari kelompok perlakuan (dengan suplementasi spermin 20 mg/kgBB) dan kelompok tanpa perlakuan (tanpa suplementasi spermin), masing-masing kelompok berasal dari induk kelinci dengan usia gestasi 24 hari, 26 hari, dan 28 hari. Jumlah masing-masing kelompok adalah 4 induk gestasi dengan berat badan berkisar antara 3-3,5 kg dengan janin berkisar 5-9 ekor per induk gestasi. Jaringan usus halus dari setiap kelompok diambil untuk pemeriksaan biokimia menggunakan teknik ELISA untuk β-actin, β-catenin, dan occludin, serta pemeriksaan histomorfologi dengan pewarnaan hematoxyllin-eosin. Analisis statistik menggunakan uji Mann-Whitney U, uji Chi Square dengan uji Fisher untuk data proporsi, dan uji korelasi Spearman untuk data numerik. Hasil. Tidak ditemukan perbedaan konsentrasi β-actin, β-catenin, dan occludin antar kelompok perlakuan dan non perlakuan. Pada kelompok perlakuan dan tidak pada kelompok non-perlakuan, ditemukan adanya korelasi positif bermakna antara konsentrasi β-actin dan β-catenin, β-actin dan occludin, serta β-catenin dan occludin. Hasil skoring maturasi barier pada kelompok dengan suplementasi spermin pada usia gestasi 24 dan 26 hari mendekati kelinci aterm. Simpulan. Suplementasi spermin dalam diet selama masa gestasi memperbaiki interaksi antar molekul tight junction pada janin kelinci prematur.

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Background. Indonesia is ranked 5th as a country with premature births. Half of the premature infants carry higher risks of death, in which 90% are due to gastrointestinal tract infection — these cases associated with the immaturity of the gastrointestinal tract system. Spermine is a polyamine molecule known for its essential role in cell proliferation, growth, and differentiation. Previous studies reported that spermine could interact with junctional proteins in the small intestine and responsible for maintaining the intestinal barrier integrity. However, to date, the efficacy of dietary spermine supplementation during the gestation period in utero remains unclear. Thus, an investigation is required. The purpose of the present study is to investigate the mechanism of spermine in improving intestinal villi barrier in premature rabbit fetus.

Aim. To investigate the effect of spermine supplementation in diet on the maturation of intestinal tight junction proteins during different rabbit gestation period.

Method. This study was an analytical, experimental study on New Zealand White Rabbits (Oryctolagus cuniculus) as animal models, performed at Laboratorium Hewan Coba Puslitbang Biomedis dan Teknologi Dasar Kesehatan Badan Litbangkes Kementrian Kesehatan Republik Indonesia, Departments of Histology FKUI, Department of Biochemistry and Molecular Biology FKUI, and Integrated Laboratory FKUI, from October 2018 until September 2019. Following general anesthesia, rabbit fetal intestinal specimens were taken and divided into six groups, consisting of groups given the intervention (spermine 20 mg/kg BW supplementation) and groups without intervention, each group based on the gestation period of 24 days, 26 days, and 28 days. β-actin, β-catenin, and occludin of ileal portion were determined and was stained by hematoxyllin-eosin for histomorphological assessment. Statistical analysis was carried out using the Mann-Whitney U test, Chi-Square test with Fisher test for data proportion, and Spearman’s rank correlation for numeric data.

Results. There was no significant difference for β-actin, β-catenin, dan occludin concentration between groups with- and without spermine supplementation. Significantly positive correlation was obtained in the groups with- but not in the groups without spermine supplementation, between concentration of β-actin and β-catenin, β-actin and occludin, as well as β-catenin and occludin. The barrier scoring of ileal histomorphology in groups with spermine supplementation at gestation period of 24 dan 26 days were similar to a mature fetus.

Conclusion. Spermine supplemented diet given during the gestation period improves the interaction between proteins composing tight junction in premature fetal rabbits."

"Pengaruh Prekondisi dan Hipotermia pada Cedera Iskemia-Reperfusi Terhadap Endotel Pembuluh Darah Perifer pada Oryctolagus cuniculusM Febriadi Ismet1 Yefta Moenadjat2 Aria Kekalih3 1Program Studi Ilmu Bedah, Fakultas Kedokteran Universitas Indonesia2Departemen Medik Ilmu Bedah, RSUPN Cipto Mangunkusumo Pendahuluan. Cedera iskemia -reperfusi CI/R merupakan masalah serius yang dihadapi pascahipoksia; menyebabkan kerusakan sel yang letaknya remote organ injury. Intervensi prekondisi iskemia-reperfusi PI/R merupakan fenomena jaringan yang diberikan stimulasi hipoksia berulang sebelum mendapatkan keadaan iskemia lama. Keadaan hipotermia iskemia reperfusi HI/R menyebabkan metabolisme sel menurun termasuk respon sel terhadap iskemia. Penelitian ini bertujuan untuk mengetahui efek intervensi PI/R dan HI/R terhadap perubahan morfologi endotel pembuluh darah dan peningkatan kadar malondialdehyde MDA sebagai respon stress oksidatif pada jaringan endotel a/v femoralis komunis distal obstruksi iskemia dan kontralateral CI/R. Metode: Studi eksperimental yang bersifat deskriptif analitik pada Oryctolagus cuniculus, Pada kelompok CI/R dilakukan ligasi arteri femoralis komunis dalam pembiusan selama empat jam untuk menginduksi iskemia. Pada kelompok PI/R dilakukan dengan ligasi berulang arteri femoralis komunis kanan selama dua menit, dilepaskan tiga menit sebanyak dua siklus, kemudian diligasi selama empat jam. Pada kelompok hipotermia, dilakukan ligasi arteri femoralis komunis selama empat jam yang disertai dengan membungkus ekstremitas bawah kanan dengan es dengan target suhu antara 31-33 C, kemudian pada ketiga intervensi ligasi dibuka dan kelinci dibiarkan beraktivitas selama delapan jam. Setelah itu, dilakukan pengambilan sampel a.v yang berasal dari distal dari ligasi ipsilateral dan kontralateral untuk pemeriksaan histopatologi dan biokimia. Pemeriksaan biokimia dilakukan menggunakan malondialdehid MDA. Hasil: Pada pemeriksaan histomorfologi menunjukan perbedaan bermakna antara skoring kerusakan endotel jaringan a.v. ipsilateral pada ketiga sampel intervensi dibanding kontrol dan nilai sampel intervensi preventif lebih baik daripada sampel CI/R p< 0,05 . Pada sampel a.v kontralateral kelompok PI/R dan HIR tidak memiliki perbedaan bermakna dengan kontrol p> 0,05 . Pada evaluasi kadar MDA ditemukan kadar MDA meningkat pada semua intervensi baik pada CIR, PI/R, dan HI/R yang tidak berbeda bermakna dengan kontrol p> 0,05. Konklusi: Keadaan CI/R menyebabkan disfungsi endotel bukan hanya pada daerah iskemik, namun pada organ yang letaknya berjauhan. Kerusakan endhotelial lining dapat dicegah dengan tindakan PI/R dan HI/R dan peningkatan kadar MDA merupakan respon fisiologis jaringan terhadap iskemia dan cedera reperfusi yang terjadi baik pada CI/R, PI/R, dan HI/R.

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The Effect of Preconditioning and Hypothermia in Ischemia Reperfusion Injury to the Endothelial Cells from Peripheral Blood Vessels in Oryctolagus cuniculusM Febriadi Ismet1 Yefta Moenadjat2 Aria Kekalih31General Surgery Science Study Program, Faculty of Medicine Universitas Indonesia2Department of Surgery, Dr. Cipto Mangunkusumo National General HospitalIntroduction. Ischemia reperfusion injury IRI is a serious problem in the post hypoxia period, which causes remote organ injury. Ischemic preconditioning IPC is a phenomenon where tissues are subjected to repeated hypoxic stimulations to protect against subsequent prolonged period of ischemia. Hypothermia during ischemia reperfusion injury HI decreases metabolism of cells including their response to ischemia. The goal of this study is to investigate the effects of interventions such as IPC and HI on the morphology of endothelial cells in blood vessels and the increased level of malondialdehyde MDA as an oxidative stress response in endothelial tissues of distal common femoral artery and vein obstruction ischemia and its contralateral IRI.

Method: This is a descriptive and analytic experimental study using Oryctolagus cuniculus. In the IRI group, the common femoral artery was ligated during anesthesia for four hours to induce ischemia. In the IPC group, the right common femoral artery was continually ligated for two minutes, which was then released for three minutes for two cycles, and then ligated for four hours. In the hypothermia group, the common femoral artery was ligated for four hours and the right lower extremity was wrapped in ice with the target temperature range between 31 33o C. Then the arteries from the three interventions were unligated and the rabbit was released to observe its activity for eight hours. Next, samples of artery and vein distal from the ligation ipsilateral and its contralateral were obtained for histopathological and biochemical examinations. The biochemical analysis was performed using malondialdehyde MDA.

Results: The histomorphological examination showed significant difference in the injury scores between the endothelial tissues from ipsilateral artery and vein in the three interventional samples compared with control, and the scores for the preventive intervention groups were better than the IRI sample p0.05.

Conclusion: Ischemic reperfusion injury can cause not only endothelial dysfunction in the ischemic area, but also remote organ injury. Endothelial lining injury can be prevented by IPC and HI. The elevated level of MDA is a physiological response of tissue after ischemia reperfusion injury which could be found on IRI, IPC, and HI."

"PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT.METHODS: Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i.p. for 2 days), and the CPT-11 and TU-100 co-treated group (1000 mg/kg, p.o. for 5 days). All of the rats were sacrificed on day 6 and their tissues were collected.RESULTS: CPT-11 and TU-100 co-treatment improved CPT-11 the related cytotoxicity in vitro. All CPT-11-treated rats developed different grades of diarrhea and BT was observed in 80% of the rats. CPT-11 caused a significant increase in the expression of TLR4, IL-6, TNF-α, IL-1β and caspase-3 mRNAs in the large intestine. The expression of tight junction (TJ) marker mRNAs (occludin, claudin-1 and 4, and ZO-1) was significantly decreased in comparison to the control group. TU-100 co-treatment significantly reversed diarrhea, BT, and the expression of TLR2, IL-6, TNF-α, IL-1β and caspase-3, and improved the expression of occludin, claudin-4 and ZO-1.CONCLUSIONS: TU-100 can suppress the adverse effects associated with CPT-11 and improve the function of the TJ. It is possible that this occurs through the TLR pathway."

"Pendahuluan: Cedera iskemia reperfusi CI/R merupakan masalah serius yang dihadapi pascahipoksia menyebabkan kerusakan sel yang letaknya berjauhan remote organ injury. Strategi yang digunakan untuk mengurangi kerusakan hepar pascaiskemia adalah melalui penerapan ischemic pre conditioning PI/R dan hiportemia. PI/R telah terbukti mengurangi kerusakan jaringan melalui mekanisme resistensi terhadap iskemia dan kebutuhan energi lebih rendah. Sedangkan hipotermia menghambat laju kematian sel sehingga dapat diterapkan sebagai terapi awal pada tatalaksana trauma dengan tujuan mencegah kerusakan bertambah berat. Penelitian ini bertujuan untuk diketahuinya efek protektif PI/R dan hipotermia terhadap perubahan morfologi jaringan hepar dan peningkatan kadar malondialdehyde MDA sebagai respon stress oksidatif. Metode: Studi eksperimental pada 24 ekor Oryctolagus cuniculus. Kelompok iskemia dilakukan ligasi arteri femoralis komunis dalam pembiusan selama empat jam untuk menginduksi iskemia, kemudian ligasi dibuka dan kelinci dibiarkan beraktivitas selama delapan jam. Pada kelompok PI/R dilakukan ligasi berulang arteri femoralis komunis kanan selama dua menit, dilepaskan tiga menit sebanyak dua siklus, kemudian diligasi selama empat jam. Kelompok hipotermia, dilakukan iskemia disertai membungkus ekstremitas bawah kanan dengan es, suhu antara 31-33oC Kemudian dilakukan laparotomi, dan diambil organ hepar. Pemeriksaan histopatologi hepar dilihat dari 3 zona, sentral, midzonal, perifer. Untuk menilai stress oksidatif jaringan dilakukan pemeriksaan biokimia dengan malondialdehyde MDA. Dilakukan uji statistik terhadap variabel tersebut dengan kemaknaan. Hasil: Pada pemeriksaan histomorfologi terdapat perbedaan perubahan histomorfologi pada sampel kontrol PI/R, dan Hipotermia terhadap iskemia (p<0,05). Derajat kerusakan histomorfologi pada kelompok PI/R lebih rendah dibandingkan kelompok iskemia reperfusi pada semua zona (p sentral = 0,015, p medial = 0,019, p perifer = 0,026). Analisis kadar MDA memperlihatkan terjadi peningkatan pada kelompok iskemia reperfusi menujukkan adanya stress oksidatif. Kadar MDA pada kelompok PI/R dan hipotermia lebih rendah dibandingkan kelompok iskemia.(p = 0,002). Konklusi: Keadaan iskemia reperfusi menyebabkan perubahan histomorfologi dan stres oksidatif sel–sel hepar. PI/R dan hipotermia mempunyai efek protektif pada cedera iskemia reperfusi. Efek protektif PI/R lebih baik dari hipotermia.

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Introduction: Ischemia-reperfusion injury IRI is a serious problem occuring after hypoxia it causes injuries to cells located remotely from one another remote organ injury. Strategies used to decrease hepatic injuries post ischemic condition are composed as ischemic pre-conditioning IPC and hypothermia management procedures. IPC has been proven to decrease tissue injuries through resistance mechanisms towards ischemia and lower energy requirements. Meanwhile, hypothermia detained the rate of cell deaths, therefore, it can be used as initial therapy on trauma management in order to prevent worsening of the injuries. This research aims to evaluate the protective effects of IPC and hypothermia towards morphological changes of hepatic tissues and the increase of malondialdehyde MDA level as a response to oxidative stress.Methods.

Methods: This research is an experimental, descriptive-analytical study on 24 Oryctolagus cuniculus. The specimens were divided into four groups, with one group as control. The ischemia group underwent femoral artery ligations under anesthesia for four hours to induce ischemia. Afterwards, the ligations were released and the rabbits were free to roam for eight hours. The IPC group underwent repeated ligations of right communal femoral artery for two minutes and three minutes of release in two cycles. Afterwards, the arteries were ligated for four hours. The hypothermia group underwent ischemia and wrapping of right lower extremities using ice, with temperature around 31-33oC. Afterwards, laparotomies were conducted on all groups to obtain and evaluate the liver. Hepatic histopathology assessment were conducted from 3 zones, the central, midzone, and peripheral zone. To evaluate the effects of oxidative stress on the tissue, a biochemical assessment with malondialdehyde MDA was conducted. Statistical tests were then conducted to assess the relationship between the variables with significance level p < 0.05.

Results: On histomorphological assessment, there were histomorphologic changes on control samples for IPC and hypothermia compared to ischemia p < 0.05. On MDA level analysis, there were increases in all four groups p < 0.05. However, there were no significant differences for the histomorphological changes when compared between central, medial, and peripheral zones.

Conclusion: Ischemic reperfusion condition causes histomorphological changes and oxidative stress on hepatic cells. IPC and hypothermia have protective effects from ischemia-reperfusion injuries. The protective effects of IPC was better than hypothermia."

"Pendahuluan: Periodontitis merupakan suatu penyakit inflamasi terkait bakteri yang dikarakteristikan dengan interaksi antara sistem pertahanan tubuh host dan patogen. Porphyromonas gingivalis (P.gingivalis) merupakan salah satu bakteri red complex yang berperan dalam menginisiasi terjadinya periodontitis. Gingiva merupakan lini pertahanan mekanis, yang disebut sebagai gingival barrier function. Tight junction gingiva merupakan salah satu yang berperan dalam fungsi pertahanan tersebut dan kemampuan tubuh dalam merespon patogen dipengaruhi oleh usia. Tujuan: Mendapatkan perbedaan ekspresi gen tight junction gingiva terhadap stimulasi P.gingivalis. Metode: Studi eksperimental menggunakan jaringan gingiva tikus usia 18 minggu dan 35 minggu. Sampel kemudian dikultur dan diberikan stimulasi live P.gingivalis dan hasil sekresi P.gingivalis. Pengukuran dilakukan untuk menilai laju proliferasi, laju metabolisme, dan ekspresi tight junction sel gingiva tikus. Hasil: Sel gingiva tikus tua menunjukkan laju proliferasi yang lebih tinggi dibandingkan sel gingiva tikus tua, namun pada uji statistik tidak terdapat perbedaan signifikan pada kedua kelompok. Terdapat kecenderungan peningkatan laju metabolisme dan ekspresi gen tight junction gingiva yang lebih tinggi pada sel gingiva tikus muda dibandingkan sel gingiva tikus tua, namun pada uji statistik tidak terdapat perbedaan signifikan pada kedua kelompok. Kesimpulan: Tidak terdapat perbedaan ekspresi gen tight junction gingiva terkait usia.

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Introduction: Periodontitis is an inflamatorry disease associated with the interaction of host immune systemn and pathogen. Porphyromonas gingivalis is one of the red complex bacteria that plays important role in initiating periodontitis. Gingiva act as mechanical defense towards the pathogen, which is known as the gingival barrier function,including gingival tight junctions. Body’s ability to respond stimuli and environmental condition is influenced by age, this also affect the respond of host immune system to pathogens. Objective: To analyse the tight junction gene expression to Porphyromonas Gingivalis intervention. Material and Methods: Aging experimental model was conducted by using two age categories male rodents, 18 and 58 weeks. Rodents gingival cell was intervened with Porphyromonas gingivalis and its product from the broth medium. Meassurements were made to analyse the proliferation rate, metabolic rate, and gingival tight junction gene expression. Result: The old rodent group shows higher proliferation rate, but there was no statistically differences between two groups. There was a tendency of increase value for the metabolic rate and gingival tight junction gene expression in young rodent group compare to old rodent group. Conclusion: There was no differences of the gingival tight junction expression in related to aging."

"Pendahuluan: Revaskularisasi segera jaringan yang telah iskemia, tidak selalu membuahkan hasil yang diharapkan. Berbagai reaksi yang timbul dari pembentukan reactive oxygen species dan aktivasi sistem komplemen menyebabkan cedera iskemia reperfusi. Ischemia preconditioning PRC dan hipotermia diduga dapat mengurangi efek dari cedera iskemia reperfusi. Metode: Penelitian eksperimental ini adalah lanjutan dari penelitian sebelumnya, di mana dilakukan uji statistika terhadap kelompok kontrol dan tiga kelompok perlakuan, yaitu cedera reperfusi IRI, ischemia preconditioning PRC, dan hipotermia. Data kelompok kontrol dan IRI diambil dari penelitian sebelumnya. Kelompok PRC dan hipotermia masing-masing menggunakan enam hewan coba Oryctolagus cuniculus. Pada kelompok PRC dilakukan ligasi arteri femoralis komunis kanan selama dua menit, dilepaskan tiga menit sebanyak dua siklus. Pada kelompok hipotermia dilakukan pembungkusan ekstremitas bawah kanan dengan es. Kemudian kedua kelompok dilanjutkan dengan dilakukan pengikatan arteri femoralis komunis kanan selama empat jam, dan kemudian ikatan dilepaskan selama delapan jam. Kemudian dilakukan laparotomi, dan diambil organ gaster. Bagian antrum diambil untuk pemeriksaan histopatologi dan biokimia. Pemeriksaan biokimia dilakukan menggunakan malondialdehid MDA. Hasil: Uji hipotesis dari perbedaan histopatologi dan biokimia secara keseluruhan bermakna secara statistik. Derajat kerusakan secara histopatologi pada kelompok ischemia preconditioning lebih rendah dengan signifikan dibandingkan kelompok IRI; namun secara biokimiawi, lebih tinggi namun tidak signifikan. Derajat kerusakan secara histopatologi pada kelompok hipotermia lebih rendah namun tidak signifikan dibandingkan dengan kelompok IRI; namun secara biokimiawi, lebih tinggi dengan signifikan dibandingkan dengan kelompok IRI. Bila membandingkan PRC dan hipotermia, secara histopatologi, PRC lebih rendah dengan signifikan. Secara biokimia, rerata PRC lebih rendah namun tidak signifikan. Kesimpulan: Ischemia preconditioning memiliki efek protektif terhadap dampak destruktif yang yang dihasilkan oleh ischemia reperfusion injury terhadap organ jauh. terhadap organ jauh. Hipotermi juga memiliki efek protektif, namun tidak sebaik ischemia preconditioning.

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Background: Immediate revascularization of ischemic tissue, does not always produce the expected results. Various reactions that arise from the formation of reactive oxygen species and the activation of the complement system cause ischemia reperfusion injury. Ischemia preconditioning PRC and hypothermia are thought to reduce the effects of ischemic reperfusion injury.

Methods: This experimental study was performed on the control group and three treatment groups, namely reperfusion injury IRI, ischemia preconditioning PRC, and hypothermia. Two experimental animals were used in control group and six experimental animals were used in IRI, PRC and hypothermia groups. In IRI group, right common femoral artery was ligated for four hours, and released for eight hours. In the PRC group, ligation of right common femoral artery was performed for two minutes and released for three minutes in two cycles. In the hypothermia group, right lower extremity was wrapped with ice. Subsequently, in the two groups, the right common femoral artery was ligated and released like IRI group. Then, laparotomy was performed and the stomach was taken. The antrum part is acquired for histopathology and biochemistry assay. Biochemical examination was performed using malondialdehyde MDA.

Results: The hypothesis test of histopathologic and biochemical differences in general was statistically significant. The degree of histopathological damage and MDA in IRI group was significantly higher than control group. The degree of histopathological damage in the PRC group was significantly lower than in the IRI group but biochemically, higher but not significant. The degree of histopathologic damage in the hypothermia group was lower, but not significant, compared to the IRI group but biochemically, significantly higher than the IRI group. When comparing PRC and hypothermia, histopathologically, PRC is significantly lower. Biochemically, the mean PRC is lower but not significant.

Conclusion: Ischemia preconditioning has a protective effect on the destructive impact of ischemia reperfusion injury in distant organs. Hypothermia also has a protective effect, but is not as good as ischemia preconditioning."

"Introduksi: Iskemia yang terjadi di suatu lokasi di tubuh mengakibatkan kerusakan pada lokasi yang berjauhan; kondisi ini dikenal dengan sebutan cedera reperfusi. Vili intestinal merupakan satu target organ terjadinya kerusakan pada cedera reperfusi dan menjadi motor kegagalan multi organ sistemik. Hipotermia yang ditakuti pada syok justru menunjukkan keuntungan karena bersifat proteksi terjadinya kerusakan vili. Penelitian ini bertujuan membandingkan efek protektif hipotermia dan pre-conditioning pada iskemia.Metode. Dilakukan penelitian eksperimental pada kelinci New Zealand White (n=18) dengan satu kelompok kontrol (iskemia) dan dua kelompok perlakuan (hipotermia dan pre-conditioning). Dilakukan ligasi a. iliaca communis selama 4 jam, hipotermia sedang (28°C), dan iskemia pre-conditioning pada masing-masing kelompok. Kemudian kelinci dibiarkan hidup selama 8 jam. Setelah dekapitasi, diambil sampel ileum untuk pemeriksaan histopatologi.Hasil: Dari 18 kelinci eksperimental, 1 mengalami drop out karena infeksi. Dilakukan skoring kerusakan vili intestinal berdasarkan kriteria Pusponegoro yang dimodifikasi dengan nilai minimal 4 dan maksimum 12. Kelompok perlakuan pre-conditioning mengalami kerusakan paling minim (= 6,2 ) diikuti kelompok hipotermia (= 7,1).Konklusi: Pre-conditioning menunjukkan kerusakan paling minim; dengan kata lain memberi efek proteksi lebih baik dibandingkan dengan kelompok lainnya.

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Introduction: Ischemia occurring in a location in the body results in damage to distant locations; this condition is known as reperfusion injury. Intestinal vilia is a target organ of the occurrence of damage to reperfusion injury and a motor failure of multi-organ systemic. The dreaded hypothermia in shock actually shows an advantage because it protects the occurrence of villous damage. This study aimed to compare the protective effect of hypothermia and pre conditioning on ischemia.

Methods: Experimental studies were conducted on New Zealand White rabbit (n = 18) with one control group (ischemia) and two treatment groups (hypothermia and pre-blocking). Conducted ligation a. iliaca communist for 4 hours, moderate hypothermia (28°C), and preconditioning ischemia in each group. Then the rabbit is left alive for 8 hours. After decapitation, ileum samples were taken for histopathologic examination.

Results: Of the 18 experimental rabbits, 1 had dropped out due to infection. Scores of villus intestinal damage were performed based on modified Pusponegoro criteria with a minimum score of 4 and a maximum of 2. The pre-treatment group experienced the least damage (=6.2) followed by the hypothermia group (=7,1).

Conclusion: Pre conditioning shows the least damage; in other words gives a better protective effect compared to other groups."

"Latar belakang: Sel punca mesenkim (SPM) telah menjadi salah satu alternatif untuk menghambat proses fibrosis dan memperbaiki fungsi hati. Berbagai jalur dapat digunakan untuk pemberian SPM, namun belum banyak studi yang membandingkan jalur pemberian. Pada studi ini dibandingkan pemberian SPM intrahepatika dan intrasplenika terhadap fungsi hati dan derajat fibrosis hati Oryctolagus cuniculus ligasi duktus bilier.Metode penelitian: Penelitian ekperimental dengan menggunakan model hewan kelinci (Oryctolagus cuniculus) yang dilakukan ligasi duktus bilier (LDB). Kelinci dibagi ke dalam 4 kelompok, yaitu kelompok sham surgery, LDB, injeksi SPM intrahepatika(LDB + SPM IH) dan injeksi SPM intrasplenika (LDB + SPM IS). Injeksi SPM tali pusat dilakukan pada hari kelima LBD, kemudian kelinci diobservasi sebelum diterminasi seluruhnya pada hari ke-14. Dinilai fungsi hati yang dinilai dengan kadar serum AST, ALT, bilirubin total dan direk, serta derajat fibrosis hati yang dinilai dengan skor Laennec.  Hasil penelitian: Dari total 23 kelinci, dibagi menjadi 4 kelompok, yaitu kelompok sham 2 ekor dan masing-masing 7 ekor untuk kelompok LDB, LDB + SPM IH, dan IS. Didapatkan mortalitas sebesar 57,1% pada kelompok LDB, mortalitas 14,3% pada kelompok LDB + SPM IH dan mortalitas 28,6 pada kelompok LDB + SPM IS sebelum penelitian selesai. Tidak didapatkan perbedaan yang bermakna untuk fungsi hati seperti AST, ALT, bilirubin total, dan direk antarkelompok, namun terkesan median fungsi hati pada kelompok LDB lebih tinggi dibanding sham surgery, serta median kelompok LDB + SPM IH dan IS lebih menyerupai normal. Fungsi hati tampak lebih baik pada kelompok LDB + SPM IS dibanding LDB + SPM IH, meskipun secara statistik tidak bermakna. Pemeriksaan histopatologi kelinci yang dilakukan ligasi duktus bilier menunjukkan derajat fibrosis Laennec 4B, yang tidak berbeda antar ketiga kelompok. Area fraction fibrosis, jumlah hepatosit yang viabel dan nekrosis, serta jumlah sel progenitor dianalisis, tidak terdapat perbedaan yang ditemukan antara kelompok LDB + SPM IH dan LDB + SPM IS, namun kelompok yang diberikan SPM memiliki jumlah hepatosit viabel yang lebih banyak dibandingkan kelompok LDB.Kesimpulan: Pemberian SPM intrahepatika dan intrasplenika tidak berpengaruh pada fungsi hati dan derajat fibrosis hati Oryctolagus cuniculus pascaligasi duktus bilier. Pemberian SPM akan meningkatkan jumlah hepatosit yang viabel pada model cuniculus pascaligasi duktus bilier.

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Background: Mesenchymal stem cell (MSC) becomes an alternative to attenuate liver fibrosis and to improve liver function. A couple of administration route had been studied, but few compared one to another. This study aims to compare intrahepatic and intrasplenic route of administration of MSC in regards of liver function and degree of liver fibrosis in Oryctolagus cuniculus bile duct ligation model.

Method: This is an experimental study using rabbit (Oryctolagus cuniculus) bile duct ligation model. The subjects were randomized into 4 groups: sham surgery, bile duct ligation (BDL), intrahepatic route of MSC (BDL + MSC IH), and intrasplenic route of MSC (BDL + MSC IS). Umbilical cord MSC was administered in the fifth day of bile duct ligation, and the subject was observed until terminated on 14th day post BDL. The liver function, such as AST, ALT, total and direct bilirubin were evaluated, and the degree of fibrosis was evaluated with Laennec score. 

Result: The subjects were grouped into 4 group: 2 sham surgery, and each had 7 in BDL, BDL + MSC IH and BDL + MSC IH groups. Mortality rate in control group was 57,1%, mortality in BDL + MSC IH group was 14,3% and in BDL + MSC IS group was 28,6%. No significant difference was found regarding liver function in each group such as AST, ALT, total and direct bilirubin, but the median of liver function in BDL group seemed worse than in sham sugery group, and the median of liver function in BDL + MSC IH and BDL + MSC IS groups were closed to sham operated (normal). Liver function seemed to be better in BDL + MSC IS group compared to BDL + MSC IH group, but showed no statistical difference. Histopathology examination in subjects undergone bile duct ligation (regardless of MSC) show the degree of fibrosis of Laennec 4B. Fibrosis area fraction, the number of viable and necrosis hepatocyte, and progenitor cell are analysed; no significant difference was found between BDL + MSC IH and BDL + MSC IS group, but the group administered with MSC shows larger number of viable hepatocyte compared to BDL group.

Conclusion: Administration of intrahepatic or intrasplenic MSC did not show significant improvement the liver function and liver fibrosis in Oryctolagus cuniculus bile duct ligation model. Administration of MSC would increase the number of viabel hepatocyte in Oryctolagus cuniculus bile duct ligation model."

"Uji klinis acak tersamar ganda paralel ini merupakan penelitian pendahuluan, bertujuan mengetahui pengaruh suplementasi serat larut dan diet rendah kalori seimbang (DRKS) selama 4 minggu terhadap kadar kolesterol low-density lipoprotein (LDL) serum pada obes I usia 30−50 tahun. Sejumlah 31 subyek dipilih dengan kriteria tertentu dan dibagi menjadi dua kelompok dengan randomisasi blok, 15 orang kelompok perlakuan (KP) dan 16 orang kelompok kontrol (KK). Subyek KP mendapat serat larut psyllium husk (PH) 8,4 g/hari dan DRKS 1200 kkal/hari, sedangkan subyek KK mendapat plasebo dan DRKS 1200 kkal/hari. Data terdiri atas usia, indeks massa tubuh (IMT), asupan zat gizi, serta kadar kolesterol LDL serum. Pemeriksaan kolesterol LDL dilakukan pada awal dan akhir penelitian. Analisis data menggunakan uji t tidak berpasangan dan Mann-Whitney, batas kemaknaan 5%. Karakteristik data dasar dan sebaran subyek kedua kelompok sebanding. Analisis lengkap dilakukan pada 28 subyek (KP dan KK masing-masing 14 subyek). Suplementasi ditoleransi baik dan tidak ditemukan efek samping serius. Median usia subyek KP dan KK berturut-turut 35,0 (30−45) tahun dan 34,50 (30−48) tahun serta rerata IMT 28,0 ± 1,1 kg/m2 dan 27,2 ± 1,4 kg/m2. Rerata kadar kolesterol LDL serum awal KP 137,0 ± 37,0 mg/dL dan KK 134,4 ± 29,1 mg/dL. Defisit energi KP lebih rendah tidak signifikan (p = 0,62) dibandingkan KK, berturut-turut -282,0 ± 482,6 kkal/hari dan -331,8 ± 578,3 kkal/hari. Persentase asupan energi terhadap anjuran KP (94,2 ± 18,5%) lebih tinggi signifikan (p = 0,02) daripada KK (85,4 ± 22,9%). Asupan karbohidrat (KH) total KP (613,1 ± 134,5 kkal/hari) lebih tinggi signifikan (p = 0,02) dibandingkan KK (545,4 ± 161,1 kkal/hari). Asupan protein, lemak total, dan kolesterol KP dan KK sesuai rekomendasi NCEP-ATP III. Pada kedua kelompok, asupan asam lemak jenuh cenderung tinggi, tetapi asupan asam lemak tak jenuh tunggal dan jamak rendah. Asupan serat subyek KP 17,2 ± 2,8 g/hari dan KK 8,6 (5,2−15,2) g/hari. Dengan suplementasi PH tidak tercapai rekomendasi asupan serat. Persentase asupan KH sederhana terhadap energi total KP 11,5±5,4% lebih tinggi signifikan (p = 0,00) dibandingkan KK 6,0 (1,2524,2)%. Penurunan kadar kolesterol LDL serum KP -2,1 ± 16,2 mg/dL lebih sedikit tidak signifikan (p = 0,15) dibandingkan pada KK -10,9 ± 15,3 mg/dL. Penelitian ini belum dapat membuktikan suplementasi PH 8,4 g/hari dan DRKS 1200 kkal/hari selama 4 minggu lebih baik dalam menurunkan kadar kolesterol LDL serum dibandingkan plasebo pada subyek obes I.

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This parallel double blind randomized clinical trial is a preliminary study that aims to investigate the effect of soluble fiber supplementation 8.4 g/day and lowcalorie balanced diet (LCBD) for 4 weeks on serum low-density lipoprotein (LDL) cholesterol level in obese I, aged 30−50 years old. A total of 31 subjects were selected using certain criteria and randomly allocated to one of two groups using block randomization; 15 subjects for treatment (T) group and 16 subjects for control (C) group, respectively. The T group received psyllium husk (PH) 8.4 g/day and LCBD 1200 kcal/day, and the C group received placebo and LCBD 1200 kcal/day. Data include age, body mass index (BMI), intake of energy, macronutrient, and fiber, as well as serum LDL cholesterol level. Serum LDL cholesterol level was examined before and after treatment. Statistical analyses include independent t-test and Mann-Whitney with significance level of 5%. Subjects characteristics of the two groups at baseline was not statistically different. Twenty eight subjects (14 subjects in each group) completed the intervention. Supplementation was well tolerated and there were no serious adverse events. The mean age in T and C group was 35.0 (30.0−45.0) and 34.5 (30.0−48.0) years, respectively, and BMI was 28.0 ± 1.1 and 27.2 ± 1.4 kg/m2, respectively. The pretreatment serum LDL cholesterol level in T and C group was 137.0 ± 37.0 and 134.4 ± 29.1 mg/dL, respectively. Energy deficit in T group was insignificantly lower (p = 0.62) than in C group; -282.0 ± 482.6 and -331.8 ± 578.3 kcal/day, respectively. Percentage of energy intake to recommendation in T group (94.2 ± 18.5%) was significantly higher (p = 0.02) than that in C group (85.4 ± 22.9%). Total carbohydrate (CHO) intake in T group (613.1 ± 134.5 kcal/day) was significantly higher (p = 0.02) than in C group (545.4 ± 161.1 kcal/day). Total protein, fat, and cholesterol intake were similar to the NCEP-ATP III recommendation in both groups. Intake of SAFA was higher than recommended, meanwhile PUFA and MUFA intake were lower than those recommended in both groups. Dietary fiber intake in T and C group was 17.2 ± 2.8 and 8.6 (5.2−15.2) g/day, respectively. During the intervention, PH supplementation did not meet the recommendation. Percentage of simple CHO to total energy in T group 11.5±5.4% was significantly higher (p = 0.00) than in C group 6.0 (1.2524.2)%. PH supplementation decreased serum LDL cholesterol level (-2.1 ± 16.2 mg/dL) lower than placebo (-10.9 ± 15.3 mg/dL), but not significant different (p = 0.15). This study shows that PH supplementation 8.4 g/day in combination with LCBD 1200 kcal/day for 4 weeks in obese I aged 30−50 years old is not proven to decrease the serum LDL cholesterol level."