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"Latar belakang: Sitoglobin (Cygb) adalah protein pengangkut O2 yang diekspresikan oleh fibroblas dan fibroblast like cells aktif. Keperluan O2 dan energi meningkat pada fibrosis akibat proliferasi fibroblas dan sintesis kolagen. Pada fibrosis terjadi hipoksia yang ditandai oleh stabilisasi hypoxia inducible factor-1α (HIF-1α), yang kemudian membentuk HIF-1 yang merupakan faktor transkripsi untuk ekspresi protein adaptasi (termasuk Cygb). Diduga Cygb berperan dalam suplai O2 pada fibrosis. Tujuan penelitian ini adalah untuk memperoleh informasi mengenai peran Cygb pada hipoksia jaringan fibrosis dengan keloid sebagai model.Metode: Penelitian bersifat observasional deskriptif. Sampel keloid diperoleh melalui biopsi, sedangkan kontrol preputium diperoleh melalui sirkumsisi, masing-masing 10 sampel jaringan. Pengukuran ekspresi mRNA Cygb, HIF-1α, kolagen I dan III dilakukan dengan real time RT-PCR; kadar protein Cygb dan HIF-1α dengan ELISA; dan ekspresi protein Cygb, HIF-1α, FGF, kolagen I dan III di lapisan dermis dengan imunohistokimia (IHK). Pengukuran kadar MDA dan GSH (tingkat stres oksidatif) serta kadar hidroksiprolin (untuk pematangan kolagen) dengan spektrofotometri, sedangkan pengukuran kepadatan kolagen dengan pewarnaan Van Gieson. Data dianalisis secara statistik menggunakan uji-t.Hasil: Pada keloid dibandingkan preputium, ekspresi mRNA Cygb meningkat 8,7 kali, protein Cygb meningkat bermakna (1,196 Vs 0,779 ng/mg protein dan 95% Vs 63% ; p <0,05). Ekspresi mRNA HIF-1α meningkat 5,1 kali, protein HIF-1α meningkat bermakna (0,201 Vs 0,122 ng/mg protein dan 80% Vs 38%; p <0,05). Terdapat korelasi kuat antara ekspresi protein HIF-1α dan mRNA Cygb (Pearson; R = 0,649; p <0,01). Ekspresi protein FGF keloid meningkat bermakna (78% Vs 41%; p <0,05). Demikian pula ekspresi mRNA prokolagen I dan III keloid meningkat bermakna (35 kali dan 27,1 kali), serta ekspresi protein kolagen I dan III (61% Vs 37% dan 39% Vs. 16%; p <0,05). Juga terdapat korelasi kuat antara protein HIF-1α dengan FGF, prokolagen I dan III (Pearson; R= 0,878; R=0,960; dan R=0884; p<0,01). Kadar hiroksiprolin lebih tinggi pada keloid (0,297 Vs 276 ng/mg protein; p >0,05) dan pematangan kolagen lebih tinggi bermakna (1,2 kali; p <0,05). Cygb berkorelasi kuat dengan pematangan kolagen (kadar hidroksiprolin) (Pearson; R = 0,790; p <0,001).Kesimpulan: Cygb berperan pada hipoksia jaringan fibrosis yang ditandai dengan peningkatan ekspresinya. Peran Cygb terkait dengan ekspresi HIF-1α yang berkorelasi dengan peningkatan FGF, pro/kolagen I dan III yang merupakan faktor penting pada fibrosis. Cygb juga berperan pada pematangan kolagen.

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Background: Cytoglobin (Cygb) is an O2 carrier protein expressed by fibroblasts and active fibroblast like cells. O2 and energy demand increased in fibrosis due to proliferation of fibroblasts and synthesis of collagen. In fibrosis hypoxia occurred which is characterized by stabilization of hypoxia inducible factor-1α (HIF-1α), which later forming the HIF-1, a transcription factor for the expression of adaptation protein (including Cygb). Cygb alleged role in the supply of O2 in fibrosis. The purpose of this study was to obtain information about Cygb role in fibrosis hypoxia with keloid tissue as a model.Methods: This was an observational descriptive study. Keloid samples were obtained from biopsy, while the preputium as control were obtained from circumcision, 10 tissue samples each. Measurement of Cygb, HIF-1α, collagen I and III mRNA expression were carried out by real time RT?PCR. Cygb and HIF-1α protein level were measured by ELISA; while Cygb, HIF-1α, FGF, and collagen I and III protein expressions in the dermis layer by immunohistochemistry (IHC). Measurement of MDA and GSH levels (oxidative stress) and hydroxyprolin concentration (marker of mature collagen) by spectrophotometry, while the collagen density measurement with van Gieson staining. Data were analyzed statistically using t-test.Results: In keloid compared preputium, Cygb mRNA expression increased 8.7 times compared to preputium, Cygb protein increased significantly (1.196 Vs 0.779 ng/mg protein and 95% Vs 63%, p <0.05). HIF-1α mRNA expression increased by 5.1 times in keloid tissue, and protein HIF-1α increased significantly (0.201 Vs 0.122 ng/mg protein and 80% Vs 38%, p <0.05). There is a strong correlation between the expression of HIF-1α protein and Cygb mRNA (Pearson; R = 0.649, p <0.01). Keloid FGF protein expression increased significantly (78% Vs 41%; p <0.05). Similarly, mRNA expression of procollagen I and III keloid increased significantly (35 times and 27.1 times), and protein expression of collagen I and III (61% Vs 37% and 39% Vs 16%, p <0.05). There is also a strong correlation between HIF-1α protein with FGF, procollagen I and III (Pearson, R = 0.878, R = 0.960; and R = 0.884, p <0.01). Hydroxyprolin concentration were higher in keloid (0.297 Vs 0.276 ng/mg protein; p >0.05) and collagen maturation was significantly higher (1.2 times, p <0.05). Cygb is correlated with maturation of collagen (hydroxyproline levels) (Pearson, R = 0.790, p <0.001).Conclusion: Cygb play role in fibrosis hypoxia which is characterized by its increased expression. Cygb role is associated with the expression of HIF-1α which are correlated with increased FGF, pro/collagen I and III, which are important factor in fibrosis. Cygb also play a role in the maturation of collagen."

"Latar belakang dan tujuan: Fibrosis hepar merupakan hal yang perlu diketahui untuk memulai terapi antiviral pada pasien hepatitis C kronik. Pemeriksaan USG Doppler yang bersifat non invasif, tersedia luas dan relatif murah dipertimbangkan sebagai metode alternatif untuk menentukan derajat fibrosis di daerah yang tidak memiliki fibroscan. Parameter splenic artery pulsatility index (SAPI) dipikirkan dapat digunakan sebagai indikator derajat fibrosis. Namun saat ini belum ditemukan nilai titik potong SAPI untuk populasi di Indonesia. Metode: Studi observasional potong lintang dilakukan pada 34 pasien dengan hepatitis C kronik di Divisi Hepatologi Departemen Ilmu Penyakit Dalam Rumah Sakit Cipto Mangunkusumo dalam kurun waktu Desember 2015 hingga Februari 2016. Indeks dan parameter Doppler lainnya merupakan data primer. Subjek dibagi menjadi dua kelompok, yaitu kelompok fibrosis non signifikan dan kelompok fibrosis signifikan. Uji komparatif dilakukan untuk membandingkan rerata indeks dan parameter Doppler lainnya diantara kedua kelompok tersebut. Analisis kurva receiver operating characteristic (ROC) dilakukan pada SAPI untuk mendapatkan nilai sensitifitas dan spesifisitasnya. Hasil: Median SAPI pada kelompok fibrosis signifikan adalah 1.02 dengan range 0.7-1.8 sedangkan median SAPI pada kelompok fibrosis non signifikan adalah 0.89 dengan range 0.7-1.3 dengan nilai p=0.021. Dengan analisis ROC didapatkan titik potong indeks 0.96 yang memberikan sensitifitas 73.9% dan spesifisitas 81.8% untuk membedakan kelompok fibrosis signifikan dan fibrosis non signifikan. Kesimpulan: Terdapat hubungan yang bermakna antara indeks SAPI secara USG dengan derajat fibrosis yang didapat dari fibroscan dan indeks tersebut dapat digunakan sebagai indikator fibrosis signifikan dengan akurasi yang cukup tinggi.

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Background and Objective: Liver fibrosis needs to be evaluated in order to begin anti viral therapy in chronic hepatitis C patients. Doppler ultrasound which is non invasive, widely available and relatively cheap is being considered as an alternative method to determine the degree of fibrosis in areas which do not have a fibroscan available. Splenic artery pulsatility index (SAPI) can be used as an indicator of significant fibrosis, however the cut off value for Indonesian population has yet to be determined.

Method: A cross-sectional observational study is conducted in 34 patients with chronic hepatitis C in the Hepatology Division Department of Internal Medicine Cipto Mangunkusumo Hospital during December 2015 to February 2016. The index and other Doppler parameters are primary data. Subjects are divided into two groups: significant fibrosis group and non significant fibrosis group. Comparative test is conducted to compare the mean index and other Doppler parameters among the two group. Analysis of receiver operating characteristic (ROC) curve was performed on parameters that are statistically significant in order to obtain the sensitivity and specificity value.

Results: Median SAPI in significant fibrosis group is 1.02 with a range of 0.7-1.8 while the median SAPI in non significant group is 0.89 with a range of 0.7-1.3, p=0.021. From ROC curve analysis, we obtained the optimal cutting point index 0.96 which gives 73.9% sensitivity and 81.8% specificity to differentiate significant fibrosis group and non significant fibrosis group.

Conclusion: There is a significant association between SAPI which is obtained by Doppler and the degree of fibrosis obtained from fibroscan which can be used as an indicator for significant liver fibrosis with quite high accuracy."

"[ABSTRAKLatar belakang: Penggunaan media kontras pada pemeriksaan radiologi dengan kondisi pasien mengalami insufisiensi fungsi ginjal dapat menyebabkan resiko terjadinya CIN pada kontras iodine dan NSF pada kontras paramagnetik. Oleh karena itu, penilaian fungsi ginjal penting dilakukan sebelum pemeriksaan radiologi kontras. Permasalahannya untuk menilai fungsi ginjal dengan baku emas sulit dilakukan sehingga digunakan formula MDRD dan CKD-EPI untuk menghitung eGFR. Faktor ras menjadi salah satu variabel dalam formula penghitungan eGFR, belum ada untuk populasi Indonesia yang termasuk ras Melanesia dan Malayan-Mongoloid. Tujuan: Menilai apakah terdapat korelasi antara pengukuran eGFR metode MDRD dan CKD-EPI dengan pengukuran GFR 99mTc-DTPA metode Gates pada pasien CKD. Metode: Penelitian potong lintang menggunakan data sekunder pasien yang menjalani pemeriksaan skintigrafi renal di RSUPN Cipto Mangunkusumo serta pemeriksaan kreatinin serum bulan Februari 2012-Januari 2015. Data kasar dinilai ulang GFR skintigrafi renal menggunakan metode Gates dari pesawat Siemens Symbia T2 dan dihitung nilai eGFR menggunakan formula MDRD dan CKD-EPI. Analisa data dilakukan untuk mendapatkan nilai korelasi eGFR formula MDRD dan CKD-EPI dengan GFR skintigrafi renal sebagai baku emas. Hasil: Jumlah subjek penelitian 47 orang, dengan hasil terdapat korelasi positif, kekuatan korelasi baik antara nilai eGFR MDRD dengan GFR skintigrafi renal dengan persamaan:nilai GFR skintigrafi renal=16,60+0,70xnilai eGFR MDRD. Terdapat korelasi positif, kekuatan korelasi baik antara nilai eGFR CKD-EPI dengan GFR skintigrafi renal dengan persamaan:nilai GFR skintigrafi renal=12,74+0,78xnilai eGFR CKD-EPI; nilai GFR dalam ml/menit/1,73m2. Kesimpulan : Formula persamaan eGFR MDRD dan CKD-EPI dapat digunakan dalam klinis untuk memperkirakan nilai GFR skintigrafi renal.

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ABSTRACTBackground: The use of contrast media for radiology examination in patients with renal function insufficiency can lead to the risk of CIN (Contrast Induced Nephropathy) on contrast iodine and NSF (Nephrogenic Systemic Fibrosis) on paramagnetic contrast. Therefore, assessment of renal function is important to be done prior to contrast radiology. The problem is assessing renal function with a gold standard, clinically difficult, therefor using MDRD and CKD-EPI formula to calculate eGFR. Factors race became one of the variables in the formula calculating eGFR, yet for Indonesian population included in the Melanesian and Malayan-Mongoloid race.Objective. To evaluate correlation value between eGFR measurement using MDRD and CKD-EPI methods with GFR Gates methods using 99mTc-DTPA in patients with CKD.Method: Cross sectional research using secondary data of patients who underwent renal scintigraphy in Cipto Mangunkusumo and serum creatinine examination in February 2012 to January 2015. The raw data then reassessed GFR renal scintigraphy using the Gates of Siemens Symbia T2 machine and eGFR values calculated using the formula MDRD and CKD-EPI. Data analysis was used to obtain a correlation value formula MDRD eGFR and CKD-EPI with GFR renal scintigraphy as the gold standard. Result: Total subject is 47 people. There is a positive correlation with good correlation value between MDRD eGFR value and renal scintigraphy GFR using this approach:renal scintigraphy GFR value=16,60+0,70xMDRD eGFR value. There is also a positive correlation with good correlation value between MDRD eGFR value and renal scintigraphy GFR value using this approach:renal scintigraphy GFR value=12,74+0,78xCKD=EPI eGFR value. Conclusion : Formula equation MDRD and CKD-EPI eGFR can be used clinically to estimate renal scintigraphy GFR, Background: The use of contrast media for radiology examination in patients with renal function insufficiency can lead to the risk of CIN (Contrast Induced Nephropathy) on contrast iodine and NSF (Nephrogenic Systemic Fibrosis) on paramagnetic contrast. Therefore, assessment of renal function is important to be done prior to contrast radiology. The problem is assessing renal function with a gold standard, clinically difficult, therefor using MDRD and CKD-EPI formula to calculate eGFR. Factors race became one of the variables in the formula calculating eGFR, yet for Indonesian population included in the Melanesian and Malayan-Mongoloid race.Objective. To evaluate correlation value between eGFR measurement using MDRD and CKD-EPI methods with GFR Gates methods using 99mTc-DTPA in patients with CKD.Method: Cross sectional research using secondary data of patients who underwent renal scintigraphy in Cipto Mangunkusumo and serum creatinine examination in February 2012 to January 2015. The raw data then reassessed GFR renal scintigraphy using the Gates of Siemens Symbia T2 machine and eGFR values calculated using the formula MDRD and CKD-EPI. Data analysis was used to obtain a correlation value formula MDRD eGFR and CKD-EPI with GFR renal scintigraphy as the gold standard. Result: Total subject is 47 people. There is a positive correlation with good correlation value between MDRD eGFR value and renal scintigraphy GFR using this approach:renal scintigraphy GFR value=16,60+0,70xMDRD eGFR value. There is also a positive correlation with good correlation value between MDRD eGFR value and renal scintigraphy GFR value using this approach:renal scintigraphy GFR value=12,74+0,78xCKD=EPI eGFR value. Conclusion : Formula equation MDRD and CKD-EPI eGFR can be used clinically to estimate renal scintigraphy GFR]"

"Latar Belakang: Risiko Non-Alcoholic Fatty Liver Disease NAFLD meningkat pada pasien dengan diabetes melitus DM tipe 2. Prevalensi dan faktor-faktor yang berhubungan dengan peningkatan risiko NAFLD pada populasi DM di Indonesia belum pernah diteliti. Profil derajat fibrosis pada populasi ini juga masih belum diketahui. Tujuan: Mengetahui perbedaan profil pasien DM dengan atau tanpa NAFLD serta derajat fibrosisnya. Metode: Penelitian dikerjakan secara potong lintang terhadap pasien DM tipe 2 dewasa yang berobat di poliklinik endokrin metabolik RSCM. Pengambilan sampel dilakukan secara konsekutif. Data yang dikumpulkan mencakup usia, lama diabetes, indeks masa tubuh IMT , lingkar pinggang, kadar HDL, trigliserida, dan HbA1C. Ultrasonografi abdomen dikerjakan pada semua pasien untuk menentukan adanya NAFLD. Pasien dengan NAFLD lalu menjalani pemeriksaan elastografi transien untuk menilai derajat fibrosis. Uji Chi Square atau Fischer's-Exact digunakan untuk analisis bivariat dan regresi logistik digunakan untuk analisis multivariat. Hasil Penelitian: Sebanyak 186 pasien dianalisis dalam studi ini, dengan 84 pasien 45,2 terbukti mengalami NAFLD. Elastografi transien berhasil dikerjakan pada 68 pasien NAFLD, dengan 17 pasien 25,0 terbukti mengalami fibrosis berat. Analisis univariat menunjukan perbedaan signifikan IMT PR=1,878; 95 CI= 1,296-2,721.

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Background: Risk of Non Alcoholic Fatty Liver Disease NAFLD is increased in patients with type 2 diabetes. Prevalence and factors related to the increased risk of NAFLD in diabetic patients in Indonesia are currently unknown. Data regarding fibrosis profile in this population is also unknown.

Aim: To understand the prevalence and fibrosis profile of Non Alcoholic Fatty Liver Disease in diabetes mellitus and factors associated with it.

Methods: This study was a cross sectional study on diabetic patients treated in the endocrinology and metabolic clinic of Cipto Mangunkusumo Hospital. Sampling was done consecutively. Data collected comprised of age, duration of diabetes, body mass index BMI, waist circumference, HDL, triglyceride, and HbA1C. Abdominal ultrasonography was conducted to every patient to determine the presence of NAFLD. Patients with NAFLD underwent transient elastography to assess their degree of liver fibrosis. Collected data were analyzed in univariate and multivariate manner.

Study Results: We analyzed 186 patients with diabetic. NAFLD were diagnosed in 84 patients 45,2. Transient elastography were carried out in 68 patients, with advanced fibrosis were found in 17 patients 25,0. Univariate analysis showed significant differences between BMI PR 1,878 95 CI 1,296 2,721 p"

"Pulmonary fibrosis due to COVID-19 is recognized as sequel of ARDS characterized by failed alveolar re-epithelization, fibroblast activation, excessive collagen deposition and other extracellular matrix components that disrupt the normal lung architecture. There are risk factor for pulmonary fibrosis namely advanced age, severe ARDS infection, mechanical ventilation due to ventilator-induced lung injury, smoking and chronic alcoholism. Diagnosis of post-COVID pulmonary fibrosis can be made by clinical symptoms and characteristic finding from lung CT scan. To date, there is no definitive treatment for post-inflammatory pulmonary fibrosis after COVID-19 infection, however some of antifibrotic therapies may be considered. Beside medical treatment, pulmonary rehabilitation program and long-term oxygen treatment should be included as part of comprehensive treatment for pulmonary fibrosis due to COVID"

"Diagnosis of non cirrhotic portal fibrosis was considered when the following criteria were fulfilled evidence of portal hypertension (oesophageal varices, hypersplenism, ascites, or increased hepatic venous pressure gradient), Doppler ultrasound showing patent portal and hepatic veins, and liver biopsy showing sign of cirrhosis. Non cirrhotic portal fibrosis clinically characterized by splenomegaly, anemia, portal hypertension, and histopathological examination portal tract showing fibrosis and sclerosis. Portal hypertension are most caused by a cirrhotic liver (85%), there are only a few reports on non cirrhotic portal hypertension, mostly in Japan and India. We reported a case of non cirrhotic portal fibrosis in young male. The clinical complications of portal hypertension are variceal bleeding and pancytopenia due to hypersplenism. Variceal band ligation and splenectomy were performed. The patient showed good clinical response"

"Prevalensi kejadian crohn?s disease dan ulcerative colitis di dunia masih terus meningkat. Kedua penyakit ini termasuk dalam inflammatory bowel disease (IBD). Meskipun telah terdapat sejumlah pilihan terapi untuk pasien dengan penyakit ini, namun tindakan pembedahan masih menjadi satu-satunya pilihan untuk mengatasi pembentukan jaringan parut (fibrosis). Tetrandrine dipilih sebagai zat aktif pada penelitian ini karena telah diketahui memiliki efek antifibrosis. Penelitian ini dilakukan untuk mengembangkan dan mengevaluasi sediaan beads kalsium pektinat tetrandrine menggunakan properti yang sensitif pH untuk menarget kolon. Beads dibuat menggunakan metode gelasi ionik dan dilanjutkan dengan proses penyalutan oleh HPMCP HP-55 atau CAP. Beads tidak tersalut dievaluasi ukuran partikel, bentuk, morfologi, kemampuan mengembang, efisiensi proses, dan efisiensi penjerapan. Dari hasil evaluasi ini diputuskan beads dengan konsentrasi larutan kalsium klorida 5% (formula 1) akan digunakan untuk penyalutan. Beads formula 1 memiliki bentuk lebih sferis, tidak terlalu lengket, dan ukuran lebih kecil bila dibandingkan dengan beads konsentrasi kalsium klorida 10% (formula 2) dan 15% (formula 3). Nilai efisiensi penjerapan dari ketiga beads secara berurutan yakni 65,67 ± 0,39%, 68,03 ± 0,12%, 56,28 ± 0,2%. Setelah disalut, beads kemudian digunakan untuk uji pelepasan secara in vitro dan uji pentargetan. Dari hasil pengujian diperoleh beads kalsium pektinat tersalut mampu menahan pelepasan tetrandrine dalam medium asam, namun belum berhasil menarget kolon.

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Prevalances of crohn?s disease and ulcerative colitis in the world are still increasing. These two diseases are categorized as inflammatory bowel disease (IBD). Even there has been some theurapetic option for patient with these diseases, but surgery still the only option to treat fibrotic strictures. Tetrandrine was chosen as drug in this research because of its antifibrotic effect. This research was conducted to develop and evaluate calcium pectinate beads exploiting pH sensitive property for colon-targeted delivery of tetrandrine. Beads were prepared by ionotropic gelation method followed by enteric coating with HPMCP HP-55 or CAP. Uncoated beads were evaluated for particle size, shape, morphology, swellability, process efficiency and encapsulation efficiency. From evaluation, beads with concentration of calcium chloride 5% (formula 1) was chosen as formula for coating. First formula were more spherical in shape, not too sticky, and smaller in size when compared with beads using calcium chloride concentration 10% (formula 2) and 15% (formula 3). Encapsulation efficiency of the three formula, 65.67 ± 0.39%, 68.03 ± 0.12%, 56.28 ± 0.2% respectively. After coating process, beads were used in in vitro drug release and targeted test. The studies showed that coated calcium pectinate beads were sufficient to resist tetrandrine released in acidic medium, but was unsuccessfully in targeting colon."

"ABSTRAKLatar Belakang: Mangiferin merupakan senyawa bioaktif yang diketahui dapat menghambat fibrosis, yaitu proses reversibel akibat jejas pada hati. Penelitian ini bertujuan untuk membuktikan efek mangiferin dalam menghambat fibrogenesis melalui hambatan terhadap ekspresi mRNA TGF-?, yaitu sitokin profibrogenik utama. Metode: Penelitian eksperimental ini menggunakan RNA yang diisolasi untuk mendapatkan cDNA, di mana kelompok perlakuan diberikan tioasetamid 200 mg/kg BB sebanyak 3 kali/minggu selama 5 minggu oleh Arozal W, dkk. Perlakuan dibagi menjadi kelompok kontrol, tioasetamid 200 mg/kg BB, tioasetamid 200 mg/kg BB mangiferin 50 mg/kg BB/hari, dan tioasetamid 200 mg/kg BB mangiferin 100 mg/kg BB/hari. Tingkat ekspresi mRNA TGF-? diukur dengan RT-PCR dan dihitung dengan metode Livak. Hasil: Terdapat peningkatan ekspresi mRNA TGF-? pada kelompok yang hanya diberikan tioasetamid terhadap kelompok kontrol. Pada kelompok yang diberikan mangiferin, terdapat penurunan ekspresi mRNA TGF-? terhadap kelompok yang hanya diberikan mangiferin, dengan penurunan ekspresi mRNA pada kelompok yang diberikan mangiferin 50 mg/kg BB/hari lebih besar. Kesimpulan: Mangiferin dapat menurunkan tingkat ekspresi mRNA TGF-? pada hati tikus yang diinduksi oleh tioasetamid, namun efeknya tidak linear antara dosis mangiferin dengan respon yang diberikan.

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ABSTRACT

Background Mangiferin is a bioactive compound that is known to inhibit fibrosis, a reversible process that occurs as a result of liver injury. This study aims to prove the antifibrotic effect of mangiferin through inhibition of mRNA expression of TGF , which is the main profibrogenic cytokine. Method This experimental design uses isolated RNA to get cDNA, which treatment groups are given thioacetamid with dose of 200 mg kg BW, three times a week for five weeks consecutively, in study from Arozal W, et al. The treatment groups are control group, thioacetamid 200 mg kg BW, thioacetamid 200 mg kg BW mangiferin 50 mg kg BW day, and thioacetamid 200 mg kg BW mangiferin 100 mg kg BW day. The expression of TGF mRNA is measured with RT PCR and quantified with Livak method. Result There is an increase mRNA expression of TGF in group that was given thioacetamide only compare to the control group. In the groups that were on treatment of mangiferin, the mRNA expressions of TGF are lower than the thioacetamid only group. The mRNA expression of TGF of the group that was given mangiferin of dose 50 mg kg BW day is also lower compare to the group that was given higher dose of mangiferin. Conclusion Mangiferin can lower the expression of TGF in rats liver induced by thioacetamide. However, mangiferin does not give linear effect between dose and response."

"mengalami kerusakan dan sirosis hati. Walaupun tidak ada data terbaru mengenai insiden kerusakan hati di Indonesia, Riskesdas 2013 menyampaikan adanya prevalensi yang tinggi dari persentase HBsAg, anti-HBs, dan anti-HBc. Selain itu, dalam kurun waktu 30 tahun (1980—2010), terdapat peningkatan tingkat kematian sirosis hati sebanyak 25,1%. Model hewan yang sesuai sangatlah penting dalam meneliti kerusakan hati. Karbon tetraklorida (CCl4) sudah lama digunakan untuk menginduksi fibrosis hati pada model tikus. Walaupun dapat menginduksi pengendapan jaringan ikat, regenerasi hepatoseluler, proliferase sel stelata, dan infiltrasi sel-sel inflamasi, kerusakan pada model tikus yang diinduksi CCl4 hanya merepresentasikan kerusakan hati sampai batas tertentu, mirip dengan kerusakan hati akibat obat. Dengan tujuan meniru kerusakan hati yang lebih parah, penelitian ini mengkombinasikan penggunaan CCl4 dengan asetilaminofluorena-2 (2AAF) karena 2AAF terbukti dapat menekan proliferasi hepatosit sehingga terjadi proliferasi sel oval yang berakibat pada proliferasi duktular. Metode: Desain penelitian ini adalah penelitian observasional terhadap penelitian analitik eksperimental dengan bahan biologis tersimpan yang diambil dari Departemen Patologi Anatomi Fakultas Kedokteran Universitas Indonesia. Penelitian ini menggunakan data primer eksperimental dengan 15 sampel yang dikategorikan dalam 3 kelompok: kontrol sehat, diinduksi CCl4, dan diinduksi 2AAF/CCl4, dan dianalis di bawah mikroskop dalam hal tingkat fibrosis, daerah cakupan fibrosis, dan jumlah proliferasi duktus. Analisis statistik yang digunakan meliputi uji Fisher, Shapiro-Wilk, Kruskal Wallis, dan Mann Whitney menggunakan program SPSS. Hasil: Kelompok 2AAF/CCl4 dan CCl4 memiliki perbedaan derajat fibrosis yang signifikan dengan kontrol sehat (p=0,024 dan p=0,048 secara berurutan), tanpa perbedaan signifikan di antara kedua kelompok tersebut (p=0,286). Perbedaan cakupan area fibrosis antara kedua kelompok juga tidak signifikan (p=0,055), walau kelompok 2AAF/CCl4 dan CCl4 berbeda signifikan dengan kontrol sehat (p=0,007 dan p=0,008 secara berurutan). Dalam hal proliferasi duktular, kelompok CCl4 tidak menunjukkan perbedaan signifikan dengan kontrol sehat (p=0,101), namun berbeda signifikan dengan kelompok 2AAF/CCl4 (p=0,000). Kesimpulan: Tidak terdapat perbedaan derajat dan cakupan area fibrosis yang signifikan antara kelompok 2AAF/CCl4 dan CCl4. Namun demikian, terjadi proliferasi duktular yang secara signifikan lebih tinggi pada kelompok 2AAF/CCl4 dibandingkan kelompok CCl4 saja.

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Background: In 2017, approximately 1.8% of adult in United States suffer from chronic liver disease and cirrhosis. Although there is not any recent data, Riskesdas 2013 showed a high percentage of HBsAg, anti-HBs, and anti-HBc prevalence in Indonesia. On top of that, in Indonesia, in the course of 30 years (1980—2010), liver cirrhosis mortality rate increased by 25,1%. In order to study liver disease, having an appropriate animal model is crucial. Carbon tetrachloride (CCl4) has been used to induce liver fibrosis in mouse model. Although able to induce connective tissue deposition, hepatocellular regeneration, stellate cells proliferation, and inflammatory infiltration, CCl4-induced rat models only represent liver injury to some extent, similar to drug-induced liver injury. In order to mimic a more severe liver injury, this study combined the use of CCl4 with 2- acetylaminofluorene (2AAF), as 2AAF has proven to be able to suppress hepatocyte proliferation and allow oval cells proliferation that leads to ductular proliferation. Method: This research design is an observational research on an analytic experimental study with stored biological material taken from the Department of Anatomy Faculty of Medicine University of Indonesia. This research uses experimental primary data, with 15 samples categorized into three groups: healthy control, CCl4-induced, and 2AAF/CCl4- induced, and analysed for the degree of fibrosis, fibrosis-affected area, and number of proliferating ductules under the microscope. A statistical analysis is then conducted using Shapiro-Wilk, Kruskal Wallis, and Mann Whitney by using SPSS programme. Result: There is a significant difference in the degree of fibrosis between both 2AAF/CCl4 and CCl4 groups with the healthy control (p=0,024 dan p=0,048 respectively), without any significant difference in between the two groups (p=0,286). The affected fibrosis area difference between the two groups is also insignificant (p=0,055), though the 2AAF/ CCl4 and CCl4 groups are significantly different to the healthy control (p=0,007 and p=0,008 respectively). For ductular proliferation, CCl4 group did not show any significant difference compared to the healthy group (p=0,101), but was significantly different to the 2AAF/CCl4 group (p=0,000). Conclusion: There is not any significant difference regarding the degree of fibrosis and its affected area between the 2AAF/CCl4 and CCl4 groups. However, there is a significant difference between the two groups in terms of ductular proliferation, in which the 2AAF/CCl4 group’s ductular proliferation was higher."

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