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Abstrak :
[ABSTRAK
Latar Belakang : Continous ambulatory peritoneal dialysis (CAPD) telah menjadi alternatif selain hemodialisis untuk pengobatan penyakit ginjal tahap akhir. Fibrosis peritoneum merupakan penyebab utama terjadinya kerusakan membran peritoneum. Mekanisme fibrosis peritoneum belum diketahui secara pasti, namun ditengarai transforming growth factor ? β (TGF ?β) berhubungan erat terhadap terjadinya fibrosis peritoneum. Tujuan : Tujuan penelitian ini adalah untuk mengetahui pengaruh kombinasi ACE inhibitor (ACEI) dan calcium channel Blocker (CCB) terhadap penurunan ekspresi TGF ? β dan fibrosis peritoneum tikus jantan yang telah dilakukan CAPD. Metode Penelitian : Penelitian eksperimental, post test only control group design. Tiga puluh tikus Dawley spraque dibagi menjadi lima kelompok yaitu kelompok kontrol (kelompok 1) dan kelompok perlakuan dengan pemberian masing-masing cairan CAPD 4,25% (kelompok2) lisinopril 1,44 mg oral dan CAPD (kelompok 3) diltiazem CD 6,48 mg oral dan CAPD (kelompok 4) lisinopril 1,44 mg dan diltiazem CD 6,48 mg oral dan CAPD (kelompok 5). Setelah 4 minggu tikus dikorbankan dengan cara dislokasi cervical kemudian diperiksa ekspresi TGF ? β dan terjadinya fibrosis pada peritoneum tikus, selanjutnya dibuat sediaan histopatologi dan diwarnai dengan hematoksilin eosin serta imunohistokimia menggunakan antihuman TGF-ß. Hasil : Dua puluh peritoneum tikus berhasil diperiksa. Rerata skor TGF-β kelompok kontrol 1,8, kelompok CAPD 2, kelompok lisinopril dan CAPD 1,8, kelompok diltiazem CD dan CAPD 1,8, kelompok lisinopril dan diltiazem CD dan CAPD 1,7 (p=0,959). Rerata skor fibrosis peritoneum kelompok kontrol 1,1, kelompok CAPD 2,6, kelompok lisinopril dan CAPD 1,2, kelompok diltiazem CD dan CAPD 1,3, kelompok lisinopril dan diltiazem CD dan CAPD1,5 (p=0,268) Simpulan : Kombinasi lisinopril dan diltiazem mempunyai kecenderungan menurunkan ekspresi TGF ? β lebih baik dibandingkan lisinopril maupun diltiazem yang diberikan secara terpisah tetapi tidak bermakna secara statistik. Kombinasi lisinopril dan diltiazem mempunyai kecenderungan mengurangi fibrosis peritoneum tetapi tidak bermakna secara statistik dan tidak lebih baik dibandingkan lisinopril maupun diltiazem bila diberikan secara terpisah.

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ABSTRACT
Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor ? β(TGF ? β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF ? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn?t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor ? β(TGF ? β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF ? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn?t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor ? β(TGF ? β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF ? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn?t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor ? β(TGF ? β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF ? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn?t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.;Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor ? β(TGF ? β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF ? β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF ? β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF ? β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn?t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis., Background : Continuous ambulatory peritoneal dialysis (CAPD) has been an alternative other than hemodialysis for end stage kidney disease treatment. Peritoneal fibrosis is the most serious cause of the damage in membrane peritoneum. Mechanism of fibrosis peritoneum is not exactly known yet, transforming growth factor – β(TGF – β) is closely related with the existence of fibrosis peritoneum. Purposes : The purpose of this study is to evaluate the effect of combination between ACE inhibitor (ACEI) dan Calcium channel blocker (CCB) in reducing expression of TGF – β and fibrosis peritoneum in a male rat treated with CAPD. Research Method : Experimental study, post test only control group design. Thirsty Dawley spraque rats are divided into five groups control group ( Group 1), CAPD liquid 4,25% (group 2), lisinopril 1,44 mg oral and CAPD (group 3) diltiazem CD 6,48 mg oral and CAPD (group 4) lisinopril 1,44mg + diltiazem CD 6,48 mg oral and CAPD (group 5). After 4 weeks, rats sacrificed. Expression of TGF – β and peritoneal fibrosis are conducted by histopatology with hematoxillineosin staining and immunology with anti human-TGF-β. Result : Twenty peritoneal of rats can be examined. Mean score TGF-β control group is 1,8, CAPD group is 2, lisinopril and CAPD group is 1,8,diltiazem CD and CAPD group is 1,8, lisinopril and diltiazem CD and CAPD group is 1,7 (p=0,959) .Mean score peritoneal fibrosis control group is 1,1, CAPD group is 2,6, lisinopril and CAPD group is 1,2, diltiazem CD and CAPD group is 1,3, lisinopril and diltiazem CD and CAPD group is 1,5 (p=0,268) Summary : Combination of lisinopril and diltiazem lower the expression of TGF – β and fibrosis peritoneum better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant and it doesn’t better than lisinopril or diltiazem. Key words: ACE inhibitor, calcium channel blocker, TGF-β, peritoneal fibrosis.]

Abstrak :
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. ...... 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.

Abstrak :
Fibrosis hati merupakan penyakit dengan tingkat morbiditas dan mortalitas yang tinggi. Terapi yang efektif dalam mengatasi fibrosis hanyalah transplantasi hati, tetapi mahal dan sulit didapatkan sehingga diperlukan alternatif lain. Umbilical cord mesenchymal stem cell (UC-MSC) mampu mendegradasi matriks ekstraselular sehingga potensial mengatasi fibrosis. Tujuan penelitian adalah mengetahui pengaruh UC-MSC terhadap fibrosis pada hati kelinci (Oryctolagus cuniculus). Jumlah sampel yang digunakan sebanyak 16 hati yang terdiri dari 2 kelompok normal, 7 kelompok fibrosis model ligasi duktus bilier (LDB), dan 7 kelompok fibrosis yang diinjeksi UC-MSC secara intrahepatika (LDB + UC-MSC). Penelitian dilakukan dengan analisis histologi dan ekspresi gen Matrix Metalloproteinase-2 (­MMP-2). Sediaan histologi diwarnai dengan pewarnaan Hematoksilin-Eosin untuk analisis sistem penilaian Laennec dan Masson Trichrome untuk analisis area fraksi kolagen. Analisis ekspresi gen MMP-2 dilakukan dengan metode qRT-PCR. Hasil analisis histologi berdasarkan sistem penilaian Laennec antara kelompok LDB dan LDB + UC-MSC tidak terdapat perbedaan, sedangkan persentase area kolagen menunjukkan perbedaan yang signifikan (p < 0,0001). Hasil analisis ekspresi gen MMP-2 pada kedua kelompok menunjukkan perbedaan yang tidak signifikan (p = 0,2593). Dapat disimpulkan bahwa UC-MSC dapat mengurangi area fraksi kolagen dengan kecenderungan peningkatan ekspresi gen MMP-2 walaupun belum terdapat perubahan secara morfologi. ......Liver fibrosis is a disease with high morbidity and mortality. The effective therapy is liver transplantation, but it is expensive and difficult, so needs alternative. Umbilical cord mesenchymal stem cell (UC-MSC) can degrade extracellular matrix which is potential to decrease fibrosis. The study aims to know the effect of UC-MSC on liver fibrosis in rabbits (Oryctolagus cuniculus). The sample is 16 livers consisting of 2 normal groups, 7 groups of biliary duct ligation fibrosis models (LDB), and 7 groups of fibrosis injected intrahepatic UC-MSC (LDB + UC-MSC). The study uses histological and matrix metalloproteinase-2 (MMP-2) gene expression analysis. Histological slides were stained by Hematoxylin-Eosin for Laennec scoring system and Masson Trichrome for analyze collagen fractions area. Analysis of MMP-2 gene expression was assessed using qRT-PCR. The results of histological analysis based on the Laennec scoring system showed no difference between the LDB and LDB + UC-MSC groups, while the percentage of collagen area showed a significant difference (p <0.0001). The results of the MMP-2 gene expression in the two groups showed no significant difference (p = 0.2593). The conclusion is UC-MSC can reduce the collagen fraction area with a tendency to increase MMP-2 gene expression although no change in morphology.

Abstrak :
Nephrotoxic effects of Doxorubicin (DXR) is still a problem in clinical practice. On the other hand Pentoxyfilline (PTX) as an electron-donor material can be nephroprotective. Therefore, combination of DXR and PTX would be expected to reduce nephrotoxic effects of DXR. In this study we examined the effects of PTX on TGF-B1 expression and interstitial fibrosis in an experimental model of DXR nephropathy in mice. Mice were divided into three groups of eight each i.e. untreated Swiss mice (controls), DXR treatment alone to induce nephropathy, and DXR treatment followed by PTX. Following 4 week treatment, each group was sacrificed. Examination of TGF-B1 expression was carried out by immunohistochemistry employing monoclonal antibody. Interstitial fibrosis examination was performed by a histopathologist using Verheoff van Giesen staining and the one way Anova was used for statistical analysis. It was observed that DXR treatment followed by PTX treatment prevented the increase of TGF-B1 expression and interstitial fibrosis in mice with DXRnephropathy (p<0.05). These findings suggested the beneficial nephroprotective effect of PTX.

Abstrak :
Latar Belakang: Fibrosis hati telah menjadi masalah kesehatan global dengan angka mortalitas 800 ribu kematian tahun 2004. Hepatitis kronis yang disebabkan oleh hepatitis C memerlukan perhatian khusus karena secara patogenesis sebelum berkembang menjadi hepatocellular carcinoma (HCC) akan melalui fase fibrosis hati. Baku emas diagnosis fibrosis hati adalah melalui biopsi hati, tetapi terdapat banyak keterbatasan antara lain kesediaan fasilitas dan efek samping. Pemeriksaan non-invasif saat ini menjadi pilihan untuk deteksi fibrosis. Tujuan: untuk mengetahui akurasi pemeriksaan non-invasif (FibroScan, skor APRI, dan FIB-4) dalam mendeteksi fibrosis hati. Metode: Penelitian ini merupakan uji diagnostik dengan menggunakan data sekunder dari rekam medis pasien yang dilakukan biopsi hati di RSPUN dr. Cipto Mangunkusumo dari Januari 2008 hingga Desember 2014. Hasil: Dari 120 orang yang menjalani biopsi hati, 56 pasien yang memenuhi kriteria seleksi. Akurasi APRI, FIB-4, dan FibroScan adalah sebagai berikut, AUC 0,692 (IK95%, 0,381-1,000), AUC 0,567 (IK95%, 0,253-0,882), dan AUC 0,712 (IK 95%, 0,398-1,000). Berdasarkan hasil analisis berjenjang, akurasi diagnostik kombinasi pemeriksaan APRI dan FibroScan, FibroScan dan FIB-4, APRI dan FIB-4, dan kombinasi ketiganya adalah sebagai berikut AUC 0,702 (IK95%, 0,375-1,000), AUC 0,798 (IK95%, 0,533-1,000), AUC 0,774 (IK95%, 0,513- 1,000), dan 0,798 (IK 95%, 0,533-1,000). Kesimpulan: FibroScan memiliki akurasi terbaik dibandingkan APRI dan FIB4 dalam mendeteksi fibrosis hati. Akurasi dengan kombinasi APRI, FIB-4, dan FibroScan meningkat jika dibandingkan dengan pemeriksaan tunggal untuk mendeteksi fibrosis hati pada pasien hepatitis C. ...... Background: Liver fibrosis has become a global health problems with the 800 thousand mortality death in 2004. Chronic hepatitis caused by hepatitis c need special attention because before it develops into Hepatocellular Carcinoma (HCC) going through the liver fibrosis. Gold standard of liver fibrosis is liver biopsy, but there are many limitations, such as facilities and side effects. Non-invasive diagnostic tools are the option for the detection fibrosis. Aim: To know the accuracy of the noninvasive diagnostic tools (FibroScan, the APRI score, FIB-4 score) in detecting liver fibrosis . Methods: This is diagnostic research which used secondary data from medical patient doing liver biopsy conducted in RSUPN dr. Cipto Mangunkusumo in January 2008 to December 2014. Results: There are 120 patients who underwent liver biopsy and 56 patients who fulfill selection criteria. The accuracy of APRI score, FIB-4, and FibroScan are AUC 0,692 (IK95%, 0,381-1,000), AUC 0,567 (IK95%, 0,253-0,882), and AUC 0,712 (IK95%, 0,398-1,000). Based on the multivariate analysis , accuracy of diagnostic combination FibroScan and APRI , FIB-4 and FibroScan , and FIB-4 and APRI, and combination of the three are as follows AUC 0,702 (IK95% , 0,375-1,000 ), AUC 0,798 (IK95%, 0,533-1,000), AUC 0,774 (IK95%, 0,513- 1,000), and 0,798 ( IK95% , 0,533-1,000 ). Conclusion: FibroScan has the highest diagnostic accuracy compared with APRI and FIB4 in detecting liver fibrosis. Accuracy of combination APRI, FIB-4, and FibroScan increase compared with the single diagnostic tools for liver fibrosis detection in hepatitis C patient.

Abstrak :
[LatarBelakang: Sekitar 3% populasi di dunia terinfeksi virus hepatitis C. Protein virus hepatitis C memodulasi apoptosis dan steatosis, cedera sel hati, mengaktifkan sel stelata hati dan fibrosis hati. Infeksi virus hepatitis C akan menimbulkan cedera pada hepatosit. Cedera pada hepatosit ini akan mengaktivasi sel stelata hati. Sel stelata berperan besar pada proses perkembangan fibrosis hati.. Tujuan: Untuk mengetahui perbedaan jumlah sel stelata hati aktif CD38+ pada berbagai derajat fibrosis serta hubungnnya dengan AST, ALT, jumlah HCV RNA kuantitatif pada hepatitis C kronik. Metoda: Penelitian ini merupakan studi potong lintang yang dilakukan pada 32 pasien hepatitis C kronik yang sudah dilakukan USG hati dan tidak menderita hepatoma serta telah dilakukan biopsi hati. Paraffin block jaringan hati pasien selanjutnya diwarnai menggunakan teknik Hematoksilin Eosin untuk menilai derajat Metavir yang dikategorikan menjadi derajat ringan-sedang atau berat. Pewarnaan khusus dilakukan untuk menilai sel stelata hati yang dihitung rata-rata pada lima lapangan pandang. Hasil: Pada penelitian ini didapatkan perbedaan jumlah sel stelata hati CD38+ yang bermakna antara fibrosis derajat berat dan derajat ringan-sedang (p <0.001), tidak didapatkan hubungan antara sel stelata hati CD38+ dengan AST (p=0,2) maupun ALT (p =0,7), dan tidak didapatkan hubungan antara sel stelata hati CD38+ dengan HCV RNA kuantitatif (r = -0,372). Kesimpulan: Jumlah sel stelata hati CD38+ pada fibrosis berat lebih tinggi daripada jumlah sel stelata hati CD38+ pada fibrosis ringan-sedang. Tidak terdapat hubungan antara nilai AST, ALT dan HCV RNA kuantitatif dengan jumlah sel stelata hati CD38+.;Background: Approximately 3% of the population in the world are infected with hepatitis C. Hepatitis C virus proteins modulate apoptosis and steatosis, liver cell injury, activate liver stellate cells and liver fibrosis. Hepatitis C virus infection will injure to hepatocytes. Hepatocytes injury will activate the liver stellate cells. Stellate cells play a major role in the development of liver fibrosis. Aim: Knowing the CD38+ active hepatic stellate cells count difference at various fibrosis stage and correlation with AST, ALT, quantitative HCV RNA in chronic hepatitis C patients Method: Cross-sectional method. 32 paraffin block sample from liver tissue patient with chronic hepatitis C without hepatocellular carcinoma who have performed an abdomen ultrasound and liver biopsy, assess the Metavir score were categorized into mild or severe degree. Samples were stained for liver stellate cells by specific staining and the average of stellate cells were calculated in 10 flat field of view. Result: In this study, the liver stellate cells count CD38+ were significantly correlate with the degree of fibrosis (p <0.001), there were no relationship between liver stellate cells CD38+ with AST levels (p = 0,2) and ALT levels (p = 0,7), and there was no relationship between liver stellate cells CD38+ with quantitative HCV RNA levels (r = -0.372). Conclution: Stellate cells count CD38+ are increasing along with the fibrosis degree. There were no relationship between level of AST, ALT and quantitative HCV RNA with the stellate cells count CD38+., Background: Approximately 3% of the population in the world are infected with hepatitis C. Hepatitis C virus proteins modulate apoptosis and steatosis, liver cell injury, activate liver stellate cells and liver fibrosis. Hepatitis C virus infection will injure to hepatocytes. Hepatocytes injury will activate the liver stellate cells. Stellate cells play a major role in the development of liver fibrosis. Aim: Knowing the CD38+ active hepatic stellate cells count difference at various fibrosis stage and correlation with AST, ALT, quantitative HCV RNA in chronic hepatitis C patients Method: Cross-sectional method. 32 paraffin block sample from liver tissue patient with chronic hepatitis C without hepatocellular carcinoma who have performed an abdomen ultrasound and liver biopsy, assess the Metavir score were categorized into mild or severe degree. Samples were stained for liver stellate cells by specific staining and the average of stellate cells were calculated in 10 flat field of view. Result: In this study, the liver stellate cells count CD38+ were significantly correlate with the degree of fibrosis (p <0.001), there were no relationship between liver stellate cells CD38+ with AST levels (p = 0,2) and ALT levels (p = 0,7), and there was no relationship between liver stellate cells CD38+ with quantitative HCV RNA levels (r = -0.372). Conclution: Stellate cells count CD38+ are increasing along with the fibrosis degree. There were no relationship between level of AST, ALT and quantitative HCV RNA with the stellate cells count CD38+.]

Abstrak :
ABSTRAK Latar Belakang: Transplantasi sel sumsum tulang dilaporkan memperbaiki fibrosis hati. Beberapa studi in vitro menunjukkan bukti mekanisme perbaikan dengan melakukan ko-kultur 2D sel sumsum tulang dan sel stelata hepatik. Pada studi tersebut, sel sumsum tulang menghambat aktivasi sel stelata hepatik dan mengurangi deposisi matriks ekstra sel. Pada penelitian ini, mekanisme perbaikan tersebut diteliti dengan melakukan ko-kultur sel sumsum tulang dan sel stelata hepatik pada model kultur 3D dan meneliti efeknya terhadap ekspresi tenascin-C, suatu glikoprotein matriks yang memiliki kontribusi dalam fibrogenesis hati. Metode: Sel stelata hepatik dan sel sumsum tulang yang diisolasi dari tikus dikultur sendiri (monokultur) dan diko-kultur direk dengan metode hanging drop. Karakterisasi sel sumsum tulang dilakukan dengan analisis flowcytometry CD90CD34. Sampel dari kedua kelompok kultur dipanen pada hari ke-7 untuk analisis imunositokimia tenascin-C. Hasil: Persentase sel CD90+CD34- dari sel sumsum tulang yang diisolasi adalah 35,2%. Hasil yang diperoleh pada penelitian ini menunjukkan bahwa sel sumsum tulang memilki efek antifibrotik yang dibuktikan dengan penurunan signifikan ekspresi tenascin-C pada kelompok ko-kultur (p < 0,05) dibandingkan dengan kelompok monokultur pada hari kultur ke-7. Kesimpulan: Temuan tersebut menunjukkan bahwa sel sumsum tulang memiliki efek terapeutik potensial terhadap proses fibrosis hati melalui efeknya dalam meminimalkan ekspresi matriks ekstra sel tenascin-C.

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ABSTRACT Background: Transplantation of bone marrow derived cells (BMCs) has been reported to improve liver fibrosis. Several in vitro studies have shown evidence for the mechanism of improvement by co-culturing BMCs and hepatic stellate cells (HSCs) in 2D models. In those studies, BMCs were reported to inhibit HSCs activation and reduce extracellular matrix deposition. In this study, we investigated the mechanism by co-culturing BMCs and HSCs in 3D model and its effect on tenascin-C expression, an extracellular matrix glycoprotein that has a contribution in liver fibrogenesis. Methods: Primary isolated rat HSCs and BMCs were cultured alone (monoculture) and directly co-cultured with hanging drop method. Characterization of BMSCs was performed by flowcytometry CD90CD34 analysis. The monoculture and co-culture samples were harvested on day 7 for tenascin-C immunocytochemistry. Results: The percentage of CD90+CD34- cells from the isolated BMCs was 35.2%. Result of the present study showed that BMCs have a significant antifibrotic effect as evidenced by the significant decrease in in tenascin-C expression in the co-culture group (p < 0.05) compared to the monoculture group on day 7. Conclusions: This finding demonstrates that BMSCs have a potential therapeutic effect against liver fibrotic process through their effect in minimizing extracellular matrix tenascin-C expression.

Abstrak :
ABSTRAK
Penyakit crohn merupakan peradangan saluran cerna kronik yang berpotensi mempengaruhi setiap bagian dari saluran pencernaan. Hal ini menyebabkan akumulasi abnormal dari matriks ekstraselular dan pembentukan fibrosis yang berkaitan dengan meningkatnya jumlah Transforming Growth Factor-? dan dapat menyebabkan penyempitan usus hingga kegagalan organ. Tujuan penelitian ini adalah identifikasi situs pentargetan yang sensitif Transforming Growth Factor-? sebagai informasi untuk penghantaran obat terapi fibrosis pada usus hewan dan manusia. Dalam penelitian ini, identifikasi situs pentargetan sensitif TGF-? dapat dilakukan dengan menggunakan PCIS Precision-Cut Intestinal Slices yang merupakan suatu model ex vivo untuk mensimulasikan terjadinya fibrosis usus. Hasil penelitian menunjukkan bahwa TGF-? tidak mempengaruhi kelangsungan hidup irisan usus dan adanya pengaruh TGF-? terhadap perubahan fenotip yang berperan dalam penyempitan usus. Oleh karena itu, dapat ditentukan terapi farmakologis atau terapi gen terkait TGF-? yang berpotensi untuk mencegah penyempitan usus pada penyakit crohn.

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ABSTRACT
Crohn rsquo s disease is a crohnic relapsing inflammatory bowel disease potentially affecting any portion of the gastrointestinal tract. It causes abnormal accumulation of extracellular matrix and formation of fibrosis which associated with the increasing amount of Transforming Growt Factor and can leads to intestinal stricture or organ failure. Aim of this research is to identification of targeting site which sensitive Transforming Growth Factor as information for drug delivery of fibrosis therapy in animal and human intestine. In this research, the identification of targeting site which sensitive to TGF can be done by using PCIS Precision Cut Intestinal Slices . It is an ex vivo models to simulate the occurrence of intestinal fibrosis. Results showed that TGF did not affect the viability of the slices and there was implication of TGF in the phenotypic transition which played a role in intestinal strictures. So that, it can be applicable for pharmacologic or targeted gene therapies related TGF which are potentially to prevent stricture of crohn rsquo s disease in the near future.

Abstrak :
Latar belakang: Fibrosis hati adalah akumulasi berlebihan dari matriks ekstraseluler, termasuk kolagen yang terjadi pada berbagai tipe penyakit hati. Aktivasi Hepatic Stellate Cell HSC memegang peran kunci dalam proses fibrogenesis. Jalur transduksi sinyal TGF-b/Smad ditengarai merupakan jalur yang paling predominan dalam aktivasi HSC yang ditandai dengan meningkatnya ekspresi marker-marker profibrogenik TGF-b, a-SMA, Col1A1 dan pSmad3. Proliferasi HSC yang teraktivasi juga berperan dalam patogenesis fibrosis hati. Pada saat ini belum ada terapi standar untuk fibrosis hati. Sorafenib, suatu multi kinase inhibitor diketahui mempunyai efek yang baik pada fibrosis hati ketika digunakan untuk indikasi karsinoma hepatoseluler. Pada saat ini, sedang dilakukan uji klinik tahap II terhadap Sorafenib untuk indikasi fibrosis hati. Alfa mangostin telah diteliti secara in vivo dapat memperbaiki fibrosis dan mempunyai efek antiproliferativ pada sel kanker. Pada penelitian ini kami menggunakan alfa mangostin untuk mengetahui aktivitasnya pada jalur TGF-b/Smad dengan pembanding Sorafenib. Metode: Ini merupakan penelitian in vitro menggunakan sel lestari HSC LX-2. Sel dibagi dalam 5 kelompok yaitu kelompok normal tanpa perlakuan , kelompok TGF-b, kelompok TGF-b Sorafenib 10mM, kelompok TGF-b Alfa mangostin 5mM dan 10mM . Dosis obat diperoleh dari perhitungan CC50 dengan MTSassay. Sel dipanen setelah induksi obat selama 24 jam. Proliferasi dilihat dari hitung sel dengan metode trypan blue exclusion method dan ekspresi Ki-67 dengan metode qRT-PCR. Ekspresi TGF-b dan Col1A1 diukur dengan qRT-PCR. Ekspresi a-SMA dan pSmad3 diukur dengan Western Blot. Hasil : Terdapat peningkatan ekspresi Ki-67 yang senada dengan peningkatan jumlah sel hidup secara pada kelompok TGF-b. Ekspresi Ki-67 maupun jumlah sel hidup menurun secara signifikan pada kelompok Sorafenib dan Alfa Mangostin 5mM dan 10mM. Ekspresi penanda fibrogenesis TGF-b, Col1A1, a-SMA dan pSmad3 meningkat secara signifikan pada kelompok TGF-b dan menurun signifikan dengan pemberian Sorafenib dan Alfa mangostin 5mM dan 10mM . Terdapat perbedaan signifikan dalam jumlah sel hidup, ekspresi Ki-67, TGF-b, Col1A1, a-SMA dan pSmad3 pada dua kelompok dosis Alfa mangostin. Kesimpulan : Alfa mangostin menghambat proliferasi HSC yang aktif dan menekan ekspresi marker-marker pro fibrogenik secara dose dependent.

Abstrak :
Fibrosis hati merupakan proses patofisiologi pada hati yang ditandai oleh proliferasi sel dan akumulasi protein matriks ekstraseluler yang berlebihan. Penelitian in vitro dan in vivo menunjukkan sel stelata hepatik mensekresikan mediator fibrogenik TGF-?. Jalur PI3K/Akt merupakan salah satu jalur TGF-? non-Smad. Alfa mangostin merupakan xanton yang terdapat pada kulit, buah, batang, dan daun manggis. Penelitian in vitro dan in vivo menunjukkan alfa mangostin dapat menurunkan ekspresi p-Akt, AST, and ALT. Akan tetapi, mekanisme kerja alfa mangostin belum diketahui. Penelitian ini bertujuan untuk menilai aktivitas alfa mangostin terhadap ekspresi penanda profibrotik sel stelata hepatik. Penelitian ini menggunakan sel LX-2 yang dibagi dalam lima kelompok, yaitu kelompok normal, TGF-?, sorafenib 10 ?M, alfa mangostin 5 ?M dan 10 ?M . Kadar TGF-? medium diukur dengan Elisa. Ekspresi penanda profibrotik diukur dengan qRT-PCR. Ekspresi proliferasi sel diukur dengan Western Blot. Berdasarkan parameter yang diperiksa, alfa mangostin dosis 5 dan 10 ?M dapat menurunkan kadar TGF-? yang dilepas ke ekstrasel, menurunkan ekspresi profibrotik sel peningkatan ekspresi mRNA MMP-3, dan penurunan ekspresi TIMP-1 dan PAI-1 , dan menghambat proliferasi sel penurunan rasio p-Akt/Akt diukur dengan Western Blot. Berdasarkan parameter yang diteliti, sel yang diberi TGF-β, menunjukkan peningkatan signifikan kadar TGF-β pada semua parameter pemeriksaan dibanding kelompok tanpa perlakuan, kecuali pada MMP-3. Alfa mangostin dosis 5 dan 10 μM dapat menghambat proliferasi sel, dilihat dari penurunan ratio p-Akt/Akt. Ekspresi penanda profibrotik juga dapat dihambat dengan alfa mangostin, terlihat dari peningkatan ekspresi MMP-3, dan penurunan ekspresi TIMP-1 dan PAI-1. Akan tetapi, efektivitas alfa mangostin dalam menghambat proliferasi dan akumulasi matriks esktraseluler tidak sebaik sorafenib. ......Liver fibrosis is a pathological process in the liver, characterized by abnormal proliferation and accumulation of extracellular matrix. In vitro and in vivo studies showed hepatic stellate cells secrete fibrogenic mediator TGF . The PI3K Akt pathway is one of the TGF non Smad pathways. Alpha mangostin is a xanthone that could be found in the skin, fruit, stems, and leaves of mangosteen. In vitro and in vivo studies have shown that alpha mangostin could decrease the expression of p Akt, AST, and ALT. But, the mechanism of action is still unknown. The purpose of this study is to assess the activity of alpha mangostin in the expression of profibrotic markers in hepatic stellate cell. In this study, we used LX 2 cells, divided into five groups normal, TGF , sorafenib 10 M, alpha mangostin 5 M and 10 M . Medium TGF level was measured by Elisa. Expression of profibrotic markers was measured by qRT PCR. Expression of cell proliferation was measured by Western Blot. Based on the parameters examined, alpha mangostin doses of 5 and 10 M can decrease extracellular TGF , decrease the expression of profibrotic cell MMP 3 expression increased and TIMP 1 and PAI 1 expression decreased , and inhibit cell proliferation decrease the ratio of p Akt Akt ratio. Expression of profibrotic marker could be inhibited by alpha mangostin too, showed by the increased level of MMP-3, and TIMP-1 and PAI-1 level decreased. But, the effectivity of alpha mangostin in inhibit cell proliferation and expression of profibrotic marker was not as good as sorafenib. Conclusion: alpha mangosteen could decrease the level of TGF-β in culture medium, inhibit expression of profibrotic marker, and inhibit cell proliferation