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Perbedaan ekspresi TGF-β1 dan fibrosis intertisial pada kejadian nefrotoksis doxorubicin dan nefroprotektif pentoxifylin
"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."
610 JKY 17: 2 (2009)
Artikel Jurnal  Universitas Indonesia Library
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Wachid Putranto
Efek kombinasi lisinopril dan diltiazem sebagai antifibrosis pada peritoneum Tikus = Effect of combination lisinopril and diltiazem as antifibrosis in peritoneum of Rats
"[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.
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.]"
2016
T-Pdf
UI - Tesis Membership  Universitas Indonesia Library
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Sisilia Triani Sisilia Triani
Formulasi beads tetrandrine menggunakan metode gelasi ionik ca-pektinat tersalut hidroksipropilmetil selulosa ftalat atau selulosa asetat ftalat sebagai sediaan kolon tertarget = Formulation of tetrandrine beads using ionic gelation method ca pectinate coated hydroxypropylmetyl cellulose phthalate or cellulose acetate phthalate as colon targeted
"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."
Depok: Fakultas Farmasi Universitas Indonesia, 2016
S63758
UI - Skripsi Membership  Universitas Indonesia Library
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Nur Azizah
Analisis Histologi dan Ekspresi Gen Matrix Metalloproteinase-2 (MMP-2) Satu Minggu Pascainjeksi Umbilical Cord-Mesenchymal Stem Cell (UC-MSC) pada Fibrosis Hati Kelinci Oryctolagus cuniculus (Linnaeus, 1758) = Histological Analysis and Gene Expression of Matrix Metalloproteinase-2 (MMP-2) One Week Postinjection Umbilical Cord-Mesenchymal Stem Cell (UC-MSC) in Rabbit Oryctolagus Cuniculus (Linnaeus, 1758) Liver Fibrosis
"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."
Depok: Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Indonesia, 2023
S-pdf
UI - Skripsi Membership  Universitas Indonesia Library
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Cystic fibrosis care: a practical guide
London : Elsevier , 2005
616.372 CYS
Buku Teks SO  Universitas Indonesia Library
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Zakky Hazami
Hubungan antara Faktor Klinis dan Laboratoris Saat Admisi dengan Kadar SST2 sebagai Penanda Fibrosis Jantung 12 Minggu Pasca Infeksi COVID-19 pada Pasien dengan Komorbid Kardiovaskular = Association between Clinical and Laboratory Factors on Admission with ST2 Levels as a Marker Of Cardiac Fibrosis 12 Weeks After COVID-19 Infection in Patient with Cardiovascular Comorbid
"Latar Belakang : Infeksi COVID-19 telah diketahui masih dapat menyebabkan gejala sampai 90 hari dan bahkan lebih, meski infeksi akutnya telah berlalu. Hal ini disebabkan karena adanya fenomena sindroma pasca COVID-19. Mekanisme kejadian tersebut sampai saat ini masih belum diketahui pasti. Hal tersebut diduga kuat akibat adanya fibrosis di beberapa organ, terutama jantung dan paru. Sementara itu, beberapa studi telah menyebutkan bahwa sST2 merupakan penanda fibrosis jantung. Meskipun demikian, sampai saat ini belum ada penelitian yang mencoba mengetahui faktor-faktor apa saja yang memiliki hubungan dengan kejadian fibrosis pasca infeksi COVID-19. Kadar sST2 pada pasien komorbid kardiovaskular tanpa COVID-19 dan populasi orang sehat, khususnya di Indonesia juga belum diketahui.
Tujuan : Mengetahui perbandingan kadar sST2 pada pasien komorbid kardiovaskular 12 minggu pasca infeksi COVID-19 dengan pasien komorbid kardiovaskular tanpa COVID-19 dan populasi orang sehat, serta hubungannya dengan faktor-faktor admisi.
Metode : Penelitian ini merupakan studi observasional potong lintang. Kadar sST2 pada pasien 12 minggu pasca infeksi COVID-19 dibandingkan dengan komorbid kardiovaskular akan dibandingkan dengan kelompok kontrol, yaitu kontrol 1 yang merupakan pasien komorbid kardiovaskular tanpa COVID-19 dan kontrol 2 yang merupakan populasi orang sehat. Kelompok kontrol dipilih menggunakan metode matching. Hubungan faktor klinis dan laboratoris saat dengan kadar sST2 pada pasien 12 minggu pasca infeksi COVID-19 dianalisis menggunakan analisis multivariat.
Hasil : Terdapat 162 subjek yang menyelesaikan rangkaian penelitian yang terdiri atas 100 subjek dengan penyintas COVID-19 disertai komorbiditas kardiovaskular (kelompok kasus), 31 subjek dengan komorbiditas kardiovaskular tanpa COVID-19 (kelompok kontrol 1), dan 31 subjek sehat tanpa riwayat COVID-19 dan komorbiditas kardiovaskular (kelompok kontrol 2). Ketiga kelompok memiliki karakteristik yang sama. Terdapat perbedaan signifikan rerata nilai sST2 antara kelompok kasus dibandingkan kontrol 1 dan kontrol 2 (2786 ± 73 vs 2666 ± 162 pg/l, p <0.001 dan 2786 ± 73 vs 2517.15 ± 321 pg/l, p < 0.001), serta kontrol 1 dibandingkan kontrol 2 (2666 ± 162 pg/l vs 2517.15 ± 321 pg/l, p < 0.001). Analisis multivariat menunjukkan PaO2 (p < 0.001) dan nilai CT (p = 0.04) memiliki hubungan dengan kadar sST2 pada pasien 12 minggu pasca infeksi COVID-19.
Kesimpulan : Terdapat perbedaan signifikan antara kadar sST2 sebagai penanda fibrosis jantung pada ketiga kelompok subjek penelitian, dengan kadar sST2 lebih tinggi pada subjek dengan penyintas COVID-19 disertai komorbiditas kardiovaskular. Terdapat hubungan PaO2 dan nilai CT saat admisi dengan kadar sST2.
Background : Recent findings showed that symptoms associated with COVID-19 infection may persist up to 90 days even after the acute disease period has passed. This condition is now termed as post COVID-19 syndrome. Several pathophysiologic mechanisms of this event had been proposed, all of which still needed further elaboration. One of the proposed mechanisms involves fibrotic processes in several organs, especially heart and the lungs. SST2 has been suggested as a novel biomarker for cardiac fibrosis. However data are still needed to further elucidate the factors which are associated with the incidence of fibrosis post COVID-19 infection. Furthermore, data regarding sST2 levels in patients with cardiovascular comorbidities and in healthy subjects are still limited.
Objective : Knowing the differences on sST2 levels between subjects with cardiovascular comorbidities 12 weeks post COVID-19 infection, those without history of COVID-19 but with cardiovascular comorbidities, and healthy population, as well as knowing its relationship with admission factors.
Methods : This study is a cross-sectional observational study on patients 3 months after COVID-19 infection presented with cardiovascular comorbidities. Age and sex-matched control groups were used as comparison. The results were compared with a group without history of COVID-19 and healthy populations. Relationship between admission factors was assessed using multivariate analysis
Results : 162 subjects completed the study series, consisting of 100 subjects with COVID-19 survivors with cardiovascular comorbidities (case group), 31 subjects with cardiovascular comorbidities without COVID-19 (control group 1), and 31 healthy subjects without a history of COVID-19 and cardiovascular comorbidities (control group 2). All three groups had similar characteristics. There was a significant difference in the mean sST2 value between the case groups compared to control 1 and control 2 (2786 ± 73 vs 2666 ± 162 pg/l, p < 0.001 and 2786 ± 73 vs 2517.15 ± 321 pg/l, p < 0.001 respectively), and control 1 compared to control 2 (2666 ± 162 pg/l vs 2517.15 ± 321 pg/l, p < 0.001). Multivariate analysis revealed PaO2 (p < 0.001 and CT values (p = 0.04) as admission factor associated with increased sST2 3 months after initial COVID-19 infection.
Conclusion : SST2 levels were found to be significantly different between the three groups, with the highest level on the case group (subjects with history of COVID-19 and cardiovascular comorbidities). Factors upon admissions which include Arterial oxygen partial pressure (PaO2) (p < 0.001) and CT value (p = 0.04) were found to be associated with increased sST2 levels."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2022
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UI - Tugas Akhir  Universitas Indonesia Library
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Averina Geffanie Suwana
Efek Alfa Mangostin dalam Sel Stelata Hepatik yang diinduksi Asetaldehida pada ekspresi mRNA MnSOD dan GPx = The Modulatory Effects of Alpha Mangostin in Acetaldehyde-induced Hepatic Stellate Cells on MnSOD and GPx mRNA expressions
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Pendahuluan: Konsumsi alkohol dalam jangka panjang dapat berakibat pada fibrosis hati. Fibrosis hati ditandai oleh matriks ekstraseluler yang berlebihan. Alkohol akan mengaktifkasi sel stelata hepatik (HSC) yang memegang peran utama dalam fibrosis hati. Saat ini, tidak ada standar manajemen untuk fibrosis hati. Alfa mangostin telah dilaporkan memiliki aktivitas antioksidan pada steatosis hati, namun aktivitas antioksidannya pada fibrosis hati masih belum diketahui. Penelitian ini menggunakan alfa mangostin untuk mengetahui pengaruhnya terhadap ekspresi mRNA antioksidan, MnSOD dan GPx, pada HSC yang diinduksi asetaldehida.

Metode: Penelitian ini merupakan eksperimen in-vitro yang menggunakan galur sel stelata hepatik-LX2 dengan 6 kelompok perlakuan: kelompok yang tidak diobati, yang mendapat perlakuan asetaldehida, asetaldehida dan sorafenib, asetaldehida dan alfa mangostin 10 µM, asetaldehida dan alfa mangostin 20 µM, dan alfa mangostin 10 µM. Ekspresi mRNA MnSOD dan GPx dari RNA diukur dengan mesin qRT PCR.

Hasil: Alfa mangostin 10 μM meningkatkan ekspresi mRNA GPx secara signifikan (p<0,05), namun tidak mempengaruhi ekspresi mRNA MnSOD. Alfa mangostin 20 µM meningkatkan ekspresi mRNA dari MnSOD dan GPx secara signifikan (p<0,05). Peningkatan ekspresi mRNA MnSOD dan GPx sebanding dengan peningkatan dosis alfa mangostin.

Kesimpulan: Alpha mangostin meningkatkan kadar antioxidan, MnSOD dan GPx, dalam model HSC yang diinduksi asetaldehida.

Background: The chronic consumption of alcohol can eventually lead to liver fibrosis. Liver fibrosis is characterized by excessive extracellular matrix. Alcohol will activate hepatic stellate cells (HSCs) which play an important role in fibrogenesis. Currently, there are no standardized treatment for liver fibrosis. Alpha mangostin has been reported to have antioxidant activity on hepatic steatosis, however its antioxidant activity on liver fibrosis is still unknown. This research will use alpha mangostin to identify its effect on the mRNA expression of antioxidant, MnSOD and GPx, in acetaldehyde-induced HSC.

Method: The research is an in vitro experiment utilizing hepatic stellate cell line – LX2 with 6 treatment groups: the untreated group, the treated groups with acetaldehyde, acetaldehyde and sorafenib, acetaldehyde and alpha mangostin 10 µM, acetaldehyde and alpha mangostin 20 µM, and alpha mangostin 10 µM. The mRNA expression of MnSOD and GPx were obtained from the RNA that was measured by qRT PCR machine.

Results: Alpha mangostin 10 µM significantly increased GPx mRNA expression (p <0,05), however it did not affect MnSOD mRNA expression. However, alpha mangostin 20 µM significantly increased the mRNA expression of MnSOD and GPx (p <0,05). The increase of the MnSOD and GPx mRNA expression is linear to the increase of alpha mangostin dose.

Conclusion: Alpha mangostin increases antioxidant, MnSOD and GPx, levels in acetaldehydeinduced HSC models.

"
Depok: Fakultas Kedokteran Universitas Indonesia , 2019
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Rini Rachmawarni Bachtiar
Akurasi diagnostik skor aspartate aminotransferase to platelet ratio index, fibrosis index based on the 4 factors dan transient elastography untuk mendeteksi fibrosis hati pada hepatitis C kronik = Diagnostic accuracy of aspartate aminotransferase to platelet ratio index score fibrosis index based on the 4 factors and transient elastography for liver fibrosis detection in chronic hepatitis C
"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."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2015
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UI - Tesis Membership  Universitas Indonesia Library
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Titos Ahimsa
Perbedaan jumlah sel stelata hati aktif cd38+ pada berbagai derajat fibrosis serta hubungnnya dengan AST, ALT, jumlah HCV RNA kuantitatif pada hepatitis c kronik = Cd38+ active hepatic stellate cells count difference at various fibrosis stage and correlation with ast alt quantitative hcv rna in chronic hepatitis c patients / Titos Ahimsa
"[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+.]"
2015
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UI - Tesis Membership  Universitas Indonesia Library
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Sitanggang, Ervina Julien Hotmangiring
Efek ko-kultur 3D sel sumsum tulang CD90 CD34 dengan sel stelata hepatik primer terhadap ekspresi tenascin C = Effect of bone marrow CD90 CD34 cells and hepatic stellate cells 3D Coculture on tenascin C expression
"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.
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."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2016
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