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Tjam Diana Samara
Abstrak :
Latar belakang: Semaphorin-3B (SEMA3B) sebagai faktor antiangiogenik dan Cullin-1 (CUL1) sebagai faktor proangiogenik merupakan contoh dua protein yang bekerja secara antagonis dalam invasi trofoblas, yang bila terjadi ketidakseimbangan akan menyebabkan preeklamsia (PE). VEGF, MMP9, E-cadherin, p21, dan CASP3 merupakan kandidat protein terkait kaskade hantaran sinyal SEMA3B dan CUL1. Tujuan umum penelitian ini adalah untuk menganalisis kadar SEMA3B dan CUL1, serta kandidat protein terkait kaskade hantaran sinyalnya pada patologi PE berdasarkan perbedaan usia kehamilan saat persalinan. Metode: Penelitian diadakan di RS Cipto Mangunkusumo dan RS Budi Kemuliaan dari April 2017-April 2018. Studi potong lintang dengan observasi analitik dilakukan untuk mengukur kadar SEMA3B dan CUL1 dan kandidat protein terkait kaskade hantaran sinyalnya dalam plasenta, serta kadar SEMA3B dan CUL1 dalam serum ibu pada 70 pasien PE berdasarkan dua kelompok usia kehamilan saat persalinan: <34 minggu dan ≥34 minggu. Pemeriksaan dilakukan di Laboratorium Terpadu Fakultas Kedokteran Universitas Indonesia. Hasil: Kadar SEMA3B, CUL1, VEGF, dan E-cadherin secara bermakna lebih rendah pada kelompok usia kehamilan <34 minggu. Pada kelompok usia kehamilan <34 minggu: terdapat korelasi positif antara usia kehamilan dengan SEMA3B, CUL1, dan protein terkait kaskade hantaran sinyalnya; terdapat korelasi positif antara SEMA3B dengan VEGF dan p21; terdapat korelasi positif antara CUL1 dengan VEGF, MMP9, E-cadherin, p21, dan CASP3; dan korelasi negatif antara rasio p21/CUL1 dengan usia kehamilan. Pada kelompok usia kehamilan ≥34 minggu: terdapat korelasi positif antara SEMA3B dalam plasenta dengan SEMA3B dalam serum ibu; tidak ada korelasi SEMA3B dengan kandidat protein terkait kaskade hantaran sinyalnya; terdapat korelasi positif antara CUL1 dengan MMP9, E-cadherin, p21, dan CASP3. Kadar proangiogenik CUL1 dan VEGF yang rendah rendah dan ratio p21/CUL1 yang tinggi secara bermakna berhubungan dengan usia kehamilan <34 minggu saat persalinan. Analisis multivariat menunjukkan kadar CUL1 yang rendah meningkatkan risiko melahirkan sebesar empat kali lebih besar pada usia kehamilan <34 minggu dibandingkan usia kehamilan ≥34 minggu. Kesimpulan: Pada PE usia kehamilan <34 minggu saat persalinan, gambaran patologi PE lebih berat, kadar SEMA3B yang lebih rendah, serta kadar CUL1 yang lebih rendah memiliki risiko empat kali lebih besar terjadi persalinan dibandingkan usia kehamilan ≥34 minggu saat persalinan. ......Background: Semaphorin-3B (SEMA3B) as an antiangiogenic factor and Cullin-1 (CUL1) as a proangiogenic factor are examples of two proteins that work antagonistically in trophoblast invasion, which will cause preeclampsia (PE) if an imbalance occurs. VEGF, MMP9, E-cadherin, p21, and CASP3 are protein candidates related to the signal transduction cascade of SEMA3B and CUL1. The aim of this study was to analyze SEMA3B and CUL1 levels, as well as protein candidates related to the signal transduction cascade in pathology of PE based on differences in gestational age at delivery. Methods: The study was conducted at Cipto Mangunkusumo Hospital and Budi Kemuliaan Hospital during April 2017 until April 2018. In this cross-sectional study SEMA3B, CUL1, and protein candidates related to the signal transduction cascade (VEGF, MMP9, E-cadherin, p21, CASP3) were measured in the placenta, as well as SEMA3B and CUL1 levels in maternal serum in 70 PE patients in two gestational age at delivery groups: <34 weeks and ≥34 weeks. Measurements were conducted at Integrated Laboratory of Faculty of Medicine Universitas Indonesia. Results: Levels of SEMA3B, CUL1, VEGF, and E-cadherin were significantly lower in the gestational age group of <34 weeks compared to ≥34 weeks. In the gestational age group of <34 weeks: there were positive correlation between age gestational age and SEMA3B, CUL1, protein candidates related to their signal transduction cascade; there were positive correlations between SEMA3B and VEGF, p21; there were positive correlations between CUL1 and MMP9, E-cadherin, p21, CASP3; there were negative correlation between p21/CUL1 ratio and gestational age. In the gestational age group of ≥34 weeks: there were positive correlation between SEMA3B in placenta and SEMA3B in maternal serum; there were positive correlations between CUL1 and MMP9, Ecadherin, p21, CASP3; there were no correlation between SEMA3B and candidate protein related to the signal transduction cascade. Significantly, low level of proangiogenic CUL1 and VEGF, and high ratio p21/CUL1 were associated with <34 weeks of gestational age at delivery. Multivariate analysis showed that at <34 weeks of gestational age, low levels of CUL1 increased the risk of giving birth by four times greater than at ≥34 weeks of gestational age. Conclusions: In PE at <34 weeks of gestation age at delivery, pathology of PE was worse, level of SEMA3B was lower, and lower level of CUL1 had four times greater risk of labor than at ≥34 weeks of gestational age at delivery.
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019
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UI - Disertasi Membership  Universitas Indonesia Library
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Made Susiyanti
Abstrak :
Latar belakang: Ulkus kornea adalah salah satu penyakit infeksi mata yang banyak ditemukan di negara berkembang termasuk Indonesia. Tatalaksana ulkus kornea bakteri konvensional umumnya dapat menimbulkan jaringan parut kornea permanen yang dapat menurunkan tajam penglihatan. Penggunaan transplantasi membran amnion (TMA) pada ulkus kornea dapat mempercepat proses penyembuhan dan mengurangi terbentuknya jaringan parut kornea. Membran amnion diduga menjadi kerangka baru dan mengekspresi beberapa komponen biologis yang berperan membantu proses epitelisasi dan pembentukan jaringan parut di kornea. Tujuan: Mengetahui dan membuktikan perbedaan perubahan klinis pada kelompok TMA dan terapi standar (non-MA) pada pasien dengan ulkus kornea bakteri, perbedaan perubahan kadar protein TNF-, MMP-9, TGF-β1 di air mata dan ekspresi mRNA TNF-, MMP-9, TGF-β1, dan TGF-β2 di air mata dan kornea. Metode: Penelitian tahap pertama, dilakukan penilaian klinis sebelum dan sesudah pada grup TMA dan terapi standar (non-TMA) dengan menilai tajam penglihatan, waktu epitelisasi total, waktu pembentukan sikatrik total dan derajat sikatrik serta uji kadar protein TNF-, MMP-9, TGF-β1 di air mata dengan pemeriksaan ELISA. Penelitian tahap kedua, dilakukan pemeriksaan ekspresi mRNA TNF-, MMP-9, TGF-β1, dan TGF-β2 di air mata dan kornea dengan pemeriksaan quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR). Hasil: Hasil penelitian pertama, pada grup TMA terjadi perbaikan yang signifikan bermakna pada tajam penglihatan (p=0.001), waktu epitelisasi total (p=0.002), waktu terbentuk sikatrik total (p=0.005), dan derajat sikatrik (p=0.001) dibandingkan grup non-TMA. Hasil kadar proteinTNF-, MMP-9, dan TGF-β1 di air mata tidak terjadi perubahan yang bermakna sebelum dan sesudah dan tidak terdapat perbedaan bermakna pada kedua grup (p>0.005). Pada hasil penelitian kedua, ekspresi mRNA TNF-α menurun paling tinggi pada grup TMA (0.824 ± 0), MMP-9 meningkat paling tinggi pada grup TMA (66.698 ± 24.948), TGF-β1 meningkat paling tinggi pada grup TMA (34.425 ± 14.025), sedangkan TGF-β2 mengalami peningkatan tertinggi pada grup non-TMA (114.049 ± 55.344). Kesimpulan: Terdapat perbaikan klinis yang signifikan pasca TMA, sejalan dengan ekspresi gen dari molekul yang terkait ditandai dengan penurunan inflamasi, re-epitelisasi yang lebih cepat, dan pengurangan pembentukan sikatrik. Kadar protein dan ekspresi gen molekul inflamasi di air mata tidak dapat dijadikan penanda untuk proses yang terjadi di kornea.
Background: Corneal ulcer is one of ocular infection disease that is commonly found in developing country like Indonesia. The conventional treatment for bacterial corneal ulcer usually causes the forming of permanent corneal scar which results in decrease of visual acuity. The use of amniotic membrane transplantation (AMT) in corneal ulcer is believed can shorten the healing process and reduce corneal scar. Amniotic membrane is expected to become as a new scaffold and have several biological properties that play a role in epithelization process and fibrotic tissue formation. Objective: To evaluate and establish the clinical differences on amniotic membrane transplantation and standard therapy of patients with bacterial corneal ulcer, and laboratory evaluation of protein level and mRNA expression changes of TNF-, MMP-9, TGF-β1 and TGF-β2 in tears and corneal tissue. Method: This study was divided into two phases on two groups of AMT and standard therapy group (non-AMT). On the first phase, clinical evaluation was examined include visual acuity, total duration of epithelization, total duration of scar formation and the degree of corneal scar, along with laboratory of protein level of TNF-, MMP-9, TGF-β1 in tears with ELISA. On the second phase, mRNA expression of TNF-, MMP-9, TGF-β1, and TGF-β2 in tears and cornea were examined with quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR). Result: The result of first phase on TMA group showed significant improvement on visual acuity (p=0.001), total duration of epithelization (p=0.002), total duration of scar formation (p=0.005), and cicatrix degree (p=0.001) compared to non-TMA group and a non-significant result on protein level of TNF-, MMP-9, TGF-β1 in tears on both groups (p>0.005).On the second phase, mRNA expression of TNF-showed the highest decrease on TMA group (0.824 ± 0), MMP-9 showed the highest increase on group TMA (66.698 ± 24.948),TGF-β1 expression increased the highest on TMA group (34.425 ± 14.025), whereas TGF-β2 showed the highest result on non-TMA group (114.049 ± 55.344). Conclusion: There was significant clinical improvement observed in TMA group parallel with related molecular genetic expression, indicated decreasing of inflammation, faster re-epithelization, and less dense scar formation. Protein level and genetic molecular expression in tears are poor predictors of processes occurring in the cornea.
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2018
D-Pdf
UI - Disertasi Membership  Universitas Indonesia Library
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