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Abstrak :
ABSTRAK Preeklampsia merupakan sindrom sistemik yang terjadi pada 3-5 % kehamilan wanita yang disebabkan oleh gangguan faktor migrasi dan faktor seluler  yang berdampak pada gangguan diferensiasi dan invasi trofoblas yang penting dalam proses perkembangan plasenta dan mempertahankan kehamilan. Protein Cullin-1 merupakan salah satu kandidat protein yang berperan dalam proses mempertahankan kehamilan, perkembangan dan invasi trofoblas di dalam  plasenta. Hingga saaat ini belum ada penelitian yang menghubungkan ekspresi Cullin-1 pada pasien preeklampsia dengan waktu terminasi kehamilan. Oleh karena itu pada penelitian ini dilakukan analisis ekspresi Cullin-1 pasien preeklampsia dan hubungannya dengan waktu terminasi kehamilan. Sampel plasenta diambil dari pasien preeklampsia yang terdiri dari tiga kelompok usia kehamilan, kemudian dilakukan perwarnaan imunohistokimia untuk dilihat dinamika ekspresi dan distribusi Cullin-1 pada berbagai kelompok usia kehamilan dan hubungannya dengan waktu terminasi kehamilan. Cullin-1 terekspresi pada sinsitiotrofoblas dan  sitotrofoblas. Kadar Cullin-1 terendah didapatkan pada kelompok usia kehamilan very preterm, dan paling tinggi didapatkan di kelompok usia kehamilan moderate preterm. Terdapat perbedaan bermakna antara ekspresi optical density (OD) Cullin-1 dengan   waktu terminasi  kehamilan, dan terdapat perbedaan bermakna  (OD) Cullin-1 pasien preeklampsia usia kehamilan very preterm dengan usia kehamilan moderate preterm. Disimpulkan bahwa Cullin-1 terekspresi pada sinsitiotrofoblas dan sitotrofoblas dan berhubungan dengan waktu terminasi kehamilan.

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ABSTRACT Preeclampsia is a systemic syndrome that occurs in 3-5% of female pregnancies caused by disorders of migration factors and cellular factors that have an impact on the disruption of trophoblast differentiation and invasion that is important in the process of developing the placenta and maintaining pregnancy. Protein Cullin-1 is one candidate protein that plays a role in the process of maintaining pregnancy, development and trophoblast invasion in the placenta. Until now there have been no studies linking the expression of Cullin-1 in preeclamptic patients with the timing of pregnancy termination. Therefore in this study an analysis of Cullin-1 expression in preeclamptic patients and their relationship to the timing of pregnancy termination was carried out. Placental samples were taken from preeclampsia patients consisting of three gestational age groups, then immunohistochemical staining was performed to see the dynamics of expression and distribution in each age group of pregnancy and to find out their relationship with  the timing of pregnancy termination. Cullin-1 was expressed in syncytiotrophoblasts and cytotrophoblasts. The lowest Cullin-1 level was obtained in the very preterm age group, and the highest was found in the moderate preterm gestational age group. There was a significant difference between Cullin-1 optical density (OD) expression and termination time of pregnancy, and there was a significant difference (OD) in Cullin-1 preeclamptic patients with very preterm gestational age with moderate preterm gestational age. It was concluded that Cullin-1 was expressed both in syncytiotrophoblasts and cytotrophoblasts and was associated with the timing of pregnancy termination.

Abstrak :
Latar Belakang : Preeklampsia masih menjadi penyebab utama morbiditas dan mortalitas pada ibu hamil. Hingga saat ini masih belum ada program penapisan untuk memprediksi preeklampsia di Indonesia. Pada tahun 2018 di Jakarta, dilakukan penelitianmengenai faktor-faktor risiko maternal dan profil biofisik yang dinilai dapat meningkatkan kejadian preeklampsia. Namun, hasil penelitian tersebut masih perlu dilakukan validasi eksternal untuk mengonfirmasi bahwa hasilnya valid dan bisa diaplikasikan pada situasi, waktu, tempat yang berbeda. Tujuan: Melakukan validasi eksternal hasilpenelitian terdahulu Metode: Desain kohort prospektif. Semua ibu hamil yang melakukan pemeriksaan kehamilan di RSCM, RSUK JoharBaru, dan RSUK Tebet dari April-November 2018 diikuti hingga bersalin/terjadi preeklampsia pada Januari 2019. Hasil: Total subjek 467 orang. Insidens preeklampsia dari ketiga rumah sakit adalah 18,2%. Hasil penelitian dianalisis secara bivariat dilanjutkan multivariat. Hasil penelitian yang secara statistik signifikan adalah hipertensi kronik, riwayat preeklampsia, tekanan arteri rerata≥ 95 mmHg, dan indeks pulsatilitas a.uterina tinggi. AUC-ROC (kemampuan diskriminasi untuk memprediksi preeklampsia) 85%. Sehingga merupakan instrumen yang baik untuk uji diagnostik. Hasil ROC dari penelitian sebelumnya menunjukkan hasil yang serupa. Cut off dari penelitian ini 0,91 (sensitivitas 79% dan spesifisitas 84%). Hasil uji validitas eksternal dari penelitian sebelumnya diterapkan pada penelitian ini dan menunjukkan hasil yang valid dan memiliki akurasi yang baik. Kesimpulan: Faktor-faktor yang meningkatkan risiko preeklampsia, yaitu hipertensi kronik, riwayat preeklampsia, tekanan arteri rerata ≥95 mmHg, dan indeks pulsatilitas a.uterina tinggi. Hasil perbandingan uji diagnostik dan uji validitas eksternalbaik. ......Background: preeclampsia is still leading causes of morbidity and mortality in pregnant women. Until today, there is still no screening program to predict preeclampsia in Indonesia. In Jakarta 2018, conducted research on maternal risk factors and biophysical profile to predict preeclampsia. However, the results still needs to be performed external validation to confirm that the results of the study are valid and can be applied on different situations, populations, and times. Objective: to perform external validation of the previous studyMethods: A prospective cohort design. Participants are all pregnant women who perform antenatal care in RSCM, RSUK JoharBaru, and RSUK Tebet from April-November 2018. They will be followed until January 2019. Results: Total participants 467 subject. Incidence of preeclampsia from 3 hospitals was 18,2%. The results had been analyzed bivariate continuing multivariate. The results of this study which statistically significant werechronic hypertension, history ofpreeclampsia, mean arterial pressure≥ 95 mmHg, and high pulsatility index of uterine artery. AUC-ROC (discrimination ability to predict preeclampsia) was 85%. Therefore, it is a good instrument fordiagnostic test. The ROC result of previous study seen shows the similar result.Cut off of this study was 0,91 (79% sensitivity and 84% specificity). The result of external validity test from previous study which applied to this study was valid and showed a good accuracy.Conclusion: Several factors increase the risk of preeclampsia, such as chronic hypertension,history of preeclampsia, mean arterial pressure≥ 95 mmHg, and high pulsatility index of uterine artery. The results of diagnostic test and external validation test are good.

Abstrak :
ABSTRAK
Latar belakang: Preeklampsia merupakan salah satu penyebab terbesar kematian ibu di Indonesia. Meskipun menjadi permasalahan kesehatan namun pathogenesis yang terjadi pada preeklampsia masih merupakan misteri. Autofagi merupakan salah satu proses yang dihubungkan dengan pathogenesis preeklampsia. Sebagai mekanisme sel dalam menghadapi suasana kurang nutrisi, autofagi menjadi faktor penting yang diperhitungkan dalam penyakit preeklampsia. Penelitian ini bertujuan melihat perbedaan protein-protein petanda autofagi secara khusus LC3 dan p62 pada plasenta normal dan preeklampsia serta melihat hubungannya. Metode: Penelitian ini berdisain potong lintang, dengan pengambilan sampel consecutive sampling. Digunakan 50 jaringan tengah plasenta preeklampsia: diperoleh dari RS Cipto Mangunkusumo = 26 dengan usia kehamilan dibawah 34 minggu, 24 sampel kehamilan normal dari RS Budi Kemuliaan. Pengukuran ekpresi relatif mRNA menggunakan RT-PCR, SYBR No ROX dan rumus Livak, dan pengukuran kadar protein menggunakan kit ELISA untuk p62 dan LC3A. Analisis statistik menggunakan non parametrik karena distribusi data tidak normal. Hasil: Konsentrasi protein LC3 plasenta preeklampsia lebih tinggi bermakna dari plasenta normal, p=0,001*. Sedangkan ekspresi relatif mRNA LC3 preeklampsia lebih tinggi dari normal namun tidak bermakna, p=0,5. Konsentrasi protein p62 preeklampsia lebih rendah dari normal namun tidak bermakna, p = 0,408. Sedangkan ekspresi relatif mRNA p62 preeklampsia lebih rendah dan bermakna terhadap normal, p = 0,006*. Kesimpulan: Penelitian ini menunjukkan bahwa autofagi (LC3A) lebih tinggi pada plasenta preeklampsia dibandingkan dengan normal.

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ABSTRACT
Background: Preeclampsia is one of the biggest causes of maternal mortality in Indonesia. Although it is a health problem, the pathogenesis that occurs preeclampsia still a mystery. Autophagy is one of the processes associated with the pathogenesis of preeclampsia. As a cell mechanism in case of a lack of nutrition, autophagy is an important factor that is considered in preeclampsia. This study aims to look at differences in autophagy protein markers specifically p62 and LC3 in the normal placenta compared with preeclampsia and see the correlation. Methods: Using cross sectional method and consecutive sampling method, 50 midportion of women placenta tissues were obtained consist of 26 placentas of preeclampsia women from Cipto Mangunkusumo National Hospital and 24 placentas of normal pregnancy were obtained from Budi Kemuliaan Hospital. Relative expression mRNA measured using RT-PCR, SYBR No ROX and Livak method, while LC3 and p62 protein level meassured by ELISA kit. In cause of abnormal data distriburion, non parametric statistical of Mann Whitney test were used. Results: Protein LC3 concentration of preeclampsia significantly higher than normal placenta p=0,001*. While relative expression of LC3 mRNA of preeclampsia not significantly higher than normal placenta, p=0,5. Protein p62 concentration of preeclampsia not significantly lower than normal placenta, p = 0,408. While relative expression of p62 mRNA significantly lower than normal placenta, p = 0,006*. Conclusion: this study shows autophagy (LC3A) in preeclampsia is higher compared to normal.

Abstrak :
Latar Belakang: Kejadian preeklamsia dilaporkan berkisar 5-15% dari seluruh kehamilan dan terkait erat dengan morbiditas dan mortalitas maternal dan perinatal. Preeklamsia merupakan penyakit dengan berbagai teori (disease of theory) yang menggambarkan ketidakpastian patofisiologi dan penyebabnya. Salah satu teori patogenesis preeklamsia adalah peningkatan stres oksidatif. Stres oksidatif merupakan ketidakseimbangan jumlah oksidan dan antioksidan dalam tubuh. Peningkatan radikal bebas pada preeklamsia diduga menyebabkan penurunan antioksidan endogen seperti superoksida dismutase (SOD) karena banyak antioksidan tersebut yang terpakai untuk menanggulangi radikal bebas. Mengingat pentingnya peranan SOD pada patogenesis preeklamsia, maka pemberian suplementasi SOD diduga dapat memberi manfaat pada preeklamsia maupun kehamilan normal. Tujuan Penelitian: Penelitian ini bertujuan untuk mengetahui perbedaan kadar SOD pada kehamilan normal dan preeklamsia. Selain itu, penelitian ini juga bertujuan untuk mengetahui kenaikan kadar SOD pasca pemberian suplementasi SOD pada kehamilan normal dan preeklamsia. Metode Penelitian: Penelitian uji klinis ini dilakukan di RSCM, RSAB Harapan Kita, RSIA Bunda, dan RSIA Brawijaya pada bulan September hingga Desember 2019. Subjek penelitian berasal dari Ibu hamil normotensi dan Ibu hamil preeklamsia yang akan dilakukan tindakan operasi sesar berencana dalam waktu 2 minggu. Pada subjek di kelompok uji, akan diberikan suplementasi Glisodin 2 x 250 U selama 14 hari. Dilakukan pengukuran kadar SOD serum pra- dan pasca- suplementasi Glisodin, SOD plasenta, dan kadar Cu, Mn dan Zn serum. Data selanjutnya diolah dengan menggunakan uji statistik dengan paket SPSS versi 15. Analisis data berupa analisis univariat, bivariat dan multivariat. Hasil Penelitian: Didapatkan 91 subjek penelitian yang terdiri dari 42 Ibu hamil normotensi dan 49 Ibu hamil dengan preeklamsia. Dari 25 subjek penelitian yang diberikan suplementasi Glisodin, 15 orang berasal dari kelompok Ibu hamil normotensi dan 10 orang berasal dari kelompok Ibu hamil preeklamsia. Kadar Zn pada kelompok preeklamsia didapatkan lebih rendah bermakna dibandingkan pada kelompok normotensi (45 (25,00-110,00) ug/dL vs 52,00 (36,00-88,00) ug/dL, p 0,025). Tidak didapatkan perbedaan bermakna kadar SOD pra- dan pasca suplementasi pada kelompok normotensi dan preeklamsia. Tidak terdapat peningkatan bermakna kadar SOD pasca suplementasi , baik pada kelompok normotensi maupun preeklamsia (+1,08 ± 2,45, p 0,069 dan +0,12 ± 2,04, p 0,721). Satu-satunya perbedaan bermakna yang ditemukan adalah kadar SOD plasenta dimana didapatkan kadar SOD plasenta lebih rendah pada kelompok preklamsia dibandingkan normotensi (26,04 (10,49-91,16) U/mL vs 37,62 (13,58-105,40) U/mL, p<0,001). Kesimpulan: Kadar SOD plasenta pada kehamilan hipertensi atau preeklamsia lebih rendah dibandingkan dengan normotensi. Tidak ada peningkatan bermakna kadar SOD pasca-suplementasi dengan Glisodin pada kehamilan normotensi dan hipertensi atau preeklamsia.

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Background: Preeclampsia incidence varies between 5-15% from all pregnancy and related to maternal and perinatal morbidity and mortality. Preeclampsia is a disease of theory which describe uncertainty in its pathogenesis and pathophysiology. One of the preeclampsia pathogenesis theory is the increasing oxidative stress level. Oxidative stress is a condition caused by imbalance between oxidant and anti-oxidant inside the body. Increased free radicals level in preeclampsia causing further decreased in endogenous antioxidant level such as superoxide dismutase (SOD) because antioxidant were used to neutralize free radicals. Given the important role of SOD in the pathogenesis of preeclampsia, supplementation of SOD is thought to be beneficial, both in the normal pregnancy and preeclampsia. Objective: The aim of this study is to determine differences in SOD levels in normal pregnancy and preeclampsia. This study is also aims to determine the increase in SOD levels after SOD supplementation in normal pregnancy and preeclampsia. Methods: This clinical trial study was conducted at RSCM, RSAB Harapan Kita, RSIA Bunda, and RSIA Brawijaya in September to December 2019. The research subjects came from normotensive pregnant women and preeclampsia pregnant women who will undergo planned cesarean operations within 2 weeks. Subjects in the test group will be given Glisodin 2 x 250 U supplementation for 14 days. Serum SOD pre-and post-supplementation with Glisodin, placental SOD, and serum Cu, Mn and Zn levels were measured. Data were then processed using statistical tests with SPSS package version 15. Data analysis was in the form of univariate, bivariate and multivariate analyzes. Results: There were 91 research subjects consisting of 42 normotensive pregnant women and 49 pregnant women with preeclampsia. Of the 25 study subjects who were given Glisodin supplementation, 15 were from the group of normotensive pregnant women and 10 were from the group of preeclampsia. The level of Zn in the preeclampsia group was significantly lower than in the normotensive group (45 (25.00-110.00) ug/dL vs 52.00 (36.00-88.00) ug/dL, p 0.025). There were no significant differences in pre- and post-supplementation SOD levels in the normotensive and preeclampsia groups. There was no significant increase in SOD levels after supplementation, both in the normotensive and preeclampsia groups (+1.08 ± 2.45, p 0.069 and + 0.12 ± 2.04, p 0.721). The only significant difference found was placental SOD levels in which placenta SOD levels were lower in the preeclampsia group than normotensive (26.04 (10.49-91.16) U / mL vs 37.62 (13.58- 105.40 ) U / mL, p <0.001). Conclusions: Placental SOD levels in pregnancy with hypertension or preeclampsia are lower than normotensive. There was no significant increase in post-Glisodin supplementation SOD levels in normotensive and hypertensive or preeclampsia pregnancy.

Abstrak :
Latar Belakang: Terlepas dari kemajuan perawatan perinatal, preeklampsia masih menjadi penyebab utama mortalitas dan morbiditas ibu dan janin di dunia. Namun, etiologi utama dan patofisiologi preeklampsia tetap diperdebatkan. Asosiasi antara preeklampsia dengan stres oksidatif tidak diragukan lagi. Hal ini telah dibuktikan dengan banyaknya publikasi yang mengukur biomarker ROS dan enzim antioksidan yang ditemukan pada plasenta dan sirkulasi darah ibu. Studi tersebut menunjukkan bukti biologis produksi berlebihan spesies oksigen reaktif sebagai konsekuensi kapasitas pertahanan antioksidan radikal bebas yang tidak memadai. Katalase adalah salah satu enzim antioksidan yang bekerja secara efisien untuk melawan spesies oksigen reaktif. Tujuan : Penelitian ini bertujuan untuk menguji apakah terdapat perbedaan yang signifikan dari tingkat aktivitas enzim katalase pada jaringan plasenta manusia pada kehamilan normal, Early Preeclampsia and Late Preeclampsia. Metode : Rancangan penelitian ini adalah penelitian cross sectional-observational untuk mengetahui tingkat rata-rata aktivitas spesifik enzim katalase yang berperan sebagai antioksidan pada plasenta baik pada kehamilan normal maupun preeklampsia. Aktivitas katalase spesifik diukur dengan menggunakan metode spektrofotometri dan kemudian dibagi dengan tingkat protein. Kegiatan kemudian dianalisis dengan menggunakan uji Kruskal-Wallis untuk menguji normalitas. Selanjutnya data dianalisis dengan menggunakan uji post hoc (Mann-Whitney). Hasil : Secara statistic, ditemuka perbedaan yang signifikan antara aktivitas spesifik enzim katalase pada jaringan plasenta late-preeclampsia dibandingkan dengan kehamilan normal. Pola ini tidak terdeteksi dalam plasenta kehamilan normal ketika dibandingkan dengan early preeclampsia, atau pada preeklamsia dini dibandingkan preeklamsia akhir. Diskusi : Ada korelasi antara stres oksidatif dan penurunan aktivitas spesifik katalase pada preeklampsia dibandingkan dengan jaringan plasenta kehamilan normal. Penurunan aktivitas spesifik enzim katalase pada kelompok preeklamsia mungkin disebabkan oleh perubahan protein akibat stres oksidatif. Oleh karena itu, enzim katalase tidak dapat bekerja dengan baik. Kesimpulan : Ketidakseimbangan antara stres oksidatif dan aktivitas katalase, dimana ini dibuktikan oleh penurunan aktivitas spesifik katalase pada preeklampsia dibandingkan dengan jaringan plasenta kehamilan normal mungkin merupakan faktor kunci terjadinya preeklamsia. ......Background : Despite the advance progress of perinatal care, preeclampsia still remains as a major cause of maternal and perinatal mortality and morbidity in the world. However, the main etiology and pathophysiology of preeclampsia remains debatable. The association of preeclampsia with oxidative stress is established beyond doubt. This has been proven by many publications which measure the biomarkers of ROS and antioxidant enzymes found in the placenta and maternal blood circulation. The study showing biological evidence of excessive production of reactive oxygen species as a consequence of inadequate capacity of antioxidant defense mechanism. Catalase is one of antioxidant enzymes which work efficiently combating reactive oxygen species. Purpose : This present study is aimed to examine whether there is significant difference of the specific catalase activity in the human placental tissue of normal pregnancy, early preeclampsia and late preeclampsia. Methods : The design of this research is cross sectional-observational study to determine the average level of specific activity of catalase enzyme which act as antioxidant in the placenta of both normal pregnancy and preeclampsia. The specific activity of catalase was measured by using spectrophotometry method and then divided with protein level. The activity then analyzed by using Kruskal-Wallis test to examine the normality. Furthermore, the data was analyzed by using post hoc (Mann-Whitney) test. Results : The specific activity of catalase enzyme was found to be statistically significant difference between the placental tissue of late preeclampsia compared to normal pregnancy. This pattern was not detected in catalase specific activity of normal pregnancy versus early preeclampsia, nor in early preeclampsia versus late preeclampsia. Discussion : There is correlation between oxidative stress and decreased specific activity of catalase in the preeclampsia compared to the normal pregnancy placental tissue. The decreased specific activity of catalase enzyme in preeclampsia groups may due to protein alteration by oxidative stress. Hence, the catalase enzyme cannot work properly. Conclusion : Imbalanced between oxidative stress and catalase specific activity which has proven by the decreased in the preeclampsia compared to the normal pregnancy placental tissue may be the key factor in the occurrence of preeclampsia.

Abstrak :
Ruang Lingkup dan Cara Penelitian. Magnesium telah lama digunakan dan diketahui, sebagai terapi medis yang efektif pada preeklampsi. Kuat dugaan magnesium dapat mengurangi vasokonstriksi pembuluh darah pada penderita preeklampsi, dengan bekerja sebagai kalsium antagonis, baik di membran sel otot polos pembuluh darah maupun di dalam sel. Preeklampsi merupakan salah satu gangguan utama pada kehamilan, dengan satu dari gejala utamanya adalah tingginya tekanan darah. Tingginya tekanan darah terjadi karena adanya vasokonstriksis dan resistensi perifer. Vasokonstriksi pembuluh darah terjadi karena kontraksi otot polos pembuluh darah. Kontraksi ini dirangsang oleh adanya peningkatan kadar kalsium bebas intrasel. Peningkatan kadar kalsium bebas intrasel dapat terjadi, melalui rangsangan yang meningkatan aktivitas biolistrik membran sel dan melalui rangsangan yang menyebabkan terjadinya pelepasan kalsium dari tempat penyimpanannya di dalam sel. Penelitian ini merupakan studi analitis eksperimental untuk melihat pengaruh pemberian magnesium terhadap amplitudo kegiatan biolistrik vena umbilikalis dari penderita preeklampsi, yang dirangsang dengan angiotensin II. Sepuluh potong umbilikus dari wanita hamil normal dan sepuluh potong dari penderita preeklampsi, yang melahirkan di Rumah Sakit Budi Kemulian pada bulan Februari 1998, digunakan dalam penelitian Sebelum dilihat aktivitas biolistrikya, vena umbilikalis diinkubasi dalam larutan risiologis `cord buffer', yang diaerasi dengan carnpuran, 02 95% dengan CO2 5%, pada suhu 37° C selama 60 menit. Amplitudo kegiatan biolistrik vena umbilikalis dilihat dan direkam dengan poligraf, setelah dirangsang dengan angiotensin II dan kemudian diberi magnesium. Pemberian magnesium dapat menurunkan amplitudo kegiatan biolistrik vena umbilikalis yang dirangsang dengan angiotensin II baik yang berasal dari penderita preeklampsi, maupun dari wanita hamil normal (p<0.01). Dari penelitian ini juga diperoleh hasil bahwa amplitudo kegiatan biolistrik vena umbilikalis yang dirangsang dengan angiotensin II pada waktu 2.5, 5 dan 7.5 detik setelah pemberian magnesium tidak berbeda nyata (p > 0.05).

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.

Abstrak :
ABSTRAK
Hipertensi merupakan kelainan yang umum dijumpai pada kehamilan. Sekitar 70% wanita hamil mengalami gestational hypertension dan preeklampsia. Disfungsi endotel pada preeklampsia menyebabkan permukaan endotel yang nontrombogenik menjadi trombogenik sehingga dapat terjadi aktivasi koagulasi. Preeklampsia meningkatkan keadaan hiperkoagulabel yang sudah ada pada kehamilan normal. Gestational hypertension pada wanita hamil adalah hipertensi yang tidak memenuhi kriteria preeklampsia. Hampir setengah dari pasien dengan gestational hypertension akan berkembang menjadi preeklampsia. Fibrin monomer merupakan petanda aktivasi koagulasi yang digunakan pada keadaan pretrombotik oleh karena terbentuk terlebih dahulu pada keadaan hiperkoagulabel daripada D-dimer yang terbentuk setelah fibrinolisis. Tujuan penelitian adalah mendapatkan gambaran fibrin monomer pada gestational hypertension dan preeklampsia. Penelitian ini adalah penelitian potong lintang pada 30 wanita hamil gestational hypertension dan 30 wanita hamil preeklampsia yang dilakukan pada Oktober sampai November 2015. Pemeriksaan FM menggunakan reagen STA-Liatest memakai koagulometer STA Compact Analyzer. Kadar fibrin monomer pada gestational hypertension didapatkan mean 4,61 µg/mL dengan standar deviasi 0,86 µg/mL. Kadar fibrin monomer pada preeklampsia didapatkan median 10,5 µg/mL dengan mean 11.99 µg/mL dan rentang 6,12 ? 23,26 µg/mL. Didapatkan perbedaan bermakna kadar fibrin monomer pada gestational hypertension dan preeklampsia dengan nilai p<0,001. ABSTRACT
Hypertension is a common disorder in pregnancy. Approximately 70% of pregnant women is gestational hypertension and preeclampsia. Endothelial dysfunction in preeclampsia causes the endothelial surface of the nonthrombogenic be thrombogenic so it can activated coagulation. Preeclampsia increase hypercoagulability state in normal pregnancy. Gestational hypertension is a hypertension in pregnancy who do not meet the criteria of preeclampsia. Nearly half of patients with gestational hypertension develop into preeclampsia. Fibrin monomers are used for coagulation activation marker on the prethrombotic state therefore formed before on hypercoagulability state hiperkoagulabel than D-dimer formed after fibrinolysis. The objective of this study is to gain description of fibrin monomer levels and it was a cross-sectional study 30 pregnant women with gestational hypertension and 30 pregnant women with preeclampsia. The study was conducted in October and November 2015. Examination of fibrin monomer using the reagent STA-Liatest and analyzer STA Compact. Mean of fibrin monomer in gestational hypertension was 4.61 µg/mL with standard deviation was 0.86 µg/mL. Median of fibrin monomer in preeclampsia was 10.5 µg / mL with range was 6.12 to 23.26 µg/mL. Fibrin monomer levels found significant differences in gestational hypertension and preeclampsia with p <0.001. ;Hypertension is a common disorder in pregnancy. Approximately 70% of pregnant women is gestational hypertension and preeclampsia. Endothelial dysfunction in preeclampsia causes the endothelial surface of the nonthrombogenic be thrombogenic so it can activated coagulation. Preeclampsia increase hypercoagulability state in normal pregnancy. Gestational hypertension is a hypertension in pregnancy who do not meet the criteria of preeclampsia. Nearly half of patients with gestational hypertension develop into preeclampsia. Fibrin monomers are used for coagulation activation marker on the prethrombotic state therefore formed before on hypercoagulability state hiperkoagulabel than D-dimer formed after fibrinolysis. The objective of this study is to gain description of fibrin monomer levels and it was a cross-sectional study 30 pregnant women with gestational hypertension and 30 pregnant women with preeclampsia. The study was conducted in October and November 2015. Examination of fibrin monomer using the reagent STA-Liatest and analyzer STA Compact. Mean of fibrin monomer in gestational hypertension was 4.61 µg/mL with standard deviation was 0.86 µg/mL. Median of fibrin monomer in preeclampsia was 10.5 µg / mL with range was 6.12 to 23.26 µg/mL. Fibrin monomer levels found significant differences in gestational hypertension and preeclampsia with p <0.001. ;Hypertension is a common disorder in pregnancy. Approximately 70% of pregnant women is gestational hypertension and preeclampsia. Endothelial dysfunction in preeclampsia causes the endothelial surface of the nonthrombogenic be thrombogenic so it can activated coagulation. Preeclampsia increase hypercoagulability state in normal pregnancy. Gestational hypertension is a hypertension in pregnancy who do not meet the criteria of preeclampsia. Nearly half of patients with gestational hypertension develop into preeclampsia. Fibrin monomers are used for coagulation activation marker on the prethrombotic state therefore formed before on hypercoagulability state hiperkoagulabel than D-dimer formed after fibrinolysis. The objective of this study is to gain description of fibrin monomer levels and it was a cross-sectional study 30 pregnant women with gestational hypertension and 30 pregnant women with preeclampsia. The study was conducted in October and November 2015. Examination of fibrin monomer using the reagent STA-Liatest and analyzer STA Compact. Mean of fibrin monomer in gestational hypertension was 4.61 µg/mL with standard deviation was 0.86 µg/mL. Median of fibrin monomer in preeclampsia was 10.5 µg / mL with range was 6.12 to 23.26 µg/mL. Fibrin monomer levels found significant differences in gestational hypertension and preeclampsia with p <0.001. ;Hypertension is a common disorder in pregnancy. Approximately 70% of pregnant women is gestational hypertension and preeclampsia. Endothelial dysfunction in preeclampsia causes the endothelial surface of the nonthrombogenic be thrombogenic so it can activated coagulation. Preeclampsia increase hypercoagulability state in normal pregnancy. Gestational hypertension is a hypertension in pregnancy who do not meet the criteria of preeclampsia. Nearly half of patients with gestational hypertension develop into preeclampsia. Fibrin monomers are used for coagulation activation marker on the prethrombotic state therefore formed before on hypercoagulability state hiperkoagulabel than D-dimer formed after fibrinolysis. The objective of this study is to gain description of fibrin monomer levels and it was a cross-sectional study 30 pregnant women with gestational hypertension and 30 pregnant women with preeclampsia. The study was conducted in October and November 2015. Examination of fibrin monomer using the reagent STA-Liatest and analyzer STA Compact. Mean of fibrin monomer in gestational hypertension was 4.61 µg/mL with standard deviation was 0.86 µg/mL. Median of fibrin monomer in preeclampsia was 10.5 µg / mL with range was 6.12 to 23.26 µg/mL. Fibrin monomer levels found significant differences in gestational hypertension and preeclampsia with p <0.001. ;Hypertension is a common disorder in pregnancy. Approximately 70% of pregnant women is gestational hypertension and preeclampsia. Endothelial dysfunction in preeclampsia causes the endothelial surface of the nonthrombogenic be thrombogenic so it can activated coagulation. Preeclampsia increase hypercoagulability state in normal pregnancy. Gestational hypertension is a hypertension in pregnancy who do not meet the criteria of preeclampsia. Nearly half of patients with gestational hypertension develop into preeclampsia. Fibrin monomers are used for coagulation activation marker on the prethrombotic state therefore formed before on hypercoagulability state hiperkoagulabel than D-dimer formed after fibrinolysis. The objective of this study is to gain description of fibrin monomer levels and it was a cross-sectional study 30 pregnant women with gestational hypertension and 30 pregnant women with preeclampsia. The study was conducted in October and November 2015. Examination of fibrin monomer using the reagent STA-Liatest and analyzer STA Compact. Mean of fibrin monomer in gestational hypertension was 4.61 µg/mL with standard deviation was 0.86 µg/mL. Median of fibrin monomer in preeclampsia was 10.5 µg / mL with range was 6.12 to 23.26 µg/mL. Fibrin monomer levels found significant differences in gestational hypertension and preeclampsia with p <0.001.

Abstrak :
Pada preeklampsia terjadi peningkatan kadar VEGF (vascular endothelial growth factor). Selain mempunyai aktivitas mitotik dan meningkatkan permeabilitas membran sel endotel, VEGF dilaporkan dapat menginduksi produksi molekul sel adhesi oleh sel endotel. Molekul sel adhesi mempunyai fungsi merangsang perlekatan sel makrofag ke dinding pembuluh darah dalam proses inflamasi. Tujuan penelitian ini ialah untuk mengetahui pengaruh VEGF dalam serum preeklampsia pada produksi sVCAM-1 (soluble vascular cell adhesion molecule) oleh sel endotel dalam kultur. Duabelas sampel serum preeklampsia dan 11 serum kehamilan normal (kontrol) dengan konsentrasi 20% dipajankan pada kultur sel endotel normal (HUVEC) selama 24 jam Semua subjek setuju berpartisipasi dalam penelitian ini dan menanda-tangani informed consent. Pengukuran kadar sVCAM-1 pada supernatan dilakukan dengan ELISA. Hasil menunjukkan kadar VEGF dalam serum preeklampsia cenderung lebih tinggi dari serum ibu dengan kehamilan normal. Kadar produksi VCAM-1 oleh sel endotel yang dipajankan pada serum preeklampsia lebih tinggi secara bermakna dari yang dipajankan oleh serum kontrol (p<0,05). Tidak ada korelasi antara kadar VEGF dalam serum preeklampsia dan kontrol terhadap produksi sVCAM-1 oleh kultur sel endotel. (Med J Indones 2004; 14: 3-6)

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Serum concentrations of VEGF (Vascular Endothelial Growth Factor) are elevated in preeclampsia. In addition to inducing mitosis and increase permeability of endothelial cells, VEGF was reported to activate endothelial cells to produce cell adhesion molecules. Cell adhesion molecules play an important role in the inflammation process by inducing adherence of leukocytes in blood stream to the endothelial cells. The aim of this study is to investigate the effect of VEGF in serum from preeclamptic patients on sVCAM-1 (soluble vascular adhesion molecules-1) production in endothelial cell culture. Twelve sera from women with preeclampsia and 11 from women with normal pregnancy (controls) in 20% concentration were added to human umbilical vein endothelial cell culture (HUVEC) and incubated for 24 hours. All subjects have agreed to participate in this study and signed the informed consent form. sVCAM-1 concentration in the supernatant was measured by ELISA. VEGF concentration tends to be higher in preeclamptic serum than control, but the difference is not stastitically significant. The production of sVCAM-1 by endothelial cells exposed to preeclamptic serum was significantly higher than the production by endothelial cells exposed to serum from control (p<0.05). No correlation was found between the difference in VEGF concentrations in preeclamptic and control sera, and sVCAM-1 production by endothelial cell culture. (Med J Indones 2004; 14: 3-6)

Abstrak :
Preeklampsia merupakan penyulit kehamilan yang ditandai dengan hipertensi, edema dan proteinuria. Berdasarkan tanda-tanda tersebut, diduga disfungsi endotel memegang peranan dalam patogenesis kedua penyakit tersebut. Penelitian ini bertujuan untuk mengetahui apakah pada preeklampsia terjadi disfungsi endotel dengan memeriksa kadar sVCAM-1, vWF dan fibrin monomer sebagai petanda aktivasi koagulasi. Juga ingin diketahui apakah terdapat hubungan antara disfungsi endotel dengan beratnya penyakit. Desain penelitian potong lintang. Subyek penelitian adalah 30 orang wanita hamil 24 - 42 minggu dengan diagnosis preeklampsia yang bersedia ikut dalam penelitian dan kelompok kontrol terdiri atas wanita hamil aterm. Pemeriksaan kadar sVCAM-1 dikerjakan dengan cara ELISA dengan reagen dari R&D system. Kadar vWF ditentukan dengan cara enzyme linked fluorescent assay (ELFA) dengan reagen dari VIDAS bioMerieux. Fibrin monomer diperiksa dengan cara ethanol gelation test. Rerata dan simpang baku kadar sVCAM-1 pada preeklampsia dan kontrol berturut-turut adalah 576,4 ng/mL dan 58,3 ng/mL serta 375,7 ng/mL dan 43 ng/mL (p<0,05). Sedang rerata dan simpang baku kadar vWF pada preeklampsia dan kontrol berturut turut 305,3% dan 107,4% serta 162,4% dan 33% (p,0,05). Didapatkan korelasi sedang antara kadar sVCAM-1 dengan tekanan sistolik maupun diastolik (r=0,71) dan (r=0,65). Demikian pula antara kadar vWF dengan tekanan sistolik dan diastolik didapatkan korelasi sedang (r=0,67) dan (r=0,77). Fibrin monomer positif didapatkan pada 28 dari 30 penderita preeklampsia sedang pada kelompok kontrol hanya 1 orang yang positif. Hasil penelitian ini menunjukkan bahwa pada preeklampsia terjadi disfungsi endotel. Pada preeklampsia terdapat korelasi antara petanda disfungsi endotel dengan tingginya tekanan darah.

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Endothelial Dysfunction In Preeclampsia. Preeclampsia is a complication of pregnancy characterized by hypertension, edema, and proteinuria. Based on these signs, it is suggested that endothelial dysfunction plays a role in the pathogenesis of preeclampsia. The aims of this study were to know whether endothelial dysfunction occur in preeclampsia by measuring the level of sVCAM-1, von Willebrand factor, and fibrin monomer. The relationship between markers of endothelial dysfunction and blood pressure would also be sought. In this cross-sectional study, 30 women at the 24-42 weeks of pregnancy with preeklampsia, were enrolled and control group comprised of fullterm pregnant women. The level of sVCAM-1 was determined by ELISA method using reagents from R&D system, while vWF level was measured by enzyme linked fluorescent assay (ELFA) using reagent from VIDAS bioMerieux, and fibrin monomer was detected by ethanol gelation test. The mean of sVCAM-1 level in the preeklampsia group and in the control group were 576.4 ng/mL, and 375.7 ng/mL, respectively while the standard deviation were 58.3 ng/mL, and 43 ng/mL, respectively. The mean of vWF level in the preeklampsia group and in the control group were 305.3% and 162.4%, respectively while the standard deviation were 107.4% and 33%, respectively. Moderate correlation were found between sVCAM-1 as well as vWF level with both systolic and diastolic pressure. Fibrin monomer was found in 28 out of 30 subjects of preeclampsia group, but only 1 out of 31 subjects in the control group. The results of this study indicated that endothelial dysfunction occurred in preeclampsia.