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Novi Resistantie
"Preeklamsia merupakan salah satu penyebab kematian utama ibu dan perinatal di dunia. Inflamasi disertai tingginya indeks apoptosis di syncytiotrophoblast dan ekspresi Cyclophilin A diduga berperan pada preeklamsia. Faktor tersebut diasumsikan menyebabkan jejas jantung/pembuluh darah yang meningkatkan risiko morbiditas dan mortalitas ibu dan perinatal. Tujuan penelitan ini adalah menganalisis peran inflamasi, indeks apoptosis dan Cyclophilin A terhadap jejas jantung/pembuluh darah pada preeklamsia awitan dini, lanjut dan kehamilan normal.
Sebanyak 47 wanita hamil yang terpilih dilakukan pemeriksaan hematologi, ekokardiografi dan ultrasonografi Doppler. Plasenta diperiksa secara histopatologis untuk mengukur ekspresi NF-KB dan PARP-1, indeks apoptosis berdasarkan pemeriksan TUNEL, ekspresi Cyclophilin A dan pemeriksaan ultrastruktur mikroskopik pada syncytiotrophoblast. Analisis Anova digunakan untuk mengidentifikasi perbedaan antara ketiga kelompok, sedangkan regresi linier digunakan untuk mengetahui korelasi faktor yang diduga terhadap jejas jantung/pembuluh darah menggunakan SPSS 20.
Usia ibu, indeks massa tubuh (IMT), hitung trombosit, NF- KB dan indeks apoptosis lebih tinggi disertai Cyclophilin A lebih rendah pada preeklamsia awitan dini dibandingkan preeklamsia awitan lanjut dan kehamilan normal. Hitung leukosit lebih tinggi pada preeklamsia awitan lanjut dibandingkan awitan dini dan normal. Total peripheral resistance (TPR) paling tinggi pada kelompok awitan dini dibandingkan awitan lanjut dan kehamilan normal, sedangkan cardiac index (CI) tidak berbeda bermakna pada ketiga kelompok. Resistensi indeks (RI) lebih tinggi pada preeklamsia awitan dini dibandingkan awitan lanjut dan kehamilan normal.
Berdasarkan analisis regresi linier multivariat, membuktikan indeks apoptosis dan Cyclophilin A memiliki hubungan dengan jejas jantung/pembuluh darah. Hal tersebut menunjukkan inflamasi, indeks apoptosis, Cyclophilin A disertai pemeriksan ekokardiografi dan ultrasonografi Doppler merupakan metode yang cepat, tepat dan noninvasif faktor risiko terhadap jejas jantung/pembuluh darah pada preeklamsia. Penelitian yang dianjurkan di masa datang adalah menilai geometri jantung dengan ekokardiografi dan volumetri plasenta dengan ultrasonografi.

Preeclampsia is one of the leading cause of maternal and perinatal death in the world. Inflammation accompanied by a high apototic index of syncytiotrophoblast and Cyclophilin A were speculated to play a role in preeclampsia. Those response were assumed to cause cardiovascular injury which lead to the risk of maternal and perinatal morbidity and mortality in preeclampsia. The objective of the study was to investigate the role of inflammation, apoptotic index and Cyclophilin A in cardiovascular injury in early and late onset preeclampsia compared to normal pregnancy.
A total of 47 pregnant women were selected, consisting almost the same size of each group (30%) and assessed for maternal hematology, echocardiography and Doppler ultrasound. Placentae were assessed histopathologically by measuring nuclear factor kappa-light-chain-enhancer of activated B cells (NF- KB) and Poly (ADP-ribose) polymerase 1 (PARP-1) expression for inflammation marker, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptotic index and Cyclophilin A. Confirmation by transmission electron microscopy (TEM) was done. Anova analysis was used to identify the differences between the three groups while linier regression was employed to assess the correlation between factors on cardiovascular injury using SPSS 20.
Maternal age, body mass index (BMI), platelet count, NF- KB and apoptotic index, resistance index (RI) were higher supported by low Cyclophilin A in early onset preeclampsia (EOP) than in late onset preeclampsia (LOP) and normal pregnancy. Leukocyte count was higher in late onset preeeclampsia than in early and normal pregnancy. Total peripheral resistance (TPR) was highest in the EOP compared to LOP and normal pregnancy, while the cardiac index (CI) was not significantly different in all groups.
Based on multivariate linear regression analysis, the apoptotic index and Cyclophilin A correlated to cardiovascular injury. Assesing inflammation, apoptotic index, Cyclophilin A, echocardiography examination and Doppler ultrasound examination might indicated timely and non-invasive detection as an alarm entry point for cardiovascular injury in both early and late onset preeclampsia. Cardiac geometry by echocardiography and placental volumetry by Doppler ultrasound should be performed in future research.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Disertasi Membership  Universitas Indonesia Library
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Murthy Mutmainah
"Latar Belakang: Prevalensi preeklamsia dalam kehamilan di Indonesia sebesar 7-10%, Asam asetilsalisilat yang mengandung senyawa aktif asam salisilat diketahui dapat mencegah terjadinya preeklamsia awitan dini terutama bila diberikan sebelum usia kehamilan 16 minggu. Tubuh memiliki asam salisilat natural yang didapatkan dari konsumsi sayuran yang mengandung asam salisilat. Asam salisilat merupakan senyawa aktif yang berperan sebagai anti inflamasi. Penelitian ini bertujuan menilai apakah kejadian preeklamsia dipengaruhi oleh kadar asam salisilat natural serum dan urin.
Metode: Penelitian ini menggunakan disain case-control berpasangan. Subjek adalah pasien hamil dengan preeklamsia awitan dini (PEAD) dibandingkan dengan hamil normotensi 20-34 minggu terdiri atas 35 pasien/kelompok, preeklamsia awitan lambat (PEAL) dibandingkan dengan hamil normotensi 34-40 minggu terdiri atas 39 pasien/ kelompok. Pemeriksaan kadar asam salisilat (SA) dan asam salisilurat (SUA) dalam serum diperiksa dari sampel darah vena, kadar SA dan SUA urin diperiksa dari sampel urin sewaktu yang terkoreksi dengan kadar kreatinin urin, semuanya diperiksa menggunakan kromatografi. Seluruh subjek dilakukan wawancara FFQ (Food Frequent Questionnaire) untuk mengetahui asupan makanan selama hamil. Analisis statistik yangdigunakan adalah uji Mann Whitney .
Hasil: Median usia kehamilan pasien PEAD adalah 31 minggu, kelompok normal adalah 30 minggu. Kadar SUA serum pada PEAD berbeda bermakna dibandingkan hamil normal dengan median 1,43 (min-max 0,001-9,32) vs 0,21 (0,002-15,78) nilai p<0,001. Kadar albumin pada PEAD berbeda bermakna dengan hamil normal median 3 (2,1 – 3,8) vs 3,7 (3,4-4,3) p<0,001. Kadar Asupan protein berbeda bermakna (13% vs 14%,
p<0,001)Kadar serat pangan pada PEAD berbeda bermakna dibandingkan hamil normal (8 gram/hari vs 9,6 g/hari, p<0,001). Kadar SA dalam serum dan urin, SUA urin pada kelompok ini tidak berbeda bermakna.
Median usia kehamilan PEAL dan normotensi adalah 37 minggu. Kadar SA serum dan urin dan SUA serum tidak berbeda bermakna antara kedua kelompok. Kadar albumin pada PEAL berbeda bermakna dengan median (3 (2,4-3,6) vs 3,4 (2,9-4,1) p<0,001).
Simpulan : Tidak terdapat perbedaan bermakna kadar asam salisilat dan asam salisilurat pada serum dan urin pada kehamilan preeklamsia dan normotensi. Kelompok PEAD terdapat kadar SUA serum yang lebih tinggi dan berkorelasi dengan kadar albumin dan asupan protein yang rendah. Asupan serat pangan berhubungan dengan kejadian PEAD, tetapi tidak berhubungan dengan kadar asam salisilat dan asam salisilurat

Background: The prevalence of preeclampsia in pregnancy in Indonesia is 7-10%. Acetylsalicylate which contains the active compound salicylic acid is known to prevent early onset preeclampsia, especially if given before 16 weeks of gestation. The body has natural salicylic acid which is obtained from the consumption of vegetables that contain salicylic acid. Salicylic acid is an active compound that acts as an anti-inflammatory. This study aims to assess whether the incidence of preeclampsia is influenced by the
levels of natural salicylic acid in the blood and urine.
Methods: : A matched case-control was adopted in this study. Subjects were pregnant patients with early onset preeclampsia (EOP) compared to normotensive pregnancies of 20-34 weeks consisting of 35 patients/group, late onset preeclampsia (LOP) compared with normotensive pregnancies of 34-40 weeks consisting of 39 patients/group. Examination of salicylic acid (SA) and salicylic acid (SUA) levels in serum was examined from venous blood samples, urine SA and SUA levels were examined from urine samples while corrected by urine creatinine levels, all were examined using chromatography. . To measure food intake during pregnancy, all subject were interviewed using the FFQ (Food Frequent Questionnaire). The Mann Whitney test was utilized in the statistical analysis.
Objective: The goal of this study is to see if natural blood and urine levels of salicylic acid affect the risk of preeclampsia.
Result :EOP subject had a median gestational age of 31 weeks, while normal group 30 wga. Serum SUA levels in EOP were considerably different from normal pregnant women, with a median of 1.43 (min-max 0.001-9.32) versus 0.21 (0.002-15.78) p value <0.001, while albumin levels in EOP were significantly different from normal pregnant women, with a median of 3 (2.1-3.8) vs. 3.7 (3.4-4.3) p<0.001, and protein intake significantly lower than normal (13 vs 14%, p<0,001).. Dietary fiber in EOP was significantly
different compared to normal pregnancy (8 g/day vs 9.6 g/day, p<0.001) SA levels in serum and urin, as well as urine SUA, were not substantially different in this group.
LOP and normotensive gestational age were both 37 weeks. The levels of SA and SUA in the serum and urine were not substantially different between the two groups. With a median of 3 (2.4-3.6) vs. 3.4, albumin levels in PEAL were substantially different (2.9-4.1).
Conclusion: In preeclampsia and normotensive pregnancies, there was no significant difference in salicylic acid and salicyluric acid levels in blood and urine. The serum SUA levels in the EOP group were greater and associated with low albumin levels and low protein intake. Fiber intake was linked to the development of EOP, but not to salicylic acid levels or salicyluric acid levels.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2022
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UI - Tugas Akhir  Universitas Indonesia Library
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Irwan Tjandra
"Latar Belakang: Hiperglikemia akut maupun kronis dapat menyebabkanperubahan patalogis pada lapisan serabut saraf retina RNFL . Pada tahap dinilapisan sel ganglion GCs mengalami apoptosis, yang diregulasi oleh proteinBrn3b. Proses ini diketahui terjadi lebih awal sebelum perubahan histopatologispada RNFL terjadi pada diabetes. Proses apoptosis ditandai dengan, peningkatanstres oksidatif, peningkatan NO, NF-??, TNF-?, dan Caspase 3 pada patogenesisglaukoma primer sudut terbuka GPSTa . Asumsi klinis saat ini bahwa penderitadiabetes melitus dalam jangka waktu lama lebih dari 5 tahun kemungkinan besarberisiko terjadinya glaukoma. Namun kenyataannya dalam pengalaman klinistidak semua pasien diabetes melitus dapat terjadi GPSTa. Berdasarkan temuanklinis tersebut diduga ada peran faktor genetik yang mendasari etiologi dariGPSTa pada pasien diabetes melitus.
Tujuan: Mengetahui peran gen Brn3b pada apoptosis di RGCs dan kaitannyadengan perubahan kuantitas NO, Caspase 3, NF-?B, dan TNF-? sebagai prediksiglaukoma dini pada tikus diabetes.
Metode: Penelitian ekperimental in vivo menggunakan tikus jantan SpraqueDawleyusia ge; 2 bulan dengan berat 150-200 gram diambil secara random sejakNopember 2015 hingga Juli 2016. Hewan coba dibagi menjadi 2 kelompok yaitu: kelompok perlakuan diinjeksi intraperitoneal STZ 50 mg/kg dalam 0.01M buffersitrat dalam ph 4.5 dan kelompok kontrol tidak ada perlakuan. Glukosa darahpuasa diperiksa 3 hari setelah injeksi STZ, dan dikonfirmasi ge; 250 mg/dL.Jaringan retina dibagi menjadi dua bagian pada kelompok perlakuan maupunkontrol yakni retina kanan untuk IHK Caspase 3 dan TNF-? dan retina kiridibagi dua bagian yaitu untuk pemeriksaan quantitative Real-time PCR RNAdiekstraksi untuk analisis ekspresi gen Brn3b dan pemeriksaan ELISA NO danNF-?B.
Hasil: Terjadi penurunan ekpresi gen Brn3b pada tikus perlakuandibandingkan ekspresi gen Brn3b kontrol sebesar 1.2677 kali bulan kedua, 1.1348kali bulan keempat, dan 2.4600 kali bulan keenam. Disisi lain terjadi penurunankuantitas NO dan peningkatan kuantitas Caspase 3, NF-?B, dan TNF-?.
Kesimpulan: Ekspresi mRNA Brn3b berbanding terbalik dengan apoptosis padaRGCs. Kuantitas NO, Caspase 3, NF-?B, dan TNF-? dipengaruhi oleh ekspresiBrn3b pada RGCs akibat hiperglikemia pada tikus diabetes.

Background: Acute and chronic hyperglycemia may pathologically changeretinal nerve fiber layer RNFL . At early stage, ganglion cells GCs undergoapoptosis, which is regulated by a Brn3b protein. This change is known to occurat earlier time before retinal histological changes can be detected in diabeticpatients. The apoptosis process is marked by an increase in oxidative stress, a risein NO, NF-??, caspase 3, and TNF-? levels in pathogenesis of primary open angleglaucoma POAG . Current clinical assumption proposes that individualssuffering from diabetes mellitus for more than 5 years have greater risk ofglaucoma. Nonetheless, clinical experience shows that not all diabetic patientsdevelop POAG. Based on clinical examinations it is suspected that there is agenetic factor that caused the etiology of POAG in diabetes mellitus patients.
Purpose: To learn the role of Brn3b gene in apoptosis of RGCs and its effect onthe changing of quantity of NO, Caspase 3, NF-?B, and TNF-? as early predictorof glaucoma in diabetic rats.
Methods: Experimental in-vivo study was carried out using male SpraqueDawleyrats with age ge; 2 months, weighing 150-200 grams. The rats wererandomly selected from November 2015 to July 2016. The animals were dividedinto two groups. Group receiving intraperitoneal injection of STZ 50 mg/kg in0.01M citric buffer and pH 4,5; 2 and control group with no treatment. Fastingblood glucose was checked 3 days after injection of STZ and hyperglycemia wasdetermined as fasting blood glucose ge; 250 mg/dL. Retinal tissue was divided intotwo parts both experimental and control groups respectively : a right retina forIHC Caspase 3 and TNF-? ; b left retina was divided into two parts for thepurpose of quantitative Real-Time PCR test RNA extraction for Brn3b geneexpression analysis and ELISA test NO and NF-?B.
Results: Experimental group showed a decrease in Brn3b expression compared tocontrol group 1.2677-fold lower on 2nd month; 1.1348-fold lower on 4th monthand 2.4600-fold lower on 6th month . On the other hand, there was a decrease ofNO and there was increased of Caspase 3, NF-?B and TNF-? quantity.
Conclusion: The expression of mRNA Brn3b is inversely proportional toapoptosis in RGCs. The quantity of NO, Caspase 3, NF-?B and TNF-? isinfluenced by expression of Brn3b in RGCs caused by hyperglycemia in diabeticrats.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2018
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UI - Disertasi Membership  Universitas Indonesia Library
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Muhammad Renaldiansyah
"Inflamasi memiliki peran penting dalam perkembangan berbagai kondisi patologis, yang dimediasi oleh aktivasi berbagai jalur pensinyalan, termasuk jalur IKK-NF-κB. Silybin, senyawa flavonolignan yang ditemukan dalam Milk Tistle (Silybum marianum L) telah digunakan secara tradisional untuk mengobati penyakit hati dan telah dilaporkan memiliki aktivitas anti-inflamasi, antifibrotik, dan imunomodulator. Namun, mekanisme molekuler silybin sebagai agen antiinflamasi potensial terhadap jalur pensinyalan IKKNF- κB masih belum jelas. Penelitian ini menggunakan simulasi penambatan molekuler menggunakan Autodock 4.0 untuk menyelidiki interaksi antara Silybin dan NF-κB. Hasil penelitian menunjukkan bahwa silybin menunjukkan inhibisi kompetitif-ATP dan memiliki afinitas pengikatan yang tinggi untuk makromolekul IkB kinase beta (IKKβ) dan NIK (NF-kB-inducing kinase), dengan energi pengikatan -9,73 kkal/mol pada rantai A dan -9,84 kkal/mol pada rantai B IkB kinase beta (IKKβ) serta -9,34 kkal/mol pada makromolekul NIK (NF-kB-inducing kinase). Konstanta Inhibisi (Ki) ditemukan masingmasing 74,14 nM pada rantai A dan 61,12 nM pada rantai B IkB kinase beta (IKKβ) serta 141,81 nM mol pada NIK (NF-kB-inducing kinase). Temuan ini menunjukkan bahwa silybin memiliki potensi untuk menghambat jalur pensinyalan IKK-NF-κB, sehingga memberikan efek anti-inflamasi. Selain itu, silybin menunjukkan afinitas pengikatan yang lebih tinggi jalur persinyalan kanonikal dibanding jalur perisnyalan alternatif. Studi ini memberikan wawasan tentang mekanisme molekuler silybin sebagai agen antiinflamasi potensial dan aplikasi terapeutiknya dalam terapi penyakit yang berhubungan dengan Inflamasi.

Inflammation has a crucial role in the progression of various pathological conditions, mediated by the activation of multiple signaling pathways, including the IKK-NF-κB pathway. Silybin, a flavonolignan compound extracted from Milk thistle (Silybum marianum L.) has been traditionally used to treat liver disorders and exhibits pharmacological properties, including anti-inflammatory, antifibrotic, and immunomodulatory activities. However, the molecular mechanisms underlying Silybin's anti-inflammatory potential, particularly its interaction with the IKK-NF-κB signaling pathway, remain unclear. This study employed molecular docking simulations using Autodock 4.0 to investigate the interaction between Silybin and NF-κB. The results showed that silybin exhibited competitive-ATP inhibition and high binding affinity for IkB kinase beta (IKKβ) and NIK (NF-kB-inducing kinase) macormolecule, with binding energies of -9.73 kcal/mol on the A chain and -9.84 kcal/mol on the B chain of IkB kinase beta (IKKβ) and -9.34 kcal/mol on NIK (NF-kB-inducing kinase). Inhibition constants (Ki) were found to be 74.14 nM on chain A and 61.12 nM on chain B of IkB kinase beta (IKKβ) and 141.81 nM mol on NIK (NF-kB-inducing kinase), respectively. Notably, silybin displays higher binding affinity for the canonical pathway compared to the alternative pathway. These findings suggest that silybin has the potential to inhibit IKKNF- κB signaling, leading to anti-inflammatory effects. This study provides valuable insights into the molecular mechanism of silybin as a potential anti-inflammatory agent and its therapeutic applications in inflammation-related diseases."
Depok: Fakultas Farmasi Universitas Indonesia, 2024
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UI - Skripsi Membership  Universitas Indonesia Library
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Popi Sopiah
"ABSTRAK
Latar belakang. Proses inflamasi kronik dan persisten mempengaruhi tingginya rekurensi dan survival endometriosis pasca pembedahan. Hal ini menjadi permasalahan endometriosis, sehingga perlu pengembangan terapi target salah satunya yaitu asam galat. Asam galat terbukti efektif sebagai antikanker, anti tumor, anti inflamasi dan antibakterial pada beberapa cell line, namun efektifitasnya pada sel endometriosis harus dibuktikan. Tujuan. membuktikan efek asam galat dan senyawa turunannya terhadap regulasi inflamasi pada kultur primer endometriosis ditinjau dari ekspresi mRNA NF-kB, serta sekresi TNF-? dan IL-6. Metode. Sel endometriosis berasal dari jaringan endometriosis pasien yang menjalani laparaskopi, diisolasi secara enzimatis dan dikultur primer. Sel kultur diberi perlakuan asam galat, heptil dan oktil galat dengan dosis 25,6 g/mL, 51,2 g/mL dan 102,4 g/mL selama 48 jam, kemudian diinduksi dengan LPS 500 ng/mL selama 24 jam. Regulasi inflamasi dinilai dari ekspresi mRNA NF-kB dengan qRT-PCR, kadar sekresi TNF-? dan IL-6 dengan ELISA, serta inhibisi viabilitas sel dengan MTS Assay. Hasil. Setelah data dirasiokan dengan kontrol, ketiga zat signifikan menghambat viabilitas sel endometriosis p value 0,000 dengan inhibisi tertinggi pada dosis 102,4 g/mL. Terjadi penurunan ekspresi relatif NF-kB yang dirasiokan dengan kontrol dan IL-6 meskipun secara statistik tidak bermakna. Konsentrasi TNF? tidak berbeda secara bermakna p value 0,340 . Kesimpulan. Asam galat dan senyawa turunannya berpengaruh terhadap inhibisi viabilitas sel, penurunan ekspresi relatif NF-kB dan IL-6, namun tidak bermakna terhadap penekanan sitokin TNF-?. Perlu dilakukan studi lanjut untuk menilai efektifitas asam galat sebagai kandidat obat antiinflamasi pada endometriosis ditinjau aspek lain.

ABSTRACT
Background. Endometriosis is a benign gynecological disorder characterized by the growth of the lining of the endometrium like tissue outside the uterus. The cause of the growth of endometriosis is not known well, chronic and persistent inflammatory process is suspected to be one of the pathogenesis that contributes to the high recurrence and survival endometriosis. One of the potential therapeutic agents is a gallic acid which proved effective in earlier studies as an anti cancer, anti tumor, anti inflammatory and antibacterial in several cell line. The Effectiveness of gallic acid to the endometriosis cell is a preliminary study and have not found evidence of publication yet. Object. Proving the effect of gallic acid and its derivatives on the inflammatory regulation of endometriosis primary culture study on mRNA expression of NF kB, TNF , and IL 6 secretion. Method. Endometriosis cells from Indonesian endometriosis patients tissues who had undergone laparoscopy surgery were isolated by the enzymatic reaction and primary cultured. Cultured cells treated by gallic acid and alkyl ester synthetic derivatives of the gallic acids heptyl gallate and octyl gallate each with the dosage of 25,6 g mL, 51,2 g mL, and 102.4 g mL for 48 hours and then induced by LPS 500 ng mL for 24 hours. Parameter research was assessed by qRT PCR for mRNA expression of NF kB, ELISA for the quantification of TNF and interleukin 6, and MTS assay was used to observe endometriosis cell viability. Results. After the data was rationalized with the control, three substances showed significant inhibition of endometriosis cell viability. The highest inhibition for all treatment was at doses 102,4 g mL. Overall there was an inhibition of relative expression of mRNA NF kB were rationalized to controls and suppression of IL 6 in octyl gallate groups. The concentration of TNF among the groups did not differ significantly p value 0.340 . Conclusion. Gallic acid and its derivatives have significantly inhibition effect toward cell viability, mRNA expression of NF kB, and IL 6 but have not significantly effect toward cytokine TNF . Further studies need to be conducted to assess the effectiveness of gallic acid as an anti inflammatory drug candidate toward to any pathway."
2017
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UI - Tesis Membership  Universitas Indonesia Library
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Subandi
"ABSTRAK
Koriokarsinoma merupakan keganasan yang sangat invasive berasal dari villi plasentra dan trofoblas. Mola invasif dan koriokarsinoma sangat reponsif terhadap kemoterapi dengan angka kesembuhan lebih dari 90 , yang memungkinkan tercapainya kesembuhan tanpa mengganggu fungsi reproduksi. Methotrexate MTX merupakan terapi yang sering digunakan pada beberapa keganasan dan merupakan protokol kemoterapi pada koriokarsinoma, namun MTX memiliki banyak efek samping. Berbagai penelitian pada setengah abad terakhir menunjukan fungsi penting nanokurkumin. Penelitian in vitro dan in vivo menujukkan perannya seperti anti inflamasi, pengeluaran sitokin, anti oksidan dan imunomodulator. Namun, sapai saat ini belum ada penelitian mengenai efek antikanker nanokurkumin pada koriokarsinoma. Penelitian eksperimental sederhana ini menggunakan uji Shapiro-Wilk, uji t sampel bebas, dan uji Anova One Way. Pada penelitianini, kami meneliti dan mebandingkan efek pemberian MTX atau kombinasi dengan nanokurkumin pada berbagai jalur sinyal. Pada penelitian ini, 4 kelompok sel BeWo diberikan kombinasi MTX dan nanokurkumin, 1 kelompok sel BeWo diberikan MTX sebagai control positif, dan 1 kelompok sel BeWo sebagai control negatif. Penelitian ini menunjukkan terdapat penurunan ekspresi telomerase, ekspresi NF- B, dan indeks proliferasi BrdU yang signifikan dengan pemberian kombinasi MTX dan nanokurkumin dibandingkan dengan MTX saja ABSTRACT
Choriocarcinoma is a highly invasive malignant tumor arising from the placental villous and extravillous trophoblast. IM and CCA, which make up the majority of these tumors, are highly responsive to chemotherapy with an overall cure rate exceeding 90 , making it usually possible to achieve cure while preserving reproductive function. Methotrexate is a frequently used for the treatment of several malignancies and is part of the chemotherapy protocols used for choriocarcinoma; however, side-effect are common. Extensive research over the last half century has revealed important functions of nanocurcumin. Invitro and in vivoresearch has shown various activities, such as anti-inflammatory, cytokines release, antioxidant, and immunomodulatory. However, to date no study has been carried out to elucidate its anticancer activity of nanocurcumin in choriocarcinoma. In this study, we investigated and compared the effects of methotrexate alone or in combination with nanocurcumin on various signalling pathway. In this simple experiment stury, we used Saphiro-Wilk test, independent sample t test, and Anova One Way test to analize data. To study the potential cooperative effect of both against, 4 BeWo cell lines were treated with the combination of methotrexate and nanocurcumin, 1 BeWO cell line was treated with methotrexate alone as a positive control, and 1 BeWo cell line as a negative control. This study demonstrated significant reduction of telomerase activity, NF- B expression, and proliferation index BrdU of BeWo cell line treated with a combination of nanocurcumin and methotrexate compared with methotrexate alone. It shows that the effect of nanocurcumin and methotrexate are syngergistic suggest potential for the clinical use of methotrexate in combination with curcumin which will allow effective anticancer effect in choriocarcinoma. "
2018
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UI - Tugas Akhir  Universitas Indonesia Library
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Ernie Setyawati
"Sepsis neonatorum awitan lambat (SNAL) masih menjadi penyebab penting kematian dan kesakitan pada bayi kurang bulan. Diagnosis yang cepat penting untuk penatalaksanaan yang sesuai. Diperlukan alat diagnostik yang sederhana, tidak mahal dan cepat hasilnya untuk mendiagnosis SNAL.Tujuan penelitian ini adalah untuk mendapatkan nilai diagnostik rasio netrofil limfosit (RNL) dan kombinasi RNL dan rasio I/T untuk mendiagnosis SNAL. Data penelitian cross sectional ini diambil dari rekam medis pasien bulan januari 2018-Desember 2019 di Divisi Neonatologi Rumah Sakit Cipto Mangunkusumo. Subyek penelitain adalah bayi kurang bulan >30-36 minggu, berusia 7-28 hari dengan klinis sepsis. Dari kultur darah, neonatus dibagi menjadi 2 kelompok, yaitu: proven sepsis dan unproven sepsis. Rasio netrofil limfosit dihitung dari data hitung jenis limfosit. Rasio I/T didapat dari rekam medis. Dari semua 126 subyek penelitian 70 termasuk kelompok proven sepsis dan 56 unproven sepsis. Analisis kurva Receiver operating characteristic RNL didapatkan area under the curve 0.953. Dengan cut off RNL 1.785 didapatkan sensitivitas 78,57%, spesifisitas 92,86%, nilai dugan positif (NDP) 93,22% dan nilai duga negative (NDN) 77,61%. Dengan titik potong rasio I/T > 0,2, didapatkan sensitivitas 55,70 %, spesifitas 83,70%, NDP 81,25% dan NDN 60,26%. Gabungan RNL dan rasio I/T meningkatkan sensitivitas dan NDP rasio I/T berturut-turut menjadi 90% dan 84,44%. Sebagai kesimpulan, RNL dengan titik potong 1,785 mempunyai nilai diagnostik yang baik untuk mendiagnosis SNAL. Kombinasi RNL dan rasio I/T akan meningkatkan nilai diagnostik rasio I/T.

Late-onset neonatal sepsis (LOS) remains an important cause of death and morbidity among preterm infants. Early diagnostic is important for appropiate management. The simple, inexpensive, and rapid diagnostic tool is required to diagnose LOS. The objective of this study is assesing diagnostic value of NLR and combination of NLR and I/T ratio for diagnosis LOS. The data for this retrospective cross-sectional study was collected from medical record from January 2018 to December 2019 at Neonatology Division Cipto Mangunkusumo Hospital. Preterm infants with >30 -36 gestational weeks, 7-28 days of postnatal age and clinically sepsis were eligible for this study. According to the result of blood cultures, all enrolled infant were classified into 2 groups: proven sepsis and unproven sepsis. The NLR was calculated as the ratio of neutrophil count to lymphocyte count. Immature-to-total neutrophil ratio was taken from medical record. A total of 126 subjects were involved: 70 proven sepsis and 56 unproven sepsis. Receiver operating curve analysis for NLR calculated and area under the curve of NLR corresponded to 0.953. Using a cut off point of 1.785 for NLR, the sensitivity was 78,57%, the specificity was 92,86%, positive predictive value (PPV) 93,22% and negative predictive value (NPV) 77,61%. Using cut off > 0,2, I/T ratio has sensitivity 55,70 %, specificity 83,70%, PPV 81,25% and NPV 60,26%. The combination NLR and ratio I/T increased sensitivity and PPV of ratio I/T became 90% and 84,44%, respectively.As conclusion The NLR with cut off 1,785 has good diagnostic value for SNAL. Combination NLR and I/T ratio can increase diagnostic value of I/T ratio."
Depok: Fakultas Kedokteran Universitas Indonesia, 2020
T55511
UI - Tugas Akhir  Universitas Indonesia Library
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Denni Hermartin
"Latar Belakang :Insidensi terjadinya ketuban pecah dini (KPD) pada kehamilan preterm adalah 3-10,% dari semua persalinan. Lama terjadinya ketuban pecah dini berpengaruh pada kejadian infeksi maternal dan sepsis pada bayi. Sepsis, termasuk sepsis neonatal awitan dini (SNAD), masih menjadi penyebab utama kematian bayi prematur. Vitamin D berperan meningkatkan imunitas tubuh terutama saat menghadapi infeksi. Tujuan penelitian ini ingin mengetahui hubungan antara lama KPD, leukosit maternal, kadar vitamin D maternal dan tali pusat dengan luaran sepsis awitan dini pada bayi prematur.
Metode : Desain penelitian kohort retrospektif dengan menggunakan rekam medis dan data penelitian sebelumnya. Mencatat lama ketuban pecah dini, kadar leukosit maternal, kadar vitamin D maternal dan tali pusat dankejadian sepsis pada bayi yang dilahirkan usia 28-34 minggudi Rumah Sakit Umum Pusat Nasional dr. Cipto Mangunkusumo dan Rumah Sakit Umum Pusat Persahabatan, Jakarta. Subjek penelitian diambil secaraConsecutivesampling.
Hasil : Selama periode penelitian didapatkan 72 subjek bayi yang dilahirkan dari ibu dengan KPD, 22 bayi (31%) diantaranya mengalami SNAD, sedangkan 50 bayi lainnya tidak mengalami SAD. Tidak terdapat hubungan antara lama KPD, jumlah leukosit maternal dengan kejadian SNAD tetapi didapatkan hubungan yang bermakna antara kadar vitamin D maternal dan tali pusat dengan kejadian SNAD.

Background:The incidence of premature rupture of membranes (PROM) in preterm pregnancy is 3-10,% of all deliveries. The duration of premature rupture of the membranes affects the incidence of maternal infection and sepsis in infants. Sepsis, including early onset neonatal sepsis (EONS), is still the main cause of premature infant mortality. Vitamin D acts to increase the body s immunity, especially when facing infection. The purpose of this study was to determine the relationship between the length of the ROM, maternal leukocytes level, maternal and umbilical cord vitamin D levels with early onset sepsis in premature infants.
Method:Design of a retrospective cohort study using medical records and previous research data. Note the duration of premature rupture of the membranes, maternal leukocyte levels, maternal vitamin D levels and umbilical cord and the incidence of sepsis in infants born 28-34 weeks at the National Center General Hospital Dr. Cipto Mangunkusumo and Center General Hospital Pesahabatan, Jakarta. The research subjects were taken by consecutive sampling.
Results: During the study period 72 subjects were born from mothers with ROM, 22 infants (31%) among them experienced EONS, while 50 other infants did not experience EONS. There was no relationship between the duration of ROM, the number of maternal leukocytes with the incidence of EONS, but a significant relationship was found between maternal vitamin D levels and umbilical cord with EONS events.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019
T59192
UI - Tesis Membership  Universitas Indonesia Library
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Puti Raykhan Rasyada Ralas
"Latar Belakang: Preeklamsia (PE) merupakan kelainan multisistem yang berkontribusi terhadap mortalitas dan morbiditas ibu. Diusulkan bahwa preeklamsia awitan dini/earlyonset preeclampsia (EOPE) menyebabkan lebih banyak komplikasi dan hasil yang lebih buruk dibandingkan preeklamsia awitan terlambat/late-onset preeclampsia (LOPE). Diagnosis dini dan tepat dari kelainan ini dapat memberikan hasil yang lebih baik bagi ibu dan janin. Salah satu patofisiologi EOPE adalah perubahan bentuk arteri spiral yang tidak memadai akibat invasi tropoblas yang abnormal, yang kemudian mengakibatkan hipoksia pada plasenta. Dalam kondisi hipoksia, metabolisme glukosa melalui glikolisis anaerobik sehingga menyebabkan peningkatan aktivitas enzim laktat dehydrogenase (LDH). Penelitian ini bertujuan untuk mengamati aktivitas LDH spesifik pada jaringan plasenta wanita dengan preeklamsia awitan dini.
Metode: Studi deskriptif cross-sectional ini menggunakan 26 sampel jaringan plasenta dengan preeklampsia awitan dini. Aktivitas spesifik LDH diukur dengan mengamati nilai OD masing-masing sampel melalui spektrofotometer pada 440 nm serta konsentrasi protein yang diperoleh dari penelitian sebelumnya. Karakteristik subjek dari setiap sampel juga diamati, termasuk usia ibu, kehamilan, tekanan darah sistolik (SBP), tekanan darah diastolik (DBP), proteinuria dan berat badan lahir. Analisis data dilakukan melalui aplikasi IBM SPSS versi 27.0.
Hasil: Median aktivitas spesifik LDH dari 26 pasien preeklamsia dini pada penelitian ini adalah 2,08 Unit/mg protein. Dari jumlah tersebut, nilai minimum aktivitas spesifik LDH adalah 0,02 Unit/mg protein dan nilai maksimum adalah 5,68 Unit / mg protein.
Kesimpulan: Studi ini menemukan bahwa setengah dari aktivitas spesifik LDH sampel adalah 2,08 Unit / mg protein atau lebih. Aktivitas spesifik LDH ditemukan lebih tinggi pada pasien dengan usia ≥ 35 tahun, multigravida, tekanan darah sistolik ≥ 160 mmHg, tekanan darah diastolic < 100 mmHg, proteinuria < +3, dan berat badan lahir ≥ 1500 g.

Introduction: Preeclampsia (PE) is a multisystem disorder that contributes to maternal mortality and morbidity. Early-onset preeclampsia (EOPE) is suggested to lead to more complications and worse outcomes compared to late-onset preeclampsia (LOPE). Early and prompt diagnosis of this disorder can lead to better outcomes for both the mother and fetus. One of the pathophysiology of EOPE is the inadequate spiral artery remodelling due to incomplete trophoblast invasion, which results in placental hypoxia. In hypoxic conditions, glucose is metabolised through anaerobic glycolysis, leading to an increase in lactate dehydrogenase (LDH) enzyme activity. This study aims to observe the specific LDH activity on the placental tissue of women with early-onset preeclampsia.
Method: 26 samples were used in this descriptive cross-sectional study. The specific LDH activity was measured by observing the OD value of each sample through a spectrophotometer at 440 nm as well as its protein concentration obtained from a previous study. Subject characteristics of each sample were observed as well, including maternal age, gravidity, systolic blood pressure (SBP), diastolic blood pressure (DBP), proteinuria, and birth weight. Finally, data analysis was done through IBM SPSS software version 27.0.
Results: Median specific LDH activity of 26 early preeclamptic patients in this study was 2.08 Unit/mg protein. Of these, the minimum value of specific LDH activity was 0.02 Unit/mg protein and the maximum value was 5.68 Unit/mg protein.
Conclusion: This study found that half of the sample’s specific LDH activity was 2.08 Unit/mg protein or more. Specific LDH activity are found higher in patients with maternal age ≥ 35 years old, multigravid, SBP ≥ 160 mmHg, DBP < 100 mmHg, proteinuria < +3, as well as birth weight ≥ 1500 g.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Tugas Akhir  Universitas Indonesia Library
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Anandha Mardhia Prefitri
"Latar Belakang : Korioamnionitis  telah dihubungkan dengan kejadian ketuban pecah dini preterm (PPROM),  persalinan preterm dan luaran kehamilan yang buruk salah satunya adalah kejadian sepsis neonatus awitan dini (SNAD). Infeksi ditengarai mempunyai peran penting terhadap kejadian korioamnionitis. Hingga saat ini pemeriksaan histopatologi merupakan standar baku emas untuk menegakkan diagnosis korioamnionitis. C-Reactive Protein (CRP), Neutrophil to Lymphocyte Ratio (NLR) dan Platelet to Lymphocyte Ratio (PLR) adalah marker inflamasi dari serum darah maternal, dan menggambarkan keadaan infeksi dan inflamasi. Tujuan penelitian ini adalah untuk mengetahui asosiasi antara kadar CRP, NLR dan PLR serum maternal serta kultur kuman membran amnion dengan kejadian korioamnionitis dan SNAD.Metode: Penelitian potong lintang terhadap 61 orang ibu dengan PPROM usia kehamilan £32 minggu. Kadar NLR dan PLR merupakan rasio neutrofil absolut dan platelet dengan limfosit absolut. Korioamnionitis ditegakkan dengan pemeriksaan histopatologi korioamnion. Dan jenis kuman diketahui dari kultur membran amnion. Hasil: Kejadian korioamnionitis pada pasien PPROM adalah 27,8%. Pada sampel dengan korioamnionitis Median NLR 8,59 (4,20–22,67) ; p = 0,03 , sedangkan PLR dan CRP berturut-turut adalah 166,10 (84,89–396,27) dan 5,80 (0,03–88);  p>0,05. Terdapat 25% sampel dengan korioamnionitis yang luarannya menderita SNAD. Kadar NLR, PLR dan CRP sampel dengan luaran SNAD berturut-turut adalah 7,13(3,03–16,15); 154,30(45,2-444,08); dan 12,40 (2,4 –67,53), semuanya mempunyai nilai p>0,05. Jenis bakteri yang terbanyak berasal dari ordo Enterobacteriales (68%) dan E. Coli (23,4%) merupakan spesies terbanyak. Namun tidak terdapat asosiasi antara jenis bakteri dengan kejadian korioamnionitis dan SNAD (p<0,05) Kesimpulan: Terdapat asosiasi NLR dengan kejadian Korioamnionitis. Namun tidak terdapat marker inflamasi maternal yang berasosiasi dengan kejadian SNAD. Pada penelitian ini tidak terdapat hubungan antara jenis bakteri dengan kejadian korioamnionitis maupun SNAD.

Background: Chorioamnionitis has been associated with the incidence of preterm premature rupture of membranes (PPROM), preterm labor and poor pregnancy outcomes, one of which is the incidence of early onset neonatal sepsis (EONS). Infection is suspected to have an important role in the occurrence of chorioamnionitis. Until now, histopathological examination is the gold standard for diagnosing chorioamnionitis. C-Reactive Protein (CRP), Neutrophil to Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) are inflammatory markers from maternal serum, and can describe the state of infection and inflammation. The purpose of this study was to determine the association between levels of CRP, NLR and PLR in maternal serum and amniotic membrane culture with the incidence of chorioamnionitis and EONS. Methods: A cross-sectional study of 61 mothers with PPROM at ≤32 weeks' gestation. NLR and PLR levels are the ratio of absolute neutrophils and platelets to absolute lymphocytes. Chorioamnionitis is confirmed by histopathological examination of the chorioamnion. And the type of germ is known from amniotic membrane culture. Results:The incidence of chorioamnionitis in PPROM patients was 27.8%. In samples with chorioamnionitis Median NLR 8.59 (4.20–22.67) ; p = 0.03 , while the PLR​​and CRP were 166.10 (84.89–396.27) and 5.80 (0.03–88) respectively; p>0.05. There are 25% of samples with chorioamnionitis whose outcome with EONS. The NLR, PLR and CRP levels of the samples with EONS were 7.13(3.03–16.15); 154.30(45.2-444.08); and 12.40 (2.4 –67.53), all of which have a value of p>0.05. The most types of bacteria come from the order Enterobacteriales (68%) and E. Coli (23.4%) are the most species. However, there was no association between the type of bacteria and the incidence of chorioamnionitis and SNAD (p<0.05). Conclusion: There is an association of NLR with chorioamnionitis. However, there were no maternal inflammatory markers associated with EONS. In this study, there was no relationship between the type of bacteria and the incidence of chorioamnionitis or EONS."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
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UI - Tesis Membership  Universitas Indonesia Library
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