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"ABSTRAKPenelitian ini bertujuan untuk mengetahui efek pemberian hidroksiklorokuin 400 mg selama 12 minggu terhadap kadar sVCAM-1 dan sE-Selectin sebagai petanda disfungsi endotel pada pasien artritis reumatoid. Penelitian ini juga melihat peran HOMA-IR, FFA dan ox-LDL terhadap perbaikan disfungsi endotel.Penelitian ini menggunakan dua disain yaitu uji klinis acak tersamar ganda dan kohort prospektif dilakukan pada pasien artritis reumatoid dengan terapi metotreksat di poliklinik Reumatologi RS Cipto Mangunkusumo, Jakarta, pada periode Februari 2016-Mei 2017. Pasien dengan terapi insulin, anti-hipertensi dan terapi lain yang mempengaruhi kadar sVCAM-1 dan sE-Selectin dieksklusi dari penelitian. Subjek yang eligibel dirandomisasi menjadi dua kelompok, kelompok yang mendapat hidroksiklorokuin HCQ 400 mg dan kelompok placebo, dan diikuti selama 12 minggu. Pemeriksaan sVCAM-1, sE-Selectin, HOMA-IR, FFA dan ox-LDL dilakukan pada awal penelitian dan pada minggu ke-12. Perbedaan persentase perubahan kadar sVCAM-1 dan sE-Selectin sebelum dan setelah perlakuan antara kedua kelompok dianalisis dengan uji-t dan uji Mann-Whitney. Persentase perubahan kadar sVCAM-1 dan sE-Selectin dikorelasikan dengan persentase perubahan HOMA-IR, FFA dan ox-LDL, dengan uji Spearman.Sebanyak 37 subjek diikutkan dalam penelitian, dan terdapat 3 subjek yang drop-out pada masing-masing kelompok, sehingga didapatkan 15 subjek pada kelompok HCQ dan 16 subjek pada kelompok placebo. Kadar sVCAM-1 serum minggu ke-12 pada kelompok HCQ menurun sebesar 17,1 median , sementara pada kelompok plasebo meningkat sebesar 9,7 , dan perbedaan tersebut bermakna secara statistik. Kadar E-Selectin pada kelompok terapi HCQ mengalami penurunan dalam persen yang lebih besar dibandingkan pada kelompok plasebo, tapi perbedaan tersebut tidak bermakna. Perubahan kadar sVCAM-1 dan sE-Selectin, juga dibuktikan tidak berkorelasi dengan perubahan HOMA-IR, FFA dan ox-LDL.Terapi hidroksiklorokuin pada pasien artritis reumatoid terbukti memperbaiki disfungsi endotel dengan menurunkan kadar sVCAM-1, namun tidak terbukti menurunkan sE-Selectin. Variable sVCAM-1 dan sE-Selectin tidak berkorelasi dengan HOMA-IR, FFA dan ox-LDL Kata kunci: artritis reumatoid, disfungsi endotel, hidroksiklorokuin, sE-Selectin, sVCAM-1.

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ABSTRACTThis study aims to evaluate the effect of hydroxychloroquine on sVCAM 1 and sE Selectin levels decreasing as endothelial dysfunction marker in rheumatoid arthritis patients. This study also assessed the correlation between changes in sVCAM 1 and sE Selectin levels with other variables of changes in HOMA IR, FFA and ox LDL.Two kinds of methods i.e. double blind randomized controlled trial and prospective cohort, were conducted, on patients with rheumatoid arthritis with methotrexate treatment at Rheumatology Outpatient Clinic of Cipto Mangunkusumo Hospital Faculty of Medicine Universitas Indonesia, Jakarta, during February 2016 July 2017. Patients with insulin, anti hypertension and other treatment which could affect sVCAM 1 and sE Selectin level, were excluded. Eligible subjects were randomly assigned into two groups. Eighteen subjects were administered hydroxychloroquine 400 mg daily and 19 patients were given placebo for 12 weeks. sVCAM 1, sE Selectin, HOMA IR, FFA dan ox LDL were examined in the beginning and in the end week 12. Differences of serum sVCAM 1 and sE Selectin level in percentage, before and after experiment, were evaluated, by T test or alternatively by Mann Whitney test. Differences of serum sVCAM 1 and sE Selectin level in percentage, were correlated with difference of serum HOMA IR, FFA and ox LDL level, by Spearman test.There were 37 subjects enrolled in the study, and there were 3 drop out subjects in each group, finally there were 15 subjects in the HCQ group and 16 in the placebo group. Serum sVCAM 1 level decreased 17.1 median in HCQ treatment group, while in placebo group, it increased 9,7 median compared with pre treatment value. The difference in percentage rate change of sVCAM between two group was significant. On the other hand, the change of E Selectin serum level in HCQ group was found a higher percentage of decrease compared with placebo group, but the difference was not significant. Changes in sVCAM 1 and sE Selectin levels were also proven no correlation with HOMA IR, FFA and ox LDL changes.Treatment of HCQ in patients with rheumatoid arthritis appears beneficial to improve endothelial dysfunction by lowering serum sVCAM 1, but not proven to decrease sE Selectin. The sVCAM 1 and sE Selectin variables were not correlated with HOMA IR, FFA and ox LDL Keywords endothelial dysfunction, hydroxychloroquine, rheumatoid arthritis, sE Selectin, sVCAM 1."

"Hidroksiklorokuin merupakan obat antimalaria yang digunakan dalam pengobatan lupus eritematosus sistemik, reumatoid artritis, dan malaria. Namun, hidroksiklorokuin memiliki efek samping seperti toksisitas okular, neurotoksisitas, gangguan gastrointestinal, hingga toksisitas berat seperti kardiotoksisitas. Oleh karena itu, diperlukan pemantauan terapi obat dalam penggunaan hidroksiklorokuin dosis tinggi atau jangka waktu yang panjang. Tujuan dari penelitian ini adalah untuk mendapatkan metode analisis dan preparasi sampel hidroksiklorokuin dalam VAMS menggunakan Kromatografi Cair Kinerja Tinggi – Photodiode Array yang optimum dan tervalidasi berdasarkan pedoman Food and Drug Administration 2018. Analisis kuantifikasi hidroksiklorokuin dilakukan dengan KCKT-PDA dengan kolom C18 (Waters, Sunfire™ 5μm; 250 x 4,6mm), volume injeksi 100 μL, dan suhu kolom 45 ºC. Fase gerak terdiri atas asetonitril-dietilamin 1% (65:35) (elusi isokratik) dengan laju alir 0,8 mL/menit dan total waktu analisis 12 menit. Preparasi sampel dalam VAMS dilakukan dengan metode ekstraksi cair-cair dengan pelarut amonia 1% dan n-heksan-etil asetat (50:50 v/v) dengan volume masing-masing 500 μL. Darah di dalam VAMS dikeringkan selama 2 jam, lalu ditambahkan baku dalam dan larutan ammonia 1%. Sampel dikocok dengan vortex selama 15 detik dan disonikasi selama 5 menit. Kemudian ditambahkan n-heksan-etil asetat (50:50) lalu dikocok kembali dengan vortex selama 15 detik dan disentrifugasi selama 5 menit pada kecepatan 10.000 rpm. Fase n-heksan-etil asetat diambil lalu dikeringkan dengan gas Nitrogen. Residu hasil pengeringan direkonstitusi dengan fase gerak sebanyak 150 μL dan dipindahkan ke vial autosampler untuk dianalisis dengan sistem KCKT-PDA. Metode ini telah memenuhi parameter validasi penuh menurut Food and Drug Administration 2018, dengan LLOQ 2 ng/mL dan rentang kurva kalibrasi 2-6500 ng/mL dengan koefisien korelasi 0,99927-0,99969.

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Hydroxychloroquine is an antimalarial drug that used for systemic lupus erythematosus, rheumatoid arthritis, and malaria treatment. However, hydroxychloroquine has several side effects such as ocular toxicity, neurotoxicity, gastrointestinal disorder, and also severe toxicity like cardiotoxicity. Therefore, therapeutic drug monitoring of high dose or long-term use of hydroxychloroquine is needed. This study aims to obtain an optimum and validated analysis and preparation method for hydroxychloroquine in VAMS using High Performance Liquid Chromatography – Photodiode Array Detector based on Food and Drug Administration guidelines (2018). Hydroxychloroquine quantification was performed using HPLC-PDA with Waters Sunfire™ C18 (5μm; 250 x 4,6mm) column with injection volume of 100 μL, and the temperature of column was controlled at 45 ºC. Mobile phase consist of acetonitrile-diethylamine 1% (65:35) (isocratic elution) and delivered at a flow rate of 0,8 mL/min through out the 12 minutes run. Sample in VAMS is extracted by liquid-liquid extraction with ammonia 1% and n-hexane-ethyl acetate (50:50 v/v), 500 μL each as a solvent. Blood in VAMS was dried for 2 hours, then added with internal standard solution and 1% ammonia solution. The samples were mixed on vortex for 15 seconds and sonicated for 5 minutes. n-hexane-ethyl acetate (50:50) was added to the samples, then mixed again on vortex for 15 second and centrifuged for 5 minuted at a speed of 10,000 rpm. n-hexane-ethyl acetate phase was separated and dried under Nitrogen gas flow. The residue from drying process as reconstituted with 150 μL mobile phase and transferred to autosampler vial for analysis. This method has successfully qualify the Food and Drug Administration (2018) parameters, with 2 ng/mL of LLOQ, range of calibration curve 2-6500 ng/mL, and coefficient of correlation 0,99927-0,99969."

"Artritis reumatoid AR adalah penyakit autoimun yang saat ini telah diketahui menunjukkan manifestasi klinis bukan hanya intraartikular, tetapi juga ekstraartikular. Kejadian kardiovaskular baik subklinis maupun klinis ditemukan lebih tinggi pada penderita AR. Mediator inflamasi aterogenik pada AR seperti interleukin-6 IL-6 diduga menjadi salah satu faktor risiko nontradisional kardiovaskular yang berkontribusi meningkatkan penanda disfungsi endotel seperti E-Selectin. Penelitian ini bertujuan mengetahui peran mediator inflamasi dalam kejadian disfungsi endotel, khususnya korelasi IL-6 dan E-selectin, pada pasien artritis reumatoid tanpa faktor risiko kardiovaskular. Studi potong-lintang dilakukan pada 40 pasien AR di Poliklinik Reumatologi RSUPN Dr. Cipto Mangunkusumo, Indonesia, pada bulan September-November 2017. Pemeriksaan IL-6 dan E-Selectin dilakukan dengan teknik enzyme-linked immunosorbent assay ELISA. Analisis korelasi bivariat dilakukan untuk menemukan korelasi kedua penanda tersebut. Rerata usia subjek penelitian ini adalah 44,9 13,1 tahun dan median durasi sakit adalah 36 bulan. Korelasi kadar IL-6 dengan kadar E-Selectin memiliki kekuatan korelasi lemah tetapi tidak bermakna secara statistik r = 0.232, p=0,149. Tidak terdapat korelasi antara IL-6 dengan E-Selectin pada pasien AR tanpa faktor risiko tradisional kardiovaskular.

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Rheumatoid arthritis RA is an autoimmune disease which has recently been recognized to manifest as not only intraarticular but also extraarticular symptoms. Cardiovascular events, presented either subclinically or clinically, were discovered more in AR patients. Atherogenic inflammatory mediator in AR including interleukin-6 IL-6 was thought to be one of nontraditional cardiovascular risk factor contributing to increase the endothelial dysfunction biomarker such as E-Selectin. This study was purposed to determine the correlation between inflammatory mediator and endothelial dysfunction event, especially between IL-6 and E-Selectin, in RA patient without traditional cardiovascular risk factor. A cross-sectional study was performed to 40 RA patients of Rheumatology Clinic of Cipto Mangunkusumo National General Hospital, Indonesia from September to November 2017. Measurement of the level of IL-6 and E-Selectin were performed using enzyme-linked immunosorbent assay ELISA. Bivariate correlation analysis was performed to determine the correlation between those two biomarkers. The mean age of this study subjects was 44.9 13.1 years and median of disease duration was 36 months. This study showed weak correlation between IL-6 and E-Selectin level, but not statistically significant.232, p=0.149 . There is no correlation between IL-6 and sE-Selectin in rheumatoid arthritis patient without traditional risk factor cardiovascular."

"Infeksi COVID-19 (Corona Virus Disease 2019) dapat meninggalkan gejala sisa multisistemik (long COVID). Gejala long COVID meliputi kelelahan, sesak napas, batuk, sakit kepala, nyeri otot, dan gangguan kesehatan kognitif atau mental seperti kecemasan atau depresi. Salah satu tata laksana long COVID adalah intervensi rehabilitasi dan telerehabilitasi disarankan sebagai salah satu strategi inovatif. Namun, belum dikembangkan model telerehabilitasi untuk pasien long COVID di Indonesia. Oleh karena itu, perlu dilakukan penelitian yang bertujuan untuk mengembangkan model telerehabilitasi dan menilai efektivitasnya terhadap perbaikan kapasitas fungsional, kualitas hidup, tingkat stres oksidatif dan disfungsi endotel pada pasien long COVID di Indonesia. Penelitian dilakukan di Jakarta pada Juni 2022 hingga Juli 2024. Tahap pertama adalah studi kualitatif pengembangan model telerehabilitasi CoFit Rehab untuk pasien long COVID menggunakan metode Delphi yang melibatkan 24 panelis. Tahap kedua adalah uji randomisasi terkontrol pada 41 pasien long COVID (21 subjek perlakuan dan 20 subjek kontrol) untuk menguji efektivitas model telerehabilitasi yang dikembangkan. Selama 12 minggu, subjek perlakuan menjalani intervensi telerehabilitasi dan subjek kontrol menjalani intervensi rehabilitasi standar. Dilakukan pengukuran parameter kapasitas fungsional (uji jalan enam menit, uji sit-to-stand 30 detik dan uji kekuatan genggam tangan), kualitas hidup (kuesioner EQ-5D-5L versi Indonesia), tingkat stres oksidatif (kadar GSH dan rasio GSH/GSSG) dan disfungsi endotel (kadar mikropartikel endotel CD31+CD42b–). Studi kualitatif mendapatkan model telerehabilitasi. Uji randomisasi terkontrol memperlihatkan peningkatan bermakna jarak tempuh uji jalan enam menit baik kelompok kontrol dan kelompok perlakuan. Peningkatan jarak tempuh uji jalan enam menit lebih besar pada kelompok perlakuan. Ditemukan peningkatan bermakna jumlah repetisi uji sit-to-stand 30 detik, kekuatan genggam tangan, skor VAS EQ-5D-5L yang bermakna pada kelompok perlakuan. Ditemukan penurunan bermakna kadar mikropartikel endotel CD31+CD42b– plasma pada kelompok perlakuan. Tidak terdapat perbaikan bermakna pada parameter lain. Model telerehabilitasi CoFit Rehab terbukti lebih unggul dalam memperbaiki kapasitas fungsional dan fungsi endotel pada pasien long COVID dibandingkan rehabilitasi standar.

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COVID-19 (Corona Virus Disease 2019) infection can result in multisystemic sequelae (long COVID). Commonly reported symptoms include fatigue, shortness of breath, cough, headache, muscle pain, and cognitive or mental health disorders such as anxiety or depression. One of the management for long COVID is rehabilitation intervention and telerehabilitation is suggested as one of the innovative strategies. However, a telerehabilitation model (CoFit Rehab) for long COVID patients has not been developed in Indonesia. This study aims to develop a telerehabilitation model for long COVID patients and assess its effectiveness in improving functional capacity, quality of life, oxidative stress levels and endothelial dysfunction in long COVID patients in Indonesia. This study was done in Jakarta from June 2022 until July 2024. The first stage was a qualitative study to obtain a telerehabilitation model for long COVID patients using the Delphi method that involved 24 panelists. The second stage was a randomized controlled trial on 41 long COVID patients (21 treatment subjects and 20 control subjects) to test the effectiveness of the telerehabilitation model that has been developed. For 12 weeks, treatment subjects received telerehabilitation intervention and control subjects received standard rehabilitation intervention. Functional capacity parameters (six-minute walk test, 30-second sit-to-stand test, and handgrip strength test), quality of life (Indonesian version of the EQ-5D-5L questionnaire), oxidative stress levels (GSH levels and GSH/GSSG ratio) and endothelial dysfunction (concentration of CD31+CD42b– endothelial microparticles) were measured. The qualitative study obtained a telerehabilitation model. Randomized controlled trial showed a significant increase in the six-minute walk test distance in both groups. Compare to the control group, the distance increase in the six-minute walk test was greater in the treatment group. There was a significant increase in the total repetitions of the 30-second sit-to-stand test, handgrip strength, and EQ-5D-5L VAS scores in the treatment group. There was a significant decrease of the endothelial microparticle plasma level (CD31+CD42b) in the treatment group. There was no significant improvement in other parameters. The telerehabilitation model (CoFit Rehab) was shown to be superior in improving functional capacity and endothelial function in long COVID patients compared to standard rehabilitation."

"Resistensi insulin adalah penurunan kemampuan jaringan (otot, hati, dan jaringan adiposa) untuk merespon insulin yang bersirkulasi secara normal dalam darah yang berisiko berkembang menjadi penyakit diabetes melitus tipe 2. Rasio tinggi asupan asam lemak omega-6/omega-3 diduga berperan dalam menurunkan sensitivitas insulin. Penelitian ini bertujuan untuk mengetahui hubungan antara rasio asupan omega-6/omega-3 dan HOMA-IR pada perempuan usia reproduktif. Studi potong lintang ini dilakukan di Jakarta, pada bulan Juli sampai Oktober 2021. Pengambilan sampel menggunakan metode consecutive sampling dan diperoleh 79 subjek perempuan yang memenuhi kriteria penelitian. Pengumpulan data dilakukan melalui wawancara 24-hours food recall sebanyak 3 kali, pengukuran antropometri untuk menilai status gizi, dan pengambilan serum untuk mengukur kadar glukosa darah puasa dan insulin. Rerata asupan omega-6 pada subjek adalah 9.43 ± 3.69 gram/hari, median asupan omega-3 pada subjek adalah 0.79 (0.23–3.53) gram/hari, dan rerata rasio asupan omega-6/omega-3 adalah 12.32 ± 4.32. Rerata HOMA-IR pada subjek adalah 3.04 ± 1.24. Terdapat korelasi positif lemah antara rasio asupan omega-6/omega-3 dan HOMA-IR, namun tidak signifikan (r=0.161, p=0.157). Ditemukan hubungan signifikan antara DHA dan HOMA-IR setelah mengontrol faktor perancu (p=0.014). Tidak ada hubungan antara rasio asupan asam lemak omega-6/omega-3 dan HOMA-IR pada perempuan usia reproduktif. Namun, ditemukan hubungan antara asupan DHA dan HOMA-IR yang menunjukkan bahwa peningkatan asupan asam lemak tidak jenuh dapat mencegah terjadinya resistensi insulin.

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Insulin resistance is a decrease in the ability of tissues (muscle, liver, and adipose tissue) to respond to insulin that circulates normally in the blood which is at risk of developing type 2 diabetes mellitus. A high ratio of omega-6/omega-3 fatty acid intake is thought to play a role in reducing insulin sensitivity. This study aims to determine the association between the ratio of omega-6/omega-3 intake and HOMA-IR in reproductive-aged women. This cross-sectional study was conducted in Jakarta, from July to October 2021. Sampling used the consecutive sampling method and obtained 79 women subjects who met the research criteria. Data was collected through 24-hour food recall interviews 3 times, anthropometric measurements to assess nutritional status, and serum sampling to measure fasting blood glucose and insulin levels. The mean omega-6 intake in the subjects was 9.43 ± 3.69 grams/day, the median omega-3 intake in the subjects was 0.79 (0.23–3.53) grams/day, and the mean ratio of omega-6/omega-3 intake was 12.32 ± 4.32. The mean HOMA-IR in the subjects was 3.04 ± 1.24. There was weak positive correlation between the ratio of omega-6/omega-3 intake and HOMA-IR, but not significant (r=0.161, p=0.157). A significant relationship was found between DHA and HOMA-IR after adjusted confounding factors (p=0.014). There was no association between the ratio of omega-6/omega-3 fatty acid intake and HOMA-IR in reproductive-aged women. However, it was found that there was a assocation between DHA intake and HOMA-IR which indicated that increasing intake of unsaturated fatty acids could prevent insulin resistance"

"Retinopati diabetik (DR) merupakan komplikasi mikrovaskular diabetes melitus (DM). Fenofibrat oral dapat mencegah progresivitas DR dengan mekanisme pengaturan kadar lipid lipid-related dan mekanisme lain nonlipid-related, antara lain dengan mencegah disfungsi endotel, mengurangi inflamasi, dan angiogenesis. Penelitian ini bertujuan mengetahui efek fenofibrat oral terhadap ketebalan makula sentral (CMT) dan volume makula, serta pengaruhnya pada kadar penanda biologis serum disfungsi endotel eNOS, inflamasi (VCAM-1), dan angiogenesis (VEGF) pada penyandang DR dengan dislipidemia.Penelitian prospektif ini menggunakan disain uji klinis acak tersamar ganda dengan membagi subjek menjadi kelompok intervensi simvastatin dan fenofibrat dan kontrol simvastatin dan plasebo. Penelitian berlangsung sejak Nopember 2016 hingga Oktober 2017, di Klinik Vitreo-retina, Departemen Medik Mata ndash;RSCM Kirana, melibatkan 60 mata dari 30 pasien penyandang DR non-proliferatif NPDR dengan dislipidemia. Penelitian pada tiap subjek dilakukan selama tiga bulan dengan evaluasi klinis, foto fundus, dan spectral domain optical coherence tomography (SD-OCT) makula tiap bulan. Pengukuran kadar eNOS, VCAM-1, dan VEGF, serta HbA1c dan profil lipid dilakukan sebelum dan setelah tiga bulan pengobatan.Sebelum intervensi, pada kedua kelompok tidak didapatkan perbedaan karakteristik demografik, klinik, dan penanda biologis serum. Tidak didapatkan perbedaan bermakna pada CMT kelompok simvastatin fenofibrat 248,0 40,4 m dibandingkan kelompok simvastatin plasebo 265,8 40,8 m, namun CMT lebih rendah secara bermakna pada bulan ke-1 pada kelompok simvastatin fenofibrat. Pada subjek dengan edema makula diabetik DME pemberian simvastatin fenofibrat setelah tiga bulan menunjukkan CMT lebih rendah secara bermakna. Volume makula setelah tiga bulan pemberian obat 10086 886,4 m3 pada kelompok simvastatin fenofibrat dan 10307 1058,6 m3 pada simvastatin plasebo. Perbedaan tersebut tidak bermakna, namun pada subjek dengan regulasi glukosa darah yang baik HbA1c 7 didapatkan volume makula lebih rendah pada bulan ke-2. Kadar penanda biologis serum setelah tiga bulan pemberian obat menunjukkan rerata kadar eNOS dan median VEGF sebesar 3878,8 873,33 pg/mL dan 242,8 86 - 1123,3 pg/mL pada kelompok simvastatin fenofibrat, dibandingkan 4031,2 742,56 pg/mL dan 370 134,8 - 810,6 pg/mL pada kelompok simvastatin plasebo, yang tidak berbeda bermakna, namun penurunan kadar VCAM-1 serum lebih besar secara bermakna pada kelompok simvastatin fenofibrat 50,7 pg/mL, 32,5 - 223,4 pg/mL vs. 40,4 pg/mL, 27,9 - 94,2 pg/mL . Pada subjek dengan kontrol glukosa darah ketat HbA1c 6,5 kadar VEGF 128,7 114,5 - 145,2 pg/mL, lebih rendah secara bermakna dibandingkan 423 86 - 1233,3 pg/mL pada subjek dengan HbA1c > 6,5 .Disimpulkan pemberian simvastatin fenofibrat selama tiga bulan pada subjek DR dengan dislipidemia secara umum tidak menurunkan CMT dan volume makula, namun menurunkan CMT khusus pada subjek DR dengan DME. Pemberian simvastatin fenofibrat pada subjek DR tidak mencegah penurunan kadar eNOS, peningkatan kadar VCAM-1 dan VEGF, namun pengendalian gula darah yang baik dapat mencegah peningkatan kadar VEGF. Simvastatin fenofibrat dapat dipertimbangkan sebagai terapi ajuvan pada penyandang DR dengan DME yang disertai dislipidemia. Pengontrolan glukosa yang baik merupakan manajemen utama pada DR.

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Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus (DM) due to structural and biochemical changes. Previous studies showed that oral fenofibrate prevents DR progression through lipid-regulating and nonlipid-related mechanisms, including preventing endothelial dysfunction, reducing inflammation and angiogenesis. This study aims to investigate the effects of oral fenofibrate on central macular thickness CMT and macular volume, and on specific biomarkers of endothelial dysfunction eNOS, inflammation VCAM-1 , and angiogenesis VEGF in DR individuals with dyslipidemia.This is a prospective, double-blind randomized clinical trial, with subjects divided into intervention group simvastatin fenofibrate and control group simvastatin placebo. This study was conducted from November 2016 to October 2017 at the Vitreo-retina Clinic, Department of Ophthalmology ndash; RSCM Kirana, involving 60 eyes from 30 non-proliferative DR patients NPDR with dyslipidemia that met inclusion criteria. Each subject was observed for three months, with monthly clinical evaluation, fundus photo, and macular spectral domain optical coherence tomography SD-OCT . Serum eNOS, VCAM-1, and VEGF biomarkers, as well as HbA1c and lipid profile, were examined before and after intervention.Before intervention, there were no differences in demographic and clinical characteristics, and serum biomarker levels between two groups. After three months of treatment, there was no significant difference between CMT in the intervention group and the control group 248 40.4 ? m vs. 265.8 40.8 ? m , but a significantly lower CMT was observed in the intervention group at the first month. There was also a significantly lower CMT compared to the control group 294 39,2 vs 263 24,4, p=0,045 in eyes with diabetic macular edema DME . Macular volume after three-month treatment was 10086 886.4 ? m3 in the intervention group and 10307 1058.6 ? m3 in the control group, this difference was not significant. However, in all subjects with good blood glucose regulation HbA1c 7 , macular volume in the second month was significantly lower compared to subjects with HbA1c > 7 . Serum biologic marker levels after three-month treatment showed no significant difference between control and intervention group, respectively, in mean eNOS 3878.8 873.33 pg/mL vs 4031.2 742.56 pg/mL and median VEGF levels 242.8 86 - 1123.3 pg/mL vs 370 134.8 - 810.6 pg/mL . Nonetheless, the decrease in VCAM-1 level was significantly higher in the intervention group 50.7 pg/mL, 32.5 - 223.4 pg/mL vs. 40.4 pg/mL, 27.9 - 94.2 pg/mL . In subjects with tighter blood glucose control HbA1c 6.5 , serum VEGF level was 128.7 114.5 - 145.2 pg/mL, which was significantly lower compared to 423 86 - 1233.3 pg/mL in subjects with HbA1c > 6.5 .In conclusion, three-month treatment with simvastatin fenofibrate does not reduce CMT and macular volume in overall DR subjects with dyslipidemia, but it reduces CMT in subjects with DME. Simvastatin fenofibrate treatment in DR subjects does not prevent lowering of serum eNOS levels, elevation of VCAM-1 levels, and elevation of VEGF levels, but tight blood sugar control prevents elevation of serum VEGF. Although good glucose control remains the most essential in the management of DR, simvastatin fenofibrate may be considered as adjuvant therapy for DR with dyslipidemia and DME."

"Latar Belakang: Berdasarkan data dari WHO, penderita penyakit kardiovaskular diduga akan terus meningkat. Salah satu proses patologis yang mendasari penyakit kardiovaskular adalah aterosklerosis. Disfungsi endotel yang mengawali aterosklerosis dimulai sejak anak-anak. Stres oksidatif dapat disebabkan oleh pertambahan usia. Salah satu herba yang memiliki efek antioksidan kuat dan dapat mencegah stres oksidatif adalah Hibiscus sabdariffa Linn.Metode: Penelitian eksperimental dilakukan pada 36 ekor tikus jantan galur Wistar usia 5 minggu selama 4 minggu, 8 minggu, dan 12 minggu. Hewan coba secara acak terbagi atas 12 kelompok, yaitu: kontrol (K4, K8, K12), latihan fisik aerobik (L4, L8, L12), pemberian H. sabdariffa Linn. 400 mg/kgBB/hari (H4, H8, H12) dan kombinasi latihan fisik aerobik dan pemberian H. sabdariffa Linn. 400 mg/kgBB/hari (HL4, HL8, HL12). Pengukuran kadar NO, ET-1, aktivitas spesifik SOD dan MDA menggunakan supernatan dari homogenat aorta abdominal.Hasil: Pola kadar NO kelompok K dan L menurun sesuai peningkatan usia. Terdapat perbedaan bermakna antara kadar NO kelompok K dan L, K dan H, dan K dan HL. Kadar ET-1 pada semua kelompok tidak bermakna secara statistik. Terdapat peningkatan aktivitas spesifik SOD pada kelompok L, H, dan HL dibandingkan K. Terdapat perbedaan bermakna Kadar MDA antara K dan H, L dan HL. Terdapat korelasi sedang antara NO dan aktivitas spesifik SOD.Kesimpulan: latihan fisik aerobik, pemberian H. sabdariffa Linn. 400 mg/kgBB/hari dan kombinasi latihan fisik aerobik dan pemberian H. sabdariffa Linn. 400 mg/kgBB/hari menurunkan kadar MDA dan ET-1, sebalikanya meningkatkan aktivitas spesifik SOD dan NO. Penurunan kadar MDA lebih jelas terlihat pada kelompok HL. Peningkatan aktivitas spesifik SOD meningkatkan produksi NO. Tidak terjadi disfungsi endotel dan stres oksidatif pada seluruh kelompok.

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Background: Based on data from WHO, patients with suspected cardiovascular disease will continue to rise. One of the pathological processes underlying cardiovascular disease is atherosclerosis. Endothelial dysfunction which is the first sign of atherosclerosis begins in childhood. Increasing age is one of the cause of oxidative stress. A herb that has strong antioxidant effects and can prevent oxidative stress is Hibiscus sabdariffa Linn.

Methods: Thirty six male Wistar rats aged 5 weeks were randomly divided into 12 groups consisting of control group (K4, K8, K12), aerobic exercise group (L4, L8, L12), administration of H. sabdariffa L. 400 mg/kgBW/day group (H4, H8, H12) and combination of aerobic exercise and H. sabdariffa L. 400 mg/kgBW/day group (HL4, HL8, HL12). NO, ET-1, MDA level, and SOD activity was measured from abdominal aorta homogenate supernatant.

Results: NO level pattern in the K and L groups tend to decline with age. NO level in L, H and HL groups were higher than K. The difference of ET-1 level in all groups were not statistically significant. Specific activity of SOD in L, H and HL groups were higher than control. The concentration of MDA of group K is significantly lower compare to groups H, L and HL. There is a moderate correlation between specific activity of SOD and NO.

Conclutions: Aerobic exercie, administration of H. sabdariffa L. 400 mg/kgBW/day, and combination of both decreases MDA and ET-1 concentration. While, specific activity of SOD and NO are increased. The decrease at MDA concentration was more prominent in HL group. An increase in spesific activity of SOD, increases the NO level. No endothelial dysfunction nor oxidative stress were observed in all groups."

"Nama : Fazria NasriatiProgram studi : Ilmu Penyakit DalamJudul : Korelasi Antara Kadar Tumor Necrosis Factor-?, Kadar Free Fatty Acid, dan Kadar Vascular Cellular Adhesion Molecule-1 Pada Pasien Artritis Reumatoid Latar Belakang: Mortalitas Artritis Reumatoid cukup tinggi, dimana sebagian besar disebabkan oleh komplikasi kardiovaskular yang disebabkan oleh proses disfungsi endotel. Salah satu mediator inflamasi penting yang berperan terhadap kerusakan sendi pasien AR yaitu TNF-?, juga terbukti berperan dalam proses disfungsi endotel serta berperan meningkatkan lipolisis intraselular sehingga meningkatkan kadar FFA yang bersirkulasi.Tujuan: Mengetahui korelasi antara kadar TNF-? dengan kadar VCAM-1, korelasi kadar TNF-? dengan kadar FFA, serta korelasi kadar FFA dengan kadar VCAM-1.Metode: Penelitian desain cross sectional dan retrospektif terhadap pasien AR dewasa yang berobat di Poliklinik Reumatologi Rumah Sakit Cipto Mangunkusumo RSCM , tanpa gangguan metabolik, infeksi akut, gangguan kardiovaskular, maupun penyakit autoimun lain. Pengumpulan data cross sectional dilakukan pada rentang bulan Oktober hingga November 2017, sedangkan sampel retrospektif telah dikumpulkan sejak Agustus 2016. Kadar TNF-?, VCAM-1, dan FFA dinilai melalui pemeriksaan darah serum dengan metode ELISA. Analisis korelasi dilakukan dengan analisis Pearson bila sebaran data normal dan dengan analisis Spearman bila sebaran data tidak normal.Hasil Penelitian: Sebanyak 35 orang subjek diikutsertakan dalam penelitian ini. Sebagian besar 97,1 merupakan perempuan dengan rerata usia 45,29 tahun, median lama sakit 48 bulan, dan sebagian besar memiliki derajat aktifitas penyakit sedang 65,7 . Tidak didapatkan adanya korelasi antara kadar TNF-? dengan kadar VCAM-1 p = 0,677; r = 0,073 . Korelasi antara kadar FFA dengan kadar VCAM-1 memperlihatkan adanya korelasi yang bermakna dengan arah korelasi negatif dan kekuatan korelasi lemah p = 0,036; r = - 0,355 . Korelasi antara kadar TNF-? dan kadar FFA memiliki arah negatif dan kekuatan korelasi yang lemah dengan hubungan yang tidak bermakna p = 0,227; r = - 0,21 .Kesimpulan: 1 Belum terdapat korelasi antara kadar TNF-? dengan kadar VCAM-1 pada pasien AR; 2 Belum terdapat korelasi antara kadar TNF-? dengan kadar FFA pada pasien AR; 3 Terdapat korelasi negatif antara kadar FFA dengan kadar VCAM-1 pada pasien AR. Kata Kunci : Tumor Necrosis Factor-?, Free Fatty Acids, Vascular Cell Adhesion Molecule-1, Artritis Reumatoid.

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Name Fazria NasriatiStudy Program Internal MedicineTitle Correlation Between Tumor Necrosis Factor levels, Free Fatty Acid Levels, and soluble Vascular Cell Adhesion Molecule 1 Levels in Rheumatoid Arthritis Patients. Backgrounds The mortality of Rheumatoid arthritis RA is quite high, which is largely due to cardiovascular complications caused by endothelial dysfunction. One of the important inflammatory mediators that contribute to AR joints arthritis of TNF , also proven to play a role in endothelial dysfunction and play a role in increasing intracellular lipolysis, thus increasing circulating FFA levels.Objectives To determine the correlation between TNF levels with VCAM 1 levels, correlation of TNF levels with FFA levels, and correlation of FFA levelswith VCAM 1 levels.Methods Cross sectional and retrospective design studies of adult AR patients treated at Cipto Mangunkusumo Hospital RSCM , without metabolic disturbances, acute infection, cardiovascular disorders, or other autoimmune diseases. The cross sectional data was collected from October to November 2017, while retrospective samples were collected since August 2016. TNF , VCAM 1, and FFA levels were assessed by serum blood test by ELISA method. Correlation analysis is done by Pearson analysis when the data distribution is normal and with Spearman analysis when the data distribution is not normal.Results A total of 35 subjects were enrolled in the study. Most 97.1 were women with an average age of 45.29 years, median duration of 48 months, and most had moderate disease status 65.7 . No correlation was found between TNF levels and VCAM 1 levels p 0.677 r 0.073 . The correlation between FFA and VCAM 1 levels showed significant correlation with negative correlation and weak correlation p 0.036 r 0.355 . The correlations between TNF levels and FFA levels had negative direction and weak correlation strength with non significant associations p 0.227 r 0.21 .Conclusions 1 There was no correlation between TNF levels and VCAM 1 levels in AR patients 2 There was no correlation between TNF levels and FFA levels in AR patients 3 There was a negative correlation between FFA levels and VCAM 1 levels in AR patients.Keywords Tumor Necrosis Factor , Free Fatty Acids, Vascular Cell Adhesion Molecule 1, Rheumatoid Arthritis."

"Latar Belakang: Hiperhidrasi menyebabkan peningkatan beban volume jantung, tekanan darah, hipertrofi ventrikel kiri, edema paru, gagal jantung kongestif. Hemodialisis yang tidak adekuat menyebabkan hiperhidrasi, peningkatan morbiditas dan mortalitas penyakit kardiovaskular. Hiperhidrasi lama menyebabkan iskemia koroner karena dilatasi jantung, hipertrofi ventrikel kiri, hipertensi, penurunan cadangan koroner. Hiperhidrasi menyebabkan vasokonstriksi sistemik berlebihan, penurunan perfusi jaringan perifer. Disfungsi endotel berperan pada vasokonstriksi yang berlebihan pada hiperhidrasi. Brain-type natriuretic peptide (BNP) merupakan parameter untuk mengukur hiperhidrasi. Asymmetrical dimethyl arginine (ADMA) merupakan inhibitor endogen, bersifat kompetitif terhadap nitric oxide synthase endotel dan digunakan sebagai parameter disfungsi endotel. Tujuan: Mengetahui hubungan hiperhidrasi dengan disfungsi endotel. Metode: Penelitian ini merupakan penelitian potong lintang pada pasien hemodialisis dua kali seminggu. Dengan menggunakan BNP dan ADMA sebagai parameter. Hasil: Dari 126 subjek, proporsi hiperhidrasi (BNP>356 pg/ml) sebesar 64,3%. Median usia 52 (47-62) dengan presumtif penyebab GGK utama adalah hipertensi (38,9%), DM (28,6%), Glomerulonefritis (21,4%). Tidak terdapat hubungan signifikan antara hiperhidrasi dengan disfungsi endotel (PR=1,042, p=0,832 IK 95%=0,714-1,521). HsCRP merupakan faktor perancu utama terhadap hubungan antara hiperhidrasi dan disfungsi endotel (OR (IK95%) 1,604 (0,551-4,666), p=0,386, ΔOR 53,37%). Simpulan: Tidak ada hubungan antara hiperhidrasi dengan disfungsi endotel (PR=1,042, p=0,832 IK95%=0,714-1,521).

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Background: Hyperhydration leads to increased cardiac volume load, blood pressure, left ventricular hypertrophy, pulmonary edema, congestive heart failure. Hemodialysis that is not adequately causes hyperhydration, increased morbidity and mortality of cardiovascular disease. Prolonged hyperhydration causes coronary ischemia due to heart dilation, left ventricular hypertrophy, hypertension, decrease in coronary reserves. Hyperhydration causes excessive systemic vasoconstriction, decreased perfusion of peripheral tissues. Endothelial dysfunction plays a role in excessive vasoconstriction pada hyperhydration. Brain-type natriuretic peptide (BNP) is a parameter for measuring hyperhydration. Asymmetrical dimethyl arginine (ADMA) is an endogenous inhibitor, competitive against endothelial nitric oxide synthase and used as a parameter of endothelial dysfunction.

Purpose: Knowing the relationship of hyperhydration with endothelial dysfunction.

Method: This study is a cross-sectional study in hemodialysis patients twice a week. By using BNP and ADMA as parameters.

Result: Of the 126 subjects, hyperhydration proportion (BNP>356 pg/ml) of 64.3%. Median age 52 (47-62) with presumptive causes of primary GGK is hypertension (38.9%), DM (28.6%), Glomerulonephritis (21.4%). There is no significant association between hyperhydration and endothelial dysfunction (PR=1,042, p=0.832 CI 95%=0.714-1.521).

Conclusion: There is no relationship between hyperhydration and endothelial dysfunction (PR=1,042, p=0.832 CI 95%=0.714-1.521)."

"Lupus eritematosus sistemik merupakan penyakit autoimun sistemik yang menghasilkan berbagai autoantibodi yang ditujukan terhadap komponen sel, seperti inti sel, sitoplasma dan membran sel. Salah satu autoantibodi tersebut yaitu antibodi anti ?2GP-1 dihubungkan dengan kejadian aterosklerosis dan penyakit kardiovaskular yang timbul lebih dini pada pasien SLE. Penelitian ini bertujuan untuk mengetahui hubungan antibodi anti ?2GP-1 dengan disfungsi endotel dan aterosklerosis pada pasien SLE dan disfungsi endotel pada HUVEC. Penelitian potong lintang pada pasien SLE yang memenuhi kriteria inklusi menurut ACR 1997 di poliklinik khusus Reumatologi, Alergi Imunologi RSCM dan poliklinik khusus Reumatologi RSUP Dr. M. Djamil dari Maret 2016 sampai dengan Juli 2017. Subjek secara acak dibagi atas 2 kelompok berdasarkan nilai CIMT. Dilakukan pemeriksaan antibodi anti ?2GP-1, ox-LDL, ADMA, ICAM-1, VCAM-1, ET-1. Dilakukan pemajanan antibodi anti ?2GP-1 yang berasal dari kelompok aterosklerosis positif dan kontrol pada HUVEC. Enam puluh enam orang subjek direkrut pada penelitian ini, terdiri atas 33 orang aterosklerosis positif dan 33 orang aterosklerosis negatif dan 6 orang kontrol dengan rentang umur 20-45 tahun. Ditemukan korelasi positif antara antibodi anti ?2GP-1 dengan CIMT,ADMA, ICAM-1, VCAM-1 dan ET-1 dengan nilai r = 0,409, 0,89, 0,36, 0,43, 0,37 dan dengan p < 0,05. Tidak ditemukan korelasi antibodi anti ?2GP-1 dengan ox-LDL dengan r = 0,025 dan p > 0,05. Ditemukan perbedaan bermakna kadar antibodi anti ?2GP-1, ADMA, ICAM-1, VCAM-1 dan ET-1 pada kelompok aterosklerosis positif dengan kelompok aterosklerosis negatif dengan nilai p < 0,05, sedangkan kadar ox-LDL tidak ada perbedaan bermakna pada kedua kelompok tersebut dengan nilai p > 0,05. Hasil pemajanan antibodi anti ?2GP-1 pada HUVEC mendapatkan perbedaan bermakna peningkatan kadar ICAM-1, VCAM-1 dan ET-1 pada kelompok SLE aterosklerosis positif dari kontrol dengan nilai p < 0,05. Antibodi anti ?2GP-1 menimbulkan disfungsi endotel pada pasien SLE.

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Systemic lupus erythematosus SLE is a multi systemic disease characterized by a wide variety of autoantibodies directed to several self molecules found in the nucleus, cytoplasm and cell membrane. One of variety autoantibodies is Antibody anti 2GP 1 which associated with atherosclerosis and premature cardiovascular disease in SLE patients. The purpose of the study is to know the association of antibody anti 2GP 1 with endothelial dysfunction and atherosclerosis in SLE and endothelial dysfunction in HUVEC. Cross sectional study was performed in SLE patients fulfill inclussion criteria according ACR 1997 out patients in Rheumatology and Alergy Immunology polyclinic of Cipto Mangunkusomo Hospital and Dr. M. Djamil Hospital from March 2016 to July 2017. Patients were divided in 2 groups based on CIMT. Examination of antibody anti 2GP 1, ox LDL, ADMA, ICAM 1, VCAM 1 and ET 1 were performed. Purified antibody anti 2GP 1 from positive atherosclerosis and controls groups were exposed to HUVEC. Sixty six patients were enrolled, consists of 33 patients with positive atherosclerosis, 33 patients with negative atherosclerosis and 6 as healthy control with range of age 20 40 year. In this study we found positive correlation between antibody anti 2GP 1 with CIMT, ADMA, ICAM 1, VCAM 1 and ET 1 with r 0.409, 0.89, 0.36, 0.43, 0.43 respectively and p value 0.05. There was no correlation between antibody anti 2GP 1 with ox LDL, r 0.025 and p 0.05. There were significantly different levels of antibody anti 2GP 1, ADMA, ICAM 1, VCAM 1 and ET 1 in positive atherosclerosis compared to negative atherosclerosis group with p 0.05. Level of ox LDL was not different between the two groups with p 0.05. There were significantly different increase of ICAM 1, VCAM 1 and ET 1 levels in HUVEC which was exposed with purified antibody anti 2GP 1 from positive atherosclerosis compared to control with p 0.05. Antibody anti 2GP 1 cause endothelial dysfunction in SLE patients. "