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Sri Bekti Subakir
"EPH Gestosis atau preeklampsia/eklampsia merupakan penyebab utama kematian ibu dan bayi. Patofisiologi dan etiologi penyakit ini belum jelas. Salah satu teori menyatakan gejala yang timbul pada preeklampsia disebabkan oleh karena kerusakan sel endotel akibat serangan radikal bebas. Kerusakan sel endotel akan menyebabkan gangguan fungsi sel endotel antara lain penurunan produksi prostasiklin dan peningkatan permeabilitas sel endotel. Pernurunan prostasiklin menyebabkan kemampuan vasodilatasi pembuluh darah berkurang sehingga terjadi peningkatan tekanan darah pada kehamilan. Peningkatan permeabilitas sel endotel yang merupakan barier antara komponen-komponen darah dengan jaringan ekstravaskuler akan menyebabkan terjadinya edema. Peningkatan permeabilitas pada kapiler glomerulus akan mengakibatkan proteinuria.
Pada wanita penderita preeklampsia, aktivitas simpatis meningkat. Perangsangan simpatis akan menyebabkan peningkatan pembuluh darah. Penurunan produksi prostasiklin dan peningkatan aktivitas simpatis mungkin dapat menjelaskan peningkatan tekanan darah pada penderita preeklampsia. Wanita yang mempunyai riwayat pernah menderita preeklampsia memberikan kenaikan tekanan darah sistolik lebih dari 20 mmHg dan diastolik > 15 mmHg pada Cold pressor test. Mungkin raja seseorang yang tonus pembuluh darahnya jenis hiperreaktor akan mempunyai kecenderungan menderita preeklampsia pada saat hamil.
Hasil sementara penelitian tahap pertama menunjukkan bahwa serum penderita preeklampsia mempunyai efek toksik terhadap sel endotel dalam kultur namun kadar peroksida lipid tidak berbeda dengan kadar pada wanita hamil normal. Mungkin kerusakan sel endotel disebabkan antioksidan pada penderita preeklampsia lebih rendah dibandingkan dengan kehamilan normal. Kerusakan sel endotel dapat dicegah dengan antioksidan. Enzim superoksida dismutase (SOD) mendekomposisikan radikal oksigen sebelum radikal tersebut membentuk radikal yang lebih toksik. Sedangkan vitamin E dapat menghambat rantai reaksi peroksidasi sehingga menghambat pembentukan lipid radikal yang lebih toksik.
Yang menjadi permasalahan dalam penelitian ini ialah apakah wanita dengan riwayat preeklampsia mempunyai tipe pembuluh darah hiper reaktor ? Apakah enzim SOD penderita preeklampsia lebih rendah dari wanita dengan kehamilan normal ? Apakah pemberian vitamin E dapat mencegah kerusakan kultur sel endotel yang terpapar serum preeklampsia. Diharapkan hasil penelitian ini dapat mengembangkan suatu upaya pencegahan EPH Gestosis (preeklampsia).
Teknik dan keterampilan laboratorium dalam penelitian ini ialah:
- pemeriksaan 'Cold pressor test'
- kultur sel endotel
- pewarnaan sel endotel
- pemeriksaan kadar SOD dalam darah"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 1996
LP-Pdf
UI - Laporan Penelitian  Universitas Indonesia Library
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Kresna Septiandy Runtuk
"Latar Belakang: Skizofrenia merupakan gangguan jiwa berat yang kompleks
dengan angka harapan hidup yang rendah karena penyakit kardiovaskular. Orang
dengan skizofrenia rentan mengalami sindroma metabolik meskipun tidak
mendapat pengobatan antipsikotika. Sebuah penelitian di RSUPN Cipto
Mangunkusumo menunjukkan prevalensi sindroma metabolik sebanyak 3,3%
sampai 68% yang berhubungan dengan stress oksidatif dan berpotensi menurunkan
produksi ATP. Penelitian ini berusaha menjelaskan patofisiologi sindroma
metabolik pada skizofrenia dan hubungannya terhadap polimorfisme gen GCLC
GAG TNR, stres oksidatif dan aktivitas metabolisme seluler.
Metode: Penelitian merupakan penelitian observasional analitik. Subjek sebanyak
25 pasien skizofrenia dan 25 pasien kontrol sehat dilakukan pengambilan fibroblas
dan PBMC kemudian dilakukan pengamatan polimorfisme gen GCLC GAG TNR,
stres oksidatif (kadar MDA, MnSOD, GSH, GSSG, dan rasio GSH/GSSG),
aktivitas metabolisme seluler (kadar ATP), dan parameter sindroma metabolik
(lingkar pinggang, Indeks Massa Tubuh (IMT), LDL-c, HDL-c, TG, HbA1C, dan
tekanan darah). Hubungan dianalisis dengan uji komparasi atau uji korelasi.
Hasil: Terdapat korelasi pada sel fibroblas dengan PBMC yaitu korelasi kuat pada
MnSOD (r=0.797) dan korelasi sedang pada GSSG (r=0.581). Didapatkan
perbedaan yang bermakna pada kadar stres oksidatif yaitu MDA (p=0.013), GSH
(p≤0.001), GSSG (p≤0.001), dan rasio GSH/GSSG (p≤0.001) pada kelompok
skizofrenia dan kontrol serta didapatkan hubungan polimorfisme gen GCLC GAG
TNR terhadap MDA (p=0.054) dan GSSG (p=0.010) pada kelompok skizofrenia
tetapi tidak ditemukan perbedaan kadar ATP dan hubungan antara polimorfisme
GCLC GAG TNR terhadap kadar ATP. Pada orang dengan skizofrenia didapatkan
lingkar pinggang, IMT, LDL-c, dan HDL-c yang lebih rendah
(p=0.025;p=0.003;p=0.022;p=0.010) dan TG yang lebih tinggi (p=0.038)
dibandingkan kelompok kontrol.
Simpulan: Polimorfisme gen GCLC GAG TNR memiliki hubungan terhadap stres
oksidatif tetapi tidak ada hubungan terhadap aktivitas metabolisme seluler. Tidak
terdapat perbedaan aktivitas metabolisme seluler pada orang dengan skizofrenia
dan tidak ditemukan hubungan antara metabolisme seluler dengan sindroma
metabolik. Terjadi perubahan kadar penanda stres oksidatif yang memiliki
hubungan terhadap sindroma metabolik pada orang dengan skizofrenia

Background: Schizophrenia is a complex severe mental disorder with low life
expectancy due to cardiovascular disease. People with schizophrenia is prone to
metabolic syndrome even if they do not receive antipsychotic. One study in Cipto
Mangunkusumo General Hospital showed the prevalence of metabolic syndrome
as much as 3.3% to 68% which correlate with oxidative stress and has the potential
to reduce ATP production. This study aims to explain the pathophysiology of the
metabolic syndrome in schizophrenia and its relationship to the GCLC GAG TNR
gene polymorphism, oxidative stress and metabolic activity.
Methods: This research is an observational analytic study. Twenty five
schizophrenic patients and 25 healthy control patients were admitted to study.
Fibroblast and PBMC (peripheral blood mononuclear cell) were taken to measure
GCLC GAG TNR gene polymorphism, oxidative stress (levels of MDA, MnSOD,
GSH, GSSG, and GSH/GSSG ratio), cellular metabolic activity (ATP levels), and
metabolic syndrome parameters (waist circumference, body mass index (BMI),
LDL-c, HDL-c, TG, HbA1C, and blood pressure). Relationship between variables
were analyzed by comparison test or correlation test.
Results: There is a correlation in fibroblast cells with PBMC with a strong
correlation in MnSOD (r=0.797) and a moderate correlation in GSSG (r=0.581).
There were significant differences in the levels of oxidative stress, namely MDA
(p=0.013), GSH (p≤0.001), GSSG (p≤0.001), and GSH/GSSG ratio (p≤0.001) in
the schizophrenia and control groups. There was correlation found for the
polymorphism of the GCLC GAG TNR gene towards MDA (p=0.054) and GSSG
(p=0.010) in the schizophrenia group but found no difference in ATP levels in the
schizophrenia and control groups alongside with GCLC GAG TNR polymorphism
and ATP levels. In people with schizophrenia, waist circumference, BMI, LDL-c,
and HDL-c were lower (p=0.025;p=0.003;p=0.022;p=0.010) and higher TG
(p=0.038) than the control group.
Conclusion: GCLC GAG TNR gene polymorphism has correlation to oxidative
stress but not to cellular metabolic activity. There is no difference in metabolic
activity in people with schizophrenia and no relationship between cellular
metabolism and the metabolic syndrome. There is alteration of oxidative stress
markers which have an association with metabolic syndrome in people with
schizophrenia.
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Depok: Fakultas Kedokteran Universitas Indonesia, 2023
SP-pdf
UI - Tugas Akhir  Universitas Indonesia Library
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Donna Adriani Kusumadewi Muhammad
"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.

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.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2015
T-Pdf
UI - Tesis Membership  Universitas Indonesia Library
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Rahayuningsih Dharma Setiabudy
"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.

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."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2005
AJ-Pdf
Artikel Jurnal  Universitas Indonesia Library
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Samuel Oetoro
"Latar belakang. Obesitas merupakan masalah kesehatan masyarakat dunia dengan prevalensi yang semakin meningkat. Obesitas meningkatan risiko sindrom metabolik dan penyakit kardiovaskular, yang diyakini akibat inflamasi dan stres oksidatif. Penurunan berat badan (BB) dengan cara diet dan olahraga merupakan strategi dasar dalam manajemen obesitas. Penyandang obesitas seringkali mengalami peningkatan dan penurunan BB yang dikenal sebagai weight cycling (WC). Penelitian menunjukkan risiko sindrom metabolik dan penyakit kardiovaskular meningkat pada WC dibandingkan dengan penyandang obesitas pemula [first encounter obesity (FEO)]. Penelitian ini bertujuan untuk menilai pengaruh program penurunan BB terhadap komposisi tubuh, petanda sindrom metabolik, petanda inflamasi dan stres oksidatif pada penyandang obesitas WC dibandingkan dengan FEO.
Metode. Penelitian ini merupakan uji klinis terbuka selama delapan minggu yang dilakukan di Balai Kota DKI Jakarta. Subyek penelitian diambil secara konsekutif dan diklasifikasikan menjadi kelompok WC dan FEO. Kedua kelompok diberikan program penurunan BB yang terdiri dari pengurangan asupan energi sebesar 1000 kkal/hari dan olah raga intensitas ringan - sedang tiga kali seminggu selama 45 menit. Pengukuran antropometri dan komposisi tubuh (BB, indeks massa tubuh/IMT, massa lemak/ML, massa bebas lemak/MBL, massa otot/MO, rating lemak viseral, intracellular water /ICW yang merupakan indikator anabolisme protein ), petanda sindrom metabolik (kadar trigliserida/TG dan LP), petanda inflamasi (high sensitivity C-reactive protein/hs-CRP, interleukin/IL-6), dan stres oksidatif (F2-isoprostan) dilakukan pada awal penelitian, minggu ke-4 dan pada akhir penelitian (minggu ke-8).
Hasil. Dari total 73 subyek (34 subyek kelompok WC dan 39 subyek kelompok FEO) didapatkan karakteristik yang setara dalam hal usia, riwayat obesitas pada keluarga, asupan makanan, proporsi komposisi makronutrien, dan aktivitas fisik, namun tidak terdapat kesetaraan dalam hal distribusi subyek laki-laki dan perempuan, riwayat lamanya obes. Kelompok WC memiliki ML yang lebih tinggi , MBL, MO dan ICW yang lebih rendah, serta petanda inflamasi yang lebih buruk dibanding kelompok FEO, sebaliknya kelompok FEO memiliki kadar TG, F2-isoprostan lebih tinggi daripada WC. Setelah intervensi diet dan olah raga selama 8 minggu, penurunan BB, IMT, ML, MBL, MO, rating lemak viseral dan kadar ICW pada kelompok WC cenderung lebih rendah daripada kelompok FEO (p >0,05). Penurunan LP pada kelompok WC cenderung lebih rendah daripada kelompok FEO (p = 0,23). Kadar TG pada kelompok WC meningkat, sedangkan pada kelompok FEO terjadi penurunan kadar TG, namun perbedaannya tidak bermakna (p = 0,055). Penurunan kadar hs-CRP dan IL-6 pada kelompok WC cenderung lebih besar daripada FEO (p >0,05). Penurunan kadar F2-isoprostan lebih tinggi pada kelompok FEO daripada kelompok WC (p = 0,017).
Kesimpulan: Penyandang obesitas WC memiliki ML yang lebih tinggi dari FEO, disamping itu memiliki anabolisme protein yang lebih rendah, oleh karena itu program diet dan olahraga pada WC harus mempertimbangkan modalitas yang mampu meningkatkan anabolisme protein.Penyandang WC memiliki petanda inflamasi yang lebih buruk dibanding FEO, sedangkan setelah menjalani program diet dan olahraga selama 8 minggu pada penelitian ini tidak didapatkan perbedaan perubahan BB, komposisi tubuh, petanda sindrom metabolik, dan petanda inflamasi, kecuali perubahan petanda stres oksidatif yang lebih baik pada penyandang FEO.

Background. The worldwide prevalance obesity is increasing rapidly and has become serious health burden globally. Obesity increases risks of metabolic syndrome and cardiovascular diseases which may partly caused by inflammation and oxidative stress. Effective weight loss programs include diet and exercise,and these interventions are considered as first line strategy of obesity management. Obese individuals often experience repeated cycles of weight loss followed by weight regain, which is recognized as weight cycling (WC). Several studies demonstrated that weight cycler has higher risk of metabolic syndrome and cardiovascular diseases than individuals with first encounter obesity (FEO). This study aimed to assess the effect of weight loss programs using diet and exercise on body composition, selected markers of metabolic syndrome, inflammation, and oxidative stress in obese subjects with WC and FEO.
Methods.This study was an 8-week open clinical trial held at Balai Kota DKI Jakarta. Subjects were recruited consecutively and classified into WC and FEO groups. All subjects were assigned to receive weight loss programs with the following goals: 1,000 Kcal reduction of total energy intake/day and 45-minute mild-to-moderate intensity exercise, three times a week. Antropometric and body composition (body weight/BW, body mass index/BMI, fat mass, fat free mass, muscle mass, visceral fat rating, intracellular water/ICW as indicator of protein anabolism), markers of metabolic syndrome (triglyceride/TG levels and waist circumference), inflammation (high sensitivity C-reactive protein/hs-CRP, interleukin/IL-6), and oxidative stress(F2-isoprostane)were measured at baseline, week 4, and the end of study (week 8).
Results. A total of 73 subjects consisting of 34 subjects with WC (WC group) and 39 subjects with FEO (FEO group). Both groups had similar characteristics in age, family history of obesity, dietary intakes, macronutrient composition, and physical activities; meanwhile, gender and duration of obesity were significantly different between groups. WC group had more body fat, less fat free mass, muscle mass and ICW, higher markers of inflammation than FEO group. On the other hand, TG and F2-isoprostane levels in FEO group were higher than WC group. Following 8-week intervention with diet and exercise, the reduction in BW, BMI, fat free mass, muscle mass, visceral fat rating, and ICW in WC group was comparable with FEO group (p>0.05). The reduction of waist circumference in WC group tended to be lower than FEO group (p = 0.23). Triglyceride levels in WC group increased, but it declined in FEO group. However, these differences were not statistically significant(p= 0.055). The decline in hs-CRP and IL-6 levels in WC group tended to be higher than FEO group (p>0.05). Meanwhile, the decrease in F2-isoprostane levels in FEO group was significantly higher than WC group (p=0.017).
Conclusion.Obese subjects with WC had more body fat but lower protein anabolic capacity than those with FEO. These results suggest that diet and exercise program for weight cycler should consider effective ways to enhance protein anabolism.In addition, obese subjects with WC had higher inflammatory process than those with FEO.Using the current model of 8-week intervention with diet and exercise, this study was not able to demonstrate differences between WC and FEO groupsin the magnitude of changes in body composition and inflammation indicators, except oxidative stress indicator.
"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2014
D-Pdf
UI - Disertasi Membership  Universitas Indonesia Library
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Idrus Alwi
"Diabetes mellitus (DM) is one of the public health problems worldwide, including in Indonesia. Cardiovascular disease was the main cause of death (75-80%) in DM, three-fourths of this death was caused by coronary heart disease (CHD). Approximately 34.2% of patients with acute coronary syndrome (ACS) receiving care at ICCU of Dr. Cipto Mangunkusumo General Hospital (RSCM) suffered from DM. Mortality rates of ACS in DM patients were still high and ACS prognosis in DM patients were still unfavorable. There are many factors playing a part in atherosclerosis and ACS incidence in DM patients, such as metabolic disorders due to hyperglycemia and the fomration of advanced glycation end product (AGE), oxidative stress, atherogenic dyslipidemia in DM in the form of high triglyceride level and low HDL cholesterol as well as an increase in small dense LDL, and insulin resistance. In addition, other risk factors of CHD frequently encountered with DM were hypertension, obesity, thrombocytc hyperaggregation and hypercoagulation. The management ofthis disease which was based on the control of risk factors was not yet satisfactory.
Inflammatory response played an important role in pathogenesis of atherosclerosis, beginning with early lesion up to acute coronary syndrome. Increase in inflammatory responses (hsCRP) could predict cardiovascular event and predict post-ACS prognosis. Studies in DM population showed an increase in inflammation. ln-depth studies on inflammatory responses in ACS DM patients have not yet been reported. In normal condition, there was a balance of proinflammatory and antiinflammatory cytokines. The ratio of proinflammatory and antiinflammatory cytokines in ACS, particularly DM patients has not been studied. The relationship between metabolic factor (blood glucose, glyco Hb and lipid) and inflammatory response in ACS DM patients has not yet also been studied.
Currently, the effort to decrease inflammatory response is made, among others, by aspirin, statin hypolipidemic medication and insulin sensitizer. Although aspirin and statin were used routinely in ACS patients and have proved to reduce inflammation, morbidity and mortality rates of ACS patients were still high. Thus, we would like to observe whether an addition of other medications in standard therapy could reduce inflammation better. Curcumin in experimental animals-and humans) showed -hypolipidemic effect (decrease 'in absorption and increase in catabolism) and hypoglycemia (effect on PPAR-7). Curcumin also demonstrated antiinflammatory effect. In this study we would like to observe the effects of curcumin on both metabolic factors and inflammatory responses in ACS patients.
PROBLEM IDENTIFICATION
The above elaboration showed a discrepancy associated with inflammatory response in DM ACS patients. Up to now, the relationship of metabolic factor and inflammatory response in DM ACS has not been clear yet. Likewise, the effects of curcumin on metabolic factor and inflammatory response in ACS have not yet been identified.
OBJECTIVES
To evaluate inflammatory responses in DM ACS and its relationship with metabolic factors (glucose, blood; glyco Hb, total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride); to evaluate the ratio of proinflammatory and antiinflammatory cytokines (IL-6/IL-10) in ACS DM patients, and to identify the effects of curcumin on metabolic factors and inflammatory responses in ACS patients.
SETTING
The study was conducted at ICCU of RSCM, ICCU of Persahabatan, ICCU of RS MMC and ICCU of Medistra Hospital, Cardiology Polyclinic, Department of Internal Medicine, Faculty of Medicine University of Indonesia! RSCM and Integrated Cardiac Service Poiyclinic of RSCM.
STUDY SUBJECTS
ACS patients (DM and non-DM) and CHD (DM and non-DM).
DESIGN
There were two studies: l. Observational design to observe inflammatory responses (hscRP, IL-6, IL-IO, VCAM and ICAM) in DM ACS, non-DM ACS, DM CI-ID, and non-DM CHD; to evaluate the relationship between metabolic factors (fasting blood glucose, blood glucose 2 hours PP, glyco Hb, total cholesterol, LDL cholesterol, HDI.. cholesterol and triglyceride) and inflammatory responses (hsCRP, IL-6, IL-10, VCAM and ICAM) in ACS DM. 2. Interventional study which was a double-blind randomized trial to evaluate the effects of curcumin at escalating doses (low dose 3:-:IS mglday, moderate dose 3x30 mg/day and high dose 3x60 mg/day on metabolic factors (fasting blood glucose. blood glucose 2 hours PP and glyco Hb) and the effects of curcumin at escalating doses on inflammatory responses (hsCRP, ll.-6, VCAM and ICAM) in ACS patients.
RESULTS
In observational study, |46 subjects were analyzed, consisting of 84 ACS patients, (30 DM ACS patients and 54 non-DM ACS), and 62 CHD (25 DM CHD patients and 37 non-DM CHD patients). The results of the study in the four groups of patients showed: 1. Inflammatory response in DM ACS was higher than in DM CHD (hsCRP, p=0.00; II..-6, p=0.00; IL-10, p=0.00) and non-DM ACS (ICAM, P=0.03). 2. The ratio of proinflammatory and antiinflammatory cytokines (IL-6/II..-10) in DM ACS did not differ from that of DM CHD (p=0.2l) and non-DM ACS (p=0.5 l). 3. There was a relationship between metabolic factors and inflammatory responses in DM ACS: triglyceride and ll.-6 (r=O.39, p=0.03) and II..-I0 (r=0.37, p=o.o4).
In interventional study we performed randomization in 75 ACS patients divided into four groups, consisting of low-dose curcumin group of 15 patients, moderate-dose curcumin group of 15 patients, high-dose curcumin group of IS patients, and placebo group of 30 patients. The results of the study in these four groups showed: l. Low-dose curcumin showed a decrease in hsCRP in one week ofthe first month after intervention, there was a significant difference liom that of placebo (p=0.04). Low-dose, moderate-dose, high-dose curcumin groups showed a decrease in IL-6, but was not significantly different from placebo. Low-dose, moderate-dose, high-dose curcumin did not show a decrease in VCAM and ICAM after intervention of 2 months. 2. Low-dose curcumin group tended to experience a decrease in glyco Hb level after intervention of 2 months (p=0.06); however, it was not significantly different from that of placebo. 3. There was a tendency that low-dose curcumin reduced total cholesterol and LDI. cholesterol; however, it was not significantly different from that of placebo. There was a tendency that low-dose curcumin increased HDL cholesterol; however, it was not significantly different from that of placebo. 4. There was a tendency that the pattern of escalating doses had some effects in inflammatory responses and metabolic factors, in which low-dose curcumin showed the best effects, followed by moderate-dose and finally high- dose curcumin.
CONCLUSIONS
In this study, inflammatory responses in DM ACS patients were higher than those in DM CHD and non-DM ACS patients. There was no difference in the ratio of proinflammatory and antiinflammatory cytokines (IL-6fIL-IO) in DM ACS compared with DM CHD and non-DM ACS. ln addition, the present study identified some of the relationships between metabolic factors and inflammatory responses. Low-dose curcumin reduced hsCRP in one week of the first month after the intervention in ACS patients. There was a tendency that low-dose curcumin reduced glyco Hb level in ACS."
Depok: Universitas Indonesia, 2006
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Nurul Paramita
"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.

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."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2024
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Christina Olly Lada
"Latar Belakang : Stunting pada anak usia di bawah dua tahun (U2) menggambarkan kekurangan nutrisi kronis dengan berbagai faktor predisposisi dan prevalensinya masih tinggi di Indonesia. Kurang nutrisi kronis menyebabkan tubuh berdaptasi pada ukuran dan fungsi organ, yang berdampak meningkatnya risiko kardiometabolik (RKM) kemudian hari. Tujuan penelitian ini membuktikan perbedaan faktor predisposisi intrauterin (FPIntra), ekstrauterin (FPEkstra), stres oksidatif (SO), adaptasi metabolik (AM) dan RKM pada anak stunting (AnS) dan tidak stunting (AnTS) usia 6-24 bulan (U6-24).
Metode : Penelitian nested -kohort, cross-sectional komparatif digunakan untuk menilai peran FPIntra, yaitu antropometri ibu sebelum hamil, asupan dan status gizi ibu hamil, berat lahir (BL) dan panjang lahir (PL) subjek, FPEkstra yaitu ASI eksklusif, berat badan (BB) dan panjang badan (PB) enam bulan pertama (U6I), antropometri anak, asupan gizi AnS dan AnTS U6-24. Indikator SO yaitu kadar MDA serum. Indikator AM yaitu ekspresi microRNA -148a. Indikator RKM yaitu ukuran lingkar pinggang (LP), kadar kolesterol-LDL, kolesterol-HDL, trigliserida, dan glukosa darah. Semua subjek merupakan peserta TKA, Bogor dan pengambilan data dilakukan sejak bulan Juli 2017 hingga Februari 2018, dilaksanakan di Rumah Kohort TKA, Bogor. Analisis statistik univariat, bivariat dan multivariat digunakan untuk membandingkan kelompok AnS dan AnTS dengan batas kemaknaan p <0,05.
Hasil : Sebanyak 38 AnS dan 46 AnTS U6-24 memenuhi kriteria penelitian dan didapatkan FPIntra AnS lebih rendah secara bermakna dibanding AnTS, yaitu kategori kadar seng serum ibu hamil, tinggi badan ibu, BL dan PL subjek (p = 0,047, p < 0,001, p = 0,009, p = 0,025). Asupan mangan (p= 0,007), isoleusin (p =0,015), pertambahan BB U6-I (p =0,002), rerata pertambahan BB/bulan U6-I (p =0,002), pertambahan PB U6-I (p <0,001), rerata pertambahan PB/bulan U6-I (p <0,001) dan kadar Hb anak (p =0,005) lebih rendah secara bermakna pada AnS, sementara RDW-CV lebih tinggi pada AnS (p =0,009). Tidak ditemukan perbedaan SO pada kedua kelompok, tetapi gambaran adanya AM pada usia dini terlihat pada normalized expression ratio microRNA -148a AnS sebesar 2,6 kali lebih cepat dibandingkan dengan AnTS, yang mengakibatkan kolesteol-LDL di sirkulasi lebih tinggi pada AnS. Ditemukan dua indikator RKM berbeda bermakna yaitu ukuran LP AnS lebih kecil bermakna, namun kadar trigliseridanya lebih tinggi pada AnS. Kadar kolesterol-LDL cenderung lebih tinggi pada AnS.
Kesimpulan : FPIntra dan FPEkstra terbukti memberikan dampak terhadap kejadian stunting anak U6-24. Adaptasi metabolik dan RKM pada AnS sudah terdeteksi pada U6-24.
Saran : Penting untuk memantau status gizi ibu sebelum hamil dan memberikan intervensi nutrisi dalam 1000 hari awal kehidupan untuk mengurangi RKM di kemudian hari.

Background : Stunting children under two years of age (U2) illustrates chronic nutritional deficiency with various predisposing factors and the prevalence is still high in Indonesia. Chronic malnutrition causes the body to adapt organ size and function, which results in increased cardio metabolic risk (CMR) in adulthood The aim of this study was to prove differences in intrauterine predisposition (PFIntra), extra uterine (PFExtra), oxidative stress (OxS), metabolic adaptation (MetAdapt) and CMR in stunting children (StC) and non stunting children (NStC) aged 6-24 months (U6-24).
Methods : A nested-cohort, comparative cross-sectional study was used to assess the role of PFIntra, namely maternal anthropometry before pregnancy, nutrition intake and nutritional status of pregnant women, birth weight (BW) and birth length (BL) of subjects, PFExtra namely exclusive breastfeeding, weight and body length in the first six months (U6I), pediatric anthropometry and nutritional intake in StC and NStC U6- 24. Indicator of OxS was serum MDA level. MetAdapt indicator was microRNA-148a expression. The CMR indicators were waist circumference (WC), LDL-cholesterol levels, HDL-cholesterol, triglycerides, and blood glucose. All subjects were participants in Bogor Longitudinal Study Child Growth and Development (BLSCGD), in Bogor Tengah sub-district. Univariate, bivariate and multivariate statistical analyzes were used to compare StC and NStC groups with significant p value <0.05.
Results : There were 38 StC and 46 NStC U6- 24 fulfilled the study criteria and obtained significantly lower PFIntra in StC compare to NStC, namely the serum zinc level category of pregnant women, maternal height, BW and BL subjects (p = 0.047, p <0.001, p = 0.009, p = 0.025). Manganese intake (p = 0.007), isoleucine intake (p = 0.015), increase in weight U6-I (p = 0.002), weight gain per month U6-I (p = 0.002), increase in length U6-I (p <0.001), length increase per month U6-I (p <0.001) and Hb levels of children (p = 0.005) were significantly lower in StC, while RDW-CV was higher in StC (p = 0.009). There were no significant differences in OxS between two groups, but MetAdapt at an early age was seen in the StC as show in normalized expression ratio of microRNA-148a was 2.6 times faster than NStC, which resulted in higher circulation of LDL in StC. Two of five CMR indicators were significantly different, namely the size of WC in StC was significantly smaller, but the triglyceride level was higher in StC. LDL-cholesterol levels tend to be higher in StC.
Conclusion : PFIntra and PFExtra proved to have an impact on the incidence of stunting children U6- 24. Metabolic adaptation and CMR in StC have been detected in U6- 24.
Suggestion: It is important to monitor the nutritional status of the mother before pregnant and provide nutritional interventions within the first 1000 days of life to reduce cardio metabolic risk in the future."
Depok: Universitas Indonesia, 2018
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Gitalisa Andayani
"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.

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."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2018
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