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"Tujuan: Mengetahui pengaruh fotokoagulasi laser terhadap kadar Hypoxia-inducible Factor-1α (HIF-1α) vitreus dan kadar Intercellular Adhesive Molecule-1 (ICAM-1) vitreus pada Retinopati Diabetik Proliferatif. Metode: Penelitian ini adalah uji klinis acak terbuka. Desain penelitian adalah uji klinis acak terbuka. Dua puluh dua mata dirandomisasi menjadi 2 kelompok, yaitu yang mendapatkan fotokoagulasi laser panretinal 1-2 minggu pre-vitrektomi dan kontrol. Kadar HIF-1α dan ICAM-1 dihitung menggunakan enzyme-linked immunosorbent assay (ELISA). Central macula thickness (CMT) diukur saat baseline, pre-vitrektomi, follow-up 2, 4, dan 12 minggu paska vitrektomi. Hasil: Analisis hasil didapatkan rerata kadar HIF-1α vitreus (dalam ng/mL) pada kelompok kontrol dan fotokoagulasi laser masing-masing 0,152±0,015 dan 0,164±0,033 sedangkan kadar ICAM-1 vitreus(dalam ng/mL) adalah 17,840±14,140 dan 27,027±10,452. Tidak terdapat perbedaan bermakna rerata kadar HIF-1α dan ICAM-1 vitreus serta CMT di setiap waktu follow up antara kedua kelompok. Terdapat korelasi antara kadar HIF-1α dan HbA1c (r=0,463, p=0,03). Pengukuran CMT pre-vitrektomi dan kadar HIF-1α vitreus pada penelitian ini mempunyai korelasi positif pada kedua kelompok (r = 0,447 dan r = 0,32). Simpulan: Fotokoagulasi laser 1-2 minggu pre-vitrektomi tidak menyebabkan kadar HIF-1α dan ICAM-1 yang lebih rendah dibandingkan dengan yang tidak mendapatkan laser. Kadar HIF-1α vitreus berkorelasi dengan tebalnya CMT, sedangkan kadar ICAM-1 vitreus tampak tidak berhubungan. Kontrol glikemik yang lebih buruk pada kelompok fotokoagulasi laser mempengaruhi hasil dari kadar HIF-1α maupun ICAM-1 vitreus.

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Purpose: to determine the effect of pre-treatment of laser panretinal photocoagulation (PRP) before vitrectomy to Hypoxia-inducible Factor-1α (HIF-1α) and Intercellular Adhesive Molecule-1 (ICAM-1) in the vitreous fluid of patients with diabetic retinopathy proliferative.

Methods: This is post-test only randomized clinical trial open label study. Twenty two eyes were recruited, and 11 eyes had pre-treatment of PRP pre-vitrectomy and other 11 eyes were served as control. HIF-1α and ICAM-1 were measured by enzyme-linked immunosorbent assay (ELISA). At the beginning of PRP and just before vitrectomy (1-2 week after PRP), and at the time of follow-up of 2,4, and 12 week after vitrectomy, central macular thickness (CMT) was measured.

Results: Mean of HIF-1α(ng/mL) were 0,152±0,015 and 0,164±0,033in control and photocoagulation group, respectively. Mean of ICAM-1(ng/mL) were 17,840±14,140 and 27,027±10,452. There were no statistically significant differences in the comparison of both HIF-1α and ICAM-1 in each group and CMT at each time of follow up. The positive correlation between ICAM-1 in the vitreous body and HbA1c was clinically significant (r=0,463, p=0,03). The positive correlation between both level of HIF-Iα the vitreous body of both groups and CMT was found (r = 0,447 dan r = 0,32).

Conclusion: Laser photocoagulation 1-2 weeks before vitrectomy did not cause lower concentration of vitreous level of HIF-1α dan ICAM-1. Glycemic control status that worse in laser photocoagulation group could influence the level of HIF-1α and ICAM-1 vitreus."

"Tujuan: menilai kadar Hypoxia-inducible Factor-1? HIF-1? dan Intercellular Adhesion Molecule-1 ICAM-1 vitreus pada retinopati diabetik proliferatif yang diberikan bevacizumab intravitreal, serta hubungan keduanya terhadap ketebalan makula sentral previtrektomi. Metode: tiga puluh dua mata dirandomisasi menjadi 2 kelompok, yaitu yang mendapatkan suntikan bevacizumab intravitreal 1-2 minggu previtrektomi dan kelompok kontrol langsung dilakukan vitrektomi . Penghitungan kadar HIF-1? dan ICAM-1 dilakukan dengan metode enzyme-linked immunosorbent assay ELISA . Ketebalan makula sentral diukur saat awal, previtrektomi, serta 2, 4, dan 12 minggu pascavitrektomi dengan menggunakan Stratus OCT. Hasil: rerata kadar HIF-1? vitreus dalam ng/mg protein pada kelompok kontrol dan bevacizumab intravitreal masing-masing 0,020 0,006;0,077 dan 0,029 0,016;0,21 . Kadar ICAM-1 vitreus dalam ng/mL adalah 20,10 3,41;40,16 dan 23,33 0,63;68,5 . Rerata kadar HIF-1? dan ICAM-1 vitreus didapatkan tidak berbeda bermakna antara kedua kelompok. Simpulan: bevacizumab intravitreal 1-2 minggu previtrektomi belum dapat membuat kadar HIF-1? lebih rendah daripada kelompok kontrol. Kadar ICAM-1 kelompok bevacizumab didapatkan lebih tinggi pada kelompok kontrol. Tidak didapatkan hubungan yang bermakna antara ketebalan makula sentral previtrektomi terhadap kadar HIF-1? dan ICAM-1.

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Purpose: To assess the levels of Hypoxia inducible factor 1 HIF 1 and intercellular adhesion molecule 1 ICAM 1 in vitreous of proliferative diabetic retinopathy patients which were given intravitreal bevacizumab IVB, as well as its relation to the central macular thickness CMT measured prior to vitrectomy.

Method: This was post test only randomized clinical trial open label, in which thirty two eyes were randomized into two groups, one that received an IVB injection at 1 2 weeks previtrectomy and the control group. Measurement of HIF 1 and ICAM 1 was conducted using enzyme linked immunosorbent assay ELISA. The CMT were measured at the initial visit, prior to vitrectomy, and at follow up time 2, 4, and 12 weeks postoperative using Stratus OCT.

Result: The mean levels of HIF 1 vitreous ng mg protein in the control group and IVB respectively 0.020 0.006 0.077 and 0.029 0.016 0.21 . Vitreous levels of ICAM 1 ng mL in control group and IVB group were 20.10 3.41 40.16 and 23.33 0.63 68.5. The mean levels of HIF 1 and ICAM 1 vitreous obtained did not differ significantly between the two groups.

Conclusion: Intravitreal bevacizumab 1 2 weeks prior to vitrectomy was not enough to make the levels of HIF 1 lower in IVB group. Median of ICAM 1 level in IVB group was higher than control group. There were no correlation between CMT with HIF 1 and ICAM 1 levels."

"Latar Belakang: Stres oksidatif merupakan salah satu faktor patogenesis terjadinya retinopati diabetik (RD). Fotokoagulasi laser dan anti-VEGF bermanfaat pada penanganan RD. Keberhasilan terapi dan prognosis dapat dilakukan melalui penilaian klinis dan penanda biologis stres oksidatif. Tujuan: Penelitian ini bertujuan membandingkan pengaruh fotokoagulasi laser dan bevacizumab intravitreal (BIV) terhadap penanda biologis stres oksidatif, antara lain aktivitas ALDH plasma, kadar VEGF, MDA dan aktivitas SOD vitreus pada penyandang RD proliferatif. Metode: Penelitian ini adalah penelitian prospektif dengan desain uji klinis acak tersamar tunggal. Sebanyak 72 mata dari 69 penyandang RD proliferatif di Rumah Sakit Cipto Mangunkusumo (RSCM) antara Februari 2011 ? Juni 2013 dirandomisasi menjadi 4 kelompok terdiri dari kelompok 1) kontrol yaitu kelompok langsung vitrektomi sesuai indikasi (n = 18), 2) kelompok yang mendapat fotokoagulasi laser pre-vitrektomi (n = 18), 3) kelompok yang mendapat BIV pre-vitrektomi(n = 18) dan 4) kelompok yang mendapat kombinasi BIV dan fotokoagulasi laser previtrektomi (n = 18). Hasil: Hasil penelitian ini mendapatkan bahwa pada kelompok 1, 2, 3 dan 4 masingmasing rerata aktivitas ALDH plasma (IU/mg protein) (0,034+0,02; 0,027+0,02; 0,025+0,02; 0,031+0,1; p = 0,66), kadar MDA vitreus (nmol/mL) (1,661+1,21; 1,557+1,32; 1,717+1,54; 1,501+1,09; p = 0,96), dan aktivitas SOD (U/mL) (0,403+0,50; 0,210+0,18; 0,399+0,49; 0,273+0,32 p = 0,38) dan tidak terdapat perbedaan bermakna, sedangkan perbandingan rerata kadar VEGF vitreus (pg/mL) (0,356+0,60; 0,393+0,45; 0,150+0,24; 0,069+0,13; p = 0,05) menunjukkan perbedaan yang bermakna. Kadar VEGF kelompok kombinasi BIV dengan fotokoagulasi laser lima kali lebih rendah dibandingkan dengan kelompok kontrol. Simpulan: Kombinasi BIV dan fotokoagulasi laser tidak berpengaruh terhadap aktivitas ALDH plasma dan SOD vitreus, namun berpengaruh terhadap kadar MDA dan VEGF vitreus penyandang RD proliferatif. Kombinasi BIV dengan fotokoagulasi laser perlu dilakukan pada RD proliferatif. Pengukuran ALDH plasma dapat digunakan sebagai faktor prognostik untuk perubahan CMT dan visus.

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Background: Diabetic Retinopathy (DR) is retinal vascular complications in patients with diabetes mellitus (DM). Oxidative stress plays a major role in the pathogenesis of this disease. The current management of DR includes laser photocoagulation (LF) and administration of anti-VEGF, such as intravitreal bevacizumab (IVB). Clinical parameters are usually applied in determining the outcomes of these methods of therapies. However, the measurement of biomarkers of oxidative stress can possibly be used to determine the prognosis.

Purpose: This study was aimed to compare the effect of LF, IVB and combined treatments on biomarkers of oxidative stress such as plasma ALDH and vitreal SOD activities, and vitreal VEGF and MDA level on proliferative DR patients.

Methods: In this single blind randomized clinical trial, 72 eyes from 69 cases of proliferative DR in Cipto Mangunkusumo Hospital (RSCM) between February 2011 - June 2013 were randomized into 4 groups : 1) control group (n = 18), 2) LF previtrectomy group (n = 18), 3) IVB pre-vitrectomy group (n = 18) and 4) combined IVB and LF pre-vitrectomy group (n = 18). In all groups, the biomarkers of oxidative stress were measured as the primary outcome and visual acuity and CMT as secondary outcome.

Results: There were no statistically significant differences in the comparison of the average plasma ALDH activity (IU/mg protein) (0.034+0.02; 0.027+0.02; 0.025+0.02; 0.031+0.1; p = 0.66), vitreal MDA level (nmol/mL) (1.661+1.21; 1.557+1.32; 1.717+1.54; 1.501+1.09; p = 0.96) and SOD activity (U/mL) (0.403+0.50; 0.210+0.18; 0.399+0.49; 0.273+0.32 p = 0.38) among these four groups, respectively. However, the average of vitreal VEGF level (pg/mL) among these 4 group showed a statistically significant difference (0.356+0.60; 0.393+0.45; 0.150+0.24; 0.069+0.13; p = 0.05), with the level of vitreal VEGF in the combined group was 5 times lower than control.

Conclusion: Combined treatments of DR by IVB and LF does not have any effect on the activities of plasma ALDH and vitreal SOD. However, these combined treatments were correlated with lower vitreal MDA and VEGF level, higher SOD activity and lower VEGF level in proliferative DR. Combined treatments with IVB and LF are recommended for the management of proliferative DR patients. The measurement of plasma ALDH can be used as a prognostic factor for determining the visual acuity and CMT."

"Latar Belakang: Faktor transkripsi Hypoxia inducible factor-1 (HIF-1 merupakanpengatur utama hipoksia, termasuk menyebabkan penekanan sistem perbaikan deoxyribose nucleic acid (DNA), sehingga menghasilkan instabilitas genetik pada sel kanker. Varian genetik HIF-1α C1772T (P582S) dan G1790A (A588T) dipercaya mempunyai aktivitas transkripsi yang lebih tinggi.Peranan polimorfisme HIF-1α ini sudah diteliti pada beberapa jenis kanker seperti kanker ginjal, payudara, ovarium, tetapi belum ada penelitian pada kanker paru. Metode: Polimorfisme HIF-1α diperiksa dengan menggunakan direct sequencing dengan total sampel 83 pasien kanker paru (42 adenokarsinoma, 30 skuamous sel karsinoma, empat adenoskuamous sel karsinoma dan tujuh kanker paru karsinoma sel kecil (KPKSK) dan 110 subjek sehat sebagai kontrol. Hubungan polimorfisme HIF-1α dengan kelainan genetik/epigentik loss of heterozygot (LOH) TP53, LOH 1p34, LOH retinoblastoma-1 (RB1), inaktivasi p16 dan kelainan epidermal growth factor receptor (EGFR) kemudian diperiksa. Hasil: Frekuensi polimorfisme HIF-1α pada kanker paru dan kontrol telah sesuai dengan keseimbangan Hardy-Weinberg. Pada penelitian ini tidak ditemukan perbedaan frekuensi genotipe C1772T atau G1790A antara kanker paru dengan kontrol sehat. Tetapi, frekuensi varian HIF1A C1772T ditemukan tinggi bermakna di pasien kanker paru dengan LOH TP53 (p=0,015). Pada pasien adenokarsinoma, individu dengan varian alel memiliki frekuensi tinggi LOH TP53 (p=0,047), LOH 1p34 (p=0,009) atau keduanya (LOH TP53 dan LOH 1p34) (p=0,008). Aktivitas transkripsi juga diperiksa secara in vitro dan ditemukan HIF1A varian pada sel kanker paru A549 mempunyai aktivitas yang meningkat secara bermakna dibanding wild type HI1F1A baik di kondisi normoksia atau hipoksia, terutama P582A di sel dengan mutan p53 (p< 0,0005 dan p< 0,005). Kesimpulan: Penelitian ini mengindikasikan polimorfisme gen HIF-1α mempunyai peranan penting dalam karsinogenesis paru terutama pada adenokarsinoma, diduga melalui peningkatan instabilitas genetik.

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Background and objective: The transcription factor, hypoxia-inducible factor-1 (HIF-1), is a master regulator of hypoxia, including repression of DNA repair systems, resulting in genomic instability in cancer cells. The roles of the polymorphic HIF-1a variants, C1772T (P582S) and G1790A (A588T), which are known to enhance transcriptional activity, were evaluated in lung cancers.

Methods: HIF-1a polymorphisms were assessed by direct sequencing in a total of 83 lung cancer patients (42 adenocarcinomas, 30 squamous cell, four adenosquamous cell and seven small cell lung carcinomas) and in 110 healthy control subjects. The relationship between these polymorphisms and the frequently observed genetic and/or epigenetic aberrations, TP53 loss of heterozygosity (LOH), 1p34 LOH, retinoblastoma-1 (RB1) LOH, p16 inactivation and epidermal growth factor receptor aberrations, was then assessed.

Results: There were no significant differences in genotype frequencies for either C1772T or G1790A between lung cancer patients and healthy controls. However, the frequency of the HIF1A C1772T variant allele was significantly higher in lung cancer patients with TP53 LOH (P = 0.015). Among adenocarcinoma patients, individuals with variant alleles of either polymorphism showed significantly higher frequencies of TP53 LOH (P = 0.047), 1p34 LOH (P = 0.009), or either of these (P = 0.008) in the tumours. The in vitro transcriptional activity of these HIF1A variants in A549 lung cancer cells was significantly greater than that of the wild type under either normoxic or hypoxic conditions, especially for P582S in cells containing mutant p53 (P < 0.0005 and P < 0.005, respectively).

Conclusions: These findings indicate that functional polymorphisms in the HIF-1a gene may have an important impact on lung carcinogenesis, especially in adenocarcinomas, possibly by increasing genomic instability."

"Tujuan: Untuk mengetahui pengaruh suplementasi pycnogenol 150 mg perhari selama 8 minggu terhadap amplitudo dan waktu implisit pada gelombang b dan oscillatory potential (OP) ERG skotopik retinopati diabetik nonproliferatif ringan dan sedang.Metode: Uji klinik acak tersamar. Empat puluh subjek dengan retinopati diabetik nonproliferatif ringan sedang diacak dan dibagi menjadi dua kelompok, 20 subjek mendapat pycnogenol, 20 subjek mendapat pycnogenol. Pengukuran objektif dilakukan sebelum pemberian suplementasi dan 8 minggu setelahnya, yang meliputi amplitudo gel.b, waktu implisit gel.b, amplitudo sum OP, waktu implisit sum OP .Hasil: Pada kelompok pycnogenol sebelum perlakuan, amp gel.b 397,9±109,6μV, waktu implisit gel.b 48,7 (44,3-68,2) ms, amp sum OP 193,05 (15,2-498,9) μV dan waktu implisit sum OP 126,18± 7,8ms. Setelah 8 minggu pada kelompok pycnogenol, amp gel.b 396,2±115,7 μV, waktu implisit gel.b 47,8 (43,4-58,4)ms, amp sum OP 228,45 (16,3-511,8) μV dan waktu implisit sum OP 126,2 (118,2-137) ms. Pada kelompok plasebo sebelum intervensi, amp gel.b 349± 79 μV, waktu implisit gel.b 48,7 (44,3-68,2) ms, amp sum OP 101,45 (28,3-301,2) μV dan waktu implisit sum OP 130 (121,6-163,5) ms. Setelah 8 minggu pada kelompok plasebo, amp gel.b 334,65±70,3 μV, waktu implisit gel.b 49,15 (44,3 -68,2) ms, amp sum OP 124,9 (51,3-303,8)μV dan waktu implisit sum OP 130 (121,6-163,5) ms. Tidak terdapat perbedaan bermakna secara statistik pada semua keluaran.Kesimpulan: Tidak terdapat perbedaan yang bermakna secara statistik parameter amplitudo gel.b, waktu implisit gel.b, amplitudo sum OP, waktu implisit sum OP dari pemberian pycnogenol 150 mg sehari selama 8 minggu pada retinopati diabetik nonproliferatif ringan sedang.

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Objective: This study is to evaluate the effect of eight weeks supplementation of 150 mg pycnogenol, to b-wave amplitude, b-wave implicit time, sum Oscillatory Potential (OP) amplitude and sum Oscillatory Potential (OP) implicit time on Electroretinography (ERG) result of mild - moderate nonproliferative diabetic retinopathy (NPDR) patient, compared to plasebo.Methods: Randomized clinical trial of 40 mild - moderate NPDR patients, which further equally divided into two groups. The b-wave amplitude (amp), b-wave implicite time (it), sum OP amplitude (amp), sum OP implicit time (it) ERG were evaluated before and after eight weeks pycnogenol supplementationResults:The ERG results of pycnogenol group before intervention were as follows: b wave amp 397,9±109,6μV, b-wave it 48,7 (44,3-68,2) ms, sum OP amp 193,05 (15,2-498,9) μV and sum OP it 126,18± 7,8ms. After 8 weeks in pycnogenol group, b wave amp 396,2±115,7 μV, b wave it 47,8 (43,4-58,4)ms, sum OP amp 228,45 (16,3-511,8) μV and sum OP it 126,2 (118,2-137) ms. Meanwhile in placebo group before intervention, the b wave amp was 349± 79 μV, b-wave it 48,7 (44,3-68,2) ms, sum OP amp 101,45 (28,3-301,2) μV and sum OP it 130,8±8,4 ms. After 8 weeks in placebo group, b wave amp 334,65±70,3 μV, b-wave it 49,15 (44,3 -68,2) ms, sum OP amp 124,9 (51,3-303,8)μV and sum OP it 130 (121,6-163,5) ms. No statistical significant differences in all outcomeConclusions: No significant differences in b-wave amplitude, b-wave implicite time, sum OP amplitude and sum OP implicit time ERG after 150 mg pycnogenol supplementation for 8 weeks in mild-moderate NPDR compare with placebo."

"Tujuan: Studi ini bertujuan untuk mengetahui efektivitas fotokoagulasi laser 810 nm durasi 20 ms dan 100 ms dalam mencegah progresivitas PDR. Metode: Penelitian ini adalah uji klinis acak tersamar ganda. Sebanyak 28 subyek yang memenuhi kriteria inklusi dibagi menjadi dua kelompok yang terdiri atas 14 subyek untuk menjalani fotokoagulasi laser 810 nm. Pada kelompok pertama mendapatkan laser dengan durasi 20 ms dan kelompok kedua dengan durasi 100 ms. Lesi derajat 3 dengan spot sized 200 μm diaplikasikan pada kedua kelompok. Penilaian progresivitas PDR dilakukan setelah 2 bulan pasca laser dengan menggunakan foto fundus 7 posisi. Fluence, power dan tajam penglihatan dibandingkan di antara kelompok. Hasil: Sebanyak 25 pasien yang mengikuti follow up selama 2 bulan. Proporsi neovaskularisasi yang tidak progresif pada kelompok 20 ms dan 100 ms sebesar 76,9% dan 75,0% (p=1,000). Power yang dibutuhkan dua kali lebih tinggi pada kelompok 20 ms (1000 vs 500 mW; p=0,000). Rerata fluence pada kelompok durasi 20 ms lebih rendah dua kali dibandingkan kelompok durasi 100 ms (15,91 vs 6,36 J/cm2; p=0,000). Perbaikan visus pasca laser pada kelompok 20 ms dan 100 ms sebesar 23,1% dan 33,3 % (p=1,000). Kesimpulan: Durasi 20 ms memiliki kemampuan mencegah progresivitas neovaskularisasi yang sama dibandingkan dengan durasi 100 ms. Fluence yang dibutuhkan lebih rendah pada durasi 20 ms.

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Aim: The aim of this study was to compare the effectiveness of laser photocoagulation 810-nm with 20 ms and 100 ms duration to prevent the progression of proliferative diabetic retinopathy.

Method: This study was prospective double blind randomized clinical trial. Twenty-eight participants who met the inclusion criteria divided into two groups to undergo laser photocoagulation by using 810 nm lasers. One group consisted of fourteen subjects received 100 ms duration and the other received 20 ms duration. Grade 3 burns with a 200 μm spot sized were placed with both modalities. The progression of PDR was evaluated in two months follow up by using seven fields fundus photographs. Fluence, power and visual acuity were compared in this study.

Result: Twenty five subjects completed the two months follow up. Nonprogressive PDR in 100 ms group was 75.0% and in 20 ms was 76.9% (p=1.000). The median power in 20 ms group increased twice than 100 ms group (1000 vs. 500 mW; p=0.000). The median fluence in 20 ms group reduced to one-half of 100 ms group (6.36 vs. 15.91 J/cm2; p=0,000). Improvement of visual acuity in 20 ms and 100 ms was comparable (23,1% vs. 33,3%; p=1,000).

Conclusion: The 20 ms duration showed similar result in preventing the progression of PDR compared to 100 ms duration. The fluence was lower in 20 ms group."

"Latar Belakang: DM merupakan salah satu penyebab morbiditas dan mortalitas tertinggi di dunia, dengan 15-25% pasien akan berkomplikasi menjadi DFU. Data pada tahun 2003 di RSCM menunjukkan bahwa angka kematian akibat DFU adalah 16% dan angka amputasi mencapai 25%. Hingga saat ini belum terdapat strategi tatalaksana DFU yang efektif karena patogenesis molekular yang menyebabkan kegagalan penyembuhan luka masih belum sepenuhnya dipahami. Selain itu pengendalian kadar glukosa darah dalam pengobatan DFU masih belum jelas dan menjadi perdebatan dalam berbagai studi.Tujuan: Penelitian ini bertujuan untuk menganalisis hubungan HbA1c dan GDS dengan faktor angiogenesis HIF-1α, sehingga dapat dijadikan dasar dalam melakukan tata laksana yang tepat untuk pasien DFU.Metode: Desain penelitian potong lintang. Subjek penelitian pasien DFU yang berobat ke RSCM, diambil data dasar (jenis kelamin dan usia), pemeriksaan klinis (TB, BB, dan IMT), pemeriksaan laboratorium (GDS, HbA1c). HIF-1α diperiksa dari sampel biopsi jaringan luka DFU saat operasi debridemen dan amputasi dengan pemeriksaan ELISA. Data dilakukan uji normalitas Saphiro-Wilk dan uji normalitas Kolmogorov Smirnov, dilanjutkan uji korelasi Spearman. Pengaruh variabel perancu dianalisa dengan uji mann whitney dan tes regresi linear sederhana.Hasil: Terdapat 64 pasien yang memenuhi kriteria inklusi dan dilakukan pemeriksaan kadar HiF1α dari sampel jaringan biopsi. Data karakteristik didapatkan hasil kelompok dominan perempuan (54.7%) dengan usia rerata 55.7 ± 10.4 tahun, IMT median 24.9 kg/m² (overweight 48.2%, obesitas 34.6%), dan komorbid anemia (84.3%). Karakteristik laboratorium, GDS median 220 (14-705)mg/dL dengan kelompok kondisi hiperglikemik >200 mg/dL sebanyak 54.7%. HbA1c median 7.7(4.1-13.7)% dengan kelompok kontrol gula darah buruk HbA1c >6.5% sebanyak 85.8%. Tidak didapatkan korelasi bermakna antara GDS dengan HIF-1α p 0.523(p>0.05). Tidak didapatkan korelasi yang bermakna antara HbA1c dengan HIF-1α p 0.792(p>0.05). Didapatkan variable perancu yang bermakna pada kondisi derajat luka DFU p 0.03 (p< 0,05).Kesimpulan: Hasil penelitian ini menunjukkan bahwa baik HbA1c atau GDS tidak mempunyai hubungan yang bermakna dengan kadar HiF-1α. Variabel perancu kondisi derajat luka DFU berpengaruh secara signifikan terhadap ekspresi HIF-1α

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Background: DM is one of the leading causes of morbidity and mortality in the world, with 15-25% of patients developing complications of DFU. Results data in 2003 at the RSCM showed that the mortality rate from DFU was 16% and the amputation rate was 25%. There is no effective DFU management strategy because the molecular pathogenesis that causes wound healing failure is still not fully understood. In addition, the control of blood glucose levels in the treatment of DFU is still unclear and has been debated in various studies.

Objective: This study aims to analyze the relationship between HbA1c and GDS with the angiogenesis factor HIF-1α, so that it can be used as a basis for appropriate management of DFU patients.

Methods: The research design was cross sectional. Body mass index, comorbid disease status were recorded. The laboratory parameters GDS, HbA1c and HiF-1a expression examined in the laboratory. Test the normality data by the Saphiro-Wilk test and the Kolmogorov Smirnov test, followed by the Spearman correlation test. The effect of confounding variables was analyzed by Mann Whitney test and simple linear regression test.

Results: There were 64 patients who met the inclusion criteria and were examined for HiF1α levels from biopsy tissue samples. Characteristic data showed that the dominant group was female (54.7%) with a mean age of 55.7 ± 10.4 years, median BMI 24.9 kg/m² (overweight 48.2%, obesity 34.6%), and comorbid anemia (84.3%). Laboratory characteristics, the median GDS of 220 (14-705)mg/dL with the hyperglycemic condition group >200 mg/dL as much as 54.7%. The median HbA1c was 7.7(4.1-13.7)% with the bad blood sugar control group HbA1c >6.5% as much as 85.8%. There was no significant correlation between GDS and HIF-1α p 0.523 (p>0.05). There was no significant correlation between HbA1c and HIF-1α p 0.792 (p>0.05). A significant confounding variable was found in the condition of the degree of wound DFU p 0.03 (p < 0.05).

Conclusion:The results of this study showed that neither HbA1c nor GDS had a significant correlation with HiF-1α . The confounding variable of DFU wound degree had a significant effect on the expression of HIF-1α"

"Kobalt klorida dapat digunakan sebagai senyawa yang dapat menimbulkan kondisi mimikri hipoksia tanpa kadar rendah oksigen di dalam tubuh, dan menstabilkan hypoxia inducible factor-1α. Kami memutuskan untuk mengobservasi apakah terdapat regulasi ekspresi renin oleh HIF-1α. Dengan demikian kami menyelenggarakan beberapa penelitian untuk memastikan kemungkinan dan memulai dengan penelitian induksi tikus secara intraperitoneal kobalt klorida (CoCl2) untuk membangkitkan kondisi mimikri hipoksia dan mendapatkan konsentrasi dan pola ekspresi HIF-1α dan mRNA.Metode: Dua puluh empat ekor tikus dibagi menjadi 4 grup: kontrol, 2, 8, dan 24 jam inkubasi pasca injeksi intraperitoneal 30 mg/kg berat badan CoCl2. Setelah tikus dikorbankan, organ ginjal digunakan untuk pemeriksaan parameter berat ginjal, kadar RNA, kadar protein HIF-1α (ELISA) dan mRNA renin (RT-PCR). Hasil: Hasil menunjukkan bahwa terdapat perbedaan rasio berat ginjal/berat badan tikus, namun secara statistik tidak bermakna (p > 0,05). Secara statistik tidak terdapat perbedaan bermakna kadar protein HIF-1α antar kelompok (p > 0,05). Ekspresi relatif mRNA renin meningkat tajam (30 x kontrol), mulai pada 8 jam inkubasi pasca induksi intraperitoneal CoCl2 dan terus meningkat sampai inkubasi 24 jam (2465 x kontrol). Korelasi antara protein HIF-1α dan ekpresi relatif mRNA renin menggunakan analisis Pearson menunjukkan positif kuat (R = 0,91) (p = 0,09). Kesimpulan: Terdapat kemungkinan yang besar bahwa gen renin diregulasi oleh HIF-1α.

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Background: Cobalt chloride can be used as an agent to stabilize hypoxia inducible factor-1α (HIF-1α) and to imitate hypoxia without low levels of oxygen inside the body. We intended to investigate if there was any regulation of renin expression by HIF-1α. Therefore, we conducted several studies to clarify this possibility starting with the induction of hypoxic mimicry in rats by intra-peritoneal (IP) injection of cobalt chloride (CoCl2) to obtain the levels and pattern of HIF-1α and renin mRNA and protein expression.

Methods: Twenty-four rats were randomly divided into four groups, control group and incubation groups 2, 8, and 24 hours after intra-peritoneal injection of 30 mg CoCl2 per kg BW. After the rats were sacrificed, kidneys were excised, weighed and kidney weight compared to BW. Tissue parameters were measured such as RNA concentration, HIF-1α protein by ELISA, and renin mRNA by RT-PCR.

Results: Differences between the groups in the ratios of kidney weight to BW and in the concentrations of HIF-1α protein were statistically not significant (p > 0.05). Relative expression of renin mRNA increased markedly starting 8 hours after CoCl2 IP injection (30 times over controls) and further rising until 24 hours (2465 times over controls). Correlation between HIF-1α and renin mRNA by Pearson analysis was strongly positive, but not significant (R = 0.91; p = 0.09).

Conclusion: Renin gene regulation in renal hypoxic mimicry strongly correlates with HIF-1α"

"ABSTRAKTujuan tesis ini adalah mengetahui pengaruh suplementasi sitikolin 1000 mg per hari selama 4 minggu terhadap hasil elektroretinografi pada pasien NPDR non-proliferative diabetic retinopathy . Desain penelitian ini adalah uji klinis acak terkontrol tersamar ganda. Tiga puluh delapan mata yang memenuhi kriteria inklusi dan eksklusi dirandomisasi untuk masuk ke dalam kelompok plasebo P-NPDR atau sitikolin 1000 mg S-NPDR . Pada akhir penelitian didapatkan 18 mata pada kelompok sitikolin dan 16 mata pada kelompok plasebo. Keluaran primer penelitian ini adalah nilai amplitudo P50 dan N95 PERG within group dan intergroup yang dinilai pada baseline dan 4 minggu paska pemberian intervensi. Analisis hasil didapatkan pada S-NPDR didapatkan perbaikan nilai rerata amplitudo N95 sebelum terapi, 4.85 1.9-10.3 V, dan setelah terapi, 5.7 1.9-17.1 V, P = 0.04 . Terdapat kecenderungan perbaikan amplitudo P50 yang lebih baik pada kelompok T-NPDR dan perbaikan amplitudo N95 yang lebih baik pada S-NPDR yang tidak bermakna secara statistik P = 0.45; P = 0.35.

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ABSTRACT

The purpose of this study was to determine the effect of citicoline 1000 mg oral supplementation given for 4 weeks on electroretinography abnormalities in patients with NPDR non proliferative diabetic retinopathy . The study design was a double blind randomized controlled clinical trial. Thirty eight patients who matched the inclusion and exclusion criteria were randomized into two groups the plasebo P NPDR and citicoline C NPDR . In the end, there were 18 eyes in citicoline group and 16 eyes in plasebo group. The primary outcome was P50 and N95 amplitude in PERG within group and intergroup which were taken at the baseline and 4 weeks after treatment. Results at the end of treatment, the N95 amplitude in C NPDR showed improvement, 4.85 1.9 10.3 V, before treatment to 5.7 1.9 17.1 V, after treatment with P 0.04. In P NPDR showed positive trend in P50 amplitude while in C NPDR showed positive trend in N95 amplitude, but these values were not statistically significant P 0.45 P 0.35."

"Pendahuluan: Penelitian dilakukan untuk mengetahui peran senyawa flavonoid mangiferin dalam meningkatkan ekspresi mRNA HIF-1α dan sebagai pencekal besi dalam menstabilkan HIF-1α pada lini sel HepG2 dan menganalisis interaksi mangiferin dengan prolil hidroksilase (PHD2) secara simulasi docking.Metode: Sel HepG2 dikultur hingga >80% konfluen dan selanjutnya diberikan mangiferin konsentrasi 25-200μM. Kuersetin digunakan sebagai pembanding flavonoid mangiferin yang bekerja di dalam inti sel, sedangkan DFO dan CuCl2 digunakan sebagai pembanding daya ikat terhadap besi. Ekspresi mRNA HIF-1α ditentukan dengan real time RT- PCR/q-PCR, dan stabilisasi protein HIF-1α ditentukan mengunakan teknik ELISA. Simulasi docking dilakukan terhadap protein PHD2 dengan mangiferin, CuCl2, deferoksamin (DFO), dan campuran mangiferin+ kuersetin.Hasil: Uji viabilitas sel menggunakan metode MTS dengan pemberian mangiferin, kuersetin, campuran mangiferin-kuersetin, DFO dan CuCl2 (25-200μM) memperlihatkan hasil diatas 85%. Ekspresi mRNA HIF-1α dengan mangiferin, kuersetin, mangiferin+kuersetin, dan DFO menunjukkan hasil sedikit lebih tinggi dibanding kontrol. Konsentrasi protein HIF-1α pada pemberian mangiferin, kuersetin, mangiferin-kuersetin, DFO dan CuCl2 lebih tinggi dibanding kontrol. Simulasi docking mangiferin terhadap PHD2 memperlihatkan ΔG= -16,22, dan DFO menunjukkan ΔG= -17,15. Terdapat interaksi antara mangiferin, dan DFO dengan besi dan asam amino pada situs katalitik domain PHD2, sedangkan CuCl2 tidak berinteraksi dengan residu asam amino pada domain PHD2, tetapi langsung menggantikan Fe. Efek penghambatan terhadap PHD2 oleh mangiferin dan kuersetin disebabkan oleh delokalisasi elektron melalui kompleks transfer elektron.Kesimpulan: Mangiferin dapat meningkatkan ekspresi mRNA HIF-1α dan meningkatkan protein HIF-1α, menurun protein PHD2 dan menurunkan protein HO-HIF-1α pada lini sel HepG2 secara in vitro. Analisis docking terdapat interaksi antara mangiferin, dan DFO dengan besi dan asam amino PHD2. Mangiferin memiliki stabilitas pengkikatan dengan besi yang berdekatan dengan DFO.

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Introduction: This research was conducted to determine the role of flavanoid mangiferin to increase expression HIF-1α mRNA, and as an iron chelator to stabilize protein HIF-1α in cell line HepG2 and analyzes the interaction of mangiferin with prolil hidroksilase (PHD2) by docking simulation.

Methods: HepG2 cells were cultured and treated by mangiferin with concentration between 25-200μM. Quercetin is used as a comparison mangiferin flavonoid that works in the nucleus and DFO, CuCl2 is used as a comparison to iron-binding. HIF- 1α mRNA expression was determined by real time RT-PCR/q-PCR, and the stability HIF-1α protein were measured by the increase in HIF-1α protein, decreased PHD2 protein and decreased HO-HIF-1α using ELISA. Docking simulation was conducted between PHD2 protein and mangiferin, CuCl2, desferoxamine (DFO), and quercetin.

Results: Cell viability with MTS assay showed that cell exposure with 25μM-200μM concentrations of mangiferin, quercetin, mangiferin+quercetin mixture, DFO, and CuCl2 is above 85%. HIF-1α mRNA expression was slightly higher than in controls with mangiferin, quercetin, mangiferin quercetin mixture and DFO. HIF-1α protein concentration and ratios vs untreated controls were above 1 with mangiferin, quercetin, mangiferin quercetin mixture, DFO, and CuCl2. Docking simulation mangiferin with PHD2 showed ΔG= -16,22. Docking simulation with DFO showed ΔG= -17,15, and interact mangiferin, and DFO with iron in the catalytic site of PHD2 and with amino acid residues, whereas CuCl2 does not react with amino acid residues in the PHD2 domain, but directly replaces Fe. The inhibitory effect to PHD2 by mangiferin and quercetin is considered by electron delocalisation through an electron transfer complex.

Conclusion: Mangiferin can increase HIF-1α mRNA expression and HIF-1α protein levels in HepG2 cell line by in vitro. Binding interaction with iron and PHD2 amino acids occurs by mangiferin and DFO. Mangiferin has stability iron binding a similar with DFO."