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"Latar Belakang: ECP mampu menurunkan frekuensi angina, meningkatkan kualitas hidup, serta memperbaiki exercise–induced ischemia time. Manfaat tersebut dapat bertahan beberapa tahun setelah ECP. Mekanisme manfaat jangka panjang ECP tersebut telah dibuktikan akibat adanya angiogenesis yang diduga diperankan VEGF-A, VEGFR-2, dan miR-92a.Tujuan: Mengetahui efek ECP terhadap VEGF-A dan VEGFR-2, serta hubungannya dengan miR-92a pada pasien angina refrakter.Metode: Studi ini merupakan uji klinis acak tersamar ganda yang melibatkan 50 subjek dengan angina refrakter. Subjek dirandomisasi (1:1) ke dalam kelompok terapi ECP atau sham, yang masing-masing dilakukan selama 1 jam, hingga 35 kali. Kadar VEGF-A, VEGFR-2, dan miR-92a plasma diukur sebelum dan sesudah terapi menggunakan metode enzyme-linked immunosorbent assay (ELISA) untuk VEGF-A dan VEGFR-2, serta quantitative reverse transcription-polymerase chain reaction (qRT-PCR) untuk miR-92a. Keluaran klinis sekunder seperti derajat angina, kualitas hidup, 6-minutes walk test (6MWT), dan ejection fraction (EF) juga dinilai.Hasil: Kadar VEGF-A dan VEGFR-2 dipertahankan pada kelompok ECP, sedangkan kadar VEGF-A dan VEGFR-2 mengalami penurunan yang signifikan pada kelompok sham [ΔVEGF-A ECP vs sham: 1 (-139 to160) vs -136 (-237 to 67) pg/ml, p = 0.026; ΔVEGFR-2 ECP vs sham: -171(-844 to +1166) vs -517(-1549 to +1407) pg/ml, p = 0.021, respectively]. Kadar miR-92a meningkat secara signifikan pada kelompok ECP [5.1 (4.2 – 6.4) to 5.9 (4.8 – 6.4), p<0.001] and sham [5.2 (4.1 – 9.4) to 5.6 (4.8 – 6.3), p=0.008]. Tidak terdapat korelasi antara perubahan kadar VEGF-A, VEGFR-2, dan miR-92a [VEGF-A vs VEGFR-2 (r = 0.243, p = 0.09; uji Spearman), VEGF-A vs miR92-a (r = 0.229, p = 0.11; uji Spearman), dan VEGR-2 vs miR92-a (r = 0.08, p = 0.581; uji Spearman)].Kesimpulan: ECP mampu mempertahankan angiogenesis dengan cara mempertahankan kadar VEGF-A dan VEGFR-2. Pada kondisi iskemia, baik high shear stress (ECP) maupun low shear stress (sham) dapat menginduksi pelepasan miR-92a. ECP mempengaruhi VEGF-A, VEGFR-2, dan miR-92a secara independen.

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Background: ECP is able to reduce angina frequency, improve quality of life, and improve exercise time-induced ischemia time. These benefits can last several years after the ECP. The mechanism for the long-term benefit of ECP has been proven by the presence of angiogenesis, which is thought to be mediated by VEGF-A, VEGFR-2, and miR-92a.

Objective: To determine the effect of ECP on VEGF-A and VEGFR-2, and its relationship with miR-92a in patients with refractory angina.

Methods: This study was a double-blind randomized clinical trial involving 50 subjects with refractory angina. Subjects were randomized (1:1) into either ECP or sham therapy groups, each administered for 1 hour, up to 35 times. Plasma VEGF-A, VEGFR-2, and miR-92a levels were measured before and after therapy using the enzyme-linked immunosorbent assay (ELISA) method for VEGF-A and VEGFR-2, as well as quantitative reverse transcription-polymerase chain reaction (qRT-PCR). ) for miR-92a. Secondary clinical outcomes such as degree of angina, quality of life, 6-minute walk test (6MWT), and ejection fraction (EF) were also assessed.

Results: VEGF-A and VEGFR-2 levels are maintained in the ECP group, while VEGF-A and VEGFR-2 levels decrease in the sham group [ΔVEGF-A ECP vs sham: 1 (-139 to160) vs -136 (-237 to 67) pg/ml, p = 0.026; VEGFR-2 ECP vs sham: -171(-844 to +1166) vs -517(-1549 to +1407) pg/ml, p = 0.021, respectively]. MiR-92a levels increase significantly in the ECP group [5.1 (4.2 – 6.4) to 5.9 (4.8 – 6.4), p<0.001] and sham [5.2 (4.1 – 9.4) to 5.6 (4.8 – 6.3), p=0.008]. There is no correlation between changes in VEGF-A, VEGFR-2, and miR-92a levels [VEGF-A vs VEGFR-2 (r = 0.243, p = 0.09; Spearman's test), VEGF-A vs miR92-a (r = 0.229 , p = 0.11; Spearman's test), and VEGR-2 vs. miR92-a (r = 0.08, p = 0.581; Spearman's test)].

Conclusion: ECP therapy is able to maintain angiogenesis by maintaining VEGF-A and VEGFR-2 levels. In ischemic conditions, both high shear stress (ECP) and low shear stress (sham) can induce the release of miR-92a. ECP affects VEGF-A, VEGFR-2, and miR-92a independently."

"Latar Belakang : External counterpulsation (ECP) ditunjukkan dapat mengurangi gejala angina dan memperbaiki kualitas hidup pasien penyakit jantung koroner (PJK) dengan angina refrakter. Efek protektif jangka panjang ini dipikirkan merupakan efek dari peningkatan pulsatile shear stress pada endotel vaskular sehingga terjadi perbaikan pada fungsi endotel. Dalam proses ini, sekelompok miRNA berfungsi meregulasi ekspresi gen dan dipengaruhi oleh shear stress, diantaranya adalah miR-92a yang bersifat proatherosklerosis. Tujuan : Mengetahui pengaruh ECP terhadap kadar miR-92a di plasma pada pasien PJK dengan angina refrakter. Metode : Sebanyak 50 pasien PJK dan angina refrakter direkrut dan diacak ke salah satu dari kelompok terapi ECP atau sham (1:1), dan menjalani 35 sesi yang berdurasi 1 jam tiap sesi. Terapi sham serupa dengan terapi ECP namun memberikan tekanan yang jauh lebih rendah. Level miR-92a di sirkulasi diukur di plasma darah sebelum dan sesudah selesai seluruh terapi, kemudian besar perubahan pada kedua kelompok dibandingkan. Hubungan antara keluaran klinis seperti keluhan angina, kapasitas fisik dan ejection fraction (EF) ventrikel kiri dengan kadar miR-92a juga dinilai.Hasil : miR-92a di plasma meningkat bermakna pada kelompok ECP [+5.1 (+4.2 s.d +6.4) menjadi +5.9 (+4.8 s.d +6.4), p value <0.001] dan sham [+5.2 (+4.1 s.d +9.4) menjadi +5.6 (+4.8 s.d +6.3), p value 0.008]. Besar perubahan dan fold changes cenderung lebih besar pada kelompok ECP namun tidak berbeda bermakna secara statistik dibandingkan kelompok sham. Kadar miR-92a post intervensi berkorelasi signifikan dengan rasio diastolik/sistolik selama terapi dan perbaikan EF pasca intervensi. Selain itu, perubahan miR-92a berkorelasi positif dengan perbaikan kapasitas fisik.

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Background : Noninvasive modality External counterpulsation (ECP) can improve angina frequency and exercise capacity in refractory angina (RA) patients. The long term benefit is thought to be the result of increase in shear stress on vascular endothelial cells resulting in improvement of endothelial dysfunction. In this process, a group of miRNA regulating gene expression in relation to shear stress is called flow-sensitive miRNA, among them is miR-92a. Aim : To evaluate ECP effect on plasma miR-92a level in RA patients. Method : Fifty subjects with RA were enrolled and randomized to either one of ECP or sham therapy (1:1 randomization). Each therapy session was one hour, for a total of 35 sessions. As a control, sham gave same sensation as ECP but with lower pressure. Plasma miR-92a level was measured before and after therapy and delta changes was compared between group. Secondary clinical outcome such as angina class, physical capacity and left ventricle Ejection Fraction (EF) were also measured and correlated with miR-92a level.

Result : Plasma miR-92a level increased in both treatment groups [in ECP group +5.1 (+4.2 to +6.4) to +5.9 (+4.8 to +6.4), p value <0.001, in sham group +5.2 (4.+1 to 9.4) to +5.6 (+4.8 to +6.3), p value =0.008]. There was higher delta increase and fold changes in ECP group, however the difference did not reach statistically significant. miR-92a level post intervention correlated significantly with Diastolic/Systolic ratio during intervention and improvement in ejection fraction (EF) post intervention. Moreover, changes in miR- 92a correlated positively with improvement in physical capacity. Conclusion : ECP did not cause significant different increase of miR-92a compared to sham."

"ABSTRAKLatar belakang: External Counter Pulsation (ECP) dapat diaplikasikan sebagai pilihan terapi pada pasien dengan angina refrakter yang tidak adekuat dikendalikan dengan terapi medis, angioplasti perkutan (IPK) ataupun bedah pintas arteri koroner (BPAK). Hasil bervariasi masih diperoleh pada perbaikan fraksi ejeksi ventrikel kiri pada pasien yang menjalani ECP. Metode 2D-Speckle Tracking Echocardiography (2D-STE) dianggap lebih unggul menilai perbaikan klinis, namun hingga kini belum ada penelitian yang mengevaluasi mekanikal ventrikel kiri dengan menggunakan 2D-STE pada pasien yang menjalani protokol standar ECP (35 sesi).Tujuan: Mengetahui perubahan mekanik ventrikel kiri sesudah dilakukan 35 protokol standar ECP dibandingkan dengan kontrol/sham pada pasien angina refrakter yang tidak ideal menjalani revaskularisasi konvensional (IPK/BPAK).Metode: Pasien dengan angina refrakter yang tidak dapat dilakukan revaskularisasi lebih lanjut secara konvensional (IPK/BPAK) dirandomisasi menjadi 2 kelompok: kelompok terapi standar ECP (300 mmHg) dan kelompok placebo/sham (75 mmHg). Terapi standar ECP diberikan selama 35 sesi, durasi 1 jam/hari/sesi, selama 5 hari/minggu, selama 7 minggu. Data 2D-STE mencakup strain longitudinal dan post systolic index (PSI) diambil sebelum dan sesudah terapi (dengan double-blind).Hasil: Terdapat 46 subjek ikut serta dalam penelitian dan tidak ada subjek yang mengalami drop-out. Tiga pasien dieksklusi karena kualitas ekokardiografi sub-optimal. Dua puluh dua subjek disertakan dalam Grup Terapi ECP dan 21 subjek dalam Grup Kontrol (sham). Karakteristik dasar strain homogen sebelum dilakukan perlakuan baik secara global (Grup Terapi 12,42±4,55 vs Grup Sham 12,00±4,92; p 0,774) maupun secara segmental/regional (Grup Terapi 12,63 (0,01-25,16) vs Grup Sham 12,43 (0,01-27,20); p 0,570). Setelah perlakuan tidak didapatkan perbedaan bermakna secara statistik antar kelompok pada parameter mekanik ventrikel kiri baik secara global (p 0,535) maupun regional (p 0,434). Parameter PSI mengalami perbaikan pada grup Terapi (p 0,049) dan segmen dengan PSI≥20% cenderung mengalami perbaikan strain longitudinal pada grup Terapi dibanding grup Sham (p 0,042).Kesimpulan: Terapi ECP sebanyak 35 sesi tidak memberikan perbaikan mekanik ventrikel kiri secara global maupun regional/segmental pada pasien angina refrakter yang tidak ideal menjalani revaskularisasi konvensional (IPK/BPAK) dibanding sham.

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ABSTRACTBackground: External Counterpulsation (ECP) can be applied as a therapeutic option in patients with debilitating refractory angina inadequately controlled by medical therapy, percutaneous angioplasty (PCI), or coronary artery bypass surgery (CABG). Varied results are still obtained in the improvement of the left ventricular ejection fraction in patients undergoing ECP. The 2D-Speckle Tracking Echocardiography (2D-STE) method is considered superior in assessing clinical improvement, but there has been no study evaluating mechanical parameters of the left ventricle using 2D-STE in patients undergoing the standard ECP protocol (35 sessions).Objective: To determine the effect of ECP on left ventricular mechanical parameters changes after performing 35 ECP standard protocols compared with sham (control) in patients with refractory angina who are not ideal for conventional revascularization (PCI/CABG).Methods: We conducted a double-blind randomized control trial. Patients with refractory angina who could not be further revascularized conventionally (PCI/CABG) were randomized into 2 groups: the ECP group (300 mmHg) and the Sham group (75 mmHg). ECP standard therapy was given for 35 sessions, duration of 1 hour/day/session, for 5 days/week, for 7 weeks. 2D-STE data including strain and post systolic index (PSI) were obtained before and after therapy.Results: There were 46 subjects included in the study without any drop-out. Three patients were excluded due to suboptimal echocardiographic images. Twenty-two subjects were included in the ECP group and 21 subjects into the sham group. A homogenous baseline strain was found either globally (ECP group 12.42 ± 4.55 vs Sham group 12.00±4.92; P=0.774) or segmentally/regionally (ECP group 12.63 (0.01-25.16) vs the Sham group 12.43 (0.01-27.20); P=0.570). After treatment, there was no statistically significant improvement between groups in the mechanical function of the left ventricle both globally (P=0.535) or regionally/segmentally (P=0.434). There were improvements in the PSI parameters found in the ECP group (P=0.049) and segments with PSI ≥20% tended to improve longitudinal strains in the Therapy group compared to the Sham group (p 0.042).Conclusion: 35 sessions of ECP therapy did not improve the global nor regional/segmental left ventricular mechanical parameters in patients with refractory angina who were not ideally suited for conventional revascularization (PCI/CABG) compared to Sham."

"Inflammatory response in the acute phase of ischemic stroke will trigger the process of neuroplasticity and determine the clinical outcomes. Angiogenesis and neurogenesis are induced by expression of vascular endothelial growth factor (VEGF) in the acute phase of stroke. The purpose of this study was to determine the association between VEGF serum level in acute of stroke with the clinical outcomes. This longitudinal cohort study was conducted on 64 patients suffering from first-attack of anterior circulation blockage as evidenced by cephalic diffusion-weighted magnetic resonance imaging (DWI). VEGF serum level was measured at 72 hours and 7 days after stroke and the clinical outcomes were assessed on day 30 post-stroke using the National Institutes of Health Stroke Scale ( NIHSS). VEGF level at hour-72 and on day-7 were 5.84+-0.736 ng/mL and 5.797 +-0.96 ng/mL, respectively (p>0.05). High VEGF levels at hour-72 can be used to predict poor clinical outcome 30 days after stroke (OR=6.5; 95% CI = 1.15-36.61 ; p=0.034). Subjects who have increasing levels of VEGF on day-7 compared to hour-72 tend to have better clinical outcomes on day-30 (NIHSS score =1.33 +-1.22 vs 3+-3.78; p=0.232). VEGF levels in the acute phase of ischemic stroke reflect the degree of brain damage, the dynamic of the increase in VEGF levels after a stroke was associated with better clinical outcomes."

"Latar Belakang: Ulkus diabetik merupakan komplikasi diabetes melitus yang menjadi salah satu masalah utama di bidang kesehatan. Di Indonesia, angka mortalitas ulkus diabetik mencapai 17-30%, dengan laju amputasi sekitar 15-30%. Pemberian terapi oksigen hiperbarik (TOHB) dapat meningkatkan oksigenasi endotel dan merangsang produksi vascular endothelial growth factor (VEGF) yang merupakan faktor pertumbuhan paling spesifik dan poten untuk proses angiogenesis sehingga dapat mempercepat proses penyembuhan luka. Tujuan: Penelitian ini bertujuan untuk mengetahui apakah TOHB berpengaruh terhadap peningkatan kadar VEGF pasien ulkus diabetik. Metode: Dilakukan penelitian uji ktinis eksperimental dari bulan Februari 2006 sampai April 2006 terhadap 12 pasien ulkus diabetik yang mendapat TOHB 3 X 30 menit per hari selama 5 hari (kelompok TOHB) dan 10 pasien ulkus diabetik yang tidak mendapat TOHB (kelompok non-TOHB, kelompok kontrol). Kadar VEGF pada kedua kelompok diukur pada hari pertama dan hari kelima. Hasil: Pada kelompok TOHB kadar VEGF hari pertama menunjukkan nilai rerata 1241,325 + 237,6533 pg/ml dan setelah 5 hari nilat rerata menjadi 1244,458 + 264,5641 pg/ml, (p = 0,583). Sedangkan pada kelompok non-TOHB kadar VEGF hari pertama menunjukkan nilai rerata 1262,350 + 227,9603 pg/ml kemudian pada hari ke-5 nilai rerata menjadi 1112,460 + 220,3795 pg/ml, (p = 0,093). Tidak didapatkan perbedaan yang bermakna nilai rerata kadar VEGF antara kelompok TOHB dan kelompok nonTOHB pada hari pertama (p= 1) maupun hari kelima (p = 0,872). Kesimpulan: Terapi oksigen hiperbarik selama 5 hari tidak meningkatkan kadar VEGF pada pasien ulkus diabetik.

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Background: Diabetic ulcer is a complication of diabetes mellitus which one of the main health problem. In Indonesia the mortality rate of diabetic ulcer is about 17-30%, while the amputation rate is about 15-30%. Hyperbaric oxygen therapy (TOHB) increase endothelial oxygenation and stimulates vascular endothelial growth factor (VEGF) as the most specific and potent growth factor for angiogenesis and increases wound heating process.

Aim of the study: The aim of the study is to know if TOHB can increase the level of VEGF in diabetic ulcer patients.

Methods: Clinical experimental study was conducted from February 2006 until April 2006 of 12 diabetic ulcer patients who received TOHB 30 minutes, 3 times a day for 5 days (TOHB group) and 10 diabetic ulcer patients as a control group who did not receive TOHB (non-TOHB group). The VEGF level in both groups was measured on days 1 and 5.

Results: In TOHB group the mean level of VEGF on day 1 was 1241.325 + 237.6533 pg/ml and became 1244.458 + 264.5641 pg/ml (p = 0.583) on day 5, while in non-TOHB group the mean level of VEGF on day | was 1262.350 + 227.9603 pg/ml and became 1112.460 + 220.3795 pg/ml (p = 0.093) on day 5. There were no significant differentiation of VEGF level between TOHB group and non-TOHB, group both on day 1 (p = 1) and day 5 (p = 0.872).

Conclusion: Hyperbaric oxygen therapy for 5 days did not increase the VEGF level of diabetic ulcer patients."

"ABSTRAKLatar Belakang: Angifibroma nasofaring belia ANB adalah tumor fibrovaskular yang jarang, secara histologi bersifat jinak tetapi secara klinis ganas dengan angka kekambuhan yang masih tinggi. Angka kekambuhan pada tumor ini banyak dihubungkan dengan karakteristik tumor yang dapat dilihat dari sosiodemografi, klinis, gambaran radiologi, teknik pembedahan dan derajat vascular endothelial growth factor VEGF . Tujuan: Mengetahui hubungan antara karakteristik sosiodemografi, klinis, gambaran radiologi, teknik pembedahan dan derajat VEGF terkait kekambuhan ANB sebagai upaya untuk memprediksi adanya kekambuhan. Metode: penelitian dengan rancangan observasional pendekatan kohort retrospektif yang mengevaluasi karakteristik sosiodemografi, klinis, gambaran radiologi, teknik pembedahan dan derajat VEGF terkait kekambuhan. Hasil: didapatkan 38 jumlah kasus ANB, dengan kasus kambuh sebanyak 11 kasus dan tidak kambuh sebanyak 27 kasus. Insiden ANB terbanyak pada usia dekade kedua 12-30 tahun dengan rerata 15,8 tahun. Keseluruhan kasus berjenis kelamin laki-laki. Sumbatan hidung dan epistaksis merupakan keluhan utama pada semua kasus. Kekambuhan banyak ditemukan pada kasus usia muda, dengan onset cepat, stadium lanjut dan intensitas pewarnaan VEGF tinggi. Proporsi kekambuhan tidak berbeda secara statistik antara karakteristik sosiodemografik, klinis, gambaran radiologi, teknik pembedahan dan derajat ekspresi VEGF. Onset, massa tenggorok, stadium, embolisasi dan intensitas perwarnaan VEGF secara klinis mempunyai perbedaan yang bermakna. Pada penelitian ini embolisasi sebelum pembedahan tidak menurunkan angka kekambuhan. Kesimpulan: proporsi kekambuhan ANB sangat dipengaruhi oleh adanya residu tumor pasca operasi. Semakin bersih tumor diangkat, angka kekambuhan akan semakin menurun

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ABSTRACTBackground Juvenile Nasopharyngeal Angiofibroma JNA is rare of fibrovascular tumor, histologically benign but clinically malignant with high recurrency rate. The recurrency rate of JNA was influenced by its characteristics that can be seen from sociodemografical, clinical, radiological, surgical and vascular endothelial growth factor VEGF . Objective the aim of this study is knowing the relation between sociodemographic, clinic, radiologic, surgical technique and expression of VEGF characteristic that influenced recurrency to predict the recurrency of JNA. Methods observasional design with retrospective cohort approach to evaluate the characteristic of sociodemografical, clinical, radiological, surgical technique, and expression of VEGF of JNA and the connection with recurrency. Result 38 cases, with 11 recurrence cases and 27 cases with disease free survival. The incidence of JNA mostly found in second decade 12 30 year with mean age 15,8 year old. All of the cases were male. Nasal blockage and epistaxis were the most common complaint in all cases. Recurrency rate is higher in young age, early onset, late stage and high expression of VEGF. Proportion of recurrency was not statistically significant among characteristics. Onset, oropharyngeal mass, stage, preoperative embolization and intensity of VEGF have clinically difference. In this study, preoperative embolization does not decrease recurrency rate. Conclusion the JNA rsquo s recurrence proportion was influenced by the residual tumor. The less residual tumor will dicrease the recurrency."

"Kanker kolorektal merupakan kanker penyebab kematian kedua tertinggi di dunia. Pengobatan kanker kolorektal memiliki kelemahan dari segi biaya, toksisitas, dan efektivitas. Lunasin mampu menghambat kanker secara in vitro sehingga lunasin dapat menjadi solusi terapi yang efektif biaya untuk kanker kolorektal. Penelitian ini menyelidiki pengaruh ekstrak kedelai kaya lunasin (EKKL) pada ekspresi vascular endothelial growth factor (VEGF) yang berperan dalam proses angiogenesis pada kanker kolorektal. Tiga puluh mencit Swiss Webster dibagi menjadi enam kelompok. Semua kelompok kecuali kelompok normal diinduksi dengan azoxymethane (AOM) dan dextran sodium sulfate (DSS). Kelompok kontrol negatif diberikan larutan garam fisiologis, sedangkan kelompok kontrol positif diberi aspirin. EKKL diberikan kepada ketiga kelompok percobaan dengan dosis yang berbeda (250 mg/KgBB, 300 mg/KgBB, dan 350 mg/KgBB). Pada minggu kelima, setelah mencit diterminasi, jaringan kolon distal mencit diambil dan diwarnai imunohistokimia, kemudian diamati di bawah mikroskop dan dianalisis menggunakan IHC profiler pada ImageJ. Indeks yang diperoleh dari IHC profiler dihitung untuk mendapatkan indeks H-score. Ekspresi VEGF menurun secara signifikan pada kelompok EKKL dosis 300 mg/KgBB (p=0,031) dengan penurunan rata-rata skor 33,202% dan 350 mg/KgBB (p=0,003) dengan penurunan rata-rata skor 43,334%. Namun, tidak ditemukan adanya perbedaan yang signifikan secara statistik antara kedua kelompok tersebut.

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Colorectal cancer is the world’s second highest cause of cancer death. Current treatments for colorectal cancer lack in cost, toxicity, and effectivity. Lunasin has the effect of inhibiting cancer in vitro, hence lunasin might offer the solution of cost-effective therapy for colorectal cancer. We investigate the effect of lunasin-rich soybean extract (LSRE) on vascular endothelial growth factor (VEGF) expression which is responsible for angiogenesis in colorectal cancer. Thirty Swiss Webster mice were divided into six groups. All groups except the normal group were induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). Negative control group received normal saline solution, whereas positive control group were treated with aspirin. LSRE were given to three experimental groups, each with different dosing (250 mg/KgBW, 300 mg/KgBW, and 350 mg/KgBW). On the fifth week, after the mice were terminated, the distal colon tissues were obtained and received immunohistochemistry staining, then observed under a microscope and analyzed using IHC profiler in ImageJ. Index acquired from IHC profiler were calculated to achieve H-score. VEGF expression was significantly decreased in 300 mg/KgBW (p=0.031) and 350 mg/KgBW (p=0.003) of EKKL by an average reduction of 33.202% and 43.334% respectively. However, there was no statistically significant difference between both groups."

"Tujuan: Membandingkan kadar vascular endothelial growth factor VEGF dan placental growth factor PlGF plasma dan vitreus pada tikus diabetes dengan kontrol gula darah GD buruk, dengan perbaikan kontrol gula darah, dan tikus nondiabetes, dan melihat pengaruh perbaikan kontrol gula darah terhadap kadar VEGF dan PlGF. Metode: Penelitian ini merupakan uji eksperimental pada hewan coba tikus strain Sprague Dawley. Sebanyak 18 ekor tikus disertakan dalam penelitian dan secara acak dibagi ke dalam kelompok perlakuan n=14 dan kontrol n=4 . Kelompok perlakuan diberikan injeksi Streptozotocin untuk menginduksi diabetes. Tikus dengan kadar GD 72 jam pasca induksi lebih dari 300 mg/dL didiagnosis diabetes. Kadar GD diperiksa secara berkala pada seluruh subyek. Setelah 4 mingu, kelompok perlakuan dibagi ke dalam kelompok I untuk terminasi dan kelompok II untuk perbaikan kontrol GD dengan injeksi insulin selama 4 minggu berikutnya, begitu pula dengan kelompok kontrol. Saat terminasi, sampel plasma darah dan vitreus diambil untuk analisis kadar VEGF dan PlGF melalui pemeriksaan enzyme-linked immunosorbent assay ELISA. Hasil: Sebanyak 17 ekor tikus bertahan hidup hingga akhir penelitian dengan 1 ekor tikus mati dari kelompok perlakuan. Kadar GD kelompok perlakuan II menurun drastis dan mencapai normoglikemia. Pemeriksaan ELISA bulan pertama menunjukkan kadar VEGF vitreus kelompok perlakuan I cenderung lebih tinggi dibandingkan kontrol I, yakni 196,36 65,24 pg/dL dan 123,64 44,99 pg/dL p=0,20 . Pemeriksaan ELISA bulan kedua menunjukkan kadar PlGF vitreus kelompok perlakuan II lebih tinggi dibandingkan kontrol II, yakni 59,04 2,48 dan 51,93 3,15 p=0,01. Kadar VEGF vitreus dan plasma kelompok perlakuan I dan II tidak berbeda bermakna, sedangkan kadar PlGF vitreus dan plasma lebih tinggi pada bulan kedua. Kesimpulan: Kadar VEGF dan PlGF vitreus mengalami peningkatan pada kelompok tikus diabetes dibandingkan nondiabetes, dan perbaikan kontrol gula darah selama 1 bulan belum dapat menurunkan kadar VEGF dan PlGF.

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Aim: To compare plasma and vitreous level of vascular endothelial growth factor VEGF and placental growth factor PlGF in diabetic rats with poor blood glucose BG control, reconstitution of good BG control, and nondiabetic rats, and to investigate the effect of reconstitution of good BG control to VEGF and PlGF plasma and vitreous level.

Methods: This is an experimental study using Sprague Dawley rats. Eighteen rats were divided into intervention group n 14 and control group n 4. Intervention group were given Streptozotocin STZ injection to induce diabetes. Rats with BG level more than 300 mg dL at 72 hours after injection were considered diabetes and successful models. BG levels were monitored periodically in all subjects. After 4 weeks, intervention group was randomly divided into group I for termination and group II for reconstitution of good BG control with insulin for following 4 weeks, and so was the control group. Plasma and vitreous samples were taken. VEGF and PlGF levels were detected with enzyme linked immunosorbent assay ELISA.

Results: Seventeen rats survived and one rat died in intervention group. BG level of intervention group II decreased dramatically to normoglycemia. ELISA at month 1 showed that VEGF vitreous level tend to be higher in intervention group I compared to control I, 196.36 65.24 pg dL and 123.64 44.99, respectively p 0.20. ELISA at month 2 showed that PlGF vitreous level of intervention group I were significantly higher compared to control I, 59.04 2.48 and 51.93 3.15, respectively p 0.01. Vitreous and plasma VEGF of intervention group I and II were not different, while vitreous and plasma PlGF were significantly higher in group II.

Conclusions: Vitreous levels of VEGF and PlGF were increased in diabetic rats compared to nondiabetic, and reconstitution of good BG control for 1 month were unable to reduce VEGF and PlGF levels. "

"ABSTRAKLatar Belakang. Tindakan pembedahan radikal pada pasien dengan kanker seringkali menyebabkan komplikasi limfedema. Limfedema dapat diatasi dengan operasi transfer jaringan atau rekonstruksi limfatik. Penelitian ini bertujuan untuk membuktikan adanya pembentukan pembuluh limfe baru dengan penambahan flap jaringan pasca diseksi kelenjar limfe, dilihat dari peningkatan ekspresi VEGF-C, infiltrasi makrofag, dan pembentukan fibrosis.Metode. Penelitian ini merupakan penelitian eksperimental pada 20 ekor tikus Sprague Clawley jantan berumur 8-12 minggu, yang dibagi rata kedalam tiap kelompok perlakuan, di Animal House Skill Lab Fakultas Kedokteran Universitas Indonesia pada Januari-Maret 2018. Tiap tikus akan menjalani diseksi, kemudian diacak untuk menerima flap jaringan maupun hanya diseksi inguinal, dan dievaluasi setelah 2 bulan. Pemeriksaan histopatologi dilakukan pada akhir penelitian untuk menilai pembentukan fibrosis dan dilanjutkan pemeriksaan immunohistokimia. Analisis data dilakukan dengan program SPSS 20.0.Hasil. Sebanyak 8 tikus 88.9 yang menerima flap jaringan menunjukkan hasil positif pada tes methylene blue dibandingkan 2 tikus 22.2 pada kelompok kontrol p < 0.05 . Pada 18 tikus tersebut, pewarnaan HE juga menunjukkan adanya pembentukan jaringan ikat pembuluh yang lebih lebar pada tikus yang diberi perlakuan, meski tidak signifikan secara statistik. Pemeriksaan immunohistokimia juga menunjukkan ekspresi VEGF-C yang lebih jelas dengan dominasi warna coklat pada tikus perlakuan p < 0.05 . Ekspresi protein CD68 juga lebih jelas pada tikus perlakuan meski perbedaannya tidak signifikan.Kesimpulan. Penambahan flap jaringan dapat membantu memperbaiki aliran limfa yang dibuktikan dengan peningkatan aliran limfe dan ekspresi VEGF-C.

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ABSTRACT

Background. Radical surgeries for patients with cancer often cause lymphedema complications. Lymphedema may be solved with tissue transfer or lymphatic reconstruction surgery. This research aims to prove new formations of lymphatic vessels by the addition of tissue flap post dissection of lymphatic vessels, marked by increased expression of VEGF-C, macrophage infiltration, and fibrosis formation.Methods. This is an experimental study on 20 male Sprague Clawley mice aged 8-12 weeks, divided evenly for each experiment group, at Animal House Skill Lab Faculty of Medicine Universitas Indonesia from January-March 2018. Each mouse underwent dissection, randomized for flap addition or only inguinal dissection, and evaluated after 2 months. Histopathologic assessment was conducted at the end of study period to evaluate fibrosis formation and followed by immunohistochemistry analysis. Data analysis was conducted with statistical program SPSS 20.0Results. 8 mice 88.9 , which received tissue flap showed positive results on methylene blue test compared to 2 mice 22.2 from control group p < 0.05 . From the 18 mice, HE staining also showed wider formation of lymphatic connective tissue on flap-receiver mice, although it was not statistically significant. Immunohistochemistry analysis also showed clearer VEGF-C formation showed by brown coloration in flap-receiver mice p < 0.05 . Expression of CD68 protein was also clearer in flap-receiver mice although the difference was not significant.Conclusion. Addition of tissue flap may help improve lymphatic circulation proven by increased lymphatic circulation and VEGF-C expression."

"Latar Belakang: Derajat keparahan karsinoma hepatoselular (KHS) yang dinilai dengan klasifikasi Barcelona Clinic Liver Cancer (BCLC) merupakan faktor prognostik utama KHS. Penilaian kadar serum Vascular Endothelial Growth Factor (VEGF) dianggap dapat mencerminkan tingkat keparahan KHS. Namun, belum ada kesepakatan mengenai hubungan tingkat keparahan KHS dengan kadar serum VEGF. Tujuan : Mengetahui hubungan kadar serum VEGF dengan tingkat keparahan KHS dengan menilai perbedaan rerata kadar serum VEGF pada berbagai tingkat keparahan KHS. Metode : Penelitian ini adalah studi potong lintang untuk menentukan hubungan antara kadar serum VEGF dengan tingkat keparahan KHS berdasarkan klasifikasi BCLC. Penelitian ini dilakukan di Rumah Sakit Cipto Mangunkusumo antara bulan Januari 2015 dan Mei 2015. Uji statistik yang digunakan untuk menilai hubungan kadar serum VEGF dengan klasifikasi BCLC ialah analisis one way ANOVA, dan dilanjutkan dengan analisis post hoc Tukey Schaffe. Hasil : Sebanyak 61 subyek KHS diikutkan dalam penelitian ini. Pada penelitian ini tidak ditemukan subyek dengan BCLC stage 0. Rerata kadar serum VEGF BCLC stage A adalah 288,26±156,6 pg/ml; BCLC stage B: 434±164,8 pg/ml; BCLC stage C: 785,57±194,25 pg/ml; BCLC stage D: 1537,97±660,62 pg/ml. Analisis one way ANOVA menunjukkan perbedaan bermakna (P<0,001) antara kadar serum VEGF dengan tingkat keparahan KHS berdasarkan klasifikasi BCLC. Analisis post hoc dengan Tukey Schaffe menunjukkan adanya perbedaan bermakna antara BCLC stage A dan C (p<0,05) serta BCLC stage A dan D (p< 0.001), BCLC stage B dan D (p<0.001), dan BCLC stage C dan D (p<0.001). Tidak ditemukan perbedaan bermakna antara subyek dengan BCLC stage A dan B, dan antara BCLC stage B dan C. Kesimpulan : Didapatkan kadar serum VEGF yang meningkat sesuai dengan tingkat keparahan KHS berdasarkan klasifikasi BCLC terutama untuk BCLC stage B ke atas.

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Background : The severity of Hepatocellular Carcinoma (HCC) stratified by Barcelona Clinic Liver Cancer (BCLC) staging classification has been one of the main prognostic factors of patients with HCC. Serum vascular endothelial growth factor (VEGF) examination can be reflect to predict the severity of HCC. Although, there is no consensus among experts about the severity of HCC staging and serum VEGF levels.

Aim : To determine the association between serum VEGF levels and severity of HCC.

Methods : A cross-sectional study to determine the association between serum VEGF levels and the severity of HCC stratified by BCLC staging classification. The study was conducted at Cipto Mangunkusumo Hospital between January 2015 and May 2015. One way ANOVA analysis was used to assess the association between serum VEGF levels and BCLC classification staging. Post hoc analysis will be done using Tukey Schaffe test.

Results: There were 61 HCC subjects included to this study. There were no subjects with BCLC stage 0. The mean VEGF serum level in patients with BCLC stage A was 288.26 ± 156.6 pg / ml; BCLC stage B: 434 ± 164.8 pg / ml; BCLC stage C: 785.57 ± 194.25 pg/ml; and BCLC stage D: 1537.97 ± 660.62 pg/ml. One way ANOVA showed significant statistical difference (P <0.001) between mean serum VEGF levels and the severity in all BCLC stages. Post hoc analysis using Tukey Schaffe test showed significant stastical difference between BCLC stage A and C (p<0.05), BCLC stage A and D (p<0.001), BCLC stage B and D (p<0.001), and BCLC stage C and D (p<0.001). There were no significant statistical differences between patients with BCLC stage A and B, and between BCLC stage B and C.

Conclusion: We found that increased levels of serum VEGF were associated with the severity of HCC based on BCLC staging classification, especially in patients with BCLC stage B and upwards."