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Abstrak :
Pendahuluan : Angiogenesis kronik pada inflammatory bowel disease (IBD) dapat meningkatkan risiko keganasan mengingat belum ditemukannya terapi definitif yang aman. Esktrak daun mahkota dewa diketahui memiliki efek antiinflamasi, namun mampu memicu toksisitas pada penggunaan dosis tinggi. Pengemasan ekstrak daun mahkota dewa dalam nanopartikel kitosan dipercaya mampu memaksimalkan paparan jaringan terhadap bahan aktif meskipun dengan pemberian dosis yang lebih rendah. Penelitian ini bertujuan untuk membuktikan efektivitas ekstrak daun mahkota dewa yang dienkapsulasi dengan nanopartikel kitosan dalam menekan angiogenesis. Metode : Penelitian ini menggunakan 30 sampel HE jaringan kolon mencit Swiss Webster tersimpan yang diberikan air mengandung DSS 2% (selama 7 hari) diikuti dengan air tanpa DSS (selama 7 hari) dalam 3 siklus. Efek antiangiogenik ekstrak daun mahkota dewa dievaluasi dalam 6 kelompok uji: normal (N), kontrol, EMD25, EMD12,5, NPMD12,5 dan NPMD6,25. Hasil : Jumlah angiogenesis pada kelompok NPMD12,5 tidak berbeda bermakna jika dibandingkan dengan kelompok kontrol (p>0,05). Adapun kelompok EMD25, EMD12,5, dan NPMD6,25 yang secara signifikan menunjukkan supresi jumlah angiogenesis jika dibandingkan dengan kelompok kontrol (p<0,05). Rerata (mean) jumlah angiogenesis dari masing-masing kelompok EMD25, EMD12,5 dan NPMD6,25 yaitu 14,6, 11,4, dan 10,8. Kesimpulan : Reduksi angiogenesis tertinggi terdapat pada kelompok mencit yang mendapatkan 6,25 mg ekstrak daun mahkota dewa dalam nanopartikel kitosan. Penggunaan nanopartikel kitosan untuk mengemas ekstrak daun mahkota dewa terbukti efektif dalam menekan jumlah angiogenesis dan menurunkan dosis efektif untuk mencegah toksisitas.

Abstrak :
Banyak faktor yang mempengaruhi aktivitas angiogenesis plasenta, misalnya VEGF dan oksigenasi dalam plasenta. Pada awal kehamilan normal b-hCG meningkatkan aktivitas VEGF untuk merangsang angiogenesis. Tujuan penelitian ini adalah untuk mengetahui hubungan antara kadar b-hCG pada kultur plasenta dengan aktivitas angiogenik plasenta preeklampsia. Sampel plasenta diambil dari 10 plasenta wanita dengan preeklampsia dan 10 kontrol (wanita dengan kehamilan normal). Semua subjek bersedia berpartisipasi dalam penelitian ini dan menandatangani informed consent. Konsentrasi b-hCG dalam supernatan kultur plasenta diukur dengan Microparticle Enzyme Immunoassay (MEIA) dan aktivitas angiogenik plasenta diukur dengan mengukur migrasi sel endotel menuju eksplan plasenta (skor 0-4). Hasil menunjukkan median skor aktivitas angiogenik plasenta pada preeklampsia lebih tinggi secara bermakna dari kontrol (p<0,05). Konsentrasi b-hCG dalam kultur plasenta preeklampsia lebih tinggi secara bermakna dari plasenta kehamilan normal (p<0,001). Konsentrasi b-hCG mempunyai korelasi positif dengan aktivitas angiogenik plasenta baik pada preeklampsia (r=0,50) maupun kehamilan normal (r=0,57). Walaupun korelasi ini lemah, bagaimanapun juga b-hCG merupakan salah satu faktor yang mempengaruhi aktivitas angiogenik plasenta. (Med J Indones 2004; 14: 67-70)

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Numerous factors, such as VEGF and intra-placental oxygenation, can influence placental angiogenic activity. Early in the normal gestation period, b-hCG enhance VEGF activity to induce angiogenesis. The aims of this study were to identify the correlation between b-hCG concentration in placental culture and placental angiogenic activity in pre-eclampsia. Ten placenta samples from women with pre-eclampsia and 10 from controls (normal pregnancy) were collected. All subjects agreed to participate in this study and signed an informed consent form. b-hCG concentration in supernatant of placental culture was measured by Microparticle Enzyme Immunoassay (MEIA) and placental angiogenic activity was measured by endothelial cell migration toward placental explant (score 0-4). The results showed that the median score of placental angiogenic activity in pre-eclampsia was significantly higher than in normal pregnancy (p<0.05). Concentration of b-hCG in pre-eclampsia was significantly higher than in normal pregnancy (p<0.001). hCG concentration in placental culture was positively correlated to placental angiogenic activity both in pre-eclampsia (r=+0.50) and in normal pregnancy (r=+0.57). Although the correlations were weak, b-hCG is considered one of the factors that influence placental angiogenic activity. (Med J Indones 2004; 14: 67-70)

Abstrak :
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. ......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.

Abstrak :
Pendahuluan: Celah orofasial (COF) memerlukan perawatan palatoplasti untuk menutup fistula yang terdapat di palatum. Akan tetapi, pembentukan jaringan parut di area operasi berkaitan erat dengan gangguan pertumbuhan. Modifikasi teknik bedah dan pendekatan farmakologi telah diteliti untuk mengetahui efeknya terhadap pembentukan jaringan parut dan keberhasilan palatoplasti. Ikan gabus, Channa striata, merupakan salah satu ikan endemik Asia Tenggara yang secara empiris dipercaya dapat membantu penyembuhan, terutama pascamelahirkan. Sejumlah penelitian telah menunjukan efek dari ekstrak Channa striata terhadap penyembuhan luka, namun belum ada penelitian pada penyembuhan luka di palatum tikus. Penelitian ini bertujuan untuk melihat efek ekstrak Channa striata terhadap penyembuhan luka di palatum tikus secara histologis. Metode: Sebanyak 36 tikus Sprague dawley dibuatkan luka pada palatum dengan metode punch biopsy. Dari 36 tikus tersebut, dibagi dalam 3 kelompok, yaitu kelompok perlakuan dengan kombinasi topikal dan peroral ekstrak Channa striata, kelompok kontrol positif diberi gel gengigel dan suplemen vitamin C, dan kelompok kontrol negatif dirawat dengan gel tanpa bahan aktif. Kemudian dilakukan pengamatan pada hari ke-3, -7, dan - 14 setelah perlakuan secara klinis untuk mengamati luas luka mikroskopik. Sebanyak 4 tikus dari masing-masing perlakuan dinekropsi pada setiap hari pengamatan untuk dibuatkan preparat pengamatan histologis. Pewarnaan hematoksilin dan eosin dilakukan untuk mengamati panjang luka mikroskopik, reepitelisasi, dan angiogenesis, sedangkan pewarnaan Masson’s trichrome digunakan untuk mengamati kerapatan kolagen. Hasil dan Pembahasan: Pada hasil pengamatan ukuran luka, didapatkan bahwa terdapat perbedaan bermakna secara statistik (p<0,05) ukuran luka makroskopik pada hari ke-3 dan -14, reepitelisasi pada hari ke -7 dan -14, dan kerapatan kolagen pada hari ke-14. Di sisi lain, tidak terdapat perbedaan bermakna antarperlakuan pada pengamatan panjang luka mikroskopik dan angiogenesis. Ekstrak Channa striata terbukti dapat berdampak pada penyembuhan luka di palatum tikus. Kesimpulan: Berdasarkan penelitian ini, terlihat bahwa pemberian ekstrak Channa striata topikal dan peroral dapat mengurangi ukuran luka tikus, meningkatkan tingkat reepitelisasi, meningkatkan kerapatan kolagen, dan meningkatkan angiogenesis secara signifikan pada beberapa titik waktu yang diukur, tetapi efektivitasnya lebih rendah daripada gel gengigel dan vitamin C. ......Introduction: Orofacial clefts (OFC) require palatoplasty treatment to close the fistulae present in the palate. However, scar tissue formation at the surgical site is closely associated with growth disturbance. Modification of surgical techniques and pharmacological approaches have been investigated for their effects on scar tissue formation and palatoplasty success. Snakehead fish, Channa striata, is one of the fish endemic to Southeast Asia that is empirically believed to aid healing, especially postpartum. A number of studies have shown the effect of Channa striata extract on wound healing, but there has been no study on wound healing in the palate of rats. This study aims to look at the effect of Channa striata extract on wound healing in the rat palate histologically. Methods: A total of 36 Sprague Dawley rats were wounded on the palate by punch biopsy method. The 36 rats were divided into 3 groups, namely the treatment group with topical and peroral combination of Channa striata extract, the positive control group was given gengigel gel and vitamin C supplement, and the negative control group was treated with gel without active ingredients. Then observations were made on day-3, -7, and -14 after clinical treatment to observe the microscopic wound area. A total of 4 rats from each treatment were necropsied on each observation day to make histological observation preparations. Hematoxylin and eosin staining was performed to observe microscopic wound length, re-epithelialization, and angiogenesis, while Masson's trichrome staining was used to observe collagen density. Results and Discussion: In the observation of wound size, there was a statistically significant difference (p<0.05) in macroscopic wound size on days 3 and 14, re-epithelialization on day 7 and 14, and collagen density on day 14. On the other hand, there was no significant difference between treatments in the observation of microscopic wound length and angiogenesis. Channa striata extract was shown to have an impact on wound healing in the rat palate. Conclusion: Based on this study, it was shown that topical and peroral administration of Channa striata extract can reduce the size of rat wounds, increase the rate of re-epithelialization, increase collagen density, and enhance angiogenesis significantly at several time points measured, but its effectiveness is lower than gengigel gel and vitamin C.

Abstrak :
ABSTRAK Insidensi kolitis ulseratif di Indonesia mulai meningkat. Sedangkan etiologi penyakit tersebut masih belum jelas sehingga pengobatan saat ini masih bersifat simptomatik, jangka panjang, dan menimbulkan banyak efek samping. Tujuan dari penelitian ini adalah untuk membuktikan efek antiinflamasi ekstrak daun Ficus deltoidea pada kolon mencit yang diinduksi dekstran sodium sulfat (DSS). Penelitian dilakukan dengan menggunakan 24 sampel materi biologik tersimpan dari penelitian sebelumnya yang dibagi menjadi empat kelompok: kontrol negatif (DSS), kontrol positif (aspirin), ekstrak daun Ficus deltoidea dosis 25 mg, dan ekstrak daun Ficus deltoidea dosis 50 mg. Preparat histologis jaringan kolon diwarnai dengan pewarnaan hematoksilin-eosin (HE) dan diamati pada perbesaran 400x. Terdapat peningkatan sel goblet secara signifikan (p < 0,001) pada kelompok ekstrak daun Ficus deltoidea dosis 50 mg dibandingkan dengan kelompok kontrol negatif. Namun tidak terdapat perbedaan bermakna pada parameter fokus inflamasi dan angiogenesis.

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ABSTRACT The incidence of ulcerative colitis in Indonesia is increasing. While its etiology is still unknown, the current treatment is still symptomatic, long term, and causes many side effects. The purpose of this study is to confirm that Ficus deltoidea leaf extract has an antiinflammatory effect on DSS-induced mice colon. This study was conducted using 24 stored tissue samples from previous study which are divided into four groups: negative control (DSS), positive control (aspirin), Ficus deltoidea leaf extract at a dose of 25 mg, and Ficus deltoidea leaf extract at a dose of 50 mg. Colon tissue histology sample is stained with hematoxylin-eosin (HE) staining and examined on magnification of 400x. There is a significant increase number of goblet cells (p < 0,001) on the Ficus deltoidea leaf extract group at a dose of 50 mg compared to negative control group. However, there is no significant effect of Ficus deltoidea leaf extract on inflammation focus and angiogenesis.

Abstrak :
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.

Abstrak :
Blood vessels of tumors display many structural and functional abnormalities. Their unusual leakiness, potential for rapid growth and remodeling, and expression of distinctive surface molecules mediate the dissemination of tumor cells in the bloodstream and maintain the tumor microenvironment. Like normal blood vessels, they consist of endothelial cells, mural cells and their enveloping basement membrane. Common features, irrespective of their origin, size and growth pattern, are absent hierarchy, formation of large-caliber sinusoidal vessels, markedly heterogeneous density, increased permeability, decreased and abnormal pericyte-endothelial cell adhesion, irregular basement membrane structure, and the incorporation of bone-marrow-derived endothelial progenitor cells in the microvasculature. A number of specific tumor endothelial markers have been identified, as well as chromosomal abnormalities. These markers may be used to deliver drugs specifically and selectively to the tumor microvasculature.

Abstrak :
This book explores the development and use of innovative computational and mathematical approaches for modeling the vascular development of tumors. Covers modeling of the angiogenesis cascade, and integrates vasculature development with tumor growth dynamics.