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"Latar belakang: Aktivitas fisik mengakibatkan peningkatan kebutuhan oksigen. Oksigen diperlukan untuk fosforilasi oksidatif dalam rangka menghasilkan ATP. Tingginya kebutuhan oksigen selama aktivitas fisik yang tidak diikuti dengan kemampuan suplai oksigen yang cukup, mengakibatkan terjadi hipoksia di jaringan otot. Dalam kondisi hipoksia gen utama yang mengalami upregulasi adalah Hypoxia Inducible Factor-1α (HIF-1α). Melalui aktivitas HIF-1α, ekspresi sejumlah gen akan mengalami peningkatan guna mengurangi ketergantungan sel terhadap oksigen sekaligus meningkatkan pasokan oksigen ke jaringan, termasuk gen VEGF. Pada otot jantung belum diketahui apakah aktivitas fisik juga mengakibatkan hipoksia serta apakah HIF-1α dan VEGF berperan dalam mekanisme adaptasi. Penelitian ini bertujuan untuk melihat korelasi antara HIF-1α dan VEGF dalam jaringan otot jantung tikus yang diberi aktivitas fisik aerobik dan anaerobik.Metode: Jaringan otot jantung berasal dari tikus yang diberi aktivitas fisik aerobik dan anaerobik menggunakan treadmill selama 1, 3, 7 dan 10 hari. Kemudian dilakukan pengukuran konsentrasi HIF-1α dan konsentrasi VEGF jaringan.Hasil: Hasil penelitian menunjukkan terjadinya peningkatan protein HIF-1α dan VEGF (p < 0,05) pada kelompok yang diberi perlakuan aktivitas fisik aerobik dan anaerobik. Peningkatan konsentrasi HIF-1α tertinggi terjadi pada hari pertama perlakuan dan konsentrasi HIF-1α kelompok anaerobik lebih tinggi dibandingkan kelompok aerobik (156,8 ± 33,1 vs 116,03 ± 5,66). Begitu pula dengan konsentrasi VEGF pada kelompok anaerobik konsentrasi tertinggi terjadi pada hari pertama (36,37 ± 2,35), sedangkan pada kelompok aerobik konsentrasi VEGF tertinggi terjadi pada hari ke-3 (40,66 ± 1,73). Terdapat korelasi antara konsentrasi HIF-1α dan konsentrasi VEGF jaringan dengan tingkat korelasi sedang (r = 0,59) pada kelompok aerobik dan korelasi yang kuat pada kelompok anaerobik (r = 0,69).Kesimpulan: Aktivitas fisik aerobik dan anaerobik mengakibatkan peningkatan konsentrasi HIF-1α dan VEGF pada otot jantung tikus dalam pola yang spesifik. Kondisi anaerobik memicu peningkatan kebutuhan vaskularisasi lebih kuat dan lebih dini dibandingkan kelompok aerobik.

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AbstractBackground: Exercise increases the need for oxygen to generate ATP through oxidative phosphorylation. If the high energy demand during exercise is not balanced by sufficient oxygen supply, hypoxia occurs in skeletal muscle tissue leading to upregulation of hypoxia inducible factor-1α (HIF-1α). The activity of HIF-1α increases the expression of various genes in order to reduce the metabolic dependence on oxygen and to increase oxygen supply to the tissue, e.g., VEGF which plays a role in angiogenesis. In myocardium, it is unlcear whether exercise leads to hypoxia and whether HIF-1α and VEGF play a role in the mechanism of hypoxic adaptation. This study aimed to investigate the correlation of HIF-1α and VEGF in heart muscle tissue of rats during aerobic and anaerobic exercise.Methods: A rat treadmill was used with a specific exercise program for 1, 3, 7 and 10 days. The concentrations of HIF-1α and VEGF were measured the myocardium.Results: Both, HIF-1α protein and VEGF were increased (p < 0.05) in the groups with aerobic and anaerobic exercise. Concentrations of HIF-1α were highest on the first day of activity, being higher in the anaerobic than in the aerobic group (156.8 ± 33.1 vs. 116.03 ± 5.66). Likewise, the highest concentration of VEGF in the group with anaerobic exercise occurred on the first day (36.37 ± 2:35), while in the aerobic group, VEGF concentration was highest on day 3 (40.66 ± 1.73). The correlation between the myocardial tissue consentrations of HIF-1α and VEGF is moderate (r = 0.59) in the aerobic group and strong in the anaerobic group (r = 0.69).Conclusion: Aerobic and anaerobic exercise increase HIF-1α and VEGF concentrations in rat myocardium in specific patterns. The anaerobic condition triggers vascularization stronger and obviously earlier than aerobic exercise."

""ABSTRAK"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.Kata kunci: retinopati diabetic proliferatif, HIF-1?, ICAM-1, bevacizumab"

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""ABSTRACT"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. "

"Luka diabetes merupakan komplikasi mikrovaskular yang sering dikeluhkan oleh pasien diabetes melitus (DM) tipe 2. Vaskularisasi berperan penting dalam penyembuhan luka, yang aktivitasnya diperantarai aktivitas hypoxia-inducible factor 1-alpha (HIF-1α) dan vascular endothelial growth factor (VEGF). Belum ada studi klinis yang mengevaluasi aktivitas HIF-1α dan VEGF pada manusia, khususnya pasien DM tipe 2 yang mengalami luka kaki diabetes. Tujuan penelitian adalah untuk mengevaluasi vaskularisasi jaringan, HIF-1α, dan VEGF pada luka kaki diabetes yang menjalani amputasi dan non-amputasi.Studi potong lintang dilakukan di Rumah Sakit Umum Pusat Nasional dr. Cipto Mangunkusumo (RSCM) pada tahun 2020–2021. Subjek penelitian adalah pasien luka kaki diabetik yang dilakukan debridemen/amputasi. Kemudian diambil jaringan viabel tepi luka untuk diperiksa vaskularisasi jaringan (densitas mikrovaskular), ekspresi VEGF, serta area granulasi, di Departemen Patologi Anatomi FKUI-RSCM. Konsentrasi HIF-1α jaringan dikuantifikasi di Departemen Biokimia dan Biologi Molekuler FKUI-RSCM. Data numerik yang diperoleh diuji normalitasnya dengan uji Saphiro-Wilk. Data distribusi normal dianalisis dengan uji t tidak berpasangan. Dilakukan uji regresi logistik bila terdapat > 2 variabel independen dengan nilai p < 0,25.Dari 67 subjek terdapat 30 pasien amputasi dan 34 pasien debridemen yang dianalisis. Proporsi subjek laki-laki pada kelompok amputasi lebih tinggi dibandingkan kelompok debridemen (p = 0,041). Tidak terdapat perbedaan bermakna pada status gizi, usia, kejadian hipertensi, gagal ginjal, dan status merokok antar kedua kelompok. Profil glikemik, hematologi rutin, penanda inflamasi, kadar elektrolit, penanda fungsi hati, fungsi ginjal tidak berhubungan dengan tindakan pasien, kecuali kadar albumin. Pada analisis bivariat, kadar albumin lebih tinggi pada kelompok debridemen 2,53/0,49 dibandingkan amputasi 2,94/0,51, p = 0,002. Kelompok amputasi memiliki nilai median HIF-1α 5,77 (0,55–53,47) pg/mg protein yang jauh lebih rendah dibandingkan kelompok debridemen 26,56 (2,23–211,12) pg/mg protein (p = 0,001). Hal serupa juga ditemukan pada nilai VEGF (p < 0,001). Pasien dengan HIF-1α < 8,8065 pg/mg protein, MVD < 68,7%, VEGF < 30,443%, dan area granulasi < 33,2802% memiliki aOR 11,116 (IK 95% 1,441–85,752), 10,934 (IK 95% 1,604–74,55), 7,973 (IK 95% 1,301–48,86), 15,589 (IK 95% 1,39–174,867) untuk mengalami amputasi. Kepadatan mikrovaskular, konsentrasi HIF-1α, ekspresi VEGF, dan area jaringan granulasi lebih banyak pada pasien non-amputasi. Pasien dengan penurunan jumlah parameter tersebut memiliki risiko lebih tinggi untuk mendapat tindakan amputasi.

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Diabetic wounds are microvascular complications often complained by people with type 2 diabetes mellitus (DM). Tissue vascularization plays an essential role in wound healing, whose activity is mediated by the activity of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF). However, no clinical studies evaluate its activity in humans, especially in type 2 diabetes mellitus patients who have diabetic foot ulcers. This study attempts to evaluate whether there are differences in tissue vascularization, HIF-1 α, and VEGF in diabetic foot wounds that received amputation and non-amputation procedures.

A cross-sectional study was conducted at the Cipto Mangunkusumo National Central General Hospital (RSCM) in 2020–2021. Diabetic foot wound patients who received debridement/amputation were included in this study. Viable tissue at the wound edges was taken. The expression of VEGF, microvascular density, and area of granulated tissue were evaluated in the Department of Pathology and Anatomy, FKUI-RSCM. HIF-1 levels in tissue were quantified at the Department of Biochemistry and Molecular Biology FKUI-RSCM. All numerical data were tested for normality by the Shapiro-Wilk test. Variables with normally distributed data were analyzed by unpaired t-test. A logistic regression test was performed if there were more than two independent variables with a p-value < 0.25.

This study included 67 patients. There were 30 amputees, and 34 debridement patients included in the data analysis. The proportion of male patients in the amputation group was found to be higher than the debridement group (p = 0.041). There were no differences in nutritional status, age, the incidence of hypertension, kidney failure, and smoking status between the two groups. The glycemic profile, routine haematological findings, markers of inflammation, electrolyte levels, markers of liver function, and markers of kidney function were not found to be related to the patient's condition, except for albumin levels. In bivariate analysis, albumin levels were found to be higher in the debridement group [2.53 (0.49)] than in the amputee [2.94 (0.51)], p = 0.002. The amputee group had a median HIF-1α value of 5,77 (0,55–53,47) pg/mg protein, which was much lower than the debridement group of 26,56 (2,23–211,12) pg/mg protein (p = 0.001). Similar condition was also found in the VEGF value (p < 0.001). Patients with HIF-1α < 8.8065 pg/mg protein, MVD < 68.7%, VEGF < 30.443%, and granulation area < 33.2802% had risk odds of 11.116 (95% CI 1.441–85.752), 10.934 (95% CI 1.604–74.55), 7,973 (95% CI 1.301–48.86), 15.589 (95% CI 1.39–174.867) for amputation. Microvascular density, HIF-1α levels, VEGF expression, and granulation tissue area were higher in non-amputated patients. Patients with a decrease in these parameters have a higher risk of amputation."

"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"

"Keadaan hipoksia dapat membuat sel melakukan adaptasi melalui ekspresi berbagai macam gen. Banyak gen tersebut adalah gen yang diinduksi oleh suatu faktor transkripsi yang disebut HIF-I HlF-la adalah subunit yang diregulasi oleh kadar oksigen untuk aktifitas faktor transkripsi tersebut.Penelitian ini bertujuan untuk mengetahui bagaimana pola mRNA HIF 1u dan ekspresi protein HIF-ln pada organ ginjal dari tikus yang mengalami kondisi hipoksia secara sistemik yang terbagi menjadi 5 kelompok berdasarkan lamanya perlakuan (kelompok kontrol, hipoksia 13, 7 dan 14 hari masing-masing 6 ekor tikus) menggunakan Hypoxic Chamber dengan kadar 02 8% dan Nitrogen 92%. Pola mRNA HIF-la dilihat berdasarkan basil RT-PCR dengan membandingksn rasio kelompok nonnoksia dan kelompok hipoksia. Ekspresi protein HIF-1a dilakukan dengan metode Western Blot dengan menggunakan anti HIF-la sebagai antibodi primer.Hasil penelitian menunjukkan terdapat penurunan ekspresi mRNA HIF-la dibandingkan kontrol pada kelompok hipoksia 1 hari dan diikuti peningkatan pada kelompok hipoksia 3 hari dan mulai mengalami penurunan kembali pada kelompok 7 hari. Sementara protein HIF-la. memperlihatkan terdapatnya peningkatan ekspresi protein HIF-la yang mulai mengalami penurunan pada kelompok hipoksia 14 hari. Dapat disimpulkan bahwa regulasi H1F-1a terjadi pada tahap transkripsi dan tahap pasca translasi.

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Hypoxia could make cell to adapt trough gene expression. Many of these gene induced by the transcription factor called HIP-1. HIF-I tz is the subunit which regulated by oxygen level to activated the transcription factor.

The aim of this study is to know the pattern of Hypoxia Inducible Factor-Ia (HIP-la) mRNA and HIF-Ia protein Expression of Renal Rat in Systemic Chronic Hypoxia which divided to 5 groups based on the duration of hypoxia (control, I, 3, 7, and I4 days of hypoxia with 6 rats each group ) using hypoxia chamber with 8% oxigen and 92% Nitrogen. The pattern was measure with RT-PCR which combine the ratio of control group and the hypoxic group. The protein expression measure with Western Blot method using anti HIF-l a as 1? antibody.

The result shows that HIP-lo. mRNA expression decrease in 1" day of hypoxia, elevated and reach a peak at 3 days of hypoxia and start to decrease since then. While the HIP-lo. protein shows an increase expression until I4 days of hypoxia which start to decrease. It can be concluded that HIF-la regulation occurs in transcription level and post translation."

" adalah salah satu penyebab penurunan performa fisik pada seseorang yang melakukan program latihan fisik jangka panjang. Kondisi overtraining dihubungkan dengan gangguan dalam regenerasi sel tubuh. Insulin-like growth factor-I (IGF-I) adalah protein yang menstimulasi pertumbuhan dan proliferasi sel. IGF-I bekerja dalam regulasi aksis GH/IGF, dimana kerja IGF dipengaruhi oleh growth hormone (GH) dan insulin-like growth factor binding protein-3 (IGFBP-3). Penelitian ini bertujuan untuk mengetahui respons tubuh terhadap latihan fisik aerobik overtraining dengan menganalisa kadar GH, IGF-I, dan IGFBP-3, mengingat hormon dan protein ini berperan dalam regenerasi sel tubuh, khususnya otot rangka. Subjek penelitian adalah 19 ekor tikus putih jantan galur Wistar (berusia 8-10 minggu, berat 150-250 gr) yang dibagi menjadi 3 kelompok (satu kelompok kontrol dan dua kelompok yaitu kelompok aerobik dan kelompok aerobik overtraining yang diberikan perlakuan masing-masing selama 11 minggu). Perlakuan latihan fisik aerobik dan aerobik overtraining dilakukan dengan Animal treadmill L-6000 sebanyak lima hari dalam seminggu. Setelah hari terakhir perlakuan, seluruh hewan coba dikorbankan. Serum darah diambil dengan cara pungsi jantung. Kadar GH, IGF-I, dan IGFBP-3 dalam serum diukur dengan metode ELISA dan data hasil penelitian dianalisis dengan one way ANOVA dan dilanjutkan dengan uji Post Hoc. Hasil pemeriksaan ELISA menunjukkan kadar IGFBP-3 yang lebih rendah secara signifikan pada kelompok aerobik overtraining dibandingkan dengan kelompok aerobik, sementara tidak ada perbedaan kadar GH dan IGF-I pada ketiga kelompok. Kadar IGFBP-3 dalam serum dapat dipertimbangkan sebagai penanda biologis kondisi overtraining.

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Overtraining is one of the causes of decline in physical performance in long-term physical exercise program. Overtraining is associated with impaired regeneration of body cells. Insulin-like growth factor-I (IGF-I) is a stimulator of cell growth and proliferation. IGF act based on the GH/IGF axis, which mean IGF-I act is regulated by growth hormone (GH) and insulin-like growth factor binding protein-3 (IGFBP-3). This study purpose is to determine the body's response to aerobic overtraining exercise by analyzing the levels of growth hormone (GH), insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-3 (IGFBP-3) as those hormone and proteins play a role in the regeneration of body cells, especially skeletal muscle cells. Subjects were 19 white male rats of the Wistar strain (8-10 weeks old, weight: 150-250 g) were divided into 3 groups (one control group and two groups of aerobic and aerobic overtraining group both were given treatment for 11 weeks). Aerobic exercise and aerobic overtraining exercise treatment were conducted five days a week using Animal treadmill L-6000. After the last day of treatment, all experimental animals were sacrificed. Blood serum collected by cardiac puncture. Levels of GH, IGF-I and IGFBP-3 in serum were measured by ELISA. The data were analyzed by one-way ANOVA followed by post hoc test. ELISA results showed significant lower levels of IGFBP-3 in aerobic overtraining group compared to the aerobic group, while there was no difference in the levels of GH and IGF-I in all groups. IGFBP-3 levels in the serum may be a suitable as biological markers for overtraining condition."

"Anaerobic physical exercise is a high intensity physical exercise is a high intensity physical exercise performed in a short time. This exercise can stimulate apoptosis in left ventricular cardiomyocytes after anaerobic exercise and detraining. Thirty two wistar rats ratus novergicus 250-350 grams (8-10 weeks old) were divided into the following groups (n=4) and given anaerobic physical exercise four and 12 weeks (group Exc-4, Exc-12-D). The control groups were only observed in the same period (group CTL-4, CTL-12, CTL-4-D, CTL-12-D). At he end of observation, the rats were sacrificed and examination of the expression of caspace-3 as an indicator of apoptasis was done using immunohistochemical staining. Data were analyzed with ANOVA test. An increase in expression of caspase-3 in the group Exc-4 (72.03%) compared to the CTL-4 (27.22%), (P<0,001); AND Exc-12 (79.30%) compared to the CTL-12 (30.53%) (p=0.027). Detraining process showed a significant decline capase-3 expression (31.12% in exc-4-D and 30.44% in the exc-12-D) Anaerobi physical exercise can increase apoptosis in rat left ventricle cardiomyocyte characterized by increase expression of of caspase-3. Detraining can improve heart condition characterized by decreased expression of caspase-3"

"Latar Belakang : Penelitian ini menganalisis respons adaptasi jaringan jantung pada paparan hipoksia hipobarik intermiten (HHI) pada tikus. Faktor transkripsi HIF-1α penting untuk mengatasi keadaan hipoksia, terdiri atas 2 subunit yaitu HIF-1α dan HIF-1β yang dalam keadaan hipoksia membentuk heterodimer dan mengatur ekspresi sejumlah gen target untuk mengatasi keadaan hipoksia. Hipoksia akan menyebabkan jantung mengalami beban yang meningkat berupa hipertrofi ventrikel. Jantung akan mengatasi keadaan tersebut melalui pembentukan Mb dan BNP-45.Metode : 25 ekor tikus jantan Sprague-Dawley dibagi dalam 5 kelompok dan 4 kelompok dipaparkan HHI menggunakan hypobaric chamber di Lakespra Saryanto TNI AU, selama 50 menit dengan variasi ketinggian, interval intermiten 1 minggu, 4 kali perlakuan (hari 1, 8, 15 dan 22). Dilakukan pengukuran protein HIF-1α dan Mb (ELISA), ekspresi relatif mRNA Mb dan BNP-45 (real time RT-PCR satu langkah).Hasil : Kadar protein HIF-1α meningkat pada paparan hipoksia hipobarik dan terus menurun hingga induksi hipoksia hipobarik intermiten 3 kali (ANOVA, p=0,0437). Ekspresi mRNA dan protein Mb meningkat pada paparan hipoksia hipobarik dan terus menurun hingga induksi hipoksia hipobarik intermiten 3 kali (ANOVA, p=0,0283; 0,0170), dan keduanya berkorelasi kuat (Pearson, r=0,6307). Ekspresi mRNA BNP-45 meningkat pada paparan hipoksia hipobarik intermiten 1 kali dan terus menurun hingga induksi hipoksia hipobarik intermiten 3 kali (ANOVA, p=0,0314). Hasil uji korelasi juga menunjukkan hubungan yang kuat antara protein HIF-1α dengan ekspresi mRNA Mb, namun sangat lemah dengan ekspresi mRNA BNP-45.Kesimpulan : Terjadi respons adaptasi HIF-1α, Mb dan BNP-45 pada paparan hipoksia hipobarik intermiten pada jantung tikus. Protein HIF-1 meregulasi ekspresi Mb dan BNP-45.

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Background: The study analyzed the adaptive responses of heart tissue after induction of intermittent hypobaric hypoxia (IHH) in rat. The transcription factor HIF-1 is important to overcome hypoxia condition, which consist of 2 subunits: HIF-1α and HIF-1β in a state of hypoxia form heterodimers and regulate the expression of a number of target genes to overcome hypoxia. Hypoxia, especially continuous one, may lead the heart to hypertroptive state. The heart will overcome the situation through the establishment of Mb and BNP-45.

Methods: Twenty five male Sprague-Dawley rats were exposed to IHH in a hypobaric chamber in Indonesian Air Force Institute of Aviation Medicine, for 50 minutes at various altitudes, 1 week interval for 4 times (day 1, 8, 15 and 22). HIF-1α and Mb protein were measured with ELISA. mRNA expression of Mb and BNP-45 were measured with one step real time RT-PCR.

Results: HIF-1α protein levels increased after induction of hypobaric hypoxia and continues to decrease after induction of intermittent hypobaric hypoxia 3 times (ANOVA, p=0.0437). mRNA expression and protein of Mb increased after induction of hypobaric hypoxia and continues to decrease after induction of intermittent hypobaric hypoxia 3 times (ANOVA, p=0.0283; 0.0170), and both are strongly correlated (Pearson, r=0.6307). mRNA expression of BNP-45 increased after induction of intermittent hypobaric hypoxia 1 time and continues to decrease after induction of intermittent hypobaric hypoxia 3 times (ANOVA, p=0.0314). Correlation test results also showed a strong relationship between HIF-1α protein with mRNA expression of Mb, but very weak with mRNA expression of BNP-45.

Conclusions: Adaptive response of HIF-1α, Mb and BNP-45 occurs after induction of intermittent hypobaric hypoxia in rat heart. HIF-1 protein regulated the expression of Mb and BNP-45."

"Fibroblast growth factors (FGFs) regulate the proliferation and differentiation of various cells via their respective receptors (FGFRs). During the early stages of tooth development in fetal mice, FGFs and FGFRs have been shown to be expressed in dental epithelia and mesenchymal cells at the initial stages of odontogenesis and to regulate cell proliferation and differentiation. However, little is known about the expression patterns of FGFs in the advanced stages of tooth development. In the present study, we focused on FGF18 expression in the rat mandibular first molar (M1) during the postnatal crown and root formation stages. FGF18 signals by RT-PCR using cDNAs from M1 were very weak at postnatal day 5 and were significantly up-regulated at days 7, 9 and 15. Transcripts were undetectable by in situ hybridization (ISH) but could be detected by in situ RT-PCR in the differentiated odontoblasts and cells of the sub-odontoblastic layer in both crown and root portions of M1 at day 15. The transcripts of FGFR2c and FGFR3, possible candidate receptors of FGF18, were detected by RT-PCR and ISH in differentiated odontoblasts throughout postnatal development. These results suggest the continual involvement of FGF18 signaling in the regulation of odontoblasts during root formation where it may contribute to dentin matrix formation and/or mineralization."

"Penelitian ini bertujuan menganalisis ekspresi HIF-1? pada hati tikus yang diracuni CCl4 dalam kondisi normoksia, dengan atau tanpa perlindungan N-asetil sistein (NAC). Sebanyak 25 ekor tikus Sprague-Dawley jantan dibagi menjadi 5 grup: kontrol, diberikan minyak kelapa, diberikan CCl4, disuntik NAC lalu diberikan CCl4, diberikan CCl4 lalu disuntik NAC. Ekspresi mRNA HIF-1? dianalisis dengan real time RT-PCR dan dikuantifikasi menggunakan metode Livak. Ekspresi protein HIF-1? diukur menggunakan ELISA. Hasil ekspresi mRNA dan protein HIF-1? tertinggi terdapat pada grup tikus yang hanya diberi CCl4, lalu lebih rendah pada grup yang diberi NAC sebelum CCl4, grup yang diberi NAC setelah CCl4, grup kontrol, dan grup yang diberi minyak kelapa. Disimpulkan bahwa pemberian CCl4 pada kondisi normoksia menyebabkan peningkatan ekspresi HIF-1?, sedangkan pemberian NAC terbukti menurunkan ekspresi HIF-1a. Hal tersebut menunjukkan bahwa mekanisme perubahan ekspresi pada HIF-1a memang dipengaruhi oleh radikal bebas yang terbentuk akibat metabolisme CCl4.

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This study analyzed the expression of HIF-1? in liver rat tissue induced by CCl4 under normoxic conditions, with or without N-acetyl cysteine (NAC) protection. Twenty five male Sprague-Dawley rats were divided into 5 group: control rats, rats administered with coconut oil, rats administered with CCl4, rats injected with NAC then administered with CCl4, rats administered with CCl4 then injected with NAC. The expression of HIF-1? mRNA was measured by real time RT-PCR using Livak method, while the HIF-1? protein was measured by ELISA assay. Results showed that the highest HIF-1? mRNA and protein expression were found in the group treated by CCl4 and then was gradually lowered in the pre-NAC group, post-NAC group, control group, and coconut oil group. The overall result of this study show the effect of CCl4-treated rats under normoxic conditions increased the expression of HIF-1?, while NAC treatment decreased the expression of HIF-1?. These findings show that free radical formed by CCl4 metabolism play a role in the regulation of HIF-1"