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"ABSTRAKHipoksia hipobarik intermiten HHI dengan menggunakan protokol profil penerbangan modifikasi Mulyawan pada ruang hipobarik dapat digunakan sebagai model hipoksia yang bersifat melindungi melalui ekspresi HIF-1? dan protein yang diregulasinya yang bermanfaat dalam mengatasi radikal bebas yang terbentuk selama induksi tersebut. Pada penelitian ini dinilai ekspresi protein sitoglobin Cygb dan neuroglobin Ngb serta aktivitas spesifik asetilkolin esterase AChE sebagai dampak dari induksi HHI pada tikus dewasa. Digunakan 25 tikus Sprague-Dawley dewasa yang terbagi atas dua kelompok kontrol yakni normoksia dan hipoksia hipobarik akut HHA , serta 3 kelompok yang terpapar HHI kelompok pertama terpapar pada hari ke-1 dan ke-8 IHH1x , kelompok ke-2 terpapar pada hari ke-1, -8 dan -15, sedangkan kelompok ke-3 terpapar pada hari ke-1, -8, -15 dan -22 . Sitoglobin dan Ngb menurun pada induksi akut dan meningkat secara signifikan seiring dengan peningkatan frekuensi paparan HHI. Aktivitas spesifik AChE meningkat secara signifikan sejak paparan pertama HHA namun kemudian menurun pada induksi terakhir IHH3x . Dari hasil penelitian ini disimpulkan bahwa pada HHI3x terjadi respons adaptasi yang bersifat melindungi jaringan otak tikus percobaan terhadap perlakuan.

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ABSTRACTProposed as a protective model of hypoxia via HIF 1 expression, intermittent hypobaric hypoxia IHH in the rat, using Mulyawan rsquo s modified flight profile in a hypobaric chamber, is known to be useful in overcoming the free radicals formed during the induction. Using the same method, this study 39 s aims are to investigate cytoglobin Cygb and neuroglobin Ngb protein expressions and specific activity of acetylcholine esterase as the impacts of the IHH induction in adult rats. We used 25 adult Sprague Dawley male, divided into 2 control groups normoxia and acute hypobaric hypoxia AHH , and 3 IHH exposed groups the first group was exposed on day 1 and 8 IHH 1x the second group on day 1, 8 and 15 IHH 2x and the third group on day 1, 8, 15 and 22 IHH 3x . Cytoglobin and Ngb were decreased in the acute induction and increased significantly along with the increasing frequency of the IHH induction. The specific activity was increased significantly since the first AHH induction of hypobaric hypoxia but then decreased in the last induction IHH3x . From these findings, it is concluded that IHH, especially IHH3x, seems to be a protective adaptive response in the rat rsquo s brain tissue. "

"Pestisida menyebabkan reaksi inhibisi irreversible pada enzim asetilkolinesterase (AChE), yang bekerja sebagai pengatur reaksi hidrolisis asetiltiokolin menjadi tiokolin dan asam asetat pada neurotransmitter manusia (Massouli, 1993). Paparan pestisida dapat menghambat kerja impuls pada system syaraf manusia karena asetiltiokolin mempengaruhi memori, tidur, dan kemampuan konsentrasi. Persediaan asetiltiokolin yang sedikit dapat dihubungkan dengan penyakit alzheimer (Tuoro, et al, 2011). Deteksi pestisida Chlorpyrifos dapat dilakukan dengan menggunakan biosensor dengan metode elektrokimia karena tiokolin yang dihasilkan dari reaksi enzimatik asetiltiokolin menggunakan AChE bersifat elektroaktif. Pada penelitian ini dikembangkan sensor pestisida menggunakan elektroda Oxidized Boron Doped Diamond (OBDD). Penambahan AChE pada asetiltiokolin klorida (ACTCl) memberikan respon arus yang menunjukkan puncak oksidasi tiokolin dengan kontak optimum antara AChE dan ACTCl adalah 30 menit pada pH 7,6. Penambahan pestisida menurunkan respon arus yang dihasilkan dengan waktu inhibisi optimum 20 menit. Pengujian juga dilakukan dengan menggunakan metode strip test untuk menghasilkan deteksi yang lebih selektif. AChE diimobilisasi pada permukaan magnetic beads sebelum diimobilisasikan pada strip test untuk mendapatkan hasil yang lebih sensitif. Linearitas yang lebih tinggi pada pengukuran variasi konsentrasi Chlorpyrifos dan nilai batas deteksi yang lebih kecil diperoleh pada pengukuran dengan metode strip test dengan AChE terimobilisasi magnetic beads. Validasi dilakukan melalui pendeteksian pada sampel air ledeng yang diinjeksikan dengan Chlorpyrifos.

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Pesticides cause irreversible inhibition to the enzymatic reaction of acetylcholinesterase (AChE), which works as a regulator for the hydrolysis of acetylcholine to choline and acetic acid in human neurotransmitters (Massouli, 1993). Pesticide inhibits the action of impulses in the human nervous system since acetylcholine affects memory, sleep, and the ability to concentrate. The decrease of acetylcholine concentration can be attributed to Alzheimer's disease (Tuoro, et al, 2011). The detection of the pesticide Chlorpyrifos can be performed using the method of electrochemical biosensors as thiocholine is electroactive. In this research, oxidized boron-doped Diamond (OBDD) was utilized as the working electrode. The addition of AChE in acetylthiocholine chloride (ACTCl) provides current responses, which can attributed to the oxidation peak of tiocholine. An optimum contact time between AChE and ACTCl of 30 min at pH 7.6 was observed. The addition of pesticides reduces the current responses at a 20 min optimum inhibition time. AChE was later modified with biotin and immobilized by using magnetic beads. The method was then applied using strip test method, to achieve a more selective detection method. AChE was immobilized at the surface of magnetic beads before imobilized at the strip test to increase the sensitivity. Better linearity and lower limits of detection can be achieved for various concentration of Chlorpyrifos. Furthermore, validation was performed for the detection of tap water injected by Chlorpyrifos."

"ABSTRAKNama : Eval HeriansyahProgram Studi : S2 Magister Kedokteran KerjaJudul : Hubungan Perubahan Akut Gambaran EKG Dengan Penurunan Aktivitas Asetilkolinesterase Plasma Pada Petani Penyemprot Laki-Laki Yang Menggunakan OrganofosfatPembimbing : Astrid Sulistomo dan Budhi SetiantoLatar Belakang. Petani di Indonesia masih banyak menggunakan pestisida golongan organofosfat. Organofosfat memiliki efek toksik terhadap berbagai sistem tubuh, salah satunya sistem kardiovaskuler. Pestisida organofosfat yang masuk ke dalam tubuh manusia memengaruhi fungsi saraf dengan jalan menghambat kerja enzim kolinesterase. Penelitian ini bertujuan untuk mengetahui hubungan perubahan akut gambaran EKG sebelum dan sesudah pajanan organofosfat pada petani penyemprot padi laki-laki.Metode. Penelitian ini menggunakan disain potong lintang dengan rancangan pre- dan post-test tanpa kontrol di desa Pada Asih, Kecamatan Cibogo, Kabupaten Subang dengan cara pengambilan sampel menggunakan cluster random sampling. Pengumpulan data dilakukan dengan wawancara menggunakan kuesioner, pemeriksaan fisis, dan pengamatan cara kerja. Pemeriksaan AChE dan EKG dilakukan sebelum dan sesudah penyemprotanHasil. Dari 80 subjek petani penyemprot padi, 20 subjek 25 mengalami perubahan gambaran EKG sesudah melakukan penyemprotan pestisida organofosfat. Jenis perubahannya, berupa sinus bradikardia 6,25 , pemanjangan interval QT 3,75 , peninggian gelombang T 2,5 , dan pembesaran atrium kiri 12,5 . Penurunan aktivitas AChE ditemukan rata-rata -2,29 3,25 . Tidak ditemukan hubungan bermakna antara semua faktor risiko yang diteliti usia, persentase perubahan AChE, merokok saat menyemprot, status gizi, penggunaan APD, masa kerja, lama penyemprotan, dan tugas kerja dengan perubahan gambaran EKG.Kesimpulan. Perubahan akut gambaran EKG yang terjadi pada populasi petani penyemprot padi laki-laki sebesar 25 . Perubahan aktivitas asetilkolinesterase terjadi berkisar -2,29 3,25 . Tidak ditemukan faktor risiko yang berhubungan.Kata kunci. Elektrokardiografi, asetilkolinesterase, petani, pestisida, organofosfat.

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ABSTRACTABSTRACTName Eval HeriansyahProgram Master of Occupational MedicineTitle Acute ECG Changes Associated with Decreased Plasma Acetylcholinesterase Activity Among Male Pesticide Spraying Farmers using OrganophosphateCounselors Astrid Sulistomo and Budhi SetiantoBackground. Many farmers in Indonesia are still using organophosphorus pesticides. Organophosphates have toxic effects on various body systems, one of them is the cardiovascular system. Organophosphate pesticides that enter the human body affect the function of the nerves by inhibiting the action of cholinesterase enzymes. This study aims to determine the relationship of acute changes of ECG images before and after exposure of organophosphates among male paddy sprayers.Method. This study used cross sectional with pre and post test design without control in Pada Asih Village, Cibogo Sub district, Subang Regency. Using cluster random sampling method for sample selection. Data were collected using questionnaires, physical examination, and observation of working process. Acetylcholinesterase and EKG examination was conducted before and after spraying,Results. From 80 rice spray farmers recruited, a total of 20 subjects 25 showed changes in ECG picture after spraying with organophosphorus pesticides. The types of changes include bradycardia sinus 6.25 , QT interval lengthening 3.75 , heightening of T wave 2.5 , and left atrial enlargement 12.5 . Decrease in activity of AChE was 2,29 3,25 . No significant association between changes in ECG graph and studied risk factors age, percentage of plasma AChE changes, smoking while spray, BMI, using PPE, working period, duration of spray, and work assignment could be identified.Conclusion. Acute change in ECG picture occurred in 25 of male pesticide spraying farmers. Changes in AChE were 2,29 3,25 . No association with studied risk factors could be found."

"Biosensor berbasis penghambatan enzim asetilkolinesterase (AChE) oleh isoprokarb berhasil dikembangkan. Elektroda pensil grafit (GPE) termodifikasi polianilin (PANI) dan nanopartikel emas (AuNPs) digunakan untuk mendeteksi perubahan respon tiokolin dengan adanya isoprokarb. Elektroda ini dipreparasi dalam dua tahap menggunakan teknik cyclic voltammetry (CV), yaitu elektropolimerisasi anilin pada GPE dan elektrodeposisi AuNPs pada permukaan GPE termodifikasi PANI. Karakterisasi yang dilakukan dengan SEM-EDX menunjukkan bahwa AuNPs berukuran 8-80 nm dapat diendapkan pada permukaan pensil grafit termodifikasi polianilin. Karakterisasi elektrokimia menggunakan CV menunjukkan peningkatan luas permukaan aktif elektroda sekitar 2 dan 3,3 kali dibandingkan dengan GPE yang tidak dimodifikasi. Selanjutnya, puncak oksidasi tiokolin yang dibentuk oleh reaksi enzimatik AChE dengan adanya asetiltiokolin dapat diamati pada potensial +0,675 V (vs. Ag/AgCl). Arus puncak yang dihasilkan turun secara linier dengan adanya isoprocarb dalam konsentrasi konstan AChE dan asetilthiocholine. Pada kondisi optimum larutan 0,1 M PBS pH 7,4 yang mengandung 100 mU/ml AChE dan 1 mM asetiltiokolin klorida, waktu kontak 15 menit dan waktu inhibisi 25 menit, kurva kalibrasi linier isoprocarb dapat dicapai pada rentang konsentrasi 0,0005 hingga 0,05 ¼M dengan batas deteksi dan kuantifikasi masing-masing 0,0106 ¼M dan 0,0355 ¼M, dengan sensitivitas 47,4810 ¼A/¼M.mm. Selanjutnya, pengukuran keberulangan menghasilkan nilai yang baik untuk 9 kali pengukuran diamati dengan RSD 4,57%, menunjukkan bahwa biosensor yang dikembangkan menjanjikan untuk mendeteksi isoprocarb.

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An analysis tool for isoprocarb has been successfully developed as a biosensor system based on enzymatic inhibition of acetylcholinesterase (AChE) by isoprocarb. A gold nanoparticles-polianiline modified graphite pencil electrode (AuNPs-PANI-GPE) was utilized to detect the change of thiocholine in the presence of isoprocarb. This electrode was prepared by two cyclic voltammetry steps, including electro-polymerization of aniline on a graphite pencil and electro-deposition of gold nanoparticles on the polyaniline surface. Characterization performed by SEM-EDX indicated that 8-80 nm size of gold nanoparticles could be deposited on the surface of polyaniline-modified graphite pencil. Electrochemical characterization using cyclic voltammetry suggested that the active surface area of the prepared electrode was 0.17019 cm2, which was about 2 and 3.3 times compared to that of the unmodified GPE. Furthermore, an oxidation peak of thiocholine was observed at a potential of +0.675 V (vs. Ag/AgCl), formed by an enzymatic reaction of AChE in the presence of acetylthiocholine. This peak current was found to increase linearly with acetyl thiocholine concentrations, while in the presence of isoprocarb in a constant concentration of AChE and acetylthiocholine the peak linearly decreased. At the optimum condition of 0.1 M PBS pH 7.4 containing 100 mU/ml acetylcholinesterase and 1 mM acetythiocholine chloride, the inhibition and the contact time of 25 min and 15 min, a linear calibration curve of isoprocarb could be achieved in the concentration range of 0.0005 to 0.05 ¼M with an estimated limits of detection and quantifications of 0.0106 ¼M and 0.0355 ¼M, respectively, with the sensitivity of 47.4810 ¼A/¼M.cm2. Furthermore, an excellent stability for 9 times measurements was observed with an RSD of 4.57%, suggesting that the developed tools is promising for the detection of isoprocarb."

"Latar belakang: Nyamuk Culex sp. merupakan nyamuk yang berperan dalam penyebaran berbagai penyakit, seperti filariasis, Japanese encephalitis, St. Louis encephalitis, dan West Nile Fever. Indonesia sebagai salah satu negara endemis filariasis memiliki program eliminasi filariasis, salah satunya dengan pengendalian vektor filariasis menggunakan insektisida. Seiring dengan semakin seringnya digunakan insektisida untuk mengendalikan vektor nyamuk lainnya, dikhawatirkan terjadi resistensi pada Cx. quenquefasciatus terutama terhadap insektisida yang sering digunakan. Resistensi metabolik dan modifikasi situs target dapat diamati dengan adanya peningkatan aktivitas enzim asetilkolinesterase karena enzim asetilkolinesterase merupakan target kerja dari insektisida golongan organofosfat, seperti malation.7 Di Jakarta, belum dilakukan penelitian mengenai tingkat resistensi Cx. quinquefasciatus terhadap malation dan deltametrin beserta aktivitas enzim asetilkolinesterase. Tujuan: Menganalisis efektivitas malation dan deltametrin pada larva Cx. quinquefasciatus. Metode: Penelitian ini menggunakan desain penelitian eksperimental. Sampel penelitian merupakan larva tahap III-IV Cx. quinquefasciatus yang diambil menggunakan teknik random sampling. Sampel akan dipaparkan dengan insektisida deltametrin dan malation dengan lima konsentrasi yang berbeda selama 24 jam. Kelompok larva mati dan hidup selanjutnya akan digunakan untuk uji biokimia enzim asetilkolinesterase menggunakan spektofotometri. Hasil: Mortalitas larva pada konsentrasi tertinggi (0,25 ppm) kelompok perlakuan deltametrin adalah 96,8%. Sedangkan mortalitas larva pada konsentrasi tertinggi (0,5 ppm) kelompok perlakuan malation adalah 100%. LC50 dan LC90 pada deltametrin terhadap larva Cx. quinquefasciatus secara berurutan adalah 0,015 ppm dan 0,106 ppm. Sedangkan LC50 dan LC90 malation secara berurutan adalah 0,052 ppm dan 0,173 ppm. Absorbansi pada uji aktivitas asetilkolinesterase pada kelompok larva hidup dan mati yang diinduksi deltametrin secara berurutan adalah 0,754 ± 0,204 dan 0,728 ± 0,257. Sedangkan absorbansi pada uji biokimia aktivitas asetilkolinesterase pada kelompok larva hidup dan mati yang diinduksi malation secara berurutan adalah 0,405 ± 0,009 dan 0,237 ± 0,003. Kesimpulan: Deltametrin dan malation memperlihatkan aktivitas larvisida terhadap larva Cx.quinquefasciatus. Berdasarkan nilai LC50 dan LC90 menyimpulkan deltametrin lebih efektif dibandingkan dengan malation. Malation menghambat aktivitas asetilkolinesterase pada larva Cx. quinquefasciatus, sedangkan deltametrin tidak menghambat aktivitas asetilkolinesterase tersebut.

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Background: Culex sp. plays an important role as a vector in spreading various diseases such as filariasis, Japanese encephalitis, St Louis encephalitis, and West Nile Fever. Indonesia as one of the countries endemic in filariasis, has a program in eliminating filariasis, with one of the program done by controlling vector using insecticide. Insecticides used in eliminating vector of filariasis, Cx. quinquefasciatus, are used concurrently in order to eliminate another vector such as Anopheles sp. and Aedes sp. The escalation of insecticide utilization leads to the concern of Cx. quinquefasciatus being resistance against insecticides, especially insecticides that are often used. Metabolic resistance and target site modification in Cx. quinquefasciatus as the proposed mechanisms in insecticide resistance can be seen by observing the activity of acetylcholinesterase due to its role as a target site for organophosphat such as malathion. Currently in Jakarta, there’s no research established regarding Cx. quinquefasciatus resistance against malathion and deltamethrin along with their acetylcholinesterase activity.

Objective: Analyzing effectivity of malathion and delamethrin in Cx. quinquefasciatus.

Method: The design study used in this research was experimental. Larva Instar stage III-IV Cx. quinquefasciatus was used as samples and chosen with random sampling technique. Samples was exposed to deltamethrin and malathion with 5 different concentrations for 24 hours. Both samples, alive and dead, after the exposure, were assessed for their acetylcholinesterase activity using spectophotometry.

Result: Mortality from the highest concentration in deltametrhin-induced group was 96,8%. Meanwhile, mortality from the highest concentration in malathioninduced group was 100%. LC50 and LC90 of deltamethrin was 0,015 ppm and 0,106 ppm while LC50 and LC90 of malathion was higher (0,052 ppm and 0,173 ppm). Absorbance in acetylcholine esterase activity assay in the group of alive and dead larva induced by deltametrhin was 0,754 ± 0,204 dan 0,728 ± 0,257. While the absorbance in malathion-induced group was lower with the result of 0,405 ± 0,009 in the group of alive larva and 0,237 ± 0,003 in the group of dead larva.

Conclusion: Deltamethrin dan malathion both showed larvacidal activity in Cx. quinquefasciatus. According to LC50 and LC90 we can conclude that deltamethrine was more effective than malathion.From the acetylcholinesterase activity assay, we can see that there was inhibition from malathion against acetylcholinesterase while we see no effect against acetylcholinesterase activity from deltamethrin."

"[ABSTRAKHipoksia berperan penting pada patofisiologi berbagai penyakit utama penyebab kematian seperti, penyakit jantung iskemia, strok, kanker, penyakit paru kronik, dan gagal jantung kongestif. Kedua protein golongan globin di otak, yaitu neuroglobin (Ngb) dan sitoglobin (Cygb) diduga berperan dalam suplai oksigen ke mitokondria dan melindungi jaringan otak dari kerusakan akibat hipoksia (neuroprotektan). Perubahan ekspresi protein merupakan salah satu bentuk adaptasi biokimia yang penting terhadap perubahan homeostasis. Oleh karena itu timbul pertanyaan bagaimana pola ekspresi Ngb dan Cygb serta peran neuroprotektan kedua protein tersebut di otak pada keadaan hipoksia sistemik kronik (HSK). Penelitian bertujuan manganalisis perbedaan pola ekspresi Ngb dan Cygb serta kaitannya dengan apoptosis pada HSK. Parameter yang diukur adalah Ngb, Cygb, sitokrom c, MDA, GSH dan HIF-lα. Rancangan penelitian yang digunakan adalah studi eksperimental in vivo model HSK pada tikus. Tikus sebagai hewan coba dibagi secara acak dalam 6 kelompok perlakuan, yaitu kelompok I adalah kelompok kontrol atau tanpa perlakuan hipoksia, sedangkan kelompok II, III, IV, V, dan VI mendapat perlakuan hipoksia dengan lama waktu hipoksia selama 1, 3, 5, 7, dan 14 hari. Parameter yang diperiksa meliputi ekspresi Ngb dan Cygb dengan teknik real time-RT PCR, ELISA dan imunofluoresen FITC, stres oksidatif, HIF-1α sebagai penanda hipoksia, dan sitokrom c sebagai penanda apoptosis. Hasil yang diperoleh HSK meningkatkan ekspresi mRNA Ngb pada hipoksia 3, 5, dan 7 hari, namun ekspresi proteinnya menurun pada hipoksia 1, 3, 5, 7, dan 14 hari dibanding dengan kontrol. Berbeda dengan ekspresi mRNA Cygb yang menurun selama hipoksia 1, 3, 5, 7, dan 14 hari, namun protein Cygb meningkat pada hipoksia 1, 3, 5, 7, dan 14 hari dibandingkan dengan kontrol. Korelasi Ngb dengan sitokrom c lemah tidak signifikan, sedangkan Cygb sangat lemah dan tidak signifikan. HSK menginduksi ekspresi HIF-lα yang meningkat tertinggi pada hipoksia 7 hari, dan menyebabkan stres oksidatif yang ditandai dengan meningkatnya MDA pada hipoksia 1, 3 dan 5 hari, serta menurunnya GSH pada hipoksia 1, 3, dan 5 hari. Penelitian ini membuktikan bahwa terdapat perbedaan pola ekspresi Ngb dan Cygb pada HSK. Ekspresi Ngb sebagai respons adaptasi terjadi lebih awal dan lebih dipengaruhi oleh lama waktu hipoksia dibandingkan dengan ekspresi Cygb. Meskipun lemah, Ngb cenderung mempunyai peran menghambat apoptosis dibandingkan dengan protein Cygb.;

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ABSTRACTHypoxia has an important role in the pathophysiology of high mortality diseases, such as ischemic cardiovascular disease, stroke, cancer, chronic lung disease, and congestive heart failure. The proteins belonged to globin protein group, included neuroglobin (Ngb) and cytoglobin (Cygb), have been presumed to play a role in regulating the oxygen supply into the mitochondria and protecting the brain tissues from damage due to hypoxia (neuroprotectant). An alteration in protein expression due to a homeostatic shift is an important adaptation process in biochemistry. Therefore, the expression pattern of Ngb and Cygb as well as their protein roles in brain during a chronic systemic hypoxia condition (CSH) remain unclear. This study aim to analyse the differences of the Ngb and Cygb expression patterns, and correlation of both protein to apoptosis in chronic systemic hypoxic condition. Ngb, Cygb, Cytochrome c, MDA, GSH, and HIF-1 α. were examined. An in vivo experimental model of CSH was carried out using rat. The experimental rats were randomly divided into 6 treatment groups, i.e. group I was a control group or without hypoxic condition, groups II, III, IV, V, and VI were treated by hypoxic condition for 1, 3, 5, 7, and 14 days, respectively. The Ngb and Cygb expressions were analysed using real time-RTPCR, ELISA, immunofluorescence with FITC, and the measurement of stress oxidative biomarkers, included HIF-1α as a biomarker of hypoxic condition and cytochrome c as a biomarker of apoptosis. The CSH was increased the mRNA expression of Ngb at 3, 5, and 7 days hypoxic groups, while the protein expression was decreased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The mRNA expression of Cygb was decreased at 1, 3, 5, 7, and 14 days hypoxic groups, whereas the Cygb protein expression was increased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The correlation between Ngb with cytochrome c was weakly statistically insignificant, and Cygb with cytochrome c was statistically insignificant. The CSH induced the HIFlα, which was shown by a high increase at 7 days hypoxic group, as well as stress oxidative which was represented by MDA at 1, 3, and 5 days hypoxic groups, and decreased GSH at 1, 3, and 5 days hypoxic groups. There are differences in expression pattern of Ngb and Cygb in CSH. The expression of Ngb, as an adaptive response, occurs earlier and is more influenced by the duration of hypoxic condition compared to Cygb. Although the correlation is weak, the Ngb seems more likely to inhibit apoptosis compared to Cygb protein;Hypoxia has an important role in the pathophysiology of high mortality diseases, such as ischemic cardiovascular disease, stroke, cancer, chronic lung disease, and congestive heart failure. The proteins belonged to globin protein group, included neuroglobin (Ngb) and cytoglobin (Cygb), have been presumed to play a role in regulating the oxygen supply into the mitochondria and protecting the brain tissues from damage due to hypoxia (neuroprotectant). An alteration in protein expression due to a homeostatic shift is an important adaptation process in biochemistry. Therefore, the expression pattern of Ngb and Cygb as well as their protein roles in brain during a chronic systemic hypoxia condition (CSH) remain unclear. This study aim to analyse the differences of the Ngb and Cygb expression patterns, and correlation of both protein to apoptosis in chronic systemic hypoxic condition. Ngb, Cygb, Cytochrome c, MDA, GSH, and HIF-1 α. were examined. An in vivo experimental model of CSH was carried out using rat. The experimental rats were randomly divided into 6 treatment groups, i.e. group I was a control group or without hypoxic condition, groups II, III, IV, V, and VI were treated by hypoxic condition for 1, 3, 5, 7, and 14 days, respectively. The Ngb and Cygb expressions were analysed using real time-RTPCR, ELISA, immunofluorescence with FITC, and the measurement of stress oxidative biomarkers, included HIF-1α as a biomarker of hypoxic condition and cytochrome c as a biomarker of apoptosis. The CSH was increased the mRNA expression of Ngb at 3, 5, and 7 days hypoxic groups, while the protein expression was decreased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The mRNA expression of Cygb was decreased at 1, 3, 5, 7, and 14 days hypoxic groups, whereas the Cygb protein expression was increased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The correlation between Ngb with cytochrome c was weakly statistically insignificant, and Cygb with cytochrome c was statistically insignificant. The CSH induced the HIFlα, which was shown by a high increase at 7 days hypoxic group, as well as stress oxidative which was represented by MDA at 1, 3, and 5 days hypoxic groups, and decreased GSH at 1, 3, and 5 days hypoxic groups. There are differences in expression pattern of Ngb and Cygb in CSH. The expression of Ngb, as an adaptive response, occurs earlier and is more influenced by the duration of hypoxic condition compared to Cygb. Although the correlation is weak, the Ngb seems more likely to inhibit apoptosis compared to Cygb protein;Hypoxia has an important role in the pathophysiology of high mortality diseases, such as ischemic cardiovascular disease, stroke, cancer, chronic lung disease, and congestive heart failure. The proteins belonged to globin protein group, included neuroglobin (Ngb) and cytoglobin (Cygb), have been presumed to play a role in regulating the oxygen supply into the mitochondria and protecting the brain tissues from damage due to hypoxia (neuroprotectant). An alteration in protein expression due to a homeostatic shift is an important adaptation process in biochemistry. Therefore, the expression pattern of Ngb and Cygb as well as their protein roles in brain during a chronic systemic hypoxia condition (CSH) remain unclear. This study aim to analyse the differences of the Ngb and Cygb expression patterns, and correlation of both protein to apoptosis in chronic systemic hypoxic condition. Ngb, Cygb, Cytochrome c, MDA, GSH, and HIF-1 α. were examined. An in vivo experimental model of CSH was carried out using rat. The experimental rats were randomly divided into 6 treatment groups, i.e. group I was a control group or without hypoxic condition, groups II, III, IV, V, and VI were treated by hypoxic condition for 1, 3, 5, 7, and 14 days, respectively. The Ngb and Cygb expressions were analysed using real time-RTPCR, ELISA, immunofluorescence with FITC, and the measurement of stress oxidative biomarkers, included HIF-1α as a biomarker of hypoxic condition and cytochrome c as a biomarker of apoptosis. The CSH was increased the mRNA expression of Ngb at 3, 5, and 7 days hypoxic groups, while the protein expression was decreased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The mRNA expression of Cygb was decreased at 1, 3, 5, 7, and 14 days hypoxic groups, whereas the Cygb protein expression was increased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The correlation between Ngb with cytochrome c was weakly statistically insignificant, and Cygb with cytochrome c was statistically insignificant. The CSH induced the HIFlα, which was shown by a high increase at 7 days hypoxic group, as well as stress oxidative which was represented by MDA at 1, 3, and 5 days hypoxic groups, and decreased GSH at 1, 3, and 5 days hypoxic groups. There are differences in expression pattern of Ngb and Cygb in CSH. The expression of Ngb, as an adaptive response, occurs earlier and is more influenced by the duration of hypoxic condition compared to Cygb. Although the correlation is weak, the Ngb seems more likely to inhibit apoptosis compared to Cygb protein;Hypoxia has an important role in the pathophysiology of high mortality diseases, such as ischemic cardiovascular disease, stroke, cancer, chronic lung disease, and congestive heart failure. The proteins belonged to globin protein group, included neuroglobin (Ngb) and cytoglobin (Cygb), have been presumed to play a role in regulating the oxygen supply into the mitochondria and protecting the brain tissues from damage due to hypoxia (neuroprotectant). An alteration in protein expression due to a homeostatic shift is an important adaptation process in biochemistry. Therefore, the expression pattern of Ngb and Cygb as well as their protein roles in brain during a chronic systemic hypoxia condition (CSH) remain unclear. This study aim to analyse the differences of the Ngb and Cygb expression patterns, and correlation of both protein to apoptosis in chronic systemic hypoxic condition. Ngb, Cygb, Cytochrome c, MDA, GSH, and HIF-1 α. were examined. An in vivo experimental model of CSH was carried out using rat. The experimental rats were randomly divided into 6 treatment groups, i.e. group I was a control group or without hypoxic condition, groups II, III, IV, V, and VI were treated by hypoxic condition for 1, 3, 5, 7, and 14 days, respectively. The Ngb and Cygb expressions were analysed using real time-RTPCR, ELISA, immunofluorescence with FITC, and the measurement of stress oxidative biomarkers, included HIF-1α as a biomarker of hypoxic condition and cytochrome c as a biomarker of apoptosis. The CSH was increased the mRNA expression of Ngb at 3, 5, and 7 days hypoxic groups, while the protein expression was decreased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The mRNA expression of Cygb was decreased at 1, 3, 5, 7, and 14 days hypoxic groups, whereas the Cygb protein expression was increased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The correlation between Ngb with cytochrome c was weakly statistically insignificant, and Cygb with cytochrome c was statistically insignificant. The CSH induced the HIFlα, which was shown by a high increase at 7 days hypoxic group, as well as stress oxidative which was represented by MDA at 1, 3, and 5 days hypoxic groups, and decreased GSH at 1, 3, and 5 days hypoxic groups. There are differences in expression pattern of Ngb and Cygb in CSH. The expression of Ngb, as an adaptive response, occurs earlier and is more influenced by the duration of hypoxic condition compared to Cygb. Although the correlation is weak, the Ngb seems more likely to inhibit apoptosis compared to Cygb protein, Hypoxia has an important role in the pathophysiology of high mortality diseases, such as ischemic cardiovascular disease, stroke, cancer, chronic lung disease, and congestive heart failure. The proteins belonged to globin protein group, included neuroglobin (Ngb) and cytoglobin (Cygb), have been presumed to play a role in regulating the oxygen supply into the mitochondria and protecting the brain tissues from damage due to hypoxia (neuroprotectant). An alteration in protein expression due to a homeostatic shift is an important adaptation process in biochemistry. Therefore, the expression pattern of Ngb and Cygb as well as their protein roles in brain during a chronic systemic hypoxia condition (CSH) remain unclear. This study aim to analyse the differences of the Ngb and Cygb expression patterns, and correlation of both protein to apoptosis in chronic systemic hypoxic condition. Ngb, Cygb, Cytochrome c, MDA, GSH, and HIF-1 α. were examined. An in vivo experimental model of CSH was carried out using rat. The experimental rats were randomly divided into 6 treatment groups, i.e. group I was a control group or without hypoxic condition, groups II, III, IV, V, and VI were treated by hypoxic condition for 1, 3, 5, 7, and 14 days, respectively. The Ngb and Cygb expressions were analysed using real time-RTPCR, ELISA, immunofluorescence with FITC, and the measurement of stress oxidative biomarkers, included HIF-1α as a biomarker of hypoxic condition and cytochrome c as a biomarker of apoptosis. The CSH was increased the mRNA expression of Ngb at 3, 5, and 7 days hypoxic groups, while the protein expression was decreased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The mRNA expression of Cygb was decreased at 1, 3, 5, 7, and 14 days hypoxic groups, whereas the Cygb protein expression was increased at 1, 3, 5, 7, and 14 days hypoxic groups compared to control group. The correlation between Ngb with cytochrome c was weakly statistically insignificant, and Cygb with cytochrome c was statistically insignificant. The CSH induced the HIFlα, which was shown by a high increase at 7 days hypoxic group, as well as stress oxidative which was represented by MDA at 1, 3, and 5 days hypoxic groups, and decreased GSH at 1, 3, and 5 days hypoxic groups. There are differences in expression pattern of Ngb and Cygb in CSH. The expression of Ngb, as an adaptive response, occurs earlier and is more influenced by the duration of hypoxic condition compared to Cygb. Although the correlation is weak, the Ngb seems more likely to inhibit apoptosis compared to Cygb protein]"

"Manusia telah beradaptasi dengan kehidupan di tempat tinggi sejak ribuan tahun lalu. Secara alami telah terjadi proses adaptasi fisiologis sebagai mekanisme kompensasi terhadap hipoksia karena berkurangnya tekanan oksigen di udara. Penelitian ini dilakukan untuk mengetahui gambaran tentang aktivitas spesifik katalase pada jaringan jantung tikus percobaan hipoksia hipobarik akut berulang. Sebanyak 25 hewan percobaan dibagi menjadi lima kelompok, yaitu kelompok perlakuan yang mendapat perlakuan hipoksia hipobarik (dalam hypobaric chamber), terdiri dari 4 (empat) kelompok yaitu kelompok E (terpapar 1 (satu) kali hipoksia hipobarik dalam hypobaric chamber), kelompok F (terpapar dua kali hipoksia hipobarik dalam hypobaric chamber), kelompok G (terpapar tiga kali hipoksia hipobarik dalam hypobaric chamber), dan terakhir kelompok H (terpapar 4 kali hipoksia hipobarik dalam hypobaric chamber), dan kelompok kontrol yang tidak diberikan perlakuan. Dari hasil penelitian diperoleh rata-rata aktivitas spesifik katalase jaringan jantung kelompok kontrol sebesar 0.06762±0.02862 U/mg protein, kelompok E sebesar 0.07480±0.02463 U/mg protein, kelompok F 0.19835±0.04879 U/mg protein, kelompok G 0.08580±0.02600 U/mg protein, dan kelompok H sebesar 0.09533±0.02691 U/mg protein.Hasil penelitian tersebut menunjukkan bahwa aktivitas spesifik katalase jantung paling tinggi didapatkan pada kelompok perlakuan dua kali prosedur hypobaric chamber (kelompok F) yang kemudian menurun kembali pada tiga kali prosedur (kelompok G) dan empat kali prosedur (kelompok H). Dari uji statistik diketahui, hanya kelompok yang dua kali terpapar hipoksia hipobarik (kelompok F) yang berbeda bermakna dengan kelompok kontrol.

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Human being has adapted well in high altitude since many years ago. There are some physiological process of adaptation as a response to hypoxia in the high altitude. This mechanism is due to the decrease of oxygen pressure in the air in the high altitude. The aim of this study was to investigate the spesific activity of catalase in rat heart tissue induced by acute intermittent hypoxia hypobaric. 25 tested animal were divided into 5 groups. The groups were the experimental groups induced by hipoxia hypobaric in hypobaric chamber and the control group. Those experimental groups then divided into four groups. They were group E (only one time induced by hypoxia hypobaric), group F (two times induced by hypoxia hypobaric), group G (three times induced by hypoxia hypobaric), and group H (four times induced by hypoxia hypobaric). This research found that mean+S.D of specific activity of catalase in rat heart tissue of each groups are 0.06762±0.02862 U/mg protein for control group, 0.07480±0.02463 U/mg protein for group E, 0.19835±0.04879 U/mg protein for group F, 0.08580±0.02600 U/mg protein for group G, and 0.09533±0.02691 U/mg protein for group H.Those results showed that the specific activity of catalase in rat heart tissue reached its peak in group F and decreased almost toward normal in group G and group H. Statistical test of those results showed that only group F was significantly different in comparison with control group."

"Hipoksia pada ketinggian diketahui menyebabkan stress oksidatif. Dilakukan penelitian mengenai aktivitas spesifik katalase pada jaringan hati tikus dengan metode spektrofotometri untuk mengukur pemecahan hidrogen peroksida. Tikus dipajankan pada hipoksia hipobarik akut berulang dengan simulasi ketinggian 35,000 kaki yang diturunkan bertahap ke ketinggian 25,000 kaki, 20,000 kaki, lalu 18,000 kaki. Hewan uji dibagi ke dalam 4 kelompok: 1) diberi 1 kali perlakuan, 2) diberi 2 kali perlakuan, 3) diberi 3 kali perlakuan, 4)diberi 4 kali perlakuan, dengan setiap prosedur diselingi periode normoksia selama 7 hari. Hipoksia menyebabkan penurunan aktivitas spesifik katalase pada semua kelompok uji. Penurunan bermakna didapatkan pada kelompok 2 (p = 0.008), 3 (p = 0.008), dan 4 (p = 0.008). Hasil pada kelompok 1 tidak menunjukkan perbedaan bermakna dibandingkan kontrol (p = 0.548). Hipoksia hipobarik menginduksi penurunan aktivitas spesifik katalase hati.

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Hypoxia at high altitude is known as a cause of oxidative stress. Specific activity of catalase in rat liver submitted to recurrent acute hypobaric hypoxia were studied by means of measuring the breakdown of hydrogen peroxide spectrophotometrically. Animals were submitted to simulated altitudes of 35,000 ft lowered gradually to 25,000 ft, 20,000, and 18,000 ft. The experimental groups were as follows: 1) rats exposed to one procedure, 2) exposed to two procedures, repeatedly, 3) exposed to three-times of procedures, and 4) exposed to four-times of procedures, each procedure was interrupted with 7 days period of normoxia. Hypoxia produced a decrease in specific activity of liver catalase in all experimental groups. Significant decreases were showed in group 2 (p = 0.008), 3 (p = 0.008), and 4 (p = 0.008). Group 1 showed no significant difference compared to control group (p = 0.548). Hypobaric hypoxia induces a decrease in the specific activity of catalase in rat liver."

"Otak merupakan organ yang memiliki kebutuhan oksigen dan glukosa tertinggi di tubuh. Rendahnya tekanan oksigen pada otak dapat memicu terjadinya kerusakan pada sel otak bahkan kematian sel. Hipoksia merupakan kondisi penurunan kadar oksigen pada organ, jaringan atau sel. Hipoksia yang diberikan pada kadar dan waktu tertentu dapat menimbulkan respons adaptasi tubuh sehingga kondisi hipoksia dapat ditanggulangi. Salah satu respons adaptasi yang dilakukan adalah autofagi. Autofagi adalah suatu proses degradasi dan daur ulang molekul sitoplasmik dan organel seperti mitokondria dengan bantuan lisosom yang berperan dalam menjaga homeostasis seluler. Penelitian ini dilakukan untuk mengetahui efek pemberian hipoksia hipobarik intermiten terhadap aktivitas autofagi sel melalui ekspresi protein LC3 dan mTOR pada jaringan otak tikus. Penelitian ini menggunakan sampel jaringan otak tikus jenis Sprague-Dawley. Tikus dibagi dalam lima kelompok, yaitu kelompok kontrol, kelompok hipoksia 1 kali (HHI 1), HHI 2, HHI 3 dan HHI 4. Setiap kelompok hipoksia akan dimasukan dalam hypobaric chamber dan dibawa sampai ketinggian 25.000 kaki selama 5 menit. Tikus kemudian dikorbankan dan dilakukan pengukuran ekspresi protein LC3 dan mTOR menggunakan metode ELISA. Ekspresi protein LC3 juga dianalisis dengan IHK. Hasil menunjukkan bahwa pemberian perlakuan hipoksia hipobarik intermiten mampu meningkatkan ekspresi protein LC3 dan mempertahankan ekspresi mTOR. Hasil pulasan IHK menunjukkan ekspresi protein LC3 lebih tinggi pada bagian cerebellum otak dibandingkan dengan bagian cerebrum pada setiap kelompok.

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The brain is an organ with the highest demand for oxygen and glucose in the body. Insufficient oxygen pressure in the brain can lead to damage to brain cells and even cell death. Hypoxia is a condition characterized by a decrease in the oxygen levels in organs, tissues, or cells. Hypoxia, when applied at specific levels and durations, can induce adaptive responses in the body, allowing it to cope with the hypoxic conditions. One such adaptive response is autophagy. Autophagy is a cellular process involving the degradation and recycling of cytoplasmic molecules and organelles, including mitochondria, facilitated by lysosomes. This process plays a crucial role in maintaining cellular homeostasis. This study aimed to investigate the effects of intermittent hypobaric hypoxia on autophagic activity in brain cells by assessing the expression of proteins LC3 and mTOR during hypoxic conditions. The experimental subjects were Sprague-Dawley rats, and they were divided into five groups: a control group, and four groups subjected to intermittent hypobaric hypoxia (IHH) for varying durations (IHH1, IHH2, IHH3, and IHH4). Each IHH group was exposed to a hypobaric chamber at an altitude of 25,000 feet for 5 minutes. Subsequently, the rats were sacrificed, and the expression of LC3 and mTOR proteins was measured using ELISA. The LC3 protein expression was also analyzed through immunohistochemistry (IHC). The results showed that intermittent hypobaric hypoxia treatment increased the expression of LC3 protein and maintained mTOR expression. Additionally, IHC feedback indicated higher LC3 protein expression in the cerebellum region compared to the cerebrum in each experimental group."

"Kondisi hipoksia sangat berhubungan dengan manusia yang tinggal di tempat yang tinggi. Kondisi ini menyebabkan perubahan-perubahan fisiologis tubuh, seperti meningkatnya pernafasan, produksi sel darah merah dan angiogenesis disertai dengan peningkatan stress oksidatif pada tingkat sel. Serebelum memiliki peran penting dalam hidup manusia. Fungsinya meliputi keseimbangan tubuh, fungsi kognitif dan koordinasi motorik. Dari penelitian sebelumnya, telah ditemukan bahwa hipoksia menyebabkan terganggunya keseimbangan dan juga meningkatnya stres oksidatif pada otak kecil. Sebelumnya, tikus-tikus telah diberikan perlakuan hipobarik hipoksia intermiten.Pada percobaan ini, aktivitas spesifik katalase pada serebelum diukur dengan metode Mates et al pada homogenat serebelum dari tikus-tikus yang telah diberikan perlakuan hipobarik hipoksia intermiten.Hasil penelitian menunjukkan aktivitas spesifik katalase tidak meningkat secara bermakna pada semua kelompok dibanding control dengan uji ANOVA p= 0.116 . Hal ini kemungkinan disebabkan oleh rendahnya aktivitas katalase dalam serebelum dan adanya perbedaan aktivitas katalase pada berbagai lapisan serebelum.

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Hypoxia condition has been linked to people that lived in higher altitudes. This particular condition has effects to the physiological of human body such as increase respiratory rate, angiogenesis and reactive oxidative stress in cellular level. Cerebellum has a key role in human physiologic function. It is responsible for balance function, cognitive function and motor coordination. From previous research, hypoxia has caused postural imbalance and increased oxidative stress in cerebellum.In this experiment, the specific activity of catalase of rat`s cerebellum is measured by Mates et al. method with the homogenate of cerebellum of rat`s which as been exposed to intermittent hypobaric hypoxia.The research showed the catalase specific activity of cerebellum did not increase significantly in all groups compared to control group after being analyzed by ANOVA p 0.116 . The insignificant result can be affected by many factors such as little amount of catalase in cerebellum and difference catalase activity in cerebellar layers."