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"BACE (β-site of APP cleaving enzyme) is a critical component in Alzheimer's Disease (AD), and the development of BACE inhibitors shows great potential as a therapy for the disease. BACE : lead target for orchestrated therapy of alzheimer's disease covers virtually all aspects of BACE from initial identification, discovery of inhibitors, and challenges in clinical development, while providing a global understanding essential for productive and successful drug discovery."

"In this ground–breaking practical reference, the family of aspartic acid proteases is described from a drug developer′s perspective. The first part provides a general introduction to the family of aspartic acid proteases, their physiological functions, molecular structure and inhibition. Parts two to five present various case studies of successful protease inhibitor drug design and development, as well as current and potential uses of such inhibitors in pharmaceutical medicine, covering the major therapeutic targets HIV–1 protease, renin, beta–secretase, gamma–secretase,plasmepsins and fungal proteases. "

"ABSTRAKLatar Belakang: Glukokortikoid berperan penting dalam pengobatan leukemia limfoblastik akut (LLA), namun dapat menimbulkan efek samping berupa gangguan pada aksis hipotalamus-hipofisis-adrenal (HHA). Penekanan aksis HHA menyebabkan respons kortisol terhadap stres berkurang sehingga merupakan penyebab morbiditas dan mortalitas LLA pada anak.Tujuan: Mengetahui fungsi kelenjar adrenal pada anak dengan LLA setelah kemoterapi fase induksi dengan glukokortikoid dosis tinggi.Metode: Penelitian bersifat before and after dengan menilai fungsi kelenjar adrenal pada pasien LLA baru sebelum kemoterapi fase induksi yang mendapatkan prednison atau deksametason oral selama 6 minggu dan setelah tapering off glukokortikoid selama 1 minggu. Sebanyak 20 subjek dari 4 rumah sakit di Jakarta direkrut dan dianalisis. Penilaian fungsi kelenjar adrenal dilakukan dengan uji stimulasi ACTH dosis standar (250 μg).Hasil: Dari 20 subjek, terdapat 14 subjek yang mengalami insufisiensi adrenal pasca-kemoterapi fase induksi berdasarkan kriteria peningkatan kortisol pasca-uji <18 μg/dL. Nilai median kadar kortisol pra-uji dan pasca-uji sebelum kemoterapi berturut-turut adalah 14,72 μg/dL (2,01 – 46,1 μg/dL) dan 29,29 μg/dL (21,65 – 55,15 μg/dL), dan kadar kortisol pra-uji dan pasca-uji sesudah kemoterapi berturut-turut adalah 5,87 μg/dL (0,2 – 20,53 μg/dL) dan 10,49 μg/dL (0,33 – 28,69 μg/dL). Gejala klinis tidak berbeda bermakna antara subjek yang mengalami insufisiensi adrenal dengan yang mereka tidak mengalami insufisiensi adrenal.Simpulan: Sebanyak 14 dari 20 subjek mengalami insufisiensi adrenal setelah mendapatkan glukokortikoid dosis tinggi selama kemoterapi fase induksi walaupun telah tapering off selama 1 minggu. Tidak ada gejala klinis yang spesifik ditemukan berkaitan dengan insufisiensi adrenal.

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ABSTRACTBackground: Glucocorticoids play an important role in the treatment of acute lymphoblastic leukemia (ALL), but can cause side effects such as suppression of the hypothalamic-pituitary-adrenal (HHA) axis. Suppression of the HHA axis causes adrenal insufficiency and disturb cortisol response to stress and may be a cause of morbidity and mortality in children ALL.Objective: To evaluate adrenal function in children with ALL after induction chemotherapy with high dose glucocorticoids.Methods: Twenty children with ALL were evaluated using standard dose (250 μg) adrenocorticotropin hormone (ACTH) test before and after their treatment with prednisone or dexamethasone for 6 weeks of induction phase followed by 1 week tapering off.Results: Adrenal insufficiency was found in 14 of 20 subjects after induction phase followed by 1-week tapering off based on cortisol post-stimulation <18 μg/dL. The median of cortisol pre- and post-stimulation before induction phase are 14,72 μg/dL (2,01 – 46,1 μg/dL) and 29,29 μg/dL (21,65 – 55,15 μg/dL), dan cortisol pre- and post-stimulation after induction phase are 5,87 μg/dL (0,2 – 20,53 μg/dL) dan 10,49 μg/dL (0,33 – 28,69 μg/dL). Clinical signs and symptoms did not differ between those who had adrenal insufficiency with those who did not have adrenal insufficiency.Conclusions: Fourteen out of 20 children with ALL developed adrenal insufficiency after a 6-week induction therapy with glucocorticoids and 1-week tapering off. No specific clinical signs and symptoms were related to adrenal insufficiency."

"Alzheimer merupakan penyebab paling umum dari demensia dan penyakit dengan jumlah pasien yang terus meningkat setiap tahunnya. β-Site Amyloid Precursor Protein Cleaving Enzyme1 (BACE1) diketahui sebagai protein yang sangat toksik dan dapat memicu penyakit Alzheimer. Propolis dengan flavonoid yang terkandung di dalamnya dilaporkan memiliki sifat pelindung saraf dalam studi in vitro dan in vivo melalui tindakan antioksidan, anti-inflamasi, dan imunomodulator. Pada penelitian ini, dilakukan studi in silico untuk mengetahui interaksi protein target BACE1 dan ligan pada senyawa propolis lokal Indonesia dengan melakukan molecular docking. Senyawa ligan yang digunakan pada penelitian ini yaitu, Sulawesin A, Broussoflanovol F, Sulawesin B, Glyasperin A, Deoxy-podophyllotoxin, Isorhamnetin, Xanthoxyletin, (--)- Isocalolongic acid, 2’,3’-Dihydro-3’-hydroxypapuanic acid, Isopapuanic acid, (1’s)-2-Cis,4 trans-abscisic acid, Curcumene, (1’s)-2-Trans,4 trans-abscisic acid, Tetraline, P-coumaric acid, dan Thymol. Hasil menunjukkan bahwa molecular docking antara protein target BACE1 dengan native ligand memiliki nilai docking terbaik yaitu, -11 kkal/mol. Sedangkan, senyawa ligan yang memiliki nilai docking terbaik yaitu, Sulawesin A dengan nilai -9,3 kkal/mol.

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Alzheimer's is the most common cause of dementia and disease with the number of patients increasing every year. β-Site Amyloid Protein Precursor Cleaving Enzyme1 (BACE1) is known as a highly toxic protein and can trigger Alzheimer's disease. Propolis with flavonoids contained in it is reported to have neuroprotective properties in in-vitro and in-vivo studies through its antioxidant, anti-inflammatory, and immunomodulatory actions. In this study, an in-silico study was conducted to determine the interaction of the target protein BACE1 and its ligand on local Indonesian propolis compounds by molecular docking. The ligand compounds used in this study were Sulawesin A, Broussoflanovol F, Sulawesin B, Glyasperin A, Deoxy-podophyllotoxin, Isorhamnetin, Xanthoxyletin, (--)-Isocalolongic acid, 2',3'-Dihydro-3'-hydroxypapuanic acid., Isopapuanic acid, (1's)-2-Cis,4 trans-abscisic acid, Curcumene, (1's)-2-Trans,4 trans-abscisic acid, Tetraline, P-coumaric acid, and Thymol. The results showed that the molecular docking between BACE1 protein target and native ligand had the best docking value, namely -11 kcal/mol. Meanwhile, the ligand compound that has the best docking value is Sulawesin A with a value of -9.3 kcal/mol."

"Penelitian ini bertujuan menilai efektivitas dan keamanan Acetylcholinesterase Inhibitor Galantamine pada penderita Alzheimer dan Alzheimer?s Disease (AD) yang disertai dengan penyakit serebrovaskular (AD+CVD atau Mixed Dementia). Galantamine diberikan selama 6 bulan pada 28 penderita AD dan AD + CVD. Evaluasi kognitif dilakukan dengan menggunakan Mini Mental State Examination (MMSE), Restricted Reminding (RR), Neuropsycholgy Assessment, evaluasi fungsi global dengan Clinical Dementia Rating (CDR), evaluasi perubahan perilaku dengan Neuropsychiatric Inventory (NPI). Hasil penelitian pada 28 penderita AD dan AD + CVD, Galantamine memberikan perbaikan fungsi kognitif yang bermakna secara klinis maupun statistik setelah terapi 6 bulan dibandingkan data dasar awal (skor MMSE p<0.05, skor RR p<0.05, NA p<0.05), perbaikan fungsi global (CDR p<0.05) dan perbaikan gejala perilaku (NPI p<0.05). Efek samping ringan (32%) mual-mual dan anokresia terjadi saat titrasi dosis obat dan dapat diatasi dengan domperidone. Disimpulkan bahwa Galantamine efektif memberikan perbaikan fungsi kognitif, fungsi global, gejala perilaku dan aman serta dapat ditoleransi dengan baik. (Med J Indones 2007; 16:94-100).

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This study was aimed to evaluate the efficacy and safety of Acetylcholinesterase Inhibitor Galantamine (Reminyl®) for patients with Alzheimer?s Disease (AD) and Alzheimer?s Disease with cerebrovascular Disease (AD+CVD or mixed Dementia). A 6-month open label observational study of Galantamine has been conducted on 28 patients with AD and AD+CVD patients. Primary endpoints were cognitive performance as assessed using the Mini Mental Scale Examination (MMSE), the Restricted Reminding Test), the Neuropsychology Assessment, the Clinical Dementia Rating (CDR) to assess global function and the Neuropsychiatric Inventory (NPI) to assess behavioral symptoms. Patients were also monitored for safety evaluation. Six month Galantamine group had a significant better outcome of cognitive performance, global function and behavioral symptoms compared with the baseline data as were assessed using the MMSE (p<0.05), the Restricted Reminding (p<0.05), the Neuropsychology Assessment (p<0.05), the CDR (p<0.05) and the NPI (p<0.05). Minimal adverse events (32%) were anorexia and nausea. It is concluded that Galantamine has a significant benefit to improve cognitive, global function, behavioral symptoms and only caused minimal adverse events. (Med J Indones 2007; 16:94-100)."

"This book provides an overview of different protein kinases, structure, function, regulation, and their role in cancer. It combines kinase biology with chemistry and pharmacology applications for discovery and development of cancer drugs. The text also describes existing and emerging kinase inhibitors, focusing mostly on small molecules but also alternative approaches like therapeutic antibodies. Provides an important resource that helps pharmaceutical researchers understand and work in this dynamic area of cancer drug research."

"Alzheimer dikategorikan sebagai salah satu dimensia berat dengan bentuk otak yang mengalami penyusutan dan volume otak berkurang secara keseluruhan. Selain itu, Alzheimer juga mengakibatkan terjadinya atrophy pada bagian hippocampus. Korelasi antara penyusutan bentuk otak dan berkurangnya volume juga mempengaruhi perubahan bentuk tekstur. Pada penelitian yang diusulkan, perluasan dari Local Binary Pattern (LBP) sebagai ekstraksi fitur diperkenalkan. Complete Local Binary Pattern of Sign and Magnitude (CLBPSM) dan Complete Local Binary Pattern of Sign and Magnitude from Three Orthogonal Planes (CLBPSM-TOP) diperkenalkan sebagai deskriptor ekstraksi fitur 2D dan 3D. Dikarenakan fitur yang begitu banyak dihasilkan, maka Principal Component Analysis (PCA), kernel PCA dan Factor Analysis (FA) digunakan sebagai salah satu metode seleksi fitur. Selanjutnya, lima buah classifier digunakan untuk klasifikasi binary class dan multiclass dari Alzheimer, mild cognitive impairment dan normal pada bagian keseluruhan otak dan hippocampus. Hasil eksperimen dengan tiga buah skenario menunjukkan bahwa metode CLBPSM dan CLBPSMTOP mampu memberikan hasil akurasi dan performance yang lain dengan nilai rata-rata antara 70% - 100% untuk bagian keseluruhan otak dan hippocampus. Pendekatan CLBPSM-TOP sebagai deskriptor 3D juga menggungguli metode LBP-TOP pada studi literatur dengan rata-rata kenaikan akurasi sebesar 30% untuk semua klasifikasi.

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Alzheimer`s disease is categorized as one of heavy dementia with the brain forms will shrink, and reduced overall volume of brain. The correlation between brain form shrinkage and reduction of brain volume also affect deformation texture. In the proposed research, the expansion of local binary pattern (LBP) as feature extraction method is introduced. Complete local binary pattern of sign and magnitude (CLBPSM) and complete local binary pattern of sign and magnitude from three orthogonal planes (CLBPSM-TOP) are introduced as a 2D and 3D feature extraction descriptor. Due to so many features are generated, then the principal component analysis (PCA), kernel PCA and Factor Analysis (FA) are used as a method of feature selection. Furthermore, five classifiers are used for binary class and multiclass classification of Alzheimer's, mild cognitive impairment and normal in the whole brain and hippocampus. The experimental results with three scenarios show that CLBPSM and CLBPSM-TOP methods are able to provide accuracy and the other performance results with an average value between of 70% - 100% for the whole brain and hippocampus. CLBPSM-TOP approach as a 3D descriptor also outperformed LBP-TOP method from the previous study with an average accuracy increase 30% for all classifications."