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"This book gives an updated and expert overview of nuclear hormone receptors in drug metabolism and drug development and equips you with the interdisciplinary understanding of these receptors and how they can be regulated. Pharmaceutical researchers will find this extremely useful in developing drugs for cancer, heart disease, and diabetes treatment. This comprehensive resource collects scattered materials into one handy, informative volume."

"The book covers a broad spectrum of topics, ranging from pioneering research in the field of classical steroid hormones to very recently discovered orphan receptors and their modulators. State of the art technologies are also discussed in the individual chapters that help to develop a deeper insight into the biochemical and pharmacological principles underlying the biological function of nuclear receptors.Edited by two experts working at the pioneering pharmaceutical company and major global player in hormone-derived drugs, this handbook and reference systematically treats the drug development aspects of all human nuclear receptors, including recently characterized receptors such as PPAR, FXR and LXR. Authors from leading pharmaceutical companies around the world present examples and real-life data from their own work."

"Opening with a general introduction on chemokine function and chemokine receptor biology, the handbook goes on to cover the known implications of these signaling molecules in human diseases, such as cancer, neural disorders, and viral infection, including HIV/AIDS. The second half of the book systematically surveys current drug development efforts at targeting individual chemokine receptors, as well as other chemokine interaction partners. Contributions in the first part of the book are mainly from academia, whereas the second part contains up-to-date reports from the pharmaceutical industry."

"The essentials of drug metabolism vital to developing new therapeutic entities.Information on the metabolism and disposition of candidate drugs is a critical part of all aspects of the drug discovery and development process. Drug metabolism, as practiced in the pharmaceutical industry today, is a complex, multidisciplinary field that requires knowledge of sophisticated analytical technologies and expertise in mechanistic and kinetic enzymology, organic reaction mechanism, pharmacokinetic analysis, animal physiology, basic chemical toxicology, preclinical pharmacology, and molecular biology. With chapters contributed by experts in their specific areas, this reference covers :- Basic concepts of drug metabolism- The role of drug metabolism in the pharmaceutical industry- Analytical techniques in drug metabolism- Common experimental approaches and protocolsDrug metabolism in drug design and development emphasizes practical considerations such as the data needed, the experiments and analytical methods typically employed, and the interpretation and application of data. Chapters highlight facts, common protocols, detailed experimental designs, applications, and limitations of techniques."

"Proses invasi Plasmodium falciparum ke dalam sel darah merah merupakan tahapan penting pada infeksi malaria. Proses ini sangat kompleks melibatkan interaksi antara protein ligan pada permukaan merozoit parasit dengan reseptor permukaan pada sel darah merah inang. Reseptor sel darah merah yang digunakan pada saat invasi parasit P. falciparum diidentifikasi berdasarkan sensitivitasnya terhadap enzim neuraminidase (N), tripsin (T) dan kimotripsin (K). Penelitian ini dilakukan pada 69 darah pasien yang terinfeksi P. falciparum yang dikultur secara ex vivo secara langsung di laboratorium di Timika. Sel darah donor yang digunakan untuk uji invasi sebelumnya diberi perlakuan dengan 50 mU/ml neuraminidase, 1 mg/ml tripsin, atau 1 mg/ml kimotripsin. Kami mengidentifikasi 8 pola invasi parasit malaria dengan tipe terbanyak yang ditemukan adalah tipe A yang resistan terhadap ketiga perlakuan enzim (NrTrKr; 28,99%) dan tipe B (NsTsKr; 21,74%). Selain itu dilakukan pula analisis untuk mengetahui ekspresi relatif protein kelompok Duffy Binding Ligand (DBL) dan Reticulocytes Homolog (Rh) yang berperan pada proses invasi dengan mendeteksi ekspresi protein tersebut dari RNA yang disintesis menjadi cDNA yang diisolasi pada stadium schizon dari masing-masing isolat klinis. Protein kelompok DBL yang dianalisis adalah EBA-140, 175, 181 sedangkan dari kelompok Rh adalah Rh-1, 2a, dan 2b. Hasil analisis kuantitatif dengan real time reverse transcription PCR menunjukkan bahwa protein EBA-140, Rh-1 dan EBA-175 merupakan tiga protein ligan P. falciparum yang paling umum ditemukan pada isolat klinis parasit malaria di Timika, Papua. Variasi genetik sel darah merah seperti Southeast Asian Ovalocytosis (SAO), Gerbich negatif, dan varian hemoglobin (HbE) tidak ditemukan pengaruhnya pada proses invasi pada penelitian ini. Informasi yang dihasilkan pada penelitian ini diharapkan dapat menjadi masukkan untuk pengembangan vaksin malaria berbasis hambatan invasi parasit ke dalam sel darah merah.

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Plasmodium falciparum invasion is a complex process involving several parasite ligands and their receptors expressed on the red blood cell surface. We reported various receptors used by the parasite ligands during their invasion based on their sensitivity to neuraminidase (N), trypsin (T) or chymotrypsin (C). Most field isolates in Timika invaded red blood cells through type A receptor that was resistant to all enzyme treatments (NrTrCr; 28,99%) and type B that was sensitive to neuraminidase and trypsin (NsTsCr; 21,74%). The expression of two invasion ligands; Plasmodium falciparum Duffy binding ligand (PfDBL) and P. falciparum reticulocyte homolog (PfRh) were quantified from the schizonts stage of each isolate. We employed quantitative real-time reverse-transcription polymerase chain reaction (QRT-RT-PCR) to detect the expression of PfDBL family including EBA-140, EBA-175 and EBL-181 and PfRh genes such as Rh-1, Rh-2a, Rh-2b. We demonstrated thatEBA-140, Rh-1 and EBA-175 werethe major invasion ligands expressed in P. falciparum of Timikan isolates. The presence of red cell polymorphisms including the Southeast Asian Ovalocytosis (SAO), Gerbich negativity, and variant hemoglobin (HbE) as detected by PCR was not found to affect parasite invasion. The present study strengthens the support to include malaria invasion proteins into the development of malaria vaccine platform."

"A valuable reference tool for professionals involved in the industry, Drug Metabolism in Pharmaceuticals covers new tools such as LC-MS and LC-MS-NMR along with experimental aspects of drug metabolism. This work fills a gap in the literature by covering the concepts and applications of pharmaceutical research, development, and assessment from the point of view of drug metabolism. By providing both a solid conceptual understanding of the drug metabolism system, and a well illustrated, detailed demonstration and explanation of cutting edge tools and techniques."

"Explaining the assessment of potential drug compounds, this is an ideal introductory reference for those new to drug discovery. It includes sections on pharmacokinetics and drug metabolism, integration of pharmaceutical development, and predictive safety assessment. Topics include: cost analysis, drug transporters, cytochrome P-450 and drug-drug interactions, plasma protein binding, assessing stability, ways to optimize drug formulation, toxicology and toxicokinetics, and more. Readers will understand why absorption-distribution-metabolism-excretion-toxicology (ADMET) is key in drug development. "

"Tuberkulosis (TBC) merupakan penyakit dengan risiko penularan yang tinggi. Ketidakpatuhan terhadap pengobatan menyebabkan respon pengobatan suboptimal sehingga muncul resistensi dan penularan penyakit terus menerus. Indonesia menempati urutan kedua sebagai negara yang memiliki jumlah kasus TBC terbesar setelah India (WHO, 2015). Reaksi obat tidak dikehendaki (ROTD) akibat penggunaan obat antituberkulosis (OAT) dapat mempengaruhi kepatuhan pasien. Tujuan penelitian ini adalah menilai pengaruh ROTD terhadap peningkatan risiko ketidakpatuhan berobat pada penderita TBC paru dewasa kategori I di RS Urip Sumoharjo Lampung. Desain penelitian yang digunakan adalah kasus kontrol dengan penggunaan data rekam medik. Kelompok kasus adalah pasien TBC paru dewasa kategori I yang tidak patuh dan ditandai dengan kejadian putus berobat, yaitu pasien TBC paru yang tidak memulai pengobatan atau menghentikan pengobatan selama dua bulan berturut-turut atau lebih. Kelompok kontrol adalah pasien dengan pengobatan lengkap dan dinyatakan sembuh. Populasi penelitian ini adalah seluruh rekam medik pasien TBC paru dewasa dengan umur ≥ 15 tahun kategori I yang berobat jalan di RS Urip Sumoharjo Lampung pada bulan Agustus 2013 s.d Juli 2015. Analisis data menggunakan uji chi square dan uji regresi logistik multivariat. Hasil penelitian menunjukkan bahwa pasien yang mengalami ROTD mempunyai risiko 2,143 kali untuk tidak patuh dibandingkan dengan pasien yang tidak mengalami ROTD setelah dikontrol oleh variabel pendidikan, penyakit penyerta, dan jenis OAT. Jenis OAT KDT merupakan faktor risiko terbesar bagi ketidakpatuhan pasien TBC paru dewasa kategori I. Pasien yang mendapatkan OAT jenis KDT berisiko sebesar 11,996 kali untuk tidak patuh dibandingkan dengan pasien TBC paru yang mendapatkan jenis OAT satuan setelah dikontrol oleh variabel ROTD, pendidikan, dan penyakit penyerta.

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Tuberculosis is a disease with a high risk of transmission. Poor adherence to treatment led to suboptimal response so it appears resistance and continuous transmission of the disease. In 2015 Indonesia ranks second of countries with the highest number of estimated incident tuberculosis cases after India. Adverse drug reactions of tuberculosis agents increase the risk of poor adherence. The objective of this study was to assess the risk of adult pulmonary TB patients non adherence caused by adverse drug reactions of antituberculosis agents at Urip Sumoharjo Hospital Lampung. This research is an observational study with design case control using data from medical record. Cases were defined as the pulmonary tuberculosis patients who didn?t begin treatment or stop their antituberculosis for 2 month or more. Controls were defined as the pulmonary tuberculosis patients with full treatment and were declared cured. The study population was all medical record of adult pulmonary tuberculosis patient age ≥ 15 years old with category I treatment at Urip Sumoharjo Hospital Lampung period august 2013 ? july 2015.. Data was analyzed by using chi square and multivariate logistic regression method. Result of this study showed that the patient who has adverse drug reactions of antituberculosis agent risk nonadherence 2,143 times higher than patient who has not adverse drug reactions of antituberculosis agent after controlled by educational variables, co-morbidities, and the type of OAT. Fixed dose combination of antituberculosis drug was the highest risk factor for patient non adherence. The patient who received fixed dose combination of antituberculosis drug risk nonadherence 11,996 times higher than patient who received separate antituberculosis drug after controlled by educational variables, co-morbidities, and adverse drug reactions."

"This volume presents a broad yet detailed review of current knowledge of muscarinic receptors. It describes the detailed insights that have been obtained on the structure, function, and cell biology of muscarinic receptors. This volume also describes physiological analyses of muscarinic receptors and their roles in regulating the function of the brain and of a variety of peripheral tissues. This volume shows how the study of muscarinic receptors continues to provide new and surprising insights not just to the cholinergic system but to the broad areas of neurobiology, cell biology, pharmacology, and therapeutics."

"ABSTRAKTelah dilakukan penelitian untuk mendapatkan ligan yang selektif dan berikatan kuat dengan reseptor estrogen melalui pengujian afinitas ikatan senyawa estradiol-17β-hemisuksinat. Untuk meningkatkan status senyawa tersebut menjadi kandidat senyawa aktif obat kanker payudara perlu diketahui selektifitasnya terhadap reseptor estrogen dengan metode Scintillation Proximity Assay (SPA). Reagen primer yang diperlukan dalam metode SPA adalah radioligan dan reseptor, dan dilakukan penandaan estradiol-17β-hemisuksinat dengan 125I sebagai radioligan. Studi ikatan radioligan dilakukan terhadap reseptor estrogen meggunakan sel MCF7. Penandaan dilakukan secara tidak langsung dengan dua tahap. Pertama dilakukan aktivasi estradiol-17β-hemisuksinat menggunakan isobutilkloroformat dan tributilamin sebagai katalis, dan penandaan histamin dengan 125I menggunakan metode kloramin-T. Tahap kedua adalah konjugasi histamin bertanda 125I dengan estradiol-17β-hemisuksinat yang sudah diaktivasi. Estradiol-17β-hemisuksinat bertanda 125I dilakukan ekstraksi menggunakan toluen dan fase organik dimurnikan dengan sistem KLT. Rendemen pemurnian yang diperoleh sebesar 79,8% untuk ekstraksi pelarut dan 84,4% untuk sistem KLT dengan kemurnian radiokimia 97,8%. Penentuan afinitas ikatan dilakukan dengan metode SPA menggunakan sel MCF7 yang mengekspresikan reseptor estrogen, dan diperoleh Kd sebesar 7,192 x 10-3 nM dan ikatan maksimum sebesar 336,1 nM. Afinitas ikatan estradiol-17β-hemisuksinat yang diperoleh tinggi, ditunjukkan dengan nilai Kd yang rendah.

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ABSTRACTResearch was carried out to get drugs that selective ligand and strongly bind estrogen receptors to determine the binding affinity to estradiol-17β-hemisuccinate. To improve the status of these compounds as a candidate for breast cancer active compound, selectivity of these compounds for estrogen receptor was studied using Scintillation Proximity Assay (SPA) method. Primary reagents required in the SPA method was radioligand and receptors, then performed with 125I labeling of estradiol-17β-hemisuccinate as a radioligand.

Radioligand binding studies were performed on MCF7 cell for estrogen receptor. The labeling process was performed by indirect method via two-stage reaction. First activation of estradiol-17β-hemisuccinate using isobutylchloroformate and tributylamine as a catalist, and labeling of histamine was carried out by 125I using Chloramin-T method. The second stage was conjugation of activated estradiol-17β-hemisuccinate with 125I-histamine. The estradiol-17β-hemisuccinate labeled with 125I was extracted using toluene and organic phase was purified by TLC system. The obtained purification yield for the extraction solvent was 79.8% and for the TLC system was 84,4% with a radiochemical purity was 97.8%. Determination of binding affinity by the SPA method using MCF7 cell lines which express estrogen receptors, were Kd of 7.192 x 10-3 nM and maximum binding of 336.1 nM. Having obtained binding affinity of estradiol-17β-hemisuccinate was obtained high, indicated by a low Kd values."