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"The medical benefits of a drug are not only dependent on its biological effect, but also on its "life cycle" within the organism, from its absorption into the blood, distribution to tissue until its eventual breakdown or excretion by the liver and kidneys.Here, the authors, all of them employed at Pfizer in the discovery and development of new active substances, discuss the significant parameters and processes important for the absorption, distribution and retention of drug compounds in the body, plus the potential problems created by their transformation into toxic byproducts. The authors cover everything from the fundamental principles right up to the latest developments using high throughput methods to analyze the pharmacokinetic properties of active substances.Particular emphasis is placed on the impact of pharmacokinetic parameters on the discovery of new drugs, one of the most challenging tasks in global pharmaceutical research."

"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."

"Latar belakang: Peran estrogen pada patofisiologi endometriosis sudah dikenal sejak lama. Namun, belum ada studi yang menganalisis rasio estradiol, estron dan estriol antara wanita dengan dan tanpa endometriosis. Tujuan: Menganalisis kadar estron (E1), estradiol (E2) dan estriol (E3) dalam darah dan rasio E2:E1, E2:E3 dan E1:E3 antara wanita dengan dan tanpa endometriosis. Metode: Penelitian dengan desain potong lintang analitik, dengan 27 wanita dengan endometriosis dan 27 wanita tanpa endometriosis yang memenuhi kriteria inklusi. Sampel didapatkan dari RS Cipto Mangunkusumo dan rumah sakit jejaring lainnya periode Oktober 2012 - April 2013. Kadar metabolit estrogen dalam darah diperiksa dengan uji enzyme-linked immunosorbent (ELISA). Perbandingan data antara dua kelompok dianalisis dengan uji Mann-Whitney. Hasil: Kadar estron ditemukan lebih rendah pada kelompok endometriosis dibandingkan kelompok kontrol (54,66 pg/ml vs 73,52 pg/ml, p 0,229). Demikian pula, kadar estradiol dan estriol lebih rendah pada kelompok endometriosis (29 pg/ml vs 35 pg/ml, p 0,815 dan 1,11 pg/ml vs 1,67 pg/ml, p 0.095, berturut-turut). Rasio E2:E1 lebih tinggi pada kelompok endometriosis (0,51 pg/ml vs 0,38 pg/ml, p 0,164), demikian pula dengan rasio E2: E3 (26,53 pg/ml vs 21,11 pg/ml , p 0,223) dan rasio E1:E3 (58,55 pg/ml vs 50,28 pg/ml, p 0,684). Namun, semua perbedaan itu tidak bermakna secara statistik. Kesimpulan: Kadar estron, estradiol, dan estriol pada wanita dengan kelompok endometriosis lebih rendah dibandingkan pada wanita tanpa endometriosis. Rasio E2: E1, E2: E3 dan E1: E3 lebih tinggi pada kelompok endometriosis. Namun, semua perbedaan itu tidak bermakna secara statistik.

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Background: The role of estrogen in the pathophysiology of endometriosis has been well known. However, no study has observed the ratio of estradiol, estrone, and estriol between women with endometriosis and without endometriosis.

Objectives: To assess the estrone (E1), estradiol (E2) and estriol (E3) blood level and its ratio (E2:E1, E2:E3 and E1:E3) between women with and without endometriosis.

Methods: An analytical cross sectional study with 27 women with endometriosis and 27 women without endometriosis who met the inclusion criteria. The samples were recruited in Cipto Mangunkusumo hospital and other satellite hospitals from October 2012 to April 2013. The blood level of estrogen metabolites was examined by enzyme-linked immunosorbent assay (ELISA). The data comparison between two groups was analyzed by using Mann-Whitney test.

Result: The level of Estrone was found to be lower in endometriosis group compared to this in control group (54,66 pg/ml vs 73,52 pg/ml, p 0.229). Similarly, the level of estradiol and estriol were lower in endometriosis group (29 pg/ml vs 35 pg/ml, p 0.815 and 1,11 pg/ml vs 1,67 pg/ml, p 0.095, consecutively). The E2:E1 ratio was higher in endometriosis group (0,51 pg/ml vs 0,38 pg/ml, p 0.164), as well as E2:E3 ratio (26,53 pg/ml vs 21,11 pg/ml, p 0.223) and the E1:E3 ratio (58.55 vs 50.28, p 0.684). However, all those differences were not statistical significant.

Conclusion: The estrone, estradiol and estriol level in women with endometriosis group was lower compared to these in women without endometriosis group. The ratio E2:E1, E2:E3 and E1:E3 was higher in endometriosis group. However, all those differences were statistically insignificant."

"ABSTRAKKulit bangunan adalah permukaan transisi yang membatasi sekaligus menghubungkan antara ruang dalam dan ruang luar. Teknologi kulit bangunan hijau hadir untuk merespon penurunan kualitas lingkungan dan efisiensi energi akibat kehadiran bangunan baru. Kulit bangunan hijau menjadi media tempat terjadinya proses metabolisme bangunan, yaitu proses pertukaran unsur-unsur antara ruang dalam dan ruang luar bangunan. Studi kasus difokuskan pada kulit bangunan hijau Perpustakaan Universitas Indonesia. Keberadaan kulit bangunan hijau membawa dampak pada dua sisi, yaitu dampak kulit bangunan hijau terhadap ruang dalam antara lain kenyamanan termal dan dampak terhadap lingkungan sekitar bangunan. Pada kulit bangunan hijau dapat terjadi proses metabolisme bangunan yang memadai secara alami antara lain berupa bio-filter terhadap polutan, memperbaiki kualitas udara, mengurangi kebisingan, meningkatkan biodiversity, memperbaiki daur air, mengatur heat transfer ke ruang dalam dan mengurangi radiasi panas ke lingkungan sekitar.

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ABSTRAKThe building skin is a transitional surface which borders and connects the inner space with the outer space. Green skin technology exists in order to respond to the decrease in environmental quality and energy efficiency which is caused by new buildings that keep arising. Green skin becomes a medium where building metabolism, which is an exchange process of the inner space and the outer space components, takes place. This case study is focused on Universitas Indonesia Library?s green skin. The existence of green skin has some impacts for both sides of the building. On the inner space, the green building shell creates thermal comfort whilst on the outer space, it affects the environment around the building. On every green skin, a building metabolism process could occur naturally; for example, bio-filter towards pollutant, air quality improvement, noise reduction, increase in biodiversity, storm water management improvement, control over heat transfer into the building and reduction of heat radiation towards the surroundings."

"ABSTRAKRuang Lingkup dan Cara Penelitian: Banyak senyawa diketahui dapat mempengaruhi aktivitas enzim mikrosom hati. Pengaruh doksazosin - suatu obat antihipertensi baru - terhadap aktivitas mikrosom hati belum diketahui. Untuk itu dilakukan penelitian efek pemberian doksazosin (D), i.p. terhadap kecepatan metabolisme aminopirin pada model perfusi hati tikus ex vivo, dibandingkan dengan pemberian fenobarbital (F) dan NaCl. (N). Juga dilakukan pemeriksaan pengaruh-penambahan doksazosin (FD) dan simetidin (FS) pada kelompok F.Tiap kelompok terdiri dari 6 ekor tikus jantan galur Wistar. Perfusi dilakukan secara resirkulasi dengan larutan dapar Krebs- Henseleit sebagai cairan perfusat, yang dijenuhkan dengan campuran gas 95% 02: 002 5% (v/v). Kadar aminopirin pada cairan perfusi diperiksa dengan metode Brodie dan Axelrod. Diukur pula berat hati; kadar GPT pada serum, perfusat awal dan akhir; serta penyerapan tripan biru oleh inti sel hati. Kecepatan metabolisme aminopirin dinyatakan dengan nilai slope dari garis regresi penurunan kadar aminopirin dalam perfusat.Hasil dan Kesimpulan: Berat badan tikus, kecepatan aliran perfusi serta nilai GPT serum, perfusat awal dan akhir dari kelima kelompok tidak berbeda bermakna. Tidak ada inti sel hati yang menyerap tripan biru pada semua sediaan histopatologik. Berat hati rata-rata kelompok D (5,78 g) tidak berbeda bermakna dengan kelompok N (5,60 g), sedangkan kelompok F (7,93 g), FS (8,03 g) dan FD (8,05 g) berbeda sangat bermakna dengan kelompok N (p <0,001). Perbandingan nilai slope yang diuji dengan i "comparison of slopes", ternyata slope kelompok D (-4,17x10 ) tidak berbeda dengan kelompok N (-37x10 ), tetapi berbeda bermakna dengan kelompok F (-8,56x10-) (p < 0,001). Slope kelompok Fl (-7,84xlO-'i berbeda bermakna dengan kelompok FS (-4,67x10 ) (p <0,01 tetapi tidak berbeda dengan kelompok F.Dan hasil tersebut dapat disimpulkan bahwa doksazosin tidak bersifat induktor maupun inhibitor terhadap metabolisme aminopirin oleh enzim mikrosom hati pada percobaan perfusi hati tikus ex vivo.

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ABSTRACTThe Effects Of Doxazosin On Aminopyrine Meetabolism In Perfused Rat LiverScope and Method of Study: Several hundreds synthetic and naturally occurring compounds with diverse structures are now known to in-crease the activity of microsomal enzymes. The effect of doxazosin - a new antihypertensive agent - on microsomal enzymes activities has not yet been investigated. This study was carried out to deter-mine the effects of doxazosin (D) on microsomal enzymes compared to NaC1. (N) and phenobarbital. (F). In addition, the effect of the addition of doxazosin (FD) to F group compared to addition of cimetidine (FS) was also evaluated.The experiment was carried out on male rats of the Wistar strain; each group consists of 6 animals. Following treatment with the respective drugs, the livers were isolated and perfuse in a recalculating system with Krebs-Henseleit buffer, saturated with 95% 02 : 5% C02 (v/v,) at 37° C and pH 7.4. Aminopyrine was introduced into the perfusion medium, and its concentration measured at intervals during a 45-minute period by the method of Brodie and Axelrod. Additional measurements were: the liver weight; GPT activity in the serum and perfusate (initial and final); per-fusion flow rate; and try pan blue uptake by the hepatocytes.Findings and Conclusions: There is no difference in body weight, per-fusion flow rate, and GPT activity in the serum and perfusates (initial and final) of the five groups. No trypan blue uptake by the hepatocytes was observed by microscopically analysis. There is no difference in total liver weight between the D group (5.78 g) and the N group (5.60 g), while the F group (7.83 g), FS group (8.03 g) and FD group (8.05 g) are significantly different compared to the N group (p <0.001). The rate of aminipyrine, metabolism rep-resented by slope of regression line of aminopyrine decreasing content in the perfusate against the time was tested by the comparison of slopes. The slope of the D. group (-4.7x10-) i not significantly different compared to the N group (3.87x10 ), but is significantly different to the F group (-8.56x10 ) (p <0.01). The slope of the FD group (-7.84x14 ) is significantly different compared to FS (-4.67x10-3) (p < 0.05), but is not significantly different compared to the F group.Thus, it can be concluded that doxazosin is neither an inducers nor an inhibitor in the metabolism of aminopyrine by the liver microsomal enzyme in the isolated rat liver perfusion model. "

"Muncul dari kehancuran Jepang pasca-perang, Metabolism Movement, gerakan avant-garde dari timur, menantang sifat statis arsitektur dengan visinya mengenai keberlanjutan dan kemampuan beradaptasi. Kehancuran Perang Dunia II menunjukkan kehancuran yang mengerikan. Melalui rekonstruksi fisik, banyak perumahan dan bangunan sementara disediakan, bersamaan dengan rencana ambisius pemerintah untuk membangun megalopolis di sepanjang kepulauan Jepang. Namun, pendekatan top-down ini sering kali berbenturan dengan persepsi masyarakat, sehingga menimbulkan pertanyaan tentang siapa yang mengendalikan masa depan kota. Di tengah pragmatisme rekonstruksi, muncullah Metabolism. Terinspirasi oleh proses biologis, arsitek Metabolism membayangkan megastruktur yang mampu merespons perubahan kebutuhan sosial dan lingkungan dalam membangun kembali keadaan kota setelah kekalahan dan kehancuran selama Perang Dunia II. Idealisme arsitektur yang ambisius ini, meskipun tidak terwujud seluruhnya, menyanggah sifat statis urbanisme tradisional, menawarkan gambaran konteks yang dapat mengubah dan merespons masa depan dengan dinamis. Skripsi ini menggali latar belakang dan prinsip-prinsip inti Metabolism Movement dan menganalisis secara kritis penerapannya untuk menghadapi berbagai tantangan arsitektur dan perkotaan pada periode aktivitasnya hingga akhir. Terlepas dari idealisme yang revolusioner, Metabolism menghadapi permasalahan dan kekhawatiran dengan keterbatasan dalam implementasinya. Melalui konteks historisnya, peninjauan kembali ke Metabolism dilakukan dengan menyelidiki relevansi gerakan ini di antara gerakan-gerakan avant-garde lainnya dengan memahami sejarah, cita-cita, dan tantangan gerakan tersebut, yang mendorong mereka untuk menciptakan urbanisme yang dinamis dan merespons kebutuhan masyarakat yang selalu berubah.

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Emerging from the ashes of post-war Japan, Metabolism Movement, the eastern avant-garde, challenged the static nature of architecture with its vision of continuity and adaptability. The devastation of World War II bore the gruesome testimony of destruction. Through the physical reconstruction, many of temporary housing and building were provided along with the ambitious masterplan of building megalopolis in the belt of the country. Yet, this top-down approach often clashed with the lived experiences of communities, raising questions about who controlled the future of the city. Amidst the pragmatism of reconstruction, Metabolism emerged. Inspired by biological processes, Metabolists envisioned megastructures capable of responding to changing social and environmental needs in rebuilding urban state after the defeat and destruction during World War II. These ambitious architectural dreams, though not always fully realized, challenged the static nature of traditional urbanism, offering a glimpse into a context that could transform and respond to the dynamic future. This thesis delves into the background and core principles of Metabolism Movement and critically analyzing their application to face several architectural and urban challenges in their prevalent time until the end of the movement. Despite its revolutionary ideals, Metabolism faced issues and raised concerns for the limitations in the implementation. Through its specific historical context, the revisit to Metabolism inquires the relevance of the movement among the other avant-gardes by understanding the movement's history, ideals, and challenges, which encourage them to create dynamic urban environments that respond to the ever-changing needs of their present and future."

"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. "