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Plasma medicine: applications of low-temperature gas plasmas in medicine and biology / edited by M. Laroussi, M. G. Kong, and G. Morfill
Cambridge, UK: Cambridge University Press, 2012
616.904 1 PLA
Buku Teks SO  Universitas Indonesia Library
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Budy Alamsjah
Epidemiologi genetik serta faktor risiko M. Tuberculosis yang resisten INH dan atau Rifampisin
"Tujuan: Untuk memahami mekanisme terjadinya resistensi terhadap obat antituberkulosis dengan mempergunakan pendekatan epidemiologik genetik.
Bahan dan metode penelitian:
Disain penelitian : kasus - kontrol.
Tempat: Rumah Sakit Persahabatan, Jakarta, Rumah Sakit Umum dr. M. Jamil, Sumatera Barat dan Rumah Sakit Umum dr. Wahidin Sudirohusodo, Makasar. Laboratorium Mikrobiologi FKUI, Jakarta, Lembaga Biologi Molekuler Eijkman, Jakarta dan Laboratorium Bioteknologi Universitas Padjajaran, Bandung.
Lama penelitian: 8 bulan ( Januari 2002 - Agustus 2002 ).
Subjek penelitian: Masing-masing 279 sampel dahak yang sensitif dan resisten INH serta 36 sampel dahak yang sensitif dan resisten rifampisin.
Bahan: sampel dahak yang dikirim dari ketiga rumah sakit tersebut, diperiksa silang di laboratorium mikrobiologi FKUI, Jakarta, lalu diadakan pemeriksaan PCR dan sequencing di Lembaga Eijkman dan laboratorium BioteknoIogi Universitas Padjajaran, Bandung. Disamping itu dilakukan wawancara untuk mendapatkan keterangan mengenai kepatuhan berobat dan pengobatan yang tidak optimal. Data yang terkumpul dianalisis dengan menggunakan analisis uji statistik.
Hasil: Prevalensi resistensi terhadap INH dari ketiga propinsi berkisar dari 11,9 % sampai 15,6 %, prevalensi resistensi terhadap rifampisin berkisar dari 1,3 % sampai 1,6 % dan prevalensi resistensi ganda berkisar dari 0,6 % sampai 1,3 %, M. tuberculosis yang mengalami mutasi padagen katG dari ketiga propinsi didapatkan sebesar 60,2 % dan mempunyai kemungkinan risiko resisten terhadap INH sebesar 32,6 kali bila dibandingkan dengan M. tuberculosis yang tidak mengalami mutasi pada gen katG. M. tuberculosis yang resisten terhadap rifampisin dari ketiga propinsi menunjukkan bahwa semua M tuberculosis tersebut mengalami mutasi padagen rpoB, dimana mutasi gen rpoB pada kodon 516 (16,6 %), kodon 526 (63,8 %), kodon 529 dan kodon 531 masing-masing sebesar 5,5 %. Hal ini dapat dikatakan bahwa M. tuberculosis dari ketiga propinsi yang resisten terhadap INH dan rifampisin mengalami beraneka ragam jenis mutasi (diversity). Di ketiga propinsi, ketidakpatuhan penderita tuberkulosis berobat didapatkan sebesar 56,3 % pada M. tuberculosis resisten terhadap INH dan 75 % M. tuberculosis yang resisten terhadap rifampisin. 65,9 % penderita tuberkulosis yang mendapatkan pengobatan monotherapy mengalami resisten terhadap INH dan 75 % penderita tuberkulosis yang mendapatkan pengobatan tidak optimal mengalami resisten terhadap rifampisin. Mutasi baru gen rpoB pada kodon 529 ditemukan 2 buah yang berasal dari propinsi Jakarta dan propinsi Sumatera Barat. Mutasi baru ini tidak mempunyai dampak klinik dan biologis karena kedua kodon tersebut menyandi asam amino yang lama yaitu arginin.
Genetic Epidemiological and Risk Factor Of M. Tuberculosis For Being Resistant To INH And Or RifampicinObjective of the Study: To understand the mechanisms of resistance to antituberculosis drugs by genetic epidemiological study.
Methods and materials of the study:
Study design: Case - control study.
Location: Persahabatan Hospital (Jakarta), M. Jamil General Hospital (West Sumatra), Wahidin Sudirohusodo General Hospital (South Sulawesi), Microbiology Laboratory FKUI (Jakarta), Eijkman Institute for biology molekuler (Jakarta) and Padjadjaran University Biotechnology Laboratory (West Java).
Duration of study: 8 months ( January 2002 - August 2002 ).
Subject: 279 samples sputum each that were sensitive and resistant to NH, 36 sample sputum each that were sensitive and resistant to rifampiscin.
Material of study: - Sputum sample from three hospitals were sent to Microbiology Laboratory FKUI for crosschecking. Subsequently PCR examination and sequencing were performed in Eijkman Institute and Padjadjaran University Biotechnology Laboratory. In addition interviews were conducted to obtain information about patient compliance and optimal treatment. All data were subjected to statistical analysis.
Results: Resistance prevalence to INH from three provinces range from 11.9 % to 15.6 %; resistance prevalence to rifampicin 1.3 % to 1.6 % and multidrug resistant prevalence: 0.6 % to 1.3 %. Mutation on gene katG M. tuberculosis from three provinces were 60.2 % and have a probability resistance risk to INH 32.6 times compared to M. tuberculosis that didn't have mutation on gene katG. All M. tuberculosis resistant to rifampicin isolated from three provinces have a mutation on gene rpoB, on codon 516 (16.66 %), codon 526 (63.8%), codon 529 and codon 531 respectively 5.5 %. This situation showed that M. tuberculosis from three provinces resistant to INH and rifampicin have a diversity mutant, In the three provinces, non compliance from tuberculosis patient - were 56.3 % of M. tuberculosis resistant to INH and 75 % of M. tuberculosis resistant to rifampicin. INH monotherapy result in 65.9 % resistance and sub optimal treatment result in 75 % resistance to rifampicin. Two new mutations have been found in gene rpoB codon 529 from Jakarta and West Sumatra. And this new mutant has no clinical and biology impact because the two codons encode amino acid was same, is arginine.
Conclusions: Resistance prevalence to NH and or rifampicin in three provinces is significantly high despite a good health infrastructure. If this problem occurs in other provinces with difference geographic characteristic, demographic, socioeconomic and health infrastructure, most probably the resistance prevalence to INH and or rifampicin will be much be more pronounced. The development of resistance of M. tuberculosis to INH and or rifampicin is influenced by mutation on gene encoding enzyme catalase peroxidase (katG) and RNA Polymerise ( rpoB ). Non-compliance and sub optimal treatment are selection factors for katG and rpoB mutant.
Recommendations: It is recommended to continue a similar study in the other provinces with difference geographic, demographic, socio economic, health infrastructure and also other study with mutant. For the Department of Health it is recommended to accelerate methods of early detection of tuberculosis cases that are sensitive or resistant to antituberculosis drugs and monitoring system to record and to report tuberculosis cases from other public health services e.g. Private practices, non government clinics, hospitals and institution to ensure continuous availability and quality of controlled drugs."
Depok: Fakultas Kesehatan Masyarakat Universitas Indonesia, 2003
D547
UI - Disertasi Membership  Universitas Indonesia Library
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Enzybiotics : antibiotic enzymes as drugs and therapeutics / edited by Tomas G. Villa and Patricia Veiga Crespo
"The book starts with four chapters in which the potential, advantages, and phylogeny of enzybiotics are reviewed. Then, the new ways of controlling infections by Gramnegative bacteria and an updated view of bacteriophage holins are presented. After a review of antistaphylococcal lytic enzymes, the book goes on to discuss membrane targeted enzybiotics, as well as the design of phage cocktails for current therapy. Finally, the last two chapters deal respectively with the novel methods to identify new enzybiotics and the use of modified phages to induce suicide in bacteria.
Enzybiotics is a promising way of fighting bacterial or fungal infectious diseases by using viruses or viral-derived lysins. Drawing from the fields of medicinal chemistry, microbiology, genetics, and biochemistry, this book presents the state of the science in enzybiotics research, fully exploring its emerging therapeutic applications.
The book begins with four chapters that review the potential applications, possible advantages, and phylogeny of enzybiotics. Next, the book explores :
- A new approach to controlling infections using Gram-negative bacteria
- Bacteriophage holins and their membrane-disrupting activity
- Anti-staphylococcal lytic enzymes
- Membrane-targeted enzybiotics
- Design of phage cocktails for therapy from a host-range point of view
- Novel methods to identify new enzybiotics
- Genetically modified phages that deliver suicidal genes to target bacteria
The authors, all active enzybiotics researchers, offer a variety of perspectives, the benefit of their own hands-on investigations, as well as a thorough review and analysis of the current literature.
As more and more bacteria become resistant to antibiotics, the development of new disease-fighting agents has become essential. This book demonstrates the full potential of the emerging field of enzybiotics to control infectious diseases. Moreover, it will serve as a springboard for new research and the development of new therapeutics."
Hoboken, New Jersey: John Wiley & Sons, 2010
e20393912
eBooks  Universitas Indonesia Library
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Ronald Irwanto Natadidjaja
Pola kepekaan dan resistensi mikroorganisme aerob penggunaan antibiotika dan manfaat kultur pada infeksi kulit dan jaringan lunak komplikata di Ruang Rawat Inap Penyakit Dalam Rumah Sakit Cipto Mangunkusumo = Sensitivity and resistance pattern of aerobic microorganism antibiotic and culture using in complicated skin and soft tissue infection in Cipto Mangunkusumo Hospital Internal Medicine Ward
"Latar belakang : Infeksi kulit dan jaringan lunak komplikata hingga saat ini masih termasuk kasus yang sering dijumpai dalam klinik. Infeksi kulit dan jaringan lunak komplikata kerap kali dapat berakibat fatal. Data yang diperoleh di ruang rawat inap penyakit dalam RSCM menunjukkan lebih dari 200 kasus infeksi kulit dan jaringan lunak komplikata sepanjang tahun 2010, dengan angka kejadian sepsis kurang lebih mencapai sekitar 10%. Manfaat diagnostik kausatif melalui temuan kultur kuman sebaiknya juga dinilai, karena pada kenyataannya, pemberian antibiotik sesuai temuan kultur kuman juga tidak sepenuhnya menjamin menurunkan morbiditas dan mortalitas pasien, hal ini seringkali dimungkinkan oleh karena banyaknya kesalahan dalam pengambilan dan pelaporan hasil spesimen.
Tujuan : Mengetahui pola sensitifitas dan resistensi mikroorganisme aerob, pola penggunaan antibiotika, serta manfaat kultur pada infeksi kulit dan jaringan lunak komplikata.
Metode : Penelitian merupakan studi kohort retrospektif dengan data sekunder pada pasien- pasien dengan infeksi kulit dan jaringan lunak komplikata yang masuk ke rawat inap penyakit dalam antara bulan Juli 2011 - Juli 2012.
Hasil : Diperoleh 90 subjek penelitian dengan temuan S. aureus dan S.epidermidis merupakan bakteri gram positif yang paling banyak dijumpai. Angka resistensi S. epidermidis terhadap oxacyllin yang dapat menjadi indikator tingginya Methycillin Resistant Staphylococcus epidermidis (MRSE) mencapai 53,8%, sedangkan untuk Methycillin Resistant Staphylococcus aureus (MRSA) hanya 15,4%. Bakteri gram negatif yang terbanyak dijumpai adalah Pseudomonas sp yang mencapai 19,5% dari seluruh temuan kultur. Angka resistensi Pseudomonas sp terhadap cephalotin selaku indikator antibiotik beta laktam pada temuan ini mencapai 90%. Pada pemberian antibiotik empirik, kombinasi ampicillin-sulbactam dengan metronidazole menempati urutan tertinggi, yaitu mencapai 63,9%. Penggunaan antibiotik meropenem tunggal tampak mendominasi kelompok dengan eskalasi antibiotik Pada kelompok de-eskalasi antibiotik, 100% subjek diberikan antibiotik tunggal. Ciprofloxacin mendominasi pemberian antibiotik pada kelompok tersebut, yaitu mencapai 32,2% Penilaian manfaat kultur dilakukan dengan terlebih dahulu mengontrol faktor perancu, dan setelah mengontrol variabel perancu, secara statistik tidak ada perbedaan keberhasilan antara antibiotik empirik yang diberikan sesuai kultur dengan antibiotik empirik yang diberikan tidak sesuai kultur. OR pada penelitian ini adalah 0,45 dengan p > 0,05.
Simpulan : Angka resistensi terhadap antibiotik beta laktam yang ditunjukkan oleh bakteri gram positif dan gram negatif cukup tinggi, dengan penggunaan antibiotik empirik yang terbanyak adalah ampisulbaktam dan metronidazole. Penggunaan meropenem tunggal paling banyak dijumpai pada kelompok dengan eskalasi antibiotik, sementara ciprofloxacin tunggal merupakan antibiotik yang paling banyak dijumpai pada kelompok de-eskalasi antibiotik. Pada penelitian ini, secara statistik tidak ada perbedaan keberhasilan antara antibiotik empirik yang diberikan sesuai kultur dengan antibiotik empirik yang diberikan tidak sesuai kultur.
Background: Complicated skin and soft tissue infection is arising as a global problem in worldwide with high fatality rate that should urgently be treated in clinical practice. Cipto Mangunkusumo Hospital, Internal Medicine Ward data showed, there were more than 200 cases during 2010, with 10% sepsis incidence rate. The culture effectiveness should be evaluated, because there are still more bias which frequently happened in sample taking or reporting procedure. This condition evokes high morbidity and mortality.
Aim: To analyze the sensitivity and resistance pattern of aerobic microorganism, empiric antibiotic and culture using in complicated skin and soft tissue infection.
Methods: July 2011-July2012 retrospective cohort study with secondary data of complicated skin and soft tissue infection patients in Cipto Mangunkusumo Hospital Internal Medicine Ward.
Result: There are 90 subjects with S. aureus and S. epidermidis as the highest finding of gram positive culture. S. epidermidis high resistance rate to oxacyllin indicates the high event of Methycillin Resistant Staphylococcus epidermidis (MRSE) infection which reaches 53,8%, for a while only 15,4% of S. aureus that present as Methycillin resistant Staphylococcus aureus (MRSA).Pseudomonas sp that reaches 19,5% is the most frequent of gram negative culture finding. This finding show high indication for beta lactam resistant. The most frequent of empiric antibiotic using is ampicillin-sulbactam in combination with metronidazole that achieves 63,9%. Single meropenem and single ciprofloxacin treatment is a majority issue in group with antibiotic escalation and antibiotic de-escalation. The culture effectiveness is searched after confounding factors statistic reduction done. There are no statistic significant improve for success between appropriate culture based antibiotic and inappropriate culture based antibiotic, with 0,45 OR and p= 0,085.
Conclusion: High resistance to beta lactam showed by both gram positive and gram negative. Ampicillin-sulbactam in combination with metronidazole is the most frequent of empiric antibiotic using, with single meropenem and single ciprofloxacin as a majority use in antibiotic escalation and de-escalation group, and the appropriate culture based antibiotic and inappropriate culture based antibiotic success shows not statistically improve."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2013
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UI - Tugas Akhir  Universitas Indonesia Library
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Fanny Arviani
Proses metalurgi serbuk Ti6Al4V melalui metode arc plasma sintering (APS) dan argon sintering dengan variasi waktu terhadap pembentukan lapisan permukaan TiO2 untuk aplikasi material implan = Process of Ti6Al4V powder metallurgy through Arc Plasma Sintering method (APS) and argon sintering with time variation on formation of TiO2 Surface layer for implant material applications
"Ti6Al4V merupakan material yang sangat reaktif terhadap atmosfer terutama pada temperatur tinggi. Pada saat proses sintering, reaktivitas titanium terhadap oksigen menyebabkan lapisan TiO2 kehilangan sifat proteksinya sehingga oksigen berdifusi ke dalam material. Hal tersebut dapat merugikan karena menurunkan kualitas ikatan material, menurunkan sifat mekanis, dan menyebabkan material brittle. Penelitian ini bertujuan untuk melindungi material dari pembentukan lapisan oksida (TiO2) pada permukaan paduan Ti6Al4V, melindungi dari difusi oksigen, dan mencegah difusi oksigen ke dalam material pada saat proses sintering dengan menggunakan teknologi baru yaitu Arc Plasma Sintering (APS). Teknologi sintering yang dilakukan menggunakan arus dan plasma sebagai sumber panas yang mampu melakukan proses sintering dengan waktu sangat singkat hanya dalam hitungan menit, dan konsumsi energi yang rendah. Dengan keunggulan yang dimiliki Arc Plasma Sintering (APS), diharapkan mampu melindungi Ti6Al4V dari oksidasi pada saat sintering. Sintering dilakukan pada arus 50 A dengan variasi waktu sintering selama 4 menit, 8 menit, dan12 menit. Hasil proses Arc Plasma Sintering (APS) dibandingkan dengan hasil sintering konvensional dengan atmosfer argon pada temperatur 1300oC selama 2 jam, 3 jam, dan 4 jam. Kemudian dilakukan karakterisasi material dengan menggunakan SEM-EDS dan XRD, serta pengujian densitas dan kekerasan vickers. Hasil penelitian ini menunjukkan bahwa dengan metode Arc Plasma Sintering (APS), material memiliki densitas dan kekerasan yang lebih baik dengan nilai densitas relatif mencapai 98,40% dan kekerasan sebesar 374,719 HV, serta ketebalan lapisan permukan TiO2 yang terus berkurang dari 16,405µm hingga 12,002µm dan tidak terjadi difusi oksigen ke dalam material jika dibandingkan dengan argon sintering.
Ti6Al4V is a material that is very reactive to the atmosphere, especially at high temperatures. During the sintering process, the reactivity of titanium to oxygen causes the TiO2 layer to lose its protective properties so that oxygen diffuses into the material. This can be detrimental because it decreases the quality of material bonds, decreases mechanical properties, and causes brittle material. This study aims to protect the material from the formation of an oxide layer (TiO2) on the Ti6Al4V alloy surface, protect it from diffusion of oxygen, and prevent the diffusion of oxygen into the material during the sintering process using the new technology, Arc Plasma Sintering (APS). Sintering technology is carried out using currents and plasma as a heat source that is capable of performing the sintering process with a very short time in just minutes, and low energy consumption. With the advantages of Arc Plasma Sintering (APS), it is expected to protect Ti6Al4V from oxidation during sintering. Sintering is carried out on 50 A currents with variations in sintering time for 4 minutes, 8 minutes and 12 minutes. The results of the Arc Plasma Sintering (APS) process were compared with the results of conventional sintering with an argon atmosphere at a temperature of 1300oC for 2 hours, 3 hours and 4 hours. Then the material characterization was performed using SEM-EDS and XRD, as well as testing Vickers density and hardness. The results of this study indicate that with the Arc Plasma Sintering (APS) method, the material has better density and hardness with a relative density value of 98.40% and hardness of 374,719 HV, and the thickness of the TiO2 surface layer continues to decrease from 16.405µm to 12,002 µm and there is no diffusion of oxygen into the material when compared to argon sintering."
Depok: Fakultas Teknik Universitas Indonesia, 2019
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UI - Skripsi Membership  Universitas Indonesia Library
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Nining Restu Kurnianingsih
Profil teofilin dalam plasma dan urine setelah pemberian kapsul teofilin 300 Mg
"Telah dilakukan penelitian tentang profile teofilin dalam plasma
dan urine setelah pemberian.peroral ka psul teofilin yang berisi 300
my teofilin..
Penelitian tersebut dilakukan terhada p 12 orang sukarelawan
yang sehat, berat badan berkisar antara 47 sampal 58 kg. umur
berkisar antara 17 sam pai 28 tahun. Pengambilan darah dilakukan
sebelum obat diberikan, 60, 120, 180, 240, 360, 480 menit setelah
ohat diminum. Urine dikump ulkan pada interval waktu tertentu selama
48 jam. Konsentrasi teofilin daiarn plasma dan urine ditetapkan secara
spektr ofotometri.
Dari hasil penelitian didapatkan kadar terapi teofilin dalam
plasma dapat dicapal dengan pembenian 300 my teofilin. Ada hubungan
antara profil teofilin dalam plasma dan urine dimana waktu untuk
mencapai ekskresi puncak.teofilin dalam urine sama dengan waktu untuk
mencapai kadar puncak teofilin dalam plasma pada t mid. Juga
diperoleh parameter-parameter farmakokinetik seperti waktu oaruh
teofilin (1 1/2), tetapan kece patan eliminasi (Ke), tetapankecepatan
abbsorpsi (Ka) dan ekskresi teofilin dalam urine kumulatif.
The studies of theophylline profile in plasma and urine after
given theophylline orally capsule which contain 300 mg theophylline -
has been carried out.
The studies involved twelve healthy male volunteers, the range
of body weight are beetwen 47 to 58 kg and the ages are between 17 to
28 years old. Blood samples were taken right before the drug was
administered and 60, 120, 180, 240, 360, 480 minutes after that.
Urine samples were collected at regular intervals over 48 hour
periods. The concentration of theophylline in plasma and urine
samples were determined by spectrophotometric method.
From the data obtained, we observed that the therapeutic
concentration of theophylline was reached after given 300 mg
theophylline. There was relationship between theophylline profile in
plasma and urine, in which the time needed to reach the maximum
theophylline excreation in urine was same as the time needed to reach
the maximum theophylline plasma concentration at t mid. From the data
we also observed the pharmacokinetic parameters as the half ii:fe-
(T1/2) elimination rate constant ( Ke ), absorption rate constant (
Ke ) and cumulative urinary excretion."
Depok: Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Indonesia, 1988
S31821
UI - Skripsi Membership  Universitas Indonesia Library
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Patterns of bacterial resistance against Ceftriaxone from 2002 to 2005 in the Clinical Microbiology Laboratory of the Faculty of Medicine, University of Indonesia
"Penyebaran mikroba yang resisten terhadap pengobatan merupakan tantangan kesehatan masyarakat yang menyeluruh, yang akan menurunkan efektivitas obat dan mengakibatkan tingginya angka kesakitan dan kematian serta bertambahnya biaya pengobatan. Pengawasan resistensi obat antimikrobial melalui laporan data tentang pola resistensi mikroba terhadap suatu antimikroba akan berguna untuk mencegah timbulnya resistensi. Pada studi ini akan dilaporkan tentang pola resistensi mikroba terhadap ceftriaxone dalam 4 tahun terakhir. Data yang dilaporkan ini berasal dari spesimen yang diperiksa di Laboratorium Mikrobiologi Klinik, Departemen Mikrobiologi FKUI dari tahun 2002 sampai dengan 2005. Spesies mikroba ditentukan melalui kultur dan uji identifikasi. Disc Diffussion Methods digunakan untuk uji sensitivitas ceftriaxone terhadap 14 bakteri Gram-negatif dan 7 bakteri Gram-positif. Hasilnya memperlihatkan, walaupun angka resistensi mikroba terhadap ceftriaxone meningkat dari tahun 2002 sampai 2005, tetapi secara umum masih kurang dari 50%. Angka resistensi yang rendah (< 3%) terlihat untuk Salmonella typhi, Salmonella paratyphi A, Shigella flexneri, Serratia marcescens, dan Streptococcus pneumoniae. Hasil ini dapat digunakan untuk menyusun pedoman penggunaan ceftriaxone di Indonesia.
Abstract
The spread of drug resistant microbes is a global public health challenge which impairs the efficacy of antimicrobial agents and causes substantial increase in morbidity and mortality rates, including healthcare-associated costs. Monitoring of antimicrobial drug resistance from documented microbial epidemiology & resistance rate is useful in preventing the emergence of resistance. This study reports on the pattern of bacterial resistance against ceftriaxone in the past 4 years. The data were obtained from specimens examined in the Clinical Microbiology Laboratory, Department of Microbiology Faculty of Medicine, University of Indonesia from 2002 to 2005. Microbial species were determined from culture and identification tests. Disc diffusion method was used for sensitivity testing of ceftriaxone to 14 Gram-negative and 7 Gram-positive bacteria. Although resistance rates were increased from 2002 to 2005, resistance rates of ceftriaxone were found to be less than 50%. Low resistance rates (< 3%) were observed for Salmonella typhi, Salmonella paratyphi A, Shigella flexneri, Serratia marcescens, and Streptococcus pneumoniae. These results could be useful in developing guidelines on the use of ceftriaxone in Indonesia. "
[Fakultas Kedokteran Universitas Indonesia, Fakultas Kedokteran Universitas Indonesia], 2007
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Artikel Jurnal  Universitas Indonesia Library
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Buhner, Stephen Harrod
The home encyclopedia of herbal medicine : natural remedies for emerging and drug-resistant infections
Emmaus: Pennsylvania Rodale, 2013
R 615.321 BUH h
Buku Referensi  Universitas Indonesia Library
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Filia Stephanie
Perancangan Senyawa Peptida Siklis sebagai Inhibitor RNA Polimerase Subunit β M. tuberculosis untuk Terapi Multi-Drug Resistant Tuberkulosis = Design of Cyclic Peptide Compound as RNA Polymerase Subunit β M. Tuberculosis Inhibitor for Multi-drug Resistant Tuberculosis Treatment.
"ABSTRAK
Rifampicin (RIF) adalah obat lini pertama untuk terapi tuberkulosis (TB) dengan kemampuan bakterisidal yang tinggi terhadap M. tuberculosis. Akan tetapi, kasus resistensi terhadap RIF telah menurunkan efektivitas terapi menggunakan obat ini. Multi-drug resistance TB (MDR/RR-TB) adalah tipe resistensi yang paling umum ditemukan pada galur MTB. Penggunaan obat berbasis peptida siklis telah banyak diminati karena peptida memiliki properti farmakologi yang baik, dan selektif. Studi ini bertujuan untuk menemukan kandidat senyawa peptida siklik yang potensial sebagai inhibitor protein RNA polimerase subunit β (RpoB) mutan S531L sebagai mutan dengan prevalensi tinggi pada MDR-TB. Struktur 3 dimensi dari RpoB wild type dan mutan S531L diunduh melalui basis data Protein Data Bank, dioptimisasi, dan dibandingkan karakteristik hidrofobisitas permukaannya untuk menentukan sekuens dari peptida siklis. Kemudian, basis data ligan peptida siklis dibuat dengan menggunakan generator kombinasi dan penggambaran. Optimisasi, kalkulasi muatan parsial dan minimisasi energi dilakukan pada basis data ligan, dan proses penapisan dilakukan dengan simulasi penambatan molekul. Simulasi ini dilakukan dengan dua tahapan rigid dan fleksibel terhadap struktur S531L RpoB, untuk menemukan ligan peptida siklis dengan interaksi paling baik dengan protein ini.  Simulasi ini menghasilkan 5 ligan terbaik dengan nilai energi bebas Gibbs terendah terhadap S531L RpoB. Ligan terpilih diprediksi sifat farmakologinya secara komputasi, dan menghasilkan 3 ligan (CYYEWC, CWYEGC, dan CQQNWC) yang memiliki karakter absorpsi, distribusi, metabolism, ekskresi, dan toksisitas yang sesuai. Ketiga ligan ini divalidasi interaksinya dengan menggunakan simulasi dinamika molekul, dan menunjukkan stabilitas interaksi yang baik sebagai kandidat obat untuk terapi MDR-TB.
ABSTRACT
Rifampicin is the first line drug for tuberculosis (TB) treatment with high bactericidal activity towards M. tuberculosis. However, the rifampicin efficacy in TB treatment has been decreased steadily due to the emerging drug resistance cases. Among all types of the rifampicin resistance, MDR-TB is the most common resistance found in the MTB strain. Cyclic peptide therapeutics shows a significant success in the industry, since they possess a favorable pharmacological property. This study aimed to find the most potent cyclic peptide inhibitor for S531L RpoB protein for MDR/RR-TB treatment. Cyclic hexapeptide ligand database was built according to the binding site of the S531L RNA polymerase subunit β (RpoB) protein, the main mutation of the rifampicin target. The 3-dimension structure of RpoB wild type and mutant S531L were retrieved from the Protein Data Bank and optimized. Both of wild type and S531L binding site were compared based on their surface hydrophobicity to determine the cyclic peptide sequences in the ligand database. After the ligand database was built with combination generator and drawing, optimization, partial charge calculation and energy minimization were done. This database underwent two steps molecular docking simulation (rigid and flexible) against the S531L RpoB to find the cyclic peptide with best interaction towards this protein. The simulation resulted in 5 best ligands with the lowest value of Gibbs free energy binding to S531L RpoB. The selected ligands were subjected to the computational pharmacological properties prediction using several tools and resulted in three cyclic peptides (CYYEWC, CWYEGC and CQQNWC) with favorable interaction and ADME-Tox properties as MDR-TB drug candidate."
2020
T55017
UI - Tesis Membership  Universitas Indonesia Library
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Physico-chemical diagnostics of plasmas: proceedings of the fifth biennial gas dynamics symposium
Evanston: Northwestern University, 1963
540 PHY
Buku Teks SO  Universitas Indonesia Library
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