1.Rational use of Polymyxins against multi-drug resistant Gram-Negative bacteria
Paul Sherwin O. Tarnate ; Cecilia C. Maramba-Lazarte
Pediatric Infectious Disease Society of the Philippines Journal 2021;22(1):3-13
The current strategy in treating multi-drug resistant gram-negative bacterial (MDR-GNB) infections is salvage therapy by using polymyxins. However, the beginning emergence of polymyxin resistance should enforce strict antimicrobial stewardship programs to preserve polymyxin efficacy. Knowledge of structural characteristics, pharmacodynamic, and pharmacokinetic profiles of polymyxins, as well as consideration of efficacy, safety, suitability, and cost, will help in the choice of the appropriate polymyxin for therapy. Polymyxin B is the recommended polymyxin for systemic use, while colistin is recommended for lower urinary tract infections, intraventricular, and intrathecal use. Either polymyxin can be used for hospital-acquired and ventilator-associated pneumonia. Combination therapy over monotherapy remains to be advantageous due to synergism and decreased resistance development. The choice of the second drug to be used should be based on full susceptibility, or if unavailable, a drug with the least minimum inhibitory concentration relative to the breakpoint set by the Clinical and Laboratory Standards Institute. Using the mnemonic ESCAPE can also guide physicians in their polymyxin prescription process: (1) Checking if the pathogen is Extensively resistant or multi-drug resistant; (2) checking the patient’s clinical status if compatible with Significant infection; (3) using Combination therapy; (4) ensuring Adequate dosing; (5) Proper preparation and administration of drug; and (6) keeping an Eye for response and adverse effects.
Polymyxin B
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Colistin
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Polymyxins
5.Analysis of Resistance to Macrolide–Lincosamide–Streptogramin B Among mecA-Positive Staphylococcus Aureus Isolates
Mahmoud KHODABANDEH ; Mohsen MOHAMMADI ; Mohammad Reza ABDOLSALEHI ; Azadeh ALVANDIMANESH ; Mehrdad GHOLAMI ; Meysam Hasannejad BIBALAN ; Abazar POURNAJAF ; Ramin KAFSHGARI ; Ramazan RAJABNIA
Osong Public Health and Research Perspectives 2019;10(1):25-31
OBJECTIVES: Genetic determinants conferring resistance to macrolide, lincosamide, and streptogramin B (MLSB) via ribosomal modification such as, erm, msrA/B and ereA/B genes are distributed in bacteria. The main goals of this work were to evaluate the dissemination of MLSB resistance phenotypes and genotypes in methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from clinical samples. METHODS: A total of 106 MRSA isolates were studied. Isolates were recovered from 3 hospitals in Tehran between May 2016 to July 2017. The prevalence of MLSB-resistant strains were determined by D-test, and then M-PCR was performed to identify genes encoding resistance to macrolides, lincosamides, and streptogramins in the tested isolates. RESULTS: The frequency of constitutive resistance MLSB, inducible resistance MLSB and MSB resistance were 56.2%, 22.9%, and 16.6%, respectively. Of 11 isolates with the inducible resistance MLSB phenotype, ermC, ermB, ermA and ereA were positive in 81.8%, 63.6%, 54.5% and 18.2% of these isolates, respectively. In isolates with the constitutive resistance MLSB phenotype, the prevalence of ermA, ermB, ermC, msrA, msrB, ereA and ereB were 25.9%, 18.5%, 44.4%, 0.0%, 0.0%, 11.1% and 0.0%, respectively. CONCLUSION: Clindamycin is commonly administered in severe MRSA infections depending upon the antimicrobial susceptibility findings. This study showed that the D-test should be used as an obligatory method in routine disk diffusion assay to detect inducible clindamycin resistance in MRSA so that effective antibiotic treatment can be provided.
Bacteria
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Clindamycin
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Diffusion
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Drug Resistance
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Genotype
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Lincosamides
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Macrolides
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Methicillin-Resistant Staphylococcus aureus
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Methods
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Phenotype
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Prevalence
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Staphylococcus aureus
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Staphylococcus
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Streptogramin B
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Streptogramins
6.Advances in protein cyclization.
Chinese Journal of Biotechnology 2016;32(4):430-439
Proteins, which exist mainly in linear form in vivo, are easily affected by the change of ambient temperature and pH. The application of proteins (enzymes) in the fields of industrial catalyzing, food manufacturing and medicine are restricted due to their properties. The cyclic structure of natural cyclic peptides confers high thermal stability on itself; such mechanism can be referred to in further enhancement of the thermal stability and transformation of the structure of enzymes. This article reviewed the latest progress in the domestic and international studies on protein cyclization and summarized the traditional methods (such as protein trans-splicing, expressed protein ligation and sortase-catalyzed transpeptidation) in protein cyclization. A novel method based on SpyTag/SpyCather-mediated enzyme cyclization was discussed in more detail.
Cyclization
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Peptides, Cyclic
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chemistry
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Protein Processing, Post-Translational
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Proteins
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chemistry
7.A IL-6R antagonist 2520A produced by a fungal species.
Feng-chang ZHU ; Rong JIANG ; Yang ZHANG ; Jian-bo WU ; Yuan LI
Acta Pharmaceutica Sinica 2006;41(7):662-665
<b>AIMb>To isolate IL-6R antagonists from the cultured broth of the strain Torulomyces ovatus.
<b>METHODSb>Various column chromatographyes were used to separate and purify the compounds with IL-6R antagonist activity. The spectral data and physic-chemical properties were measured for structure identification.
<b>RESULTSb>One compound namely 2520 was isolated from the cultured broth of Torulomyces ovatus.
<b>CONCLUSIONb>2520A is a known compound (ferrichrome). It is first reported about its antagonistic activity of IL-6R and identification of iron atom in its structure.
Anti-Bacterial Agents ; chemistry ; isolation & purification ; pharmacology ; Antineoplastic Agents ; chemistry ; isolation & purification ; pharmacology ; Bacillus subtilis ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Fermentation ; Ferric Compounds ; chemistry ; isolation & purification ; pharmacology ; Ferrichrome ; chemistry ; isolation & purification ; pharmacology ; Humans ; Mitosporic Fungi ; chemistry ; Molecular Structure ; Peptides, Cyclic ; chemistry ; isolation & purification ; pharmacology ; Receptors, Interleukin-6 ; antagonists & inhibitors
8.Research development of chemistry and bioactive activity of plant peptides.
Yan LIANG ; Xiao-qin WU ; Ying ZHANG
China Journal of Chinese Materia Medica 2006;31(9):709-714
As the technologies of separation, purification and determination develop rapidly, more and more peptide compounds, which have special bioactive and medical value, have been separated from natural plants, such as oligopeptides and cyclopeptides. The chemical structures and function of these plant peptides have been researched profoundly. This paper mainly reviews the composition, structure, bioactive function and medicine value of representative plant peptides in recent years, and can give some references about research and application of plant bioactive peptides.
Animals
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Antihypertensive Agents
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chemistry
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isolation & purification
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pharmacology
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Antineoplastic Agents, Phytogenic
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chemistry
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isolation & purification
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pharmacology
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Antioxidants
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chemistry
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isolation & purification
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pharmacology
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Glutathione
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chemistry
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isolation & purification
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pharmacology
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Gramicidin
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chemistry
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isolation & purification
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pharmacology
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Humans
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Hypoglycemic Agents
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chemistry
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isolation & purification
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pharmacology
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Oligopeptides
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chemistry
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isolation & purification
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pharmacology
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Peptides
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chemistry
;
isolation & purification
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pharmacology
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Peptides, Cyclic
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chemistry
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isolation & purification
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pharmacology
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Plants
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chemistry
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Plants, Medicinal
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chemistry
9.Anti-citrullinated protein antibodies in rheumatoid arthritis: a bridge between genetic predisposition and autoimmunity.
The Korean Journal of Internal Medicine 2013;28(1):25-28
No abstract available.
Arthritis, Rheumatoid/*epidemiology/*immunology
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Autoantibodies/*blood
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Female
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Humans
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Male
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Peptides, Cyclic/*immunology
10.Binding characteristics between RGD-containing cyclic peptide and rat hepatic stellate cells: an in vitro study.
Shi-lin DU ; Ji-yao WANG ; Wei-yue LU
Chinese Journal of Hepatology 2005;13(5):362-365
<b>OBJECTIVEb>To investigate the binding characteristics between an artificial Arg-Gly-Asp (RGD)-containing cyclic peptide [cyclo(CGRGDSPK)] and rat hepatic stellate cells (HSC).
<b>METHODSb>An artificial RGD-containing cyclic peptide was labeled with fluorescein isothiocyanate (FITC). HSCs were isolated by collagenase in situ liver recirculating and purified by density gradient centrifugation from normal rats. The cells were cultured for 5 days of primary culture (quiescent phenotype) or for 7 days of secondary culture (activated phenotype). To access the binding and uptake, HSCs were incubated with FITC-cRGD of different concentrations at 4 degree C or 37 degree C, and then the binding and uptake were investigated by flow cytometry. The location of FITC-cRGD in HSC was investigated by fluorescent microscopy. Kd and maximal binding sites per cell were calculated by radioligand binding assay (RBA) of receptors using 3H-cRGD. In the interim, FITC-cAGA was used as a peptide control devoid of any binding site.
<b>RESULTSb>The binding between FITC-cRGD and HSC was saturable, time- and dose-dependent and could compete with overdosed unlabeled cRGD. The fluorescence was mainly distributed in cytoplasma, especially near the nuclei. Kd was 7.05 x 10(-9) mol/L and Bmax per cell was nearly 6.79 x 10(5).
<b>CONCLUSIONSb>The results demonstrate that cRGD are specifically taken up by HSC through a receptor-mediated pathway. The information is useful for understanding the ligand-receptor interaction of HSC. FITC labeled cyclic RGD-peptides meet the standards of special ligands and FITC does not change the binding activation of cyclic RGD-peptides.
Animals ; Binding Sites ; Cells, Cultured ; Hepatocytes ; cytology ; metabolism ; Oligopeptides ; pharmacology ; Peptides, Cyclic ; pharmacology ; Protein Binding ; Rats