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Pesquisa : D20.215 [Categoria DeCS]
Referências encontradas : 16771 [refinar]
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  1 / 16771 MEDLINE  
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PMID:29231144
Autor:Castellano G; Redondo L; Torrens F
Endereço:Departamento de Ciencias Experimentales y Matematicas, Facultad de Veterinaria y Ciencias Experimentales, Universidad Catolica de Valencia San Vicente Martir, Guillem de Castro-94, E-46001 Valencia, Spain.
Título:QSAR of Natural Sesquiterpene Lactones as Inhibitors of Myb-dependent Gene Expression.
Fonte:Curr Top Med Chem; 17(30):3256-3268, 2018 Feb 09.
ISSN:1873-4294
País de publicação:Netherlands
Idioma:eng
Resumo:BACKGROUND: Protein c-Myb is a therapeutic target. Some sesquiterpene lactones suppress Myb-dependent gene expression, which results in their potential anti-cancer activity. MATERIAL & METHODS: Database ChEMBL is a representative of lactones for physicochemical and physiochemical properties. Data presented for 31 natural lactones are discussed in terms of quantitative structureactivity relationships with the objective to predict inhibitors of Myb-induced gene expression. Several constitutional descriptors are related to structure-activity. α-Methylene-γ-lactone groups enhance while OH functions worsen potency. The latter feature is in agreement with the fact that the more lipophilic the lactone, the greater the cytotoxicity because of the ability to cross lipoidal biomembranes. In general, numbers of π-systems and atoms, and polarizability enhance activity. Linear and nonlinear structure-activity models are developed, between lactones of a great structural diversity, to predict inhibitors of Myb-induced gene expression. Four variables (ML, UNC, TCO+OCOR, UNC+UNA) related to ATOM show a positive correlation because of the partial anionic and H-acceptor characters of O-atom. In most, CO group is conjugated. RESULT AND CONCLUSION: Term OH shows negative coefficients because of the partial cationic quality of H-atom and because OH forms H-bonds with CO, causing them to be less H-acceptor. s-trans-s-trans-Germacranolide structure is the most active. Coefficients standard errors result acceptable in almost all equations. After cross-validation, linear equations for lactones, pseudoguaianolides and germacranolides are the most predictive. Most descriptors are constitutional variables.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Biological Products); 0 (Lactones); 0 (Proto-Oncogene Proteins c-myb); 0 (Sesquiterpenes)


  2 / 16771 MEDLINE  
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PMID:29358154
Autor:Turner AD; Waack J; Lewis A; Edwards C; Lawton L
Endereço:Centre for Environment, Fisheries and Aquaculture Science, Barrack Road, The Nothe, Weymouth, Dorset DT4 8UB, United Kingdom. Electronic address: andrew.turner@cefas.co.uk.
Título:Development and single-laboratory validation of a UHPLC-MS/MS method for quantitation of microcystins and nodularin in natural water, cyanobacteria, shellfish and algal supplement tablet powders.
Fonte:J Chromatogr B Analyt Technol Biomed Life Sci; 1074-1075:111-123, 2018 Feb 01.
ISSN:1873-376X
País de publicação:Netherlands
Idioma:eng
Resumo:A simple, rapid UHPLC-MS/MS method has been developed and optimised for the quantitation of microcystins and nodularin in wide variety of sample matrices. Microcystin analogues targeted were MC-LR, MC-RR, MC-LA, MC-LY, MC-LF, LC-LW, MC-YR, MC-WR, [Asp3] MC-LR, [Dha7] MC-LR, MC-HilR and MC-HtyR. Optimisation studies were conducted to develop a simple, quick and efficient extraction protocol without the need for complex pre-analysis concentration procedures, together with a rapid sub 5min chromatographic separation of toxins in shellfish and algal supplement tablet powders, as well as water and cyanobacterial bloom samples. Validation studies were undertaken on each matrix-analyte combination to the full method performance characteristics following international guidelines. The method was found to be specific and linear over the full calibration range. Method sensitivity in terms of limits of detection, quantitation and reporting were found to be significantly improved in comparison to LC-UV methods and applicable to the analysis of each of the four matrices. Overall, acceptable recoveries were determined for each of the matrices studied, with associated precision and within-laboratory reproducibility well within expected guidance limits. Results from the formalised ruggedness analysis of all available cyanotoxins, showed that the method was robust for all parameters investigated. The results presented here show that the optimised LC-MS/MS method for cyanotoxins is fit for the purpose of detection and quantitation of a range of microcystins and nodularin in shellfish, algal supplement tablet powder, water and cyanobacteria. The method provides a valuable early warning tool for the rapid, routine extraction and analysis of natural waters, cyanobacterial blooms, algal powders, food supplements and shellfish tissues, enabling monitoring labs to supplement traditional microscopy techniques and report toxicity results within a short timeframe of sample receipt. The new method, now accredited to ISO17025 standard, is simple, quick, applicable to multiple matrices and is highly suitable for use as a routine, high-throughout, fast turnaround regulatory monitoring tool.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Biological Products); 0 (Microcystins); 0 (Peptides, Cyclic); 0 (Tablets); 0 (Water Pollutants, Chemical); 0979BIK2QU (nodularin)


  3 / 16771 MEDLINE  
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PMID:29311542
Autor:Cao J; Perez-Pinera P; Lowenhaupt K; Wu MR; Purcell O; de la Fuente-Nunez C; Lu TK
Endereço:Synthetic Biology Group, Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Título:Versatile and on-demand biologics co-production in yeast.
Fonte:Nat Commun; 9(1):77, 2018 01 08.
ISSN:2041-1723
País de publicação:England
Idioma:eng
Resumo:Current limitations to on-demand drug manufacturing can be addressed by technologies that streamline manufacturing processes. Combining the production of two or more drugs into a single batch could not only be useful for research, clinical studies, and urgent therapies but also effective when combination therapies are needed or where resources are scarce. Here we propose strategies to concurrently produce multiple biologics from yeast in single batches by multiplexing strain development, cell culture, separation, and purification. We demonstrate proof-of-concept for three biologics co-production strategies: (i) inducible expression of multiple biologics and control over the ratio between biologic drugs produced together; (ii) consolidated bioprocessing; and (iii) co-expression and co-purification of a mixture of two monoclonal antibodies. We then use these basic strategies to produce drug mixtures as well as to separate drugs. These strategies offer a diverse array of options for on-demand, flexible, low-cost, and decentralized biomanufacturing applications without the need for specialized equipment.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
Nome de substância:0 (Antibodies, Monoclonal); 0 (Biological Products); 0 (Pharmaceutical Preparations)


  4 / 16771 MEDLINE  
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PMID:29184405
Autor:Hureaux J; Lacoeuille F; Lagarce F; Rousselet MC; Contini A; Saulnier P; Benoit JP; Urban T
Endereço:Unité Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire.
Título:Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules in rats.
Fonte:Int J Nanomedicine; 12:8159-8170, 2017.
ISSN:1178-2013
País de publicação:New Zealand
Idioma:eng
Resumo:Lipid nanocapsules (LNCs) are potential drug carriers for pulmonary delivery since they can be nebulized without any structural or functional changes, and the aerosols produced are highly compatible with pulmonary drug delivery in human beings. The alveolar surface tension, in vitro cytotoxicity, biodistribution and pulmonary toxicity in rats of a single endotracheal spray of LNCs or paclitaxel-loaded LNCs were studied. In vitro cytotoxicity of LNCs after a spray remained unchanged. Biodistribution study showed a homogeneous repartition in the lungs in rats with an improvement in lung retention of the radiolabeled tracer loaded in LNCs compared to the absence of LNCs with a lung half-time of 8.8±0.7 hours. Bronchoalveolar fluid analysis revealed transient 7-day alveolar inflammation, reaching a maximum between days 2 and 4, characterized by a peak of granulocytes at day 1 followed by a peak of lymphocytes at day 3. Alveolar protein levels were increased at days 3 and 7. Acute inflammation was increased with paclitaxel-loaded LNCs in comparison with blank LNCs but dropped out at day 7. No histological pulmonary lesion was observed at day 60. LNCs lowered surface tension to a greater degree than Curosurf in a physicochemical model of the pulmonary alveolus. A single pulmonary delivery of LNCs induces a short-term alveolar inflammation with no residual lesions in rats at day 60. These data permit to start the study of LNCs in surfactant replacement therapy.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Aerosols); 0 (Biological Products); 0 (Drug Carriers); 0 (Lipids); 0 (Nanocapsules); 0 (Phospholipids); KE3U2023NP (poractant alfa); P88XT4IS4D (Paclitaxel)


  5 / 16771 MEDLINE  
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PMID:29353722
Autor:Xu GB; Xiao YH; Zhang QY; Zhou M; Liao SG
Endereço:School of Pharmacy/State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550004, Guizhou, China; National Engineering Research Center of Miao's Medicines & Engineering Research Center for the Development and Application of Ethnic Medicine and
Título:Hepatoprotective natural triterpenoids.
Fonte:Eur J Med Chem; 145:691-716, 2018 Feb 10.
ISSN:1768-3254
País de publicação:France
Idioma:eng
Resumo:Liver diseases are one of the leading causes of death in the world. In spite of tremendous advances in modern drug research, effective and safe hepatoprotective agents are still in urgent demand. Natural products are undoubtedly valuable sources for drug leads. A number of natural triterpenoids were reported to possess pronounced hepatoprotective effects, and triterpenoids have become one of the most important classes of natural products for hepatoprotective agents. However, the significance of natural triterpenoids has been underestimated in the hepatoprotective drug discovery, with only very limited triterpenoids being covered in the reviews of hepatoprotective natural products. In this paper, ca 350 natural triterpenoids with reported hepatoprotective effects in ca 120 references between 1975 and 2016 will be reviewed, and the structure-activity relationships of certain types of natural triterpenoids, if available, will be discussed. Patents are not included.
Tipo de publicação: JOURNAL ARTICLE; REVIEW
Nome de substância:0 (Biological Products); 0 (Protective Agents); 0 (Triterpenes)


  6 / 16771 MEDLINE  
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PMID:29289883
Autor:Rejhová A; Opattová A; Cumová A; Slíva D; Vodicka P
Endereço:Institute of Experimental Medicine of the Czech Academy of Sciences, Department of Molecular Biology of Cancer, Prague, 14220, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, 12800, Czech Republic. Electronic address: alexandra.rejhov
Título:Natural compounds and combination therapy in colorectal cancer treatment.
Fonte:Eur J Med Chem; 144:582-594, 2018 Jan 20.
ISSN:1768-3254
País de publicação:France
Idioma:eng
Resumo:Colorectal cancer (CRC) therapy using conventional chemotherapeutics represents a considerable burden for the patient's organism because of high toxicity while the response is relatively low. Our review summarizes the findings about natural compounds as chemoprotective agents for decreasing risk of CRC. It also identifies natural compounds which possess anti-tumor effects of various characteristics, mainly in vitro on colorectal cell lines or in vivo studies on experimental models, but also in a few clinical trials. Many of natural compounds suppress proliferation by inducing cell cycle arrest or induce apoptosis of CRC cells resulting in the inhibition of tumor growth. A novel employment of natural substances is a so-called combination therapy - administration of two or more substances - conventional chemotherapeutics and a natural compound or more natural compounds at a time. Some natural compounds may sensitize to conventional cytotoxic therapy, reinforce the drug effective concentration, intensify the combined effect of both administered therapeutics or exert cytotoxic effects specifically on tumor cells. Moreover, combined therapy by targeting multiple signaling pathways, uses various mechanisms to reduce the development of resistance to antitumor drugs. The desired effect could be to diminish burden on the patient's organism by replacing part of the dose of a conventional chemotherapeutic with a natural substance with a defined effect. Many natural compounds are well tolerated by the patients and do not cause toxic effects even at high doses. Interaction of conventional chemotherapeutics with natural compounds introduces a new aspect in the research and therapy of cancer. It could be a promising approach to potentially achieve improvements, while minimizing of adverse effects associated with conventional chemotherapy.
Tipo de publicação: JOURNAL ARTICLE; REVIEW
Nome de substância:0 (Biological Products)


  7 / 16771 MEDLINE  
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PMID:29391009
Autor:Huang C; Li W; Zhang Q; Chen L; Chen W; Zhang H; Ni Y
Endereço:Department of Pharmacy, Wuhan No.1 Hospital (Wuhan Integrated TCM & Western Medicine Hospital), 215 Zhongshan Avenue, Wuhan, 430022, China.
Título:Anti-inflammatory activities of Guang-Pheretima extract in lipopolysaccharide-stimulated RAW 264.7 murine macrophages.
Fonte:BMC Complement Altern Med; 18(1):46, 2018 Feb 01.
ISSN:1472-6882
País de publicação:England
Idioma:eng
Resumo:BACKGROUND: Guang-Pheretima, which is originated from Pheretima aspergillum, has been documented in academic Chinese herbal studies for nearly 2000 years for its prominent treating effects of various inflammatory diseases such as asthma, cough and fever. However, the anti-inflammatory activity and mechanism of Guang-Pheretima has been rarely reported. Hence, we investigated the inhibitory effect and the underlying mechanism of Guang-Pheretima aqueous extracts on inflammatory response in RAW 264.7 cells. METHOD: RAW 264.7 macrophages were pretreated with various concentrations of Guang-Pheretima decoction (GPD) or protein-free Guang-Pheretima decoction (PF-GPD) and subsequently stimulated with lipopolysaccharide (LPS) to trigger the inflammatory response. Productions of nitric oxide (NO) were determined by Griess reaction, and prostaglandin E (PGE ), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6 were measured by enzyme-linked immunosorbent assays (ELISA). The protein expressions and messenger ribonucleic acid (mRNA) amounts of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were analyzed by Western Blot and Real-Time polymerase chain reaction (PCR), respectively. Finally, the translocation of nuclear factor (NF)-κB was observed by Western Blot. RESULTS: GPD of the experimental concentrations showed no anti-inflammatory activity. In contrast, PF-GPD at concentrations of 40-320 µg/mL significantly inhibited NF-κB activation and reduced the production of inflammatory mediators, such as NO, PGE , TNF-α, as well as the related key synthases including iNOS and COX-2. Moreover, PF-GPD markedly suppressed the release of inflammatory cytokines, such as IL-1ß and IL-6. CONCLUSION: These results demonstrate the excellent anti-inflammatory properties of PF-GPD, and suggest that Guang-Pheretima may be used to treat and prevent certain inflammatory diseases.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Anti-Inflammatory Agents); 0 (Biological Products); 0 (Cytokines); 0 (Lipopolysaccharides); EC 1.14.99.1 (Cyclooxygenase 2)


  8 / 16771 MEDLINE  
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PMID:29190135
Autor:Fonseca VA; Bloomgarden ZT; Dagogo-Jack S; Grunberger G; Einhorn D; Garber AJ; Handelsman Y; Hirsch IB; Umpierrez GE
Título:AACE/ACE POSITION STATEMENT ON THE USE OF FOLLOW-ON BIOLOGICS AND BIOSIMILARS FOR ENDOCRINE DISEASES.
Fonte:Endocr Pract; 23(11):1345-1349, 2017 Nov.
ISSN:1530-891X
País de publicação:United States
Idioma:eng
Resumo:This document represents the official position of the American Association of Clinical Endocrinologists and American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position and consensus statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician. ABBREVIATIONS: BPCIA = Biologics Price Competition and Innovation Act; FDA = Food and Drug Administration; FFDC = Federal Food Drug and Cosmetics Act; PHS = Public Health Services Act; TE = therapeutic equivalence.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Biological Products); 0 (Biosimilar Pharmaceuticals)


  9 / 16771 MEDLINE  
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PMID:29185959
Autor:Marchesoni A; Olivieri I; Salvarani C; Pipitone N; D'Angelo S; Mathieu A; Cauli A; Punzi L; Ramonda R; Scarpa R; Maccarone M; Lubrano E
Endereço:Day Hospital of Rheumatology, ASST Gaetano Pini-CTO, Milano, Italy. antonio.marchesoni@asst-pini-cto.it.
Título:Recommendations for the use of biologics and other novel drugs in the treatment of psoriatic arthritis: 2017 update from the Italian Society of Rheumatology.
Fonte:Clin Exp Rheumatol; 35(6):991-1010, 2017 Nov-Dec.
ISSN:0392-856X
País de publicação:Italy
Idioma:eng
Resumo:OBJECTIVES: To update the 2011 Italian Society of Rheumatology (SIR) recommendations for the use of biologics and other novel agents in the treatment of psoriatic arthritis (PsA). METHODS: To create this new set of recommendations, the SIR "Spondyloartritis and Psoriatic Arthritis study group - A. Spadaro" went through the following steps: literature search, identification of the items of interests for each of the four previously identified clinical domains of PsA and the different treatment phases, achievement of the consensus on all topics, and generation of the recommendations. RESULTS: An update on the available evidence on all of the biologics and new small molecules tested in PsA is reported, comprising the data for each of the individual articular manifestation. Indications for therapy inclusion criteria, choice of the drug, disease assessment, response definition, therapy failure management, and disease remission management for PsA peripheral joint arthritis, enthesitis, dactylitis, and spondylitis are provided. Suggestions for the treatment of patients with PsA and concomitant extra-articular manifestations are also given. CONCLUSIONS: These evidence-based recommendations may be used for guidance in the complex and fast-evolving field of the treatment of PsA.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies, Monoclonal, Humanized); 0 (Antirheumatic Agents); 0 (Biological Products); 0 (Interleukin-17); 0 (Tumor Necrosis Factor-alpha); 0 (clazakizumab); 7D0YB67S97 (Abatacept)


  10 / 16771 MEDLINE  
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PMID:29386433
Autor:Hatakeyama S
Endereço:Graduate School of Biomedical Sciences, Nagasaki University.
Título:[Stereocontrolled Total Synthesis of Biologically Active Natural Products].
Fonte:Yakugaku Zasshi; 138(2):191-209, 2018.
ISSN:1347-5231
País de publicação:Japan
Idioma:jpn
Resumo: This review article describes the total syntheses of englerin A, ophiodilactones A and B, marinomycin A, N-methylwelwitindolinone C isothiocyanate, tirandamycins A-D, and tirandalydigin, which possess intriguing biological activities and challenging structures with characteristic ring systems. The focus is on the synthetic methodologies that lead to the highly stereocontrolled assembly of these natural products.
Tipo de publicação: JOURNAL ARTICLE; REVIEW
Nome de substância:0 (Alkenes); 0 (Aminoglycosides); 0 (Benzene Derivatives); 0 (Biological Products); 0 (Indole Alkaloids); 0 (Lactones); 0 (Macrolides); 0 (N-methylwelwitindolinone B isothiocyanate); 0 (Sesquiterpenes, Guaiane); 0 (englerin A); 0 (marinomycin A); 0 (ophiodilactone A); 0 (ophiodilactone B); 0 (tirandamycin C); 0 (tirandamycin D); 114118-91-1 (tirandalydigin); 34429-70-4 (tirandamycin A); 60587-14-6 (tirandamycin B)



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