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[PMID]:29279438
[Au] Autor:Ebitani M; Ebitani T
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University.
[Ti] Título:[Rotational Isomers of Diphenhydramine].
[So] Source:Yakugaku Zasshi;138(3):417-424, 2018 Mar 01.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo: Diphenhydramine (DP), an antihistaminic agent, may become colored and daker or more fluorescent during storage. Herein, we spectroscopically examined the causes of this phenomenon under various DP storage conditions and durations. The infrared vibration-rotation spectrum shows multiple Gauche (G)-type conformers with different intramolecular n→π interaction strengths. The splitting pattern of the dimethylamino group protons in the H-NMR spectrum indicates that DP is mainly in the G-type with a small portion in the Trans (T)-type. The correlation between the red-shifted peak intensity in the UV•VIS absorbance spectrum and the coloring progression indicates a decreased intramolecular n→π interaction of the G-type under elevated temperature during storage. Enhanced fluorescence detected in the Excitation•Fluorescence spectrum demonstrates G-type (quenching) to T-type (fluorescent) conformation conversion, which is due to activated internal rotation of the dimethylamino group under elevated storage temperature and electronic excitation in the phenyl groups under light irradiation during storage. A signal detected in the ESR spectrum corresponds to the G-type charge transfer (CT) structure wherein part of the nonbonding electron pair on the N atom is intramolecularly redistributed to the phenyl groups. The CT structure presents the G-type quenching characteristics, whereas weak CT bonding corresponds to coloring. The results indicate that the quenching G-type is converted to T-type by heat or light to become color faded and bright with enhanced fluorescence and that T-type is reverted to G-type after storage under cool and dark conditions or by vacuum distillation to lose fluorescence.
[Mh] Termos MeSH primário: Difenidramina/química
Estabilidade de Medicamentos
Armazenamento de Medicamentos
Antagonistas dos Receptores Histamínicos/química
[Mh] Termos MeSH secundário: Cor
Espectroscopia de Ressonância de Spin Eletrônica
Fluorescência
Isomerismo
Luz
Espectroscopia de Ressonância Magnética
Conformação Molecular
Rotação
Espectrometria de Fluorescência
Espectrofotometria Infravermelho
Análise Espectral
Temperatura Ambiente
Vibração
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histamine Antagonists); 8GTS82S83M (Diphenhydramine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00175


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[PMID]:29296163
[Au] Autor:Oli AN; Agu RU; Ihekwereme CP; Esimone CO
[Ad] Endereço:Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Agulu, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria.
[Ti] Título:An evaluation of the cold chain technology in South-East, Nigeria using Immunogenicity study on the measles vaccines.
[So] Source:Pan Afr Med J;27(Suppl 3):28, 2017.
[Is] ISSN:1937-8688
[Cp] País de publicação:Uganda
[La] Idioma:eng
[Ab] Resumo:Introduction: Vaccines are biological products and their efficacy is affected by storage conditions. They are vital in promoting public health. Failures in immunization programmes often times are blamed on disruption in vaccine cold-chain. This study assessed the immunogenicity/potency of the measles vaccines utilized in childhood immunization in South-East, Nigeria and indirectly assessed the effectiveness of the cold-chain technology in the region. Methods: This was an experimental study carried out between December 2011 and June 2013. Antibody induction method was used to evaluate the immunogenicity/potency of the measles vaccines sourced from the central cold chain facilities in South-east, Nigeria and indirectly, the effectiveness of the cold chain technology in the zone in maintaining vaccine potency. The neutralizing antibodies in a control group (administered with measles vaccines stored at 37°C for 12 months) and in immunized group were determined after 30 days of immunization using ELISA. Results: The mean storage temperature of the vaccines at the states vaccines central cold chain facilities was -2.4°C and before storage at study site, it was 5.8°C but at the study site it was -4.54°C. Mean ±Standard Error in the Mean (SEM) IgG titers for the measles vaccines sourced from "Open Market", Ebonyi, Enugu, Imo, Anambra and Abia States were 0.793±0.051, 1.621±0.015, 1.621±0.015, 1.715±0.081, 1.793±0.051 and 1.683±0.078 respectively while the mean ±Standard Error in the Mean (SEM) IgM titres were 0.857±0.037, 1.400±0.030, 1.391±0.032, 1.339±0.037, 1.405±0.066 and 1.279±0.025 respectively. One way analysis of variance shows that there is statistical difference in the IgG and IgM antibodies titers produced by the control compared to the vaccines (P value < 0.0001). Also, Bartlett's test for equal variances showed that there was statistical difference (P value < 0.0001 for IgG and = 0.036 for IgM). The antibodies elicited by the vaccines from the states were enough to confer protection but the vaccine samples from "Open Market" (control) could not evoke enough antibodies. Conclusion: The cold-chain technology in the region was judged to be optimal as at the time of vaccine sampling since all the measles vaccines had good immunogenicity profile. However, efforts are still needed to maintain these facilities in good condition in order to ensure effective immunization program in the region.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/imunologia
Vacina contra Sarampo/imunologia
Refrigeração
Vacinação
[Mh] Termos MeSH secundário: Animais
Armazenamento de Medicamentos
Ensaio de Imunoadsorção Enzimática
Programas de Imunização
Imunoglobulina G/imunologia
Imunoglobulina M/imunologia
Vacina contra Sarampo/provisão & distribuição
Camundongos
Nigéria
Temperatura Ambiente
Fatores de Tempo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Immunoglobulin G); 0 (Immunoglobulin M); 0 (Measles Vaccine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.11604/pamj.supp.2017.27.3.11491


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[PMID]:29296162
[Au] Autor:Mvundura M; Lydon P; Gueye A; Diaw IK; Landoh DE; Toi B; Kahn AL; Kristensen D
[Ad] Endereço:Devices and Tools Program, PATH, Seattle, USA.
[Ti] Título:An economic evaluation of the controlled temperature chain approach for vaccine logistics: evidence from a study conducted during a meningitis A vaccine campaign in Togo.
[So] Source:Pan Afr Med J;27(Suppl 3):27, 2017.
[Is] ISSN:1937-8688
[Cp] País de publicação:Uganda
[La] Idioma:eng
[Ab] Resumo:Introduction: A recent innovation in support of the final segment of the immunization supply chain is licensing certain vaccines for use in a controlled temperature chain (CTC), which allows excursions into ambient temperatures up to 40°C for a specific number of days immediately prior to administration. However, limited evidence exists on CTC economics to inform investments for labeling other eligible vaccines for CTC use. Using data collected during a MenAfriVac™ campaign in Togo, we estimated economic costs for vaccine logistics when using the CTC approach compared to full cold chain logistics (CCL) approach. Methods: We conducted the study in Togo's Central Region, where two districts were using the CTC approach and two relied on a fullCCL approach during the MenAfriVac™ campaign. Data to estimate vaccine logistics costs were obtained from primary data collected using costing questionnaires and from financial cost data from campaign microplans. Costs are presented in 2014 US dollars. Results: Average logistics costs per dose were estimated at $0.026±0.032 for facilities using a CTC and $0.029±0.054 for facilities using the fullCCL approach, but the two estimates were not statistically different. However, if the facilities without refrigerators had not used a CTC but had received daily deliveries of vaccines, the average cost per dose would have increased to $0.063 (range $0.007 to $0.33), with larger logistics cost increases occurring for facilities that were far from the district. Conclusion: Using the CTC approach can reduce logistics costs for remote facilities without cold chain infrastructure, which is where CTC is designed to reduce logistical challenges of vaccine distribution.
[Mh] Termos MeSH primário: Armazenamento de Medicamentos/economia
Programas de Imunização
Meningite Meningocócica/prevenção & controle
Vacinas Meningocócicas/provisão & distribuição
[Mh] Termos MeSH secundário: Seres Humanos
Vacinas Meningocócicas/economia
Refrigeração
Inquéritos e Questionários
Togo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MenAfriVac); 0 (Meningococcal Vaccines)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.11604/pamj.supp.2017.27.3.12087


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[PMID]:28873648
[Au] Autor:González-Ferrero C; Irache JM; González-Navarro CJ
[Ad] Endereço:Food Ingredients Line Research, National Centre for Food Technology and Safety - CNTA, 31570 San Adrián, Spain. Electronic address: cgferrero@cnta.es.
[Ti] Título:Soybean protein-based microparticles for oral delivery of probiotics with improved stability during storage and gut resistance.
[So] Source:Food Chem;239:879-888, 2018 Jan 15.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The present work describes the encapsulation of probiotics using a by-product as wall material and a process feasible to be scaled-up: coacervation of soybean protein concentrate (SPC) by using calcium salts and spray-drying. SPC was extracted from soybean flour, produced during the processing of soybean milk, by alkaline extraction following isoelectric precipitation. Two probiotic strains were selected for encapsulation (Lactobacillus plantarum CECT 220 and Lactobacillus casei CECT 475) in order to evaluate the ability of SPC to encapsulate and protect bacteria from stress conditions. The viability of these encapsulated strains under in vitro gastrointestinal conditions and shelf-life during storage were compared with the most common forms commercialized nowadays. Results show that SPC is a feasible material for the development of probiotic microparticles with adequate physicochemical properties and enhanced significantly both probiotic viability and tolerance against simulated gastrointestinal fluids when compared to current available commercial forms.
[Mh] Termos MeSH primário: Proteínas de Soja/química
[Mh] Termos MeSH secundário: Animais
Dessecação
Armazenamento de Medicamentos
Intestinos
Lactobacillus plantarum
Viabilidade Microbiana
Leite
Probióticos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Soybean Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE


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[PMID]:29064356
[Au] Autor:Tohme RA; Francois J; Cavallaro KF; Paluku G; Yalcouye I; Jackson E; Wright T; Adrien P; Katz MA; Hyde TB; Faye P; Kimanuka F; Dietz V; Vertefeuille J; Lowrance D; Dahl B; Patel R
[Ad] Endereço:Global Immunization Division, Centers for Disease Control and Prevention, Atlanta, Georgia.
[Ti] Título:Expansion of Vaccination Services and Strengthening Vaccine-Preventable Diseases Surveillance in Haiti, 2010-2016.
[So] Source:Am J Trop Med Hyg;97(4_Suppl):28-36, 2017 Oct.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Following the 2010 earthquake, Haiti was at heightened risk for vaccine-preventable diseases (VPDs) outbreaks due to the exacerbation of long-standing gaps in the vaccination program and subsequent risk of VPD importation from other countries. Therefore, partners supported the Haitian Ministry of Health and Population to improve vaccination services and VPD surveillance. During 2010-2016, three polio, measles, and rubella vaccination campaigns were implemented, achieving a coverage > 90% among children and maintaining Haiti free of those VPDs. Furthermore, Haiti is on course to eliminate maternal and neonatal tetanus, with 70% of communes achieving tetanus vaccine two-dose coverage > 80% among women of childbearing age. In addition, the vaccine cold chain storage capacity increased by 91% at the central level and 285% at the department level, enabling the introduction of three new vaccines (pentavalent, rotavirus, and pneumococcal conjugate vaccines) that could prevent an estimated 5,227 deaths annually. Haiti moved from the fourth worst performing country in the Americas in 2012 to the sixth best performing country in 2015 for adequate investigation of suspected measles/rubella cases. Sentinel surveillance sites for rotavirus diarrhea and meningococcal meningitis were established to estimate baseline rates of those diseases prior to vaccine introduction and to evaluate the impact of vaccination in the future. In conclusion, Haiti significantly improved vaccination services and VPD surveillance. However, high dependence on external funding and competing vaccination program priorities are potential threats to sustaining the improvements achieved thus far. Political commitment and favorable economic and legal environments are needed to maintain these gains.
[Mh] Termos MeSH primário: Monitoramento Epidemiológico
Programas de Imunização/organização & administração
Vigilância de Evento Sentinela
[Mh] Termos MeSH secundário: Armazenamento de Medicamentos
Haiti
Seres Humanos
Sarampo/epidemiologia
Sarampo/prevenção & controle
Vacina contra Sarampo/uso terapêutico
Meningite Meningocócica/epidemiologia
Meningite Meningocócica/prevenção & controle
Vacinas Meningocócicas/uso terapêutico
Infecções Pneumocócicas/epidemiologia
Infecções Pneumocócicas/prevenção & controle
Vacinas Pneumocócicas/uso terapêutico
Poliomielite/epidemiologia
Poliomielite/prevenção & controle
Vacinas contra Poliovirus/uso terapêutico
Infecções por Rotavirus/epidemiologia
Infecções por Rotavirus/prevenção & controle
Vacinas contra Rotavirus/uso terapêutico
Rubéola (Sarampo Alemão)/epidemiologia
Rubéola (Sarampo Alemão)/prevenção & controle
Vacina contra Rubéola/uso terapêutico
Tétano/epidemiologia
Tétano/prevenção & controle
Toxoide Tetânico/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Measles Vaccine); 0 (Meningococcal Vaccines); 0 (Pneumococcal Vaccines); 0 (Poliovirus Vaccines); 0 (Rotavirus Vaccines); 0 (Rubella Vaccine); 0 (Tetanus Toxoid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171025
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.16-0802


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[PMID]:28858135
[Au] Autor:Fang BX; Wang LH; Liu HM; Chen FC; Liu J
[Ad] Endereço:aDepartment of Pharmacy, Dongfeng Hospital bDepartment of Pharmacy, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, P.R. China.
[Ti] Título:Stability study of dezocine in 0.9% sodium chloride solutions for patient-controlled analgesia administration.
[So] Source:Medicine (Baltimore);96(35):e7979, 2017 Sep.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Dezocine, a mixed agonist/antagonist of opioid receptors, has been used in iv patient-controlled analgesia (PCA) pumps for postoperative pain control. The aim of this study was to investigate the physicochemical stability of dezocine solutions in 0.9% sodium chloride for injection for PCA administration. METHODS: Solutions of dezocine (0.3, 0.45, or 0.6 mg/mL in 0.9% sodium chloride for injection) were stored in polyolefin bags and glass bottles. Their stabilities at storage conditions of 4°C for 14 days and 25°C for 72 hours were studied. For all preparations, physical characteristics (including pH, color, and presence of precipitates) were evaluated. Each preparation of dezocine was also analyzed using a stability-indicating high-performance liquid chromatography method. A solution was considered stable if it maintained at least 90% of its initial concentration. RESULTS: No notable changes in pH, color, or precipitation were observed in any of the prepared solutions over the testing period. All formulations maintained >97% of the initial dezocine concentration under the storage conditions evaluated. CONCLUSIONS: Dezocine solutions at 0.3, 0.45, or 0.6 mg/mL in 0.9% sodium chloride for PCA administration were stable for 72 hours at 25°C and for 14 days at 4°C when packaged in polyolefin bags or glass bottles and protected from light.
[Mh] Termos MeSH primário: Analgesia Controlada pelo Paciente
Analgésicos Opioides/química
Compostos Bicíclicos Heterocíclicos com Pontes/química
Estabilidade de Medicamentos
Tetra-Hidronaftalenos/química
[Mh] Termos MeSH secundário: Analgésicos Opioides/administração & dosagem
Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem
Cromatografia Líquida de Alta Pressão
Armazenamento de Medicamentos/métodos
Seres Humanos
Concentração de Íons de Hidrogênio
Plásticos
Polienos
Solução Salina Hipertônica
Tetra-Hidronaftalenos/administração & dosagem
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (Plastics); 0 (Polyenes); 0 (Saline Solution, Hypertonic); 0 (Tetrahydronaphthalenes); 83136-87-2 (PL 732); VHX8K5SV4X (dezocine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007979


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[PMID]:28739601
[Au] Autor:Fialho MFP; Brusco I; da Silva Brum E; Piana M; Boligon AA; Trevisan G; Oliveira SM
[Ad] Endereço:Neurotoxicity and Psychopharmacology Laboratory, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
[Ti] Título: Lam. crude extract presents antinociceptive effect on an arthritic pain model in mice.
[So] Source:Biochem J;474(17):2993-3010, 2017 Aug 17.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Arthritis is a chronic inflammatory disease which reduces the life quality of affected individuals. Therapeutic tools used for treating inflammatory pain are associated with several undesirable effects. Lam., known as 'Barbasco' or 'Cambara', is mostly used in several disorders and possesses antirheumatic, anti-inflammatory, and analgesic properties. Here, we investigated the antinociceptive and anti-inflammatory effects of the crude extract applied orally and topically in acute pain models and an arthritic pain model induced by complete Freund's adjuvant (CFA) paw injection in male mice (25-30 g). The high-performance liquid chromatography (HPLC) of the extract crude revealed the presence of the lupeol, stigmasterol, and ß-sitosterol. The stability study of the gel did not show relevant changes at low temperatures. The oral treatment with the extract prevented the capsaicin-induced spontaneous nociception and the acetic acid-induced abdominal writhing, but did not alter the thermal threshold in the tail immersion test. The antinociceptive effect was not reversed by naloxone in the capsaicin test. The oral or topical treatment reversed the CFA-induced mechanical allodynia and thermal hyperalgesia with maximum inhibition ( ) of 69 ± 6 and 68 ± 5% as well as 78 ± 15 and 87 ± 12%, respectively. Moreover, the topical but not oral treatment inhibited the CFA-induced cell infiltration, but did not reduce the paw edema significantly. The oral treatment with did not cause adverse effects. These findings suggest that the oral or topical treatment with presents antinociceptive actions in an arthritic pain model without causing adverse effects.
[Mh] Termos MeSH primário: Analgésicos não Entorpecentes/uso terapêutico
Anti-Inflamatórios não Esteroides/uso terapêutico
Artrite Experimental/tratamento farmacológico
Buddleja/química
Extratos Vegetais/uso terapêutico
Folhas de Planta/química
[Mh] Termos MeSH secundário: Dor Aguda/tratamento farmacológico
Administração Cutânea
Administração Oral
Analgésicos não Entorpecentes/administração & dosagem
Analgésicos não Entorpecentes/efeitos adversos
Analgésicos não Entorpecentes/química
Animais
Anti-Inflamatórios não Esteroides/administração & dosagem
Anti-Inflamatórios não Esteroides/efeitos adversos
Anti-Inflamatórios não Esteroides/química
Brasil
Buddleja/crescimento & desenvolvimento
Estabilidade de Medicamentos
Armazenamento de Medicamentos
Etnofarmacologia
Géis
Temperatura Alta/efeitos adversos
Masculino
Camundongos
Triterpenos Pentacíclicos/administração & dosagem
Triterpenos Pentacíclicos/efeitos adversos
Triterpenos Pentacíclicos/análise
Triterpenos Pentacíclicos/uso terapêutico
Extratos Vegetais/administração & dosagem
Extratos Vegetais/efeitos adversos
Extratos Vegetais/química
Folhas de Planta/crescimento & desenvolvimento
Sitosteroides/administração & dosagem
Sitosteroides/efeitos adversos
Sitosteroides/análise
Sitosteroides/uso terapêutico
Estigmasterol/administração & dosagem
Estigmasterol/efeitos adversos
Estigmasterol/análise
Estigmasterol/uso terapêutico
Viscosidade
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Non-Narcotic); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Gels); 0 (Pentacyclic Triterpenes); 0 (Plant Extracts); 0 (Sitosterols); 5LI01C78DD (gamma-sitosterol); 99WUK5D0Y8 (Stigmasterol); O268W13H3O (lupeol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170008


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[PMID]:28685564
[Ti] Título:Hepatitis B vaccines: WHO position paper ­ July 2017.
[Ti] Título:Vaccins anti-hépatite B: note de synthèse de l'OMS ­ juillet 2017..
[So] Source:Wkly Epidemiol Rec;92(27):369-92, 2017 07 07.
[Is] ISSN:0049-8114
[Cp] País de publicação:Switzerland
[La] Idioma:eng; fre
[Mh] Termos MeSH primário: Armazenamento de Medicamentos/normas
Vacinas contra Hepatite B/administração & dosagem
Vacinas contra Hepatite B/provisão & distribuição
Hepatite B/prevenção & controle
Programas de Imunização/normas
Esquemas de Imunização
Organização Mundial da Saúde
[Mh] Termos MeSH secundário: Adolescente
Adulto
Comitês Consultivos
Criança
Pré-Escolar
Hepatite B/diagnóstico
Hepatite B/terapia
Hepatite B/transmissão
Antígenos de Superfície da Hepatite B/sangue
Vacinas contra Hepatite B/imunologia
Vírus da Hepatite B/imunologia
Vírus da Hepatite B/patogenicidade
Hepatite B Crônica/epidemiologia
Hepatite B Crônica/prevenção & controle
Hepatite B Crônica/terapia
Hepatite B Crônica/transmissão
Seres Humanos
Hospedeiro Imunocomprometido
Lactente
Recém-Nascido
Transmissão Vertical de Doença Infecciosa/prevenção & controle
Profilaxia Pós-Exposição
[Pt] Tipo de publicação:JOURNAL ARTICLE; PRACTICE GUIDELINE
[Nm] Nome de substância:
0 (Hepatitis B Surface Antigens); 0 (Hepatitis B Vaccines)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE


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[PMID]:28655766
[Au] Autor:De Nardis C; Hendriks LJA; Poirier E; Arvinte T; Gros P; Bakker ABH; de Kruif J
[Ad] Endereço:From the Crystal and Structural Chemistry Group, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
[Ti] Título:A new approach for generating bispecific antibodies based on a common light chain format and the stable architecture of human immunoglobulin G .
[So] Source:J Biol Chem;292(35):14706-14717, 2017 Sep 01.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bispecific antibodies combine two different antigen-binding sites in a single molecule, enabling more specific targeting, novel mechanisms of action, and higher clinical efficacies. Although they have the potential to outperform conventional monoclonal antibodies, many bispecific antibodies have issues regarding production, stability, and pharmacokinetic properties. Here, we describe a new approach for generating bispecific antibodies using a common light chain format and exploiting the stable architecture of human immunoglobulin G We used iterative experimental validation and computational modeling to identify multiple Fc variant pairs that drive efficient heterodimerization of the antibody heavy chains. Accelerated stability studies enabled selection of one Fc variant pair dubbed "DEKK" consisting of substitutions L351D and L368E in one heavy chain combined with L351K and T366K in the other. Solving the crystal structure of the DEKK Fc region at a resolution of 2.3 Å enabled detailed analysis of the interactions inducing CH3 interface heterodimerization. Local shifts in the IgG backbone accommodate the introduction of lysine side chains that form stabilizing salt-bridge interactions with substituted and native residues in the opposite chain. Overall, the CH3 domain adapted to these shifts at the interface, yielding a stable Fc conformation very similar to that in wild-type IgG. Using the DEKK format, we generated the bispecific antibody MCLA-128, targeting human EGF receptors 2 and 3. MCLA-128 could be readily produced and purified at industrial scale with a standard mammalian cell culture platform and a routine purification protocol. Long-term accelerated stability assays confirmed that MCLA-128 is highly stable and has excellent biophysical characteristics.
[Mh] Termos MeSH primário: Anticorpos Biespecíficos/metabolismo
Anticorpos Monoclonais Humanizados/metabolismo
Antineoplásicos/metabolismo
Imunoglobulina G/metabolismo
Modelos Moleculares
Engenharia de Proteínas
Receptor ErbB-2/antagonistas & inibidores
Receptor ErbB-3/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Anticorpos Biespecíficos/química
Anticorpos Biespecíficos/genética
Anticorpos Biespecíficos/farmacocinética
Anticorpos Monoclonais Humanizados/química
Anticorpos Monoclonais Humanizados/genética
Anticorpos Monoclonais Humanizados/farmacocinética
Afinidade de Anticorpos
Antineoplásicos/sangue
Antineoplásicos/química
Antineoplásicos/farmacocinética
Reatores Biológicos
Células CHO
Biologia Computacional
Cricetulus
Estabilidade de Medicamentos
Armazenamento de Medicamentos
Feminino
Meia-Vida
Seres Humanos
Imunoglobulina G/química
Imunoglobulina G/genética
Camundongos Endogâmicos BALB C
Simulação de Acoplamento Molecular
Conformação Proteica
Estabilidade Proteica
Receptor ErbB-2/metabolismo
Receptor ErbB-3/metabolismo
Proteínas Recombinantes/sangue
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Proteínas Recombinantes/farmacocinética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Bispecific); 0 (Antibodies, Monoclonal, Humanized); 0 (Antineoplastic Agents); 0 (Immunoglobulin G); 0 (MCLA-128); 0 (Recombinant Proteins); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (ERBB3 protein, human); EC 2.7.10.1 (Receptor, ErbB-2); EC 2.7.10.1 (Receptor, ErbB-3)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170629
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.793497


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[PMID]:28590906
[Au] Autor:Franc A; Kurhajec S; Pavloková S; Sabadková D; Muselík J
[Ad] Endereço:.
[Ti] Título:Influence of concentration and type of microcrystalline cellulose on the physical properties of tablets containing Cornelian cherry fruits.
[So] Source:Acta Pharm;67(2):187-202, 2017 Jun 27.
[Is] ISSN:1846-9558
[Cp] País de publicação:Croatia
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to find the optimal tablet composition with maximum content of dried fruits (Cornus mas L.). The effect of three different concentrations (12.5, 25 and 50 %) of two types of microcrystalline cellulose (Avicel® PH 101 and Avicel® PH 200) and three different compression pressures (20, 60 and 100 MPa) on the physical properties of tablet blends and tablets was studied. Tablets containing 50 % Avicel® PH 101 compressed under 100 MPa were found to have the best physical properties. This combination of composition and compression pressure resulted in stable tablets even after storage under accelerated stability conditions (6 months, 40 °C and 75 % RH).
[Mh] Termos MeSH primário: Celulose/química
Cornus/química
Comprimidos/química
[Mh] Termos MeSH secundário: Estabilidade de Medicamentos
Armazenamento de Medicamentos
Frutas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tablets); 9004-34-6 (Cellulose); OP1R32D61U (microcrystalline cellulose)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170608
[St] Status:MEDLINE



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