Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
J R Army Med Corps ; 160(1): 46-51, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24109090

RESUMO

OBJECTIVES: To explore the first period of sick leave in military patients following a traumatic battle injury, and the role of primary care. To identify if and where patients perceived difficulties. METHOD: Participants were recruited from The Defence Medical Rehabilitation Centre (DMRC) Headley Court on their second admission. Purposive sampling was used to access a range of different injuries and experiences. Nine patients were interviewed at DMRC where they were asked to recount their stories throughout rehabilitation. Thematic and structural analysis of the narrative accounts was applied. RESULTS: The majority of problems encountered by the participants occurred during their initial period of sick leave between Royal Centre for Defence Medicine (RCDM), Queen Elizabeth Hospital, Birmingham, and DMRC. Participants often had difficulty identifying who to contact if they had a problem on sick leave, with many ringing secondary care directly. Time spent travelling to medical reviews was identified as affecting the quality of leave. CONCLUSIONS: There is a need for greater patient understanding regarding whom to contact should they develop problems while on sick leave. A patient passport containing all discharge documentation and simplified contact details may help reduce patient confusion regarding whom to contact. GPs require greater awareness and understanding of the complexity of these patients' injuries and the need for early secondary care review to prevent delayed or inappropriate admissions. Most problems that patients face will occur on their first period of sick leave. Reducing the time spent on sick leave before admission to DMRC would limit the likelihood of problems occurring at this high-risk time.


Assuntos
Medicina Geral , Necessidades e Demandas de Serviços de Saúde , Militares , Ferimentos e Lesões/psicologia , Ferimentos e Lesões/reabilitação , Adulto , Campanha Afegã de 2001- , Traumatismos por Explosões , Humanos , Masculino , Medicina Militar , Pesquisa Qualitativa , Licença Médica , Reino Unido , Guerra , Ferimentos por Arma de Fogo
2.
Antiviral Res ; 211: 105520, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36603771

RESUMO

Molluscum contagiosum (MC) is an infectious disease that occurs only in humans with a tropism that is narrowly restricted to the outermost epidermal layer of the skin. Molluscum contagiosum virus (MCV) is the causative agent of MC which produces skin lesions that can persist for months to several years. MCV is efficiently transmitted by direct physical contact or by indirect contact with fomites. MC is most prevalent in children and immune compromised patients. The failure to develop a drug that targets MCV replication has been hampered for decades by the inability to propagate MCV in cell culture. To address this dilemma, we recently engineered a surrogate poxvirus expressing the MCV processivity factor (mD4) as the drug target. The mD4 protein is essential for viral replication by keeping the viral polymerase tethered to the DNA template. In this study we have designed and synthesized a lead compound (7269) that is able to prevent mD4 dependent processive DNA synthesis in vitro (IC50 = 6.8 µM) and effectively inhibit propagation of the mD4-VV surrogate virus in BSC-1 cells (EC50 = 13.2 µM) with negligible cytotoxicity. In human liver microsomes, 7269 was shown to be stable for almost 2 h. When tested for penetration into human cadaver skin in a formulated gel, the level of 7269 in the epidermal layer was nearly 100 times the concentration (EC50) needed to inhibit propagation of the mD4-VV surrogate virus in BSC-1 cells. The gel formulated 7269 was scored as a non-irritant on skin and shown to have a shelf-life that was completely stable after several months. In summary, 7269 is a potential Lead for becoming the first MCV anti-viral compound to treat MC and thereby, addresses this unmet medical need that has persisted for many decades.


Assuntos
Molusco Contagioso , Vírus do Molusco Contagioso , Criança , Humanos , Vírus do Molusco Contagioso/genética , Vírus do Molusco Contagioso/metabolismo , Proteínas Virais/genética , DNA/metabolismo
3.
Bioorg Med Chem Lett ; 22(4): 1546-9, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22297111

RESUMO

Structure-activity relationship on a novel ketone class of H(3)R antagonists/inverse agonists is disclosed. Compound 4 showed excellent target potency, selectivity and brain penetration. Evaluation of antagonist 4 in the rat EEG/EMG model demonstrated robust wake activity thereby establishing preclinical proof of concept.


Assuntos
Agonistas dos Receptores Histamínicos/farmacologia , Cetonas/química , Morfolinas/química , Receptores Histamínicos H3 , Vigília/efeitos dos fármacos , Animais , Eletroencefalografia , Agonistas dos Receptores Histamínicos/química , Humanos , Cetonas/farmacologia , Masculino , Estrutura Molecular , Morfolinas/farmacologia , Ratos , Relação Estrutura-Atividade
4.
Bioorg Med Chem Lett ; 22(1): 120-3, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22153937

RESUMO

7-Arylsulfonyl substituted benzofuropiperidine was discovered as a novel scaffold for 5HT(6) receptor antagonists. Optimization by substitution at C-1 position led to identification of selective, orally bioavailable, brain penetrant antagonists with reduced hERG liability. An advanced analog tested in rat social recognition model showed significant activity suggesting potential utility in the enhancement of short-term memory.


Assuntos
Benzofuranos/química , Piperidinas/química , Receptores de Serotonina/química , Antagonistas da Serotonina/farmacologia , Animais , Encéfalo/embriologia , Encéfalo/metabolismo , Canal de Potássio ERG1 , Canais de Potássio Éter-A-Go-Go/metabolismo , Humanos , Concentração Inibidora 50 , Cinética , Memória de Curto Prazo/efeitos dos fármacos , Modelos Químicos , Ratos , Esquizofrenia/tratamento farmacológico , Relação Estrutura-Atividade
5.
Bioorg Med Chem Lett ; 21(18): 5493-7, 2011 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-21782432

RESUMO

H(3)R structure-activity relationships on a novel class of pyridazin-3-one H(3)R antagonists/inverse agonists are disclosed. Modifications of the pyridazinone core, central phenyl ring and linker led to the identification of molecules with excellent target potency, selectivity and pharmacokinetic properties. Compounds 13 and 21 displayed potent functional H(3)R antagonism in vivo in the rat dipsogenia model and demonstrated robust wake activity in the rat EEG/EMG model.


Assuntos
Ingestão de Líquidos/efeitos dos fármacos , Agonistas dos Receptores Histamínicos/farmacologia , Piridazinas/farmacologia , Vigília/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Agonistas dos Receptores Histamínicos/síntese química , Agonistas dos Receptores Histamínicos/química , Humanos , Masculino , Estrutura Molecular , Piridazinas/síntese química , Piridazinas/química , Ratos , Receptores Histamínicos H3/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade
6.
J Med Chem ; 50(7): 1442-4, 2007 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-17335190

RESUMO

A series of novel, potent orthopoxvirus egress inhibitors was identified during high-throughput screening of the ViroPharma small molecule collection. Using structure--activity relationship information inferred from early hits, several compounds were synthesized, and compound 14 was identified as a potent, orally bioavailable first-in-class inhibitor of orthopoxvirus egress from infected cells. Compound 14 has shown comparable efficaciousness in three murine orthopoxvirus models and has entered Phase I clinical trials.


Assuntos
Antivirais/síntese química , Benzamidas/síntese química , Indóis/síntese química , Orthopoxvirus/efeitos dos fármacos , Administração Oral , Animais , Antivirais/farmacocinética , Antivirais/farmacologia , Benzamidas/farmacocinética , Benzamidas/farmacologia , Disponibilidade Biológica , Linhagem Celular , Cristalografia por Raios X , Humanos , Técnicas In Vitro , Indóis/farmacocinética , Indóis/farmacologia , Isoindóis , Macaca fascicularis , Camundongos , Estrutura Molecular , Orthopoxvirus/fisiologia , Ratos , Estereoisomerismo , Relação Estrutura-Atividade
7.
Antiviral Res ; 69(2): 86-97, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16343651

RESUMO

Category A arenaviruses as defined by the National Institute of Allergy and Infectious Diseases (NIAID) are human pathogens that could be weaponized by bioterrorists. Many of these deadly viruses require biosafety level-4 (BSL-4) containment for all laboratory work, which limits traditional laboratory high-throughput screening (HTS) for identification of small molecule inhibitors. For those reasons, a related BSL-2 New World arenavirus, Tacaribe virus, 67-78% identical to Junín virus at the amino acid level, was used in a HTS campaign where approximately 400,000 small molecule compounds were screened in a Tacaribe virus-induced cytopathic effect (CPE) assay. Compounds identified in this screen showed antiviral activity and specificity against not only Tacaribe virus, but also the Category A New World arenaviruses (Junín, Machupo, and Guanarito). Drug resistant variants were isolated, suggesting that these compounds act through inhibition of a viral protein, the viral glycoprotein (GP2), and not through cellular toxicity mechanisms. A lead compound, ST-294, has been chosen for drug development. This potent and selective compound, with good bioavailability, demonstrated protective anti-viral efficacy in a Tacaribe mouse challenge model. This series of compounds represent a new class of inhibitors that may warrant further development for potential inclusion in a strategic stockpile.


Assuntos
Antivirais/química , Arenavirus do Novo Mundo/efeitos dos fármacos , Chumbo/química , Proteínas Virais/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Antivirais/farmacologia , Infecções por Arenaviridae/tratamento farmacológico , Infecções por Arenaviridae/virologia , Chlorocebus aethiops , Efeito Citopatogênico Viral , Febres Hemorrágicas Virais/tratamento farmacológico , Febres Hemorrágicas Virais/virologia , Humanos , Chumbo/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Ratos , Ratos Sprague-Dawley , Sulfonamidas/química , Sulfonamidas/farmacologia , Ureia/análogos & derivados , Ureia/química , Ureia/farmacologia , Células Vero , Proteínas Virais/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA