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1.
Eur J Pain ; 22(9): 1673-1677, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29770535

RESUMO

INTRODUCTION: Pectoral Nerves Block (PECS) and Serratus Plane Block (SPB) have been used to treat persistent post-surgical pain after breast and thoracic surgery; however, they cannot block the internal mammary region, so a residual pain may occur in that region. Parasternal block (PSB) and Thoracic Transversus Plane Block (TTP) anaesthetize the anterior branches of T2-6 intercostal nerves thus they can provide analgesia to the internal mammary region. METHODS: We describe a 60-year-old man suffering from right post-thoracotomy pain syndrome with residual pain located in the internal mammary region after a successful treatment with PECS and SPB. We performed a PSB and TTP and hydrodissection of fascial planes with triamcinolone and Ropivacaine. RESULTS: Pain disappeared and the result was maintained 3 months later. DISCUSSION: This report suggests that PSB and TTP with local anaesthetic and corticosteroid with hydrodissection of fascial planes might be useful to treat a post thoracotomy pain syndrome located in the internal mammary region. SIGNIFICANCE: The use of Transversus Thoracic Plane and Parasternal Blocks and fascial planes hydrodissection as a novel therapeutic approach to treat a residual post thoracotomy pain syndrome even when already treated with Pectoral Nerves Block and Serratus Plane Block.


Assuntos
Dissecação , Fasciotomia , Bloqueio Nervoso/métodos , Dor Pós-Operatória/terapia , Toracotomia/efeitos adversos , Anestésicos Locais/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Ropivacaina/uso terapêutico , Nervos Torácicos
3.
Sci Transl Med ; 7(290): 290ra89, 2015 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-26041706

RESUMO

Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration-approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections.


Assuntos
Antivirais/uso terapêutico , Aprovação de Drogas , Doença pelo Vírus Ebola/terapia , Sondas Moleculares , Animais , Bepridil/farmacologia , Ebolavirus/efeitos dos fármacos , Humanos , Camundongos , Sertralina/farmacologia
4.
Antiviral Res ; 112: 1-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25265598

RESUMO

The cyanobacterial lectin scytovirin (SVN) binds with high affinity to mannose-rich oligosaccharides on the envelope glycoprotein (GP) of a number of viruses, blocking entry into target cells. In this study, we assessed the ability of SVN to bind to the envelope GP of Zaire Ebola virus (ZEBOV) and inhibit its replication. SVN interacted specifically with the protein's mucin-rich domain. In cell culture, it inhibited ZEBOV replication with a 50% virus-inhibitory concentration (EC50) of 50 nM, and was also active against the Angola strain of the related Marburg virus (MARV), with a similar EC50. Injected subcutaneously in mice, SVN reached a peak plasma level of 100 nm in 45 min, but was cleared within 4h. When ZEBOV-infected mice were given 30 mg/kg/day of SVN by subcutaneous injection every 6h, beginning the day before virus challenge, 9 of 10 animals survived the infection, while all infected, untreated mice died. When treatment was begun one hour or one day after challenge, 70-90% of mice survived. Quantitation of infectious virus and viral RNA in samples of serum, liver and spleen collected on days 2 and 5 postinfection showed a trend toward lower titers in treated than control mice, with a significant decrease in liver titers on day 2. Our findings provide further evidence of the potential of natural lectins as therapeutic agents for viral infections.


Assuntos
Antivirais/uso terapêutico , Proteínas de Bactérias/uso terapêutico , Proteínas de Transporte/uso terapêutico , Ebolavirus/efeitos dos fármacos , Lectinas/uso terapêutico , Proteínas do Envelope Viral/metabolismo , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/administração & dosagem , Antivirais/metabolismo , Antivirais/farmacologia , Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/farmacologia , Proteínas de Transporte/administração & dosagem , Proteínas de Transporte/metabolismo , Proteínas de Transporte/farmacologia , Modelos Animais de Doenças , Ebolavirus/fisiologia , Glicoproteínas/metabolismo , Doença pelo Vírus Ebola/prevenção & controle , Doença pelo Vírus Ebola/virologia , Concentração Inibidora 50 , Injeções Subcutâneas , Lectinas/administração & dosagem , Lectinas/metabolismo , Lectinas/farmacologia , Fígado/virologia , Marburgvirus/efeitos dos fármacos , Proteínas de Membrana , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Soro/virologia , Baço/virologia , Análise de Sobrevida , Carga Viral
5.
Antimicrob Agents Chemother ; 58(8): 4885-93, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24841273

RESUMO

Outbreaks of emerging infections present health professionals with the unique challenge of trying to select appropriate pharmacologic treatments in the clinic with little time available for drug testing and development. Typically, clinicians are left with general supportive care and often untested convalescent-phase plasma as available treatment options. Repurposing of approved pharmaceutical drugs for new indications presents an attractive alternative to clinicians, researchers, public health agencies, drug developers, and funding agencies. Given the development times and manufacturing requirements for new products, repurposing of existing drugs is likely the only solution for outbreaks due to emerging viruses. In the studies described here, a library of 290 compounds was screened for antiviral activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). Selection of compounds for inclusion in the library was dependent on current or previous FDA approval or advanced clinical development. Some drugs that had a well-defined cellular pathway as target were included. In total, 27 compounds with activity against both MERS-CoV and SARS-CoV were identified. The compounds belong to 13 different classes of pharmaceuticals, including inhibitors of estrogen receptors used for cancer treatment and inhibitors of dopamine receptor used as antipsychotics. The drugs identified in these screens provide new targets for in vivo studies as well as incorporation into ongoing clinical studies.


Assuntos
Antivirais/farmacologia , Reposicionamento de Medicamentos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Antipsicóticos/farmacologia , Chlorocebus aethiops , Aprovação de Drogas , Antagonistas de Estrogênios/farmacologia , Ensaios de Triagem em Larga Escala , Humanos , Concentração Inibidora 50 , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/fisiologia , Células Vero , Replicação Viral/efeitos dos fármacos
6.
Proc Natl Acad Sci U S A ; 109(44): 18030-5, 2012 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-23071322

RESUMO

Filovirus infections can cause a severe and often fatal disease in humans and nonhuman primates, including great apes. Here, three anti-Ebola virus mouse/human chimeric mAbs (c13C6, h-13F6, and c6D8) were produced in Chinese hamster ovary and in whole plant (Nicotiana benthamiana) cells. In pilot experiments testing a mixture of the three mAbs (MB-003), we found that MB-003 produced in both manufacturing systems protected rhesus macaques from lethal challenge when administered 1 h postinfection. In a pivotal follow-up experiment, we found significant protection (P < 0.05) when MB-003 treatment began 24 or 48 h postinfection (four of six survived vs. zero of two controls). In all experiments, surviving animals that received MB-003 experienced little to no viremia and had few, if any, of the clinical symptoms observed in the controls. The results represent successful postexposure in vivo efficacy by a mAb mixture and suggest that this immunoprotectant should be further pursued as a postexposure and potential therapeutic for Ebola virus exposure.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença pelo Vírus Ebola/prevenção & controle , Planticorpos/uso terapêutico , Animais , Anticorpos Monoclonais/isolamento & purificação , Células CHO , Cricetinae , Cricetulus , Macaca mulatta , Planticorpos/isolamento & purificação
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