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1.
J Virol ; 93(8)2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30700611

RESUMO

Antiviral therapies that impede virus entry are attractive because they act on the first phase of the infectious cycle. Drugs that target pathways common to multiple viruses are particularly desirable when laboratory-based viral identification may be challenging, e.g., in an outbreak setting. We are interested in identifying drugs that block both Ebola virus (EBOV) and Lassa virus (LASV), two unrelated but highly pathogenic hemorrhagic fever viruses that have caused outbreaks in similar regions in Africa and share features of virus entry: use of cell surface attachment factors, macropinocytosis, endosomal receptors, and low pH to trigger fusion in late endosomes. Toward this goal, we directly compared the potency of eight drugs known to block EBOV entry with their potency as inhibitors of LASV entry. Five drugs (amodiaquine, apilimod, arbidol, niclosamide, and zoniporide) showed roughly equivalent degrees of inhibition of LASV and EBOV glycoprotein (GP)-bearing pseudoviruses; three (clomiphene, sertraline, and toremifene) were more potent against EBOV. We then focused on arbidol, which is licensed abroad as an anti-influenza drug and exhibits activity against a diverse array of clinically relevant viruses. We found that arbidol inhibits infection by authentic LASV, inhibits LASV GP-mediated cell-cell fusion and virus-cell fusion, and, reminiscent of its activity on influenza virus hemagglutinin, stabilizes LASV GP to low-pH exposure. Our findings suggest that arbidol inhibits LASV fusion, which may partly involve blocking conformational changes in LASV GP. We discuss our findings in terms of the potential to develop a drug cocktail that could inhibit both LASV and EBOV.IMPORTANCE Lassa and Ebola viruses continue to cause severe outbreaks in humans, yet there are only limited therapeutic options to treat the deadly hemorrhagic fever diseases they cause. Because of overlapping geographic occurrences and similarities in mode of entry into cells, we seek a practical drug or drug cocktail that could be used to treat infections by both viruses. Toward this goal, we directly compared eight drugs, approved or in clinical testing, for the ability to block entry mediated by the glycoproteins of both viruses. We identified five drugs with approximately equal potencies against both. Among these, we investigated the modes of action of arbidol, a drug licensed abroad to treat influenza infections. We found, as shown for influenza virus, that arbidol blocks fusion mediated by the Lassa virus glycoprotein. Our findings encourage the development of a combination of approved drugs to treat both Lassa and Ebola virus diseases.


Assuntos
Antivirais/farmacologia , Ebolavirus/metabolismo , Doença pelo Vírus Ebola/tratamento farmacológico , Indóis/farmacologia , Febre Lassa/tratamento farmacológico , Vírus Lassa/metabolismo , Animais , Células COS , Chlorocebus aethiops , Cricetinae , Avaliação Pré-Clínica de Medicamentos , Células HEK293 , Doença pelo Vírus Ebola/metabolismo , Doença pelo Vírus Ebola/patologia , Humanos , Febre Lassa/metabolismo , Febre Lassa/patologia , Células Vero , Internalização do Vírus/efeitos dos fármacos
4.
Br J Dermatol ; 156(5): 1032-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17419693

RESUMO

Sclerodermatous graft-versus-host disease (GVHD) is a rare complication of bone marrow transplantation. While GVHD is often associated with the beneficial graft vs. tumour effect, it also contributes towards significant morbidity and mortality. No reliably effective treatment has yet been established. We present 10 patients with haematological malignancies who underwent an allogeneic stem cell transplant and developed sclerodermatous GVHD. Donor lymphocyte infusion administered for relapse or reducing donor T-cell chimerism was a known trigger for sclerodermatous GVHD in four of the patients. Treatment with immunosuppressants, psoralen plus ultraviolet A (PUVA) and extracorporeal photopheresis has been largely unsuccessful in their management. Intensive immunosuppression including the use of anti-CD20 monoclonal antibody may have contributed to relapse of leukaemia in one patient 10 years after her transplant. Sclerodermatous GVHD may occur without a preceding lichenoid stage. Clinical heterogeneity is common, although sclerodermatous GVHD has a predilection for the limbs. Treatment options are largely unsatisfactory if conventional immunosuppression fails. PUVA may give some symptomatic benefit and extracorporeal photopheresis seems to be less efficacious than previously published work suggests.


Assuntos
Esclerodermia Localizada/terapia , Adulto , Idoso , Anemia Refratária/cirurgia , Transplante de Medula Óssea/efeitos adversos , Feminino , Doença de Hodgkin/cirurgia , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia PUVA , Plasmocitoma/cirurgia , Recidiva , Esclerodermia Localizada/classificação , Esclerodermia Localizada/etiologia , Transplante de Células-Tronco/efeitos adversos , Trombocitose/cirurgia , Falha de Tratamento
5.
Langmuir ; 22(15): 6549-54, 2006 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-16830996

RESUMO

On solvent-cleaned and piranha-etched single-crystal Al2O3(0001) surfaces, uniform, robust, self-assembled monolayers of octadecylsiloxane (ODS) are formed by 48 h exposure to a solution containing octadecyltrichlorosilane (OTS) in an anhydrous atmosphere. X-ray photoelectron spectroscopy, atomic force microscopy, ellipsometry, and water contact angle measurements confirm the presence of a uniform, complete monolayer. Reducing the exposure time or omitting the piranha-etch leads to much less uniform coverage. The ODS monolayers are stable when stored in ambient atmospheres for month-long periods. Thermal desorption in a vacuum environment (10(-9) Torr) shows the ODS monolayer is thermally stable up to at least 420 K. When heated in 200 mTorr of flowing forming gas (N2-10% H2) for 1 h at 520 K, slow loss of ODS was indicated. A schematic model is proposed which involves island nucleation by covalent bonding of OTS to surface hydroxyl groups followed by growth through the addition of mobile ODS species.


Assuntos
Óxido de Alumínio/química , Membranas Artificiais , Siloxanas/química , Microscopia de Força Atômica/métodos , Sensibilidade e Especificidade , Espectrofotometria/métodos , Análise Espectral/métodos , Propriedades de Superfície , Temperatura , Água/química , Raios X
6.
Caries Res ; 39(3): 241-50, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15914988

RESUMO

OBJECTIVE: This double-blinded, placebo-controlled clinical trial tested the safety and efficacy of a topical secretory IgA antibody manufactured in tobacco plants (plantibody) in preventing recolonization of mutans streptococci (MS) in human plaque as measured by whole stimulated saliva samples. METHODS: Following a 9-day antimicrobial treatment with chlorhexidine (CHX), 56 eligible adults (enrollment salivary MS > or = 10(4) CFU/ml; no current caries) were randomized equally to a group receiving 0, 2, 4, or 6 topical applications of plantibody followed by 6, 4, 2, or 0 applications of placebo, respectively, over a 3-week period. RESULTS: Among the 54 subjects who completed the trial, the CHX regimen eliminated salivary MS in 69%. After 6 months, there were no significant differences in MS levels by number of applications, relative to placebo (p > 0.43). No adverse effects were observed. CONCLUSION: Plantibody is safe but not effective at the frequency, concentration, and number of applications used in this study.


Assuntos
Imunoglobulina A Secretora/uso terapêutico , Nicotiana/imunologia , Planticorpos/uso terapêutico , Streptococcus mutans/efeitos dos fármacos , Adulto , Idoso , Anti-Infecciosos Locais/uso terapêutico , Clorexidina/uso terapêutico , Placa Dentária/tratamento farmacológico , Placa Dentária/metabolismo , Placa Dentária/microbiologia , Método Duplo-Cego , Feminino , Humanos , Imunoglobulina A Secretora/metabolismo , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/metabolismo , Extratos Vegetais/uso terapêutico , Planticorpos/metabolismo , Saliva/microbiologia , Estatísticas não Paramétricas
7.
Clin Exp Dermatol ; 28(3): 254-6, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12780705

RESUMO

Argyria is a rare cause of cutaneous discolouration caused by silver deposition. We report a case of dramatic and diffuse argyria secondary to ingestion of colloidal silver protein over a 1-year period. Stained electron microscopy with spectral analysis was used to confirm the clinical diagnosis. Silver-protein complexes are deposited in the skin and reduced to inert silver salts by sunlight in a process similar to that harnessed in photography. Our patient had obtained the silver for consumption via mail order. It had been advertised as a cure for a variety of diseases. Colloidal silver protein is commercially available as a 'food supplement', hence circumventing the strict controls placed on medicines.


Assuntos
Argiria/etiologia , Dermatoses Faciais/induzido quimicamente , Prata/efeitos adversos , Argiria/patologia , Terapias Complementares/efeitos adversos , Dermatoses Faciais/patologia , Humanos , Masculino , Pessoa de Meia-Idade
8.
Nurs Clin North Am ; 36(1): 83-92, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11342404

RESUMO

Music interventions have been used in medicine and nursing throughout history. Music therapy is an easy-to-administer, relatively inexpensive, noninvasive intervention that has been used to reduce heart rate, blood pressure, myocardial oxygen consumption, gastrointestinal function, anxiety, and pain. A review of theoretic and empirical base for the use of music therapy to improve patient outcomes in a variety of areas of clinical practice is presented. Implications for practice and future research are suggested.


Assuntos
Musicoterapia , Córtex Auditivo/fisiologia , Audição/fisiologia , História do Século XVIII , História do Século XIX , História do Século XX , História Antiga , Enfermagem Holística/métodos , Humanos , Música/psicologia , Musicoterapia/história
9.
Epidemiol Infect ; 125(2): 377-83, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11117961

RESUMO

We describe the epidemiology of the first nationwide outbreak of measles infection in the UK since the implementation of a mass vaccination campaign. Notifications of infectious diseases, interview and postal questionnaire identified 293 clinical cases, 138 of which were confirmed by salivary IgM, measles virus isolation and PCR. Twelve were epidemiologically linked to confirmed cases. The outbreak began in London, after contact with measles infection probably imported from Italy. Measles genotyping determined by sequence analysis confirmed spread to other unimmunized anthroposophic communities in the north, south west and south coast of England. Only two cases had been vaccinated against measles infection, and 90% of cases were aged under 15 years. Measles virus can selectively target non-immune groups in countries with high vaccine uptake and broader herd immunity. Without harmonization of vaccination policies and uniform high coverage across Europe, the importation and spread of measles virus amongst non-immune groups may prevent the elimination of measles.


Assuntos
Surtos de Doenças , Vacina contra Sarampo , Sarampo/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Estudos Epidemiológicos , Europa (Continente)/epidemiologia , Feminino , Humanos , Programas de Imunização , Lactente , Recém-Nascido , Masculino , Sarampo/prevenção & controle , Sarampo/transmissão , Pessoa de Meia-Idade , Reino Unido/epidemiologia
10.
Crit Care Nurs Clin North Am ; 12(2): 219-25, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11249367

RESUMO

Music therapy is an easy to administer, relatively inexpensive, noninvasive intervention that can reduce anxiety and pain in critical care and perioperative patients. Libraries of relaxing music selections need to be compiled, reflecting diverse musical tastes. Providing patients with the opportunity to partake in music therapy sessions, selecting their own music, and providing them with quiet, uninterrupted time to listen to the music provides patients with a sense of control and separation from the multiple environmental stressors they are experiencing. Although there is now an extensive empirical base for the therapeutic usefulness of music therapy, particularly with the myocardial infarction population, few hospitals have adopted music therapy programs. Patient satisfaction and outcomes clearly have improved after music therapy sessions have been implemented. Further study with more diverse samples with a wider variety of medical conditions is indicated. Most of these studies used only one or two music sessions. It is not known whether effectiveness of music therapy sessions improves with repeated exposures. Further, there are little data with respect to optimal time for implementation of music therapy, length of music therapy sessions, or types of music to use. The effects of cultural diversity have not been addressed. Music therapy can improve the quality of care that critical care and perioperative nurses deliver to their patients.


Assuntos
Cuidados Críticos/métodos , Enfermagem Holística/métodos , Musicoterapia , Enfermagem Perioperatória/métodos , Humanos
11.
Am J Crit Care ; 8(4): 220-30, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10392221

RESUMO

BACKGROUND: Acute myocardial infarction places additional demands on an already compromised myocardium. Relaxing music can induce a relaxation response, thereby reversing the deleterious effects of the stress response. OBJECTIVES: To compare the effects of relaxing music; quiet, uninterrupted rest; and "treatment as usual" on anxiety levels and physiological indicators of cardiac autonomic function. METHODS: A 3-group repeated measures experimental design was used. Forty-five patients, 15 per group, with acute myocardial infarction were assigned randomly to 20 minutes of (1) music in a quiet, restful environment (experimental group); (2) quiet, restful environment without music (attention); or (3) treatment as usual (control). Anxiety levels and physiological indicators were measured. RESULTS: Immediately after the intervention, reductions in heart rate, respiratory rate, and myocardial oxygen demand were significantly greater in the experimental group than in the control group. The reductions in heart rate and respiratory rate remained significantly greater 1 hour later. Changes in heart rate, respiratory rate, and myocardial oxygen demand in the attention group did not differ significantly from changes in the other 2 groups. The 3 groups did not differ with respect to systolic blood pressure. Increases in high-frequency heart rate variability were significantly greater in the experimental and attention groups than in the control group immediately after the intervention. State anxiety was reduced in the experimental group only; the reduction was significant immediately and 1 hour after the intervention. CONCLUSIONS: Patients recovering from acute myocardial infarction may benefit from music therapy in a quiet, restful environment.


Assuntos
Ansiedade/prevenção & controle , Sistema Nervoso Autônomo/fisiopatologia , Musicoterapia/normas , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/psicologia , Análise de Variância , Ansiedade/etiologia , Eletrocardiografia Ambulatorial , Feminino , Ambiente de Instituições de Saúde , Frequência Cardíaca , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Ruído/efeitos adversos , Consumo de Oxigênio , Respiração , Fatores de Tempo
12.
Dermatol Surg ; 25(3): 250-2; discussion 252-3, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10193977

RESUMO

BACKGROUND: Pulsed dye laser treatment of port-wine stains is safe and effective. However, the pain associated with this treatment is often difficult to tolerate, especially for children. A laser-coupled delivery system known as dynamic epidermal cooling has recently been developed to improve local anesthesia. OBJECTIVE: To report laser ignition of a commercially-available, hand-held cryogen spray used for local anesthesia, and describe possible mechanisms of the fire; to define the chemical characteristics of other skin coolants suitable and unsuitable for skin cooling with laser treatment. METHODS: Case report and literature review. CONCLUSIONS: Clinicians must be aware of the thermodynamic properties, potential for skin damage, cost and environmental consequences of commercially available cryogens before considering their use for topical anesthesia with laser surgery.


Assuntos
Anestesia Local/efeitos adversos , Cloreto de Etil/efeitos adversos , Dermatoses Faciais/cirurgia , Incêndios , Terapia a Laser/efeitos adversos , Mancha Vinho do Porto/cirurgia , Criança , Humanos , Masculino
13.
Drug Alcohol Rev ; 17(4): 445-52, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16203511

RESUMO

The debate regarding therapeutic use of cannabis is being confused by a lack of distinction between therapeutic and social use of cannabis. Separate consideration of therapeutic and social use would enable strategies to minimise any negative social impact of therapeutic use. For therapeutic use of cannabis to be considered on its own merits, greater emphasis needs to be placed on scientific evidence of therapeutic efficacy. At present the evidence is limited, it mostly relates to the use of synthetic cannabinoids, and much of it fails to compare cannabis with the best therapies available for the conditions of interest. Claims of therapeutic efficacy tend to be based on opinion and anecdote rather than the results of controlled studies. Further research is needed to clarify the potential therapeutic benefits, to enable claims of therapeutic use to be objectively assessed and to enable informed decisions to be made about the relative risks and benefits for any individual using cannabis for therapeutic purposes. Further research is required to clarify the efficacy of pure, synthetic cannabinoids compared to cannabis, the most effective route of administration, and the importance of delivering a known dose. The most likely value of cannabis is as an adjunct, rather than a replacement for, current medical approaches. The potential therapeutic benefits of cannabis will be greatest for those conditions where long-term cannabis use, with its attendant health risks, is not an issue and where the patient has the capacity to titrate dose against symptoms. There is sufficient evidence of potential therapeutic benefit to justify the facilitation of further research.

14.
J Virol ; 71(11): 8808-20, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9343241

RESUMO

Past efforts to employ a structure-based approach to design an inhibitor of the fusion-inducing conformational change in the influenza virus hemagglutinin (HA) yielded a family of small benzoquinones and hydroquinones. The most potent of these, tert-butyl hydroquinone (TBHQ), inhibits both the conformational change in HA from strain X:31 influenza virus and viral infectivity in tissue culture cells with 50% inhibitory concentrations in the micromolar range (D. L. Bodian, R. B. Yamasaki, R. L. Buswell, J. F. Stearns, J. M. White, and I. D. Kuntz, Biochemistry 32:2967-2978, 1993). A new structure-based inhibitor design search was begun which involved (i) the recently refined crystal structure (2.1-A resolution) of the HA ectodomain, (ii) new insights into the conformational change, and (iii) improvements in the molecular docking program, DOCK. As a result, we identified new inhibitors of HA-mediated membrane fusion. Like TBHQ, most of these molecules inhibit the conformational change. One of the new compounds, however, facilitates rather than inhibits the HA conformational change. Nonetheless, the facilitator, diiodofluorescein, inhibits HA-mediated membrane fusion and, irreversibly, infectivity. We further characterized the effects of inhibitors from both searches on the conformational change and membrane fusion activity of HA as well as on viral infectivity. We also isolated and characterized several mutants resistant to each class of inhibitor. The implications of our results for HA-mediated membrane fusion, anti-influenza virus therapy, and structure-based inhibitor design are discussed.


Assuntos
Antivirais/farmacologia , Fluoresceínas/farmacologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/ultraestrutura , Orthomyxoviridae/ultraestrutura , Conformação Proteica/efeitos dos fármacos , Sítios de Ligação , Bromelaínas , Linhagem Celular , Desenho de Fármacos , Hemólise/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Hidroquinonas/farmacologia , Ligantes , Fusão de Membrana , Modelos Moleculares , Orthomyxoviridae/crescimento & desenvolvimento , Fragmentos de Peptídeos , Relação Estrutura-Atividade
15.
Dev Biol ; 182(2): 314-30, 1997 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-9070330

RESUMO

Embryonic development involves a series of cell adhesive interactions that provide mechanical and instructive information required for morphogenesis. The ADAMs family of membrane-anchored proteins, containing a disintegrin and metalloprotease domain, is well suited for participating in such developmental events. They encode not only a potential adhesive function, through an integrin-binding disintegrin domain, but also a potential antiadhesive function, through a zinc-dependent metalloprotease domain. In order to investigate the role of ADAMs in early development we cloned a cDNA encoding a novel member of the ADAM family from a Xenopus laevis neurula stage library. We call this cDNA, and the 915-amino-acid protein it encodes, ADAM 13, X-ADAM 13 RNA is expressed during embryogenesis from the midblastula stage through tadpole stage 45. X-ADAM 13 is localized to somitic mesoderm and cranial neural crest cells during gastrulation, neurulation, and in tail bud stages. Sequence analyses of the X-ADAM 13 metalloprotease and disintegrin domains indicate that the protein is likely to be involved in both proteolytic and cell-adhesive functions. The X-ADAM 13 sequence is most closely related to that of mouse meltrin alpha, which is implicated in myoblast fusion. Our data suggest that X-ADAM 13 may be involved in neural crest cell adhesion and migration as well as myoblast differentiation.


Assuntos
Proteínas de Membrana/genética , Crista Neural/metabolismo , Somitos/metabolismo , Proteínas de Xenopus , Células 3T3 , Proteínas ADAM , Sequência de Aminoácidos , Animais , Clonagem Molecular , DNA Complementar , Desintegrinas/genética , Desintegrinas/fisiologia , Embrião não Mamífero/metabolismo , Humanos , Mamíferos , Proteínas de Membrana/fisiologia , Metaloendopeptidases/genética , Metaloendopeptidases/fisiologia , Camundongos , Dados de Sequência Molecular , Crista Neural/citologia , RNA Mensageiro/biossíntese , Homologia de Sequência de Aminoácidos , Xenopus laevis/embriologia
16.
Addiction ; 91(1): 39-45, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8822013

RESUMO

This study used the SF-36 general health questionnaire to measure the health status of heroin users at entry to a public methadone maintenance programme. Their results were compared to those from the general population and from three clinical groups: patients with minor medical, major medical and psychiatric problems. One hundred consecutive clients were interviewed in the first week on the programme using the SF-36 health questionnaire. Data were also gathered on their drug use, use of medical services and HIV risk behaviour. The results showed that heroin users at entry to the methadone maintenance programme had significantly worse physical and psychological health than the general population. Their scores were most similar to the psychiatrically depressed patients, although they had worse physical health than this comparison group. The greater the amount of heroin used by clients before entering the programme, the more pain they reported. Alcohol and marijuana use were associated with better social and physical health. The relationship between general health status and amount or frequency of drug use is not a clear one. Heroin users experience severe emotional and physical problems at the time of entering methadone maintenance treatment.


Assuntos
Nível de Saúde , Inquéritos Epidemiológicos , Dependência de Heroína/reabilitação , Metadona/uso terapêutico , Admissão do Paciente , Adolescente , Adulto , Comorbidade , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Comportamentos Relacionados com a Saúde , Dependência de Heroína/epidemiologia , Humanos , Masculino , Austrália do Sul/epidemiologia
17.
Scanning Microsc ; 7(3): 979-87, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8146624

RESUMO

Conventional cleaning and shaping of root canal spaces involves the use of hand and rotary instruments with irrigation. The procedure results in the formation of a smear layer consisting of dentin shavings, organic tissue remnants and microorganisms. The laser has been suggested as an aid in root canal preparation. In this study, pulsed and continuous wave 1.06 microns wavelength Nd:YAG lasers were used to compare their abilities to clean and shape root canal spaces to conventional methods. After preparation, the test teeth were sectioned longitudinally and examined by scanning electron microscopy. The results demonstrated that the laser was capable of removing the smear layer in its entirety and could occasionally alter dentin walls.


Assuntos
Dentina/ultraestrutura , Terapia a Laser , Tratamento do Canal Radicular/instrumentação , Humanos , Microscopia Eletrônica de Varredura , Camada de Esfregaço , Dente/ultraestrutura
18.
Biochemistry ; 32(12): 2967-78, 1993 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-8457561

RESUMO

Influenza hemagglutinin (HA) undergoes a conformational change that is required for viral entry. The rearrangement includes exposure of the fusion peptide, a hydrophobic segment buried in the trimer interface of the native protein. Since fusion peptide release triggers the membrane fusion event crucial for viral replication, inhibition of fusion peptide exposure should prevent infection. We reasoned that small molecules that bind to HA and stabilize its nonfusogenic conformation would block viral activity. A computer-assisted method was used to select putative HA ligands. One of the selected compounds, 4A,5,8,8A-tetrahydro-5,8-methano-1,4-naphthoquinone, prevented the conversion of X31 HA to a conformation recognized by alpha-fusion peptide antisera. Several derivatives of this compound, including both benzoquinones and hydroquinones, also showed inhibition. The most effective compounds tested have IC50S between 1 and 20 microM. Representative compounds also inhibited virus-induced syncytia formation, HA-mediated hemolysis, and viral infectivity in vitro. The inhibitors are attractive leads for the development of antiviral drugs and can serve as probes of the mechanism of the conformational change of HA.


Assuntos
Benzoquinonas/farmacologia , Hemaglutininas Virais/química , Hidroquinonas/farmacologia , Fusão de Membrana/fisiologia , Orthomyxoviridae/química , Benzoquinonas/metabolismo , Bromelaínas/metabolismo , Linhagem Celular , Simulação por Computador , Fluorescência , Hemaglutinação/efeitos dos fármacos , Hemaglutininas Virais/metabolismo , Hemaglutininas Virais/fisiologia , Hemólise , Concentração de Íons de Hidrogênio , Hidroquinonas/metabolismo , Cinética , Fusão de Membrana/efeitos dos fármacos , Modelos Moleculares , Orthomyxoviridae/efeitos dos fármacos , Orthomyxoviridae/patogenicidade , Fragmentos de Peptídeos/metabolismo , Conformação Proteica/efeitos dos fármacos
19.
Clin Nurse Spec ; 6(2): 58-63, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1617576

RESUMO

The purpose of this study was to examine the effects of relaxing music on elevated state anxiety in patients with a confirmed medical diagnosis of acute myocardial infarction. In addition, the relationship between trait anxiety and state anxiety was analyzed. A purposive sample of 40 myocardial infarction patients was randomly assigned to an experimental or control group. Statistically significant reduction in heart rate, respiratory rate, and state anxiety scores were found in the group that listened to relaxing music. A statistically significant positive correlation was found between trait anxiety scores and baseline state anxiety scores. Statistically significant negative correlations were found between trait anxiety scores and the degree of change in posttreatment state anxiety scores when examined as a net change, as well as a percent change. Results suggested that music therapy may be an effective intervention to reduce state anxiety levels in the acute myocardial infarction patient.


Assuntos
Musicoterapia/normas , Infarto do Miocárdio/complicações , Estresse Psicológico/enfermagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diagnóstico de Enfermagem , Pesquisa em Avaliação de Enfermagem , Estresse Psicológico/etiologia
20.
Proc Natl Acad Sci U S A ; 79(4): 968-72, 1982 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-6951181

RESUMO

A conformational change in the hemagglutinin glycoprotein of influenza virus has been observed to occur to pH values corresponding to those optimal for the membrane fusion activity of the virus. CD, electron microscopic, and sedimentation analyses show that, in the pH range 5.2-4.9, bromelain-solubilized hemagglutinin (BHA) aggregates as protein-protein rosettes and acquires the ability to bind both lipid vesicles and nonionic detergent. Trypsin treatment of BHA in the pH 5.0-induced conformation indicates that aggregation is a property of the BHA2 component and that the conformation change also involves BHA1. The implications of these observations for the role of the glycoprotein in membrane fusion are discussed.


Assuntos
Glicoproteínas/fisiologia , Hemaglutininas Virais , Vírus da Influenza A/fisiologia , Proteínas Virais/fisiologia , Bromelaínas , Detergentes/metabolismo , Concentração de Íons de Hidrogênio , Vírus da Influenza A/imunologia , Bicamadas Lipídicas/metabolismo , Conformação Proteica , Tripsina
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