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1.
Int J Tuberc Lung Dis ; 27(6): 465-470, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37231609

RESUMO

BACKGROUND: The severity of non-tuberculous mycobacterial pulmonary disease (NTM-PD) can be classified based on an assessment of the patient´s body mass index, age, presence of cavity, erythrocyte sediment rate and sex (BACES). In this study, changes in lung function according to disease severity were analysed.METHODS: Patients with NTM-PD who underwent at least two lung function tests between 1 January 2011 and 31 December 2021, were classified according to their BACES score into mild (0-1), moderate (2-3) and severe (4-5) groups, and changes in lung function were assessed using BACES scores.RESULTS: A total of 354 patients were divided into three groups: mild (n = 108), moderate (n = 216) and severe (n = 30). As disease severity increased, the decrease in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) was greater: respectively 26.4 mL/year, 31.3 mL/year and 35.7 mL/year in case of FEV1 (P for trend = 0.002); 18.9 mL/year, 25.5 mL/year and 48.9 mL/year in case of FVC (P for trend = 0.002); and 0.7%/year, 1.3%/year and 2.5%/year for DLCO (P for trend = 0.023) in the mild, moderate and severe groups.CONCLUSION: The decrease in lung function in NTM-PD was correlated with disease severity.


Assuntos
Pneumopatias , Pulmão , Humanos , Micobactérias não Tuberculosas , Volume Expiratório Forçado , Capacidade Vital , Gravidade do Paciente , Capacidade de Difusão Pulmonar
2.
Int J Tuberc Lung Dis ; 23(7): 850-857, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31439118

RESUMO

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) poses a threat to public health as a result of high treatment costs and unsatisfactory outcomes.OBJECTIVE: To elucidate trend, demographic and clinical characteristics and treatment outcomes of patients with MDR-TB between 2011 and 2015 in South Korea.METHOD: Data of patients with MDR-TB diagnosed between 1 January 2011 and 31 December 2015 were retrieved from the nationwide Internet-based TB notification system and analysed retrospectively.RESULTS: During the study period, 5192 MDR-TB patients were notified. We identified an increasing number of MDR-TB patients among foreign populations (from 1.3% to 7.7%), decreasing resistance rates to other anti-TB drugs (e.g., resistance to pyrazinamide, from 40.9% to 28.2%), a decreasing interval from treatment initiation to negative conversion of sputum culture (from 165.7 to 103.7 days) and shortening of treatment duration (719.7 to 613.2 days). However, treatment success rates did not change, and had an average of 65.7%.CONCLUSION: Despite decreasing resistance rates to other drugs and faster treatment responses, treatment outcomes did not improve during the study period. Strict management of MDR-TB patients on treatment should be adopted to improve treatment outcomes.


Assuntos
Antituberculosos/uso terapêutico , Notificação de Doenças , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/farmacologia , Criança , Pré-Escolar , Demografia , Feminino , Humanos , Lactente , Recém-Nascido , Internet , Masculino , Programas de Rastreamento , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/prevenção & controle , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/prevenção & controle , Adulto Jovem
3.
Int J Tuberc Lung Dis ; 23(2): 174-180, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30808449

RESUMO

SETTING: A referral centre in South Korea. OBJECTIVE: To investigate trends in drug resistance, treatment modalities and outcomes, and adverse events of multidrug-resistant tuberculosis (MDR-TB) over two decades. DESIGN: MDR-TB patients treated at Seoul National Hospital University between 1996 and 2015 were divided into four 5-year cohorts according to the date of initial diagnosis. Changes in demographic characteristics, drug resistance, drugs used, treatment outcomes and adverse events over time were elucidated. RESULTS: Between 1996 and 2015, 418 patients were treated for MDR-TB: 86 patients between 1996 and 2000, 125 between 2001 and 2005, 123 between 2006 and 2010, and 84 between 2011 and 2015. The proportion of patients with positive acid-fast bacilli sputum (60.5-29.7%, P < 0.001) or cavities on chest radiographs (86.0-40.5%, P < 0.001) decreased over time. Resistance to pyrazinamide, fluoroquinolones, cycloserine and p-aminosalicylic acid decreased. Later-generation fluoroquinolones (77.9-90.5%) and linezolid (0-26.2%) became more frequently prescribed. The treatment success rate increased (45.3-88.1%, P < 0.001); neurological adverse events, including peripheral neuropathy also increased (4.7-13.1%, P = 0.027). CONCLUSION: MDR-TB patients presented with less severe disease and better resistance profiles over time in South Korea, with treatment outcomes improving continuously.


Assuntos
Antituberculosos/administração & dosagem , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Antituberculosos/farmacologia , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Escarro/microbiologia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
4.
Int J Tuberc Lung Dis ; 19(5): 525-30, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25868019

RESUMO

SETTING: After several changes in treatment modalities, it is time to re-evaluate treatment outcomes of multidrug-resistant tuberculosis (MDR-TB). OBJECTIVE: To evaluate treatment outcomes, elucidate changes in outcomes over time and identify predictors of treatment success for MDR-TB. DESIGN: Patients diagnosed with MDR-TB at a tertiary referral centre in South Korea between January 2006 and December 2010 were included. Treatment modalities and outcomes were assessed. Predictors of treatment success were analysed using multiple logistic regression. The treatment modalities and outcomes of these patients were compared with those of MDR-TB patients between January 1996 and December 2005. RESULTS: Of the 123 MDR-TB patients diagnosed during the later study period, treatment was successful in 103 (83.7%). Extensive drug resistance (OR 0.31, P = 0.044) and additional resistance to fluoroquinolones (OR 0.23, P = 0.039) were inversely associated with treatment success. The treatment success rate improved from 53.5% in 1996-2000 to 68.8% in 2001-2005 and 83.7% in 2006-2010 (P < 0.001). Improved outcomes were accompanied with more frequent use of later-generation fluoroquinolones and linezolid and less frequent surgical resection. CONCLUSION: Treatment outcomes for MDR-TB improved at a tertiary referral centre in South Korea. The improvement was associated with more frequent use of later-generation fluoroquinolones and linezolid.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Antituberculosos/farmacologia , Estudos de Coortes , Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Feminino , Seguimentos , Hospitais Universitários , Humanos , Modelos Logísticos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Recidiva , República da Coreia , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento
5.
Int J Tuberc Lung Dis ; 19(1): 81-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25519795

RESUMO

SETTING: The Xpert(®) MTB/RIF assay has been endorsed by the World Health Organization for the detection of pulmonary and extra-pulmonary tuberculosis (EPTB). OBJECTIVE: To determine the accuracy of the Xpert assay in diagnosing EPTB in South Korea, a country with an intermediate TB burden. DESIGN: We retrospectively reviewed the medical records of 1429 patients in whom the Xpert assay using EPTB specimens was requested between 1 January 2011 and 31 October 2013 in a tertiary referral hospital in South Korea. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of EPTB and detection of rifampicin (RMP) resistance were calculated. RESULTS: Using culture as gold standard, the sensitivity, specificity, PPV and NPV of the assay were respectively 67.7%, 98.1%, 60% and 98.6%. Using a composite reference standard, the sensitivity, specificity, PPV and NPV were respectively 49.3%, 100%, 100% and 95.1%. The sensitivity, specificity, PPV and NPV for the detection of RMP resistance among specimens with positive results for Mycobacterium tuberculosis were respectively 80%, 100%, 100% and 97.7%. CONCLUSION: The Xpert assay showed acceptable sensitivity in certain groups and excellent specificity in diagnosing EPTB and detecting RMP resistance in an intermediate TB burden country.


Assuntos
Antibióticos Antituberculose/farmacologia , Farmacorresistência Bacteriana Múltipla , Rifampina/farmacologia , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Valor Preditivo dos Testes , República da Coreia , Estudos Retrospectivos , Sensibilidade e Especificidade , Manejo de Espécimes , Adulto Jovem
6.
J Med Syst ; 35(2): 265-75, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20703564

RESUMO

This paper deals with strategic enterprise resource planning (ERP) in a health-care system using a multicriteria decision-making (MCDM) model. The model is developed and analyzed on the basis of the data obtained from a leading patient-oriented provider of health-care services in Korea. Goal criteria and priorities are identified and established via the analytic hierarchy process (AHP). Goal programming (GP) is utilized to derive satisfying solutions for designing, evaluating, and implementing an ERP. The model results are evaluated and sensitivity analyses are conducted in an effort to enhance the model applicability. The case study provides management with valuable insights for planning and controlling health-care activities and services.


Assuntos
Tomada de Decisões Assistida por Computador , Tomada de Decisões Gerenciais , Atenção à Saúde/métodos , Atenção à Saúde/organização & administração , Alocação de Recursos para a Atenção à Saúde , Planejamento em Saúde , Humanos , Coreia (Geográfico) , Modelos Organizacionais
7.
Water Sci Technol ; 55(1-2): 251-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17305147

RESUMO

To treat cutting oil wastewater produced in metal surface treatment industry, Ultrasonication (US)-Fenton process, which is one of the advanced oxidation processes, was used. The optimum conditions to treat non-biodegradable pollutants using the US-Fenton process were that the application rates of H2O2 and FeSO4 were 10% and 3 g/L, respectively, the value of pH was 3, and the ultrasonication time was 30 min. It identified non-degradable pollutants such as ethylene diamine tetraacetic acid (EDTA) and Triethanolamine (TEA) in the cutting oil wastewater. TLC analysis of two compounds of treated water by the coagulation process was similar to that of raw water. However, TLC analysis of two compounds of US-Fenton process was different from that of raw water, meaning that US-Fenton process decomposed the EDTA and TEA. To study the possibility of application with the US-Fenton process to pilot plant, the pollutants treatment efficiency of three different methods, such as US-Fenton process, activated sludge process and coagulation process, in continuous experiments were compared. The removal rate of pollutants by the US-Fenton process according to the effluent time was higher than any other processes. The removal rates of COD, SS, T-N and T-P by US-Fenton process were 98, 93, 75 and 95%, respectively.


Assuntos
Peróxido de Hidrogênio/química , Resíduos Industriais , Ferro/química , Ultrassom , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/química , Purificação da Água/métodos , Biodegradação Ambiental , Recuperação e Remediação Ambiental , Compostos Ferrosos/química , Compostos Ferrosos/metabolismo , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Ferro/metabolismo , Metais/química , Óleos , Oxirredução , Fatores de Tempo , Poluentes Químicos da Água/metabolismo
8.
J Biosci ; 28(1): 77-81, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12682428

RESUMO

The present study was carried out to observe the cytotoxicity of yellow sand in comparison with silica and titanium dioxide in a rat alveolar type II cell line (RLE-6TN). Yellow sand (China Loess) was obtained from the loess layer in the Gunsu Province of China. The mean particle diameter of yellow sand was about 0.003 +/- 0.001 mm. Major elements of yellow sand were Si(27.7 +/- 0.6%), Al(6.01 +/- 0.17%), and Ca(5.83 +/- 0.23%) in that order. Silica and yellow sand significantly decreased cell viability and increased [Ca2+]i. All three particles increased the generation of H2O2. TiO2 did not change Fenton activity, while silica induced a slight increase of Fenton activity. In contrast, yellow sand induced a significant increase of Fenton activity. Silica, yellow sand and TiO2 induced significant nitrite formations in RLE-6TN cells. Silica showed the highest increase in nitrite formation, while yellow sand induced the least formation of nitrite. Silica and yellow sand increased the release of TNF-a. Based on these results, we suggest that yellow sand can induce cytotoxicity in RLE-6TN cells and reactive oxygen species, Fenton activity and reactive nitrogen species might be involved in this toxicity.


Assuntos
Células Epiteliais/metabolismo , Pulmão/citologia , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Dióxido de Silício/toxicidade , Alumínio/química , Animais , Cálcio/análise , Cálcio/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/química , Células Epiteliais/efeitos dos fármacos , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/síntese química , Macrófagos Alveolares/efeitos dos fármacos , Nitritos/análise , Tamanho da Partícula , Ratos , Silício/química , Dióxido de Silício/química , Titânio/efeitos adversos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
9.
J Med Syst ; 26(5): 427-38, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12182207

RESUMO

This study presents an application of linear programming discriminant analysis (LPDA) to classify and to predict the symptomatic status of HIV/AIDS patients. We applied LPDA as well as several traditional discriminant analysis methods to the AIDS Cost and Services Utilization Survey data set in order to demonstrate the use of LPDA to classify the symptomatic status of HIV/AIDS patients. The potential benefit of LPDA in terms of the classification accuracy was also analyzed.


Assuntos
Análise Discriminante , Infecções por HIV/fisiopatologia , Programação Linear , Diagnóstico por Computador , Feminino , Infecções por HIV/classificação , Humanos , Masculino , Índice de Gravidade de Doença
10.
IEEE Trans Neural Netw ; 13(1): 143-59, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-18244416

RESUMO

Feature selection plays an important role in classifying systems such as neural networks (NNs). We use a set of attributes which are relevant, irrelevant or redundant and from the viewpoint of managing a dataset which can be huge, reducing the number of attributes by selecting only the relevant ones is desirable. In doing so, higher performances with lower computational effort is expected. In this paper, we propose two feature selection algorithms. The limitation of mutual information feature selector (MIFS) is analyzed and a method to overcome this limitation is studied. One of the proposed algorithms makes more considered use of mutual information between input attributes and output classes than the MIFS. What is demonstrated is that the proposed method can provide the performance of the ideal greedy selection algorithm when information is distributed uniformly. The computational load for this algorithm is nearly the same as that of MIFS. In addition, another feature selection algorithm using the Taguchi method is proposed. This is advanced as a solution to the question as to how to identify good features with as few experiments as possible. The proposed algorithms are applied to several classification problems and compared with MIFS. These two algorithms can be combined to complement each other's limitations. The combined algorithm performed well in several experiments and should prove to be a useful method in selecting features for classification problems.

11.
Crit Rev Food Sci Nutr ; 41(6): 465-79, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11592685

RESUMO

Attempts are being made at the international level within the framework of the Codex Alimentarius to establish guidelines for health claims. An important issue that has to be addressed is the process of substantiating any health claim. Previous papers have addressed aspects relating to the development and regulatory control of functional foods and certain issues relating to claims. This paper addresses several issues concerning the substantiation of health claims through the examination of the regulations and guidelines in several countries. They include (1) importance of human- and product-based studies; (2) concept of scientific consensus; (3) authorization of claim wording; (4) availability of scientific evidence to public (confidentiality). The paper finally proposes a system based on generic and innovative health claims.


Assuntos
Alimentos Orgânicos/normas , Legislação sobre Alimentos/normas , Animais , Medicina Baseada em Evidências , Saúde Global , Humanos , Cooperação Internacional , Política Nutricional
13.
Am J Ment Retard ; 106(3): 231-52, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11408960

RESUMO

In 1994 and 1995, the National Health Interview Survey included a Disability Supplement (NHIS-D) to collect extensive information about disabilities among individuals sampled as part of annual census-based household interview surveys. Here we describe the development and application of operational definitions of mental retardation and developmental disabilities to items in the NHIS-D to estimate prevalence. In our analyses, we estimate the prevalence of mental retardation in the noninstitutionalized population of the United States to be 7.8 people per thousand (.78%); of developmental disabilities, 11.3 people per thousand (1.13%); and the combined prevalence of mental retardation and/or developmental disabilities to be 14.9 per thousand (1.49%). Differences in prevalence estimates for mental retardation and developmental disabilities and among people of various ages are explored.


Assuntos
Deficiências do Desenvolvimento/epidemiologia , Avaliação da Deficiência , Deficiência Intelectual/epidemiologia , Inquéritos e Questionários , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Deficiências do Desenvolvimento/diagnóstico , Humanos , Deficiência Intelectual/diagnóstico , Prevalência , Estudos Prospectivos
14.
Phys Rev Lett ; 86(14): 2950-4, 2001 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-11290080

RESUMO

We report results of a search for B-->tau(nu) in a sample of 9.7 x 10(6) charged B meson decays. We exclusively reconstruct the companion B decay to suppress background. We set an upper limit on the branching fraction B(B-->tau(nu))<8.4 x 10(-4) at 90% confidence level. We also establish B(B+/--->K+/-nu(nu))<2.4 x 10(-4) at 90% confidence level.

15.
Phys Rev Lett ; 86(7): 1167-70, 2001 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-11178035

RESUMO

Using data recorded with the CLEO II and CLEO II.V detector configurations at the Cornell Electron Storage Rings, we report the first observation and mass measurement of the Sigma(*+)(c) charmed baryon, and an updated measurement of the mass of the Sigma(+)(c) baryon. We find M(Sigma(*+)(c))-M(Lambda(+)(c)) = (231.0+/-1.1+/-2.0) MeV, and M(Sigma(+)(c))-M(Lambda(+)(c)) = (166.4+/-0.2+/-0.3) MeV, where the errors are statistical and systematic, respectively.

16.
Phys Rev Lett ; 86(1): 30-34, 2001 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-11136086

RESUMO

In a sample of 9.66x10(6)B&Bmacr; pairs collected with the CLEO detector we make the first observation of B decays to an eta(c) and a kaon. We measure branching fractions B(B+-->eta(c)K+) = (0.69(+0.26)(-0.21)+/-0.08+/-0.20)x10(-3) and B(B degrees -->eta(c)K degrees ) = (1.09(+0.55)(-0.42)+/-0.12+/-0.31)x10(-3), where the first error is statistical, the second is systematic, and the third is from the eta(c) branching fraction uncertainty. From these we extract the eta(c) decay constant in the factorization approximation, f(eta(c)) = 335+/-75 MeV. We also search for B decays to a chi(c0) and a kaon. No evidence for a signal is found and we set 90% C.L. upper limits: B(B+-->chi(c0)K+)<4.8x10(-4) and B(B degrees -->chi(c0)K degrees )<5.0x10(-4).

17.
Phys Rev Lett ; 85(15): 3095-9, 2000 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-11019275

RESUMO

Using 13.4 fb(-1) of data collected with the CLEO detector at the Cornell Electron Storage Ring, we have observed 300 events for the two-photon production of ground-state pseudoscalar charmonium in the decay eta(c)-->K(0)(S)K-/+pi(+/-). We have measured the eta(c) mass to be [2980.4+/-2.3 (stat)+/-0.6 (syst)] MeV and its full width as [27.0+/-5.8 (stat)+/-1.4 (syst)] MeV. We have determined the two-photon partial width of the eta(c) meson to be [7.6+/-0.8 (stat)+/-0.4 (syst)+/-2.3 (br)] keV, with the last uncertainty associated with the decay branching fraction.

18.
Phys Rev Lett ; 84(19): 4292-5, 2000 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-10990669

RESUMO

We report results of a search for the rare radiative decay &Bmacr;(0)-->D(*0)gamma. Using 9.66x10(6) B&Bmacr; meson pairs collected with the CLEO detector at the Cornell Electron Storage Ring, we set an upper limit on the branching ratio for this decay of 5.0x10(-5) at 90% C.L. This provides evidence that the anomalous enhancement is absent in W-exchange processes and that weak radiative B decays are dominated by the short-distance b-->sgamma mechanism in the standard model.

19.
Invest Ophthalmol Vis Sci ; 41(10): 3158-64, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10967078

RESUMO

PURPOSE: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a major stimulatory factor for retinal neovascularization in ischemic retinopathies such as diabetic retinopathy. This study sought to determine if VEGF is a stimulatory factor in a murine model of choroidal neovascularization (CNV). METHODS: Mice with laser-induced ruptures in Bruch's membrane were treated with vehicle alone; a drug that inhibits both VEGF and platelet-derived growth factor (PDGF) receptor kinases; a drug that inhibits PDGF, but not VEGF receptor kinase; or genistein, a nonspecific kinase inhibitor. After two weeks, CNV was quantified and compared. RESULTS: Blockade of phosphorylation by VEGF and PDGF receptors caused dramatic, almost complete inhibition of CNV. Genistein also had an inhibitory effect, but less so than the VEGF/PDGF receptor blocker. Blockade of phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on CNV. CONCLUSIONS: These data and our previous study, which demonstrated that a kinase inhibitor that blocks VEGF and PDGF receptors and several isoforms of protein kinase C causing dramatic inhibition of CNV, suggest that VEGF signaling plays a critical role in the development of CNV in this model. If safety is established, the effect of inhibiting VEGF receptor kinase activity should be investigated in patients with CNV.


Assuntos
Neovascularização de Coroide/metabolismo , Fatores de Crescimento Endotelial/fisiologia , Linfocinas/fisiologia , Animais , Neovascularização de Coroide/patologia , Neovascularização de Coroide/prevenção & controle , Inibidores Enzimáticos/farmacologia , Genisteína/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Ftalazinas/farmacologia , Fator de Crescimento Derivado de Plaquetas/fisiologia , Proteína Quinase C/antagonistas & inibidores , Piridinas/farmacologia , Pirimidinas/farmacologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores de Fatores de Crescimento/antagonistas & inibidores , Receptores do Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
20.
J Cell Physiol ; 185(1): 135-42, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10942527

RESUMO

Fibroblast growth factor-2 (FGF2) is a potent mitogen for vascular endothelial cells and exogenous administration of FGF2 stimulates angiogenesis. However, increased expression of FGF2 in the retina does not cause angiogenesis. One possible explanation is that FGF2 may not be capable of initiating angiogenesis unless it is administered in pharmacologic levels or there is coexpression of another angiogenic factor. Alternatively, there may be control mechanisms that sequester FGF2 in vivo, preventing it from manifesting its in vitro angiogenic activity. We tested the first hypothesis by crossing mice that express FGF2 in the retina with mice that express vascular endothelial growth factor (VEGF) in the retina. Surprisingly, despite comparable levels of VEGF expression, mice that expressed both FGF2 and VEGF had significantly less neovascularization than mice that expressed VEGF alone. The second hypothesis was tested by treating Rho/FGF2 transgenic mice with low-intensity laser photocoagulation that disrupts photoreceptors, but does not rupture Bruch's membrane, or intense laser that ruptures Bruch's membrane. In Rho/FGF2 transgenics, but not wild type mice, choroidal neovascularization developed in areas of low-intensity laser. Both wild type and transgenic mice developed choroidal neovascularization in areas of intense laser that ruptured Bruch's membrane, but the area of neovascularization was significantly greater in transgenics. These data suggest that increased retinal expression of FGF2 is angiogenic only when it is accompanied by cell injury that overcomes sequestration control mechanisms.


Assuntos
Fatores de Crescimento Endotelial/fisiologia , Fator 2 de Crescimento de Fibroblastos/fisiologia , Regulação da Expressão Gênica/fisiologia , Linfocinas/fisiologia , Neovascularização Retiniana , Animais , Camundongos , Camundongos Transgênicos , Retina/patologia , Retina/fisiologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
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