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Id: lil-785805
Autor: Mansur, Antonio de Padua; Roggerio, Alessandra; Takada, Júlio Yoshio; Caribé, Pérola Michelle Vasconcelos; Avakian, Solange Desirée; Strunz, Célia Maria Cassaro.
Título: Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome / Mutações gênicas das glicoproteínas plaquetárias e resposta ao tirofiban na síndrome coronariana aguda
Fonte: Säo Paulo med. j;134(3):199-204tab.
Idioma: en.
Resumo: CONTEXT AND OBJECTIVES: Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations. DESIGN AND SETTING: Prospective study at Emergency Unit, Heart Institute (InCor), University of São Paulo. METHOD: Intrahospital evolution and platelet aggregation in response to tirofiban were analyzed in relation to four glycoprotein mutations in 50 patients indicated for percutaneous coronary intervention: 17 (34%) with unstable angina and 33 (66%) with non-ST-segment elevation myocardial infarction. Platelet aggregation was analyzed using the Born method. Blood samples were obtained before and one hour after tirofiban infusion. Glycoproteins Ia (807C/T ), Ib (Thr/Met) , IIb (Ile/Ser ) and IIIa (PIA ) were the mutations selected. RESULTS: Hypertension, dyslipidemia, diabetes, smoking, previous coronary artery disease and stroke were similar between the groups. Mutant glycoprotein IIIa genotypes had lower platelet aggregation before tirofiban administration than that of the wild genotype (41.0% ± 22.1% versus 55.9% ± 20.8%; P = 0.035). Mutant glycoprotein IIIa genotypes correlated moderately with lower platelet inhibition (r = -0.31; P = 0.030). After tirofiban administration, platelet glycoprotein Ia, Ib, IIb and IIIa mutations did not influence the degree of inhibition of platelet aggregation or intrahospital mortality. CONCLUSIONS: Mutations of glycoproteins Ia, Ib, IIb and IIIa did not influence platelet aggregation in response to tirofiban in patients with unstable angina and non-ST-segment elevation myocardial infarction.

RESUMO CONTEXTO E OBJETIVOS: Inibidores da glicoproteína (abciximab, eptifibatide, tirofiban) são utilizados em pacientes com angina instável e infarto do miocárdio sem elevação do segmento ST (IAMSSST) antes da intervenção coronária percutânea. Dentre eles, o tirofiban é o menos eficaz. Nossa hipótese é que a resposta ao tirofiban possa estar associada a mutações no gene da glicoproteína. DESENHO E LOCAL: Estudo prospectivo na Unidade de Emergência do Instituto do Coração (InCor), Universidade de São Paulo (USP). MÉTODOS: Foram analisadas a evolução intra-hospitalar e agregabilidade plaquetária em resposta ao tirofiban de 4 mutações da glicoproteína em 50 pacientes com indicação para intervenção coronária percutânea, 17 (34%) com angina instável e 33 (66%) com IAMSSST. A agregação plaquetária foi analisada pelo método de Born. Amostras de sangue foram obtidas antes e uma hora após infusão do tirofiban. As glicoproteínas Ia (807C/T ), Ib (Thr/Met ), IIb (Ile/Ser ) e IIIa (PIA ) foram as mutações selecionadas. RESULTADOS: Hipertensão, dislipidemia, diabetes, tabagismo, doença coronariana e acidente vascular cerebral prévios foram semelhantes entre os grupos. Observou-se menor agregabilidade plaquetária dos genótipos mutantes da glicoproteína IIIa antes da administração de tirofiban do genótipo selvagem (41% ± 22% versus 56% ± 21%; P = 0,035). Genótipos mutantes da glicoproteína IIIa correlacionaram-se moderadamente com menor inibição plaquetária (r = -0,31; P = 0,030). Após a administração tirofiban, as mutações das glicoproteínas Ia, Ib, IIb, e IIIa não influenciaram o grau de inibição da agregação plaquetária e mortalidade intra-hospitalar. CONCLUSÕES: Mutações das glicoproteínas Ia, Ib, IIb e IIIa não influenciaram a agregação plaquetária em resposta ao tirofiban nos pacientes com angina instável e IAMSSST.
Descritores: Tirosina/análogos & derivados
Inibidores da Agregação Plaquetária/uso terapêutico
Glicoproteínas da Membrana de Plaquetas/genética
Síndrome Coronariana Aguda/tratamento farmacológico
Mutação
-Peptídeos/uso terapêutico
Tirosina/uso terapêutico
Fragmentos Fab das Imunoglobulinas/uso terapêutico
Agregação Plaquetária/efeitos dos fármacos
Agregação Plaquetária/genética
Reação em Cadeia da Polimerase
Estudos Prospectivos
Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores
Complexo Glicoproteico GPIIb-IIIa de Plaquetas/genética
Síndrome Coronariana Aguda/genética
Abciximab
Tirofibana
Eptifibatida
Genótipo
Angina Instável/genética
Angina Instável/tratamento farmacológico
Anticorpos Monoclonais/uso terapêutico
Limites: Humanos
Masculino
Feminino
Pessoa de Meia-Idade
Idoso
Responsável: BR1.1 - BIREME


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Id: biblio-1148055
Autor: Instituto de Efectividad Clínica y Sanitaria.
Título: Inmunoglobulinas equinas fragmentos F(ab')2 (suero equino hiperinmune) en COVID-19 / Equine immunoglobulins F (ab ') 2 fragments (hyperimmune equine serum) in COVID-19.
Fonte: Buenos Aires; IECS; 4 feb. 2021.
Idioma: es.
Descritores: Vírus da SARS/efeitos dos fármacos
COVID-19/tratamento farmacológico
-Avaliação em Saúde
Fragmentos Fab das Imunoglobulinas/administração & dosagem
Análise Custo-Benefício
Limites: Humanos
Tipo de Publ: Revisão
Estudo de Avaliação
Responsável: BR1.1 - BIREME


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Id: biblio-954857
Autor: Squaiella-Baptistão, Carla Cristina; Magnoli, Fábio Carlos; Marcelino, José Roberto; Sant'Anna, Osvaldo Augusto; Tambourgi, Denise V.
Título: Quality of horse F(ab')2 antitoxins and antirabies immunoglobulins: protein content and anticomplementary activity
Fonte: J. venom. anim. toxins incl. trop. dis;24:16, 2018. tab, ilus.
Idioma: en.
Projeto: FAPESP.
Resumo: Among other applications, immunotherapy is used for the post-exposure treatment and/or prophylaxis of important infectious diseases, such as botulism, diphtheria, tetanus and rabies. The effectiveness of serum therapy is widely proven, but improvements on the immunoglobulin purification process and on the quality control are necessary to reduce the amount of protein aggregates. These may trigger adverse reactions in patients by activating the complement system and inducing the generation of anaphylatoxins. Herein, we used immunochemical methods to predict the quality of horse F(ab′)2 anti-botulinum AB, anti-diphtheric, antitetanic and anti-rabies immunoglobulins, in terms of amount of proteins and protein aggregates. Methods Samples were submitted to protein quantification, SDS-PAGE, Western blot analysis and molecular exclusion chromatography. The anticomplementary activity was determined in vitro by detecting the production of C5a/C5a desArg, the most potent anaphylatoxin. Data were analyzed by one-way ANOVA followed by Tukey's post-test, and differences were considered statistically significant when p < 0.05. Results Horse F(ab′)2 antitoxins and anti-rabies immunoglobulin preparations presented different amounts of protein. SDS-PAGE and Western blot analyses revealed the presence of protein aggregates, non-immunoglobulin contaminants and, unexpectedly, IgG whole molecules in the samples, indicating the non-complete digestion of immunoglobulins. The chromatographic profiles of antitoxins and anti-rabies immunoglobulins allowed to estimate the percentage of contaminants and aggregates in the samples. Although protein aggregates were present, the samples were not able to induce the generation of C5a/C5a desArg in vitro, indicating that they probably contain acceptable levels of aggregates. Conclusions Anti-botulinum AB (bivalent), anti-diphtheric, antitetanic and anti-rabies horse F(ab′)2 immunoglobulins probably contain acceptable levels of aggregates, although other improvements on the preparations must be carried out. Protein profile analysis and in vitro anticomplementary activity of F(ab′)2 immunoglobulin preparations should be included as quality control steps, to ensure acceptable levels of aggregates, contaminants and whole IgG molecules on final products, reducing the chances of adverse reactions in patients.(AU)
Descritores: Imunoglobulinas/imunologia
Fragmentos Fab das Imunoglobulinas/isolamento & purificação
Antitoxina Botulínica/isolamento & purificação
Vacinas Antirrábicas/análise
-Imunoglobulinas
Cavalos/imunologia
Limites: Animais
Masculino
Feminino
Responsável: BR33.1 - Divisão Técnica de Biblioteca e Documentação


  4 / 18 LILACS  
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Id: lil-773435
Autor: Gale, Stephen C; Peters, Jo Ann; Allen, LaDonna; Creath, Robert; Dombrovskiy, Viktor Y.
Título: FabAV antivenin use after copperhead snakebite: clinically indicated or knee-jerk reaction?
Fonte: J. venom. anim. toxins incl. trop. dis;22:2, 2016. tab.
Idioma: en.
Resumo: Abstract Background Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) antivenin is commonly recommended after pit viper snakebites. Because copperhead envenomations are usually self-limited, some physicians are reluctant to use this costly treatment routinely, while others follow a more liberal approach. We hypothesized that, in practice, only patients with evidence of significant (moderate or severe) copperhead envenomation [those with snakebite severity score (SSS) > 3] receive FabAV and examined a large cohort to determine the relationship between clinical findings and FabAV administration. Methods All data from patients evaluated for copperhead snakebite at a rural tertiary referral center from 5/2002 to 10/2013 were compiled. Demographics, transfer status, antivenin use, and clinical findings were collected; SSS was calculated. The relationships among FabAV use, clinical findings, and SSS were analyzed using t-test, chi-square, and Pearson’s coefficient (p < 0.05 was significant). Results During the study period, 318 patients were treated for copperhead snakebite; 44 (13.8 %) received antivenin. Median dose was four vials (range: 1–10; IQR: 4,6). There were no deaths. Most patients receiving FabAV (63.6 %) were admitted. With regard to demographics and symptoms, only the degree of swelling (moderate vs. none/mild; p < 0.01) and bite location (hand/arm vs. leg: p < 0.0001) were associated with FabAV use. A SSS > 3, indicating moderate or severe envenomation, was only very weakly correlated with antivenin use (r = 0.217;p < 0.0001). The majority of patients with SSS > 3 (65.8 %) did not receive antivenin while most patients who did receive antivenin (70.5 %) had SSS ≤ 3 (indicating mild envenomation). Conclusions Considerable variation occurs in antivenin administration after copperhead snakebite. Use of FabAV appears poorly correlated with patients’ symptoms. This practice may expose patients to the risks of antivenin and increasing costs of medical care without improving outcomes. Guidelines used for treating other pit viper strikes, such as rattlesnake or cottonmouth snakebite may be too liberal for copperhead envenomations. Our data suggests that most patients with mild or moderate envenomation appear to do well independent of FabAV use. We suggest, for patients with copperhead snakebite, that consideration be given to withholding FabAV for those without clinical evidence of severe envenomation until prospective randomized data are available.
Descritores: Antivenenos/uso terapêutico
Venenos de Crotalídeos
Fragmentos Fab das Imunoglobulinas/uso terapêutico
Mordeduras de Serpentes/terapia
-Antivenenos/economia
Fragmentos Fab das Imunoglobulinas/administração & dosagem
Fragmentos Fab das Imunoglobulinas/economia
Texas
Limites: Humanos
Masculino
Feminino
Pré-Escolar
Criança
Adolescente
Adulto
Pessoa de Meia-Idade
Idoso
Idoso de 80 Anos ou mais
Responsável: BR1.1 - BIREME


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Id: lil-685367
Autor: Álvarez-Camarena, Bernardino; Frutos-Rangel, Enrique; Rico-Curiel, Enrique; García-y Otero, José María; Frutos-Rodríguez, Enrique.
Título: Trombocitopenia aguda profunda asociada al uso de abciximab: a propósito de un caso / Acute profound thrombocytopenia associated with the use of abciximab: case report
Fonte: Arch. cardiol. Méx;81(4):317-321, oct.-dic. 2011. ilus.
Idioma: es.
Resumo: Se presenta un paciente con angina inestable e intervención coronaria percutánea con stents, que desarrolló púrpura mucocutánea y hematoma inguinal asociados a trombocitopenia aguda profunda inducida por abciximab con nadir de 1 x 10(9)/L (1000 plaquetas/mm³), su recuperación con el tratamiento instituido y la complicación de trombosis subaguda intrastent asociada a cuenta plaquetaria funcional que requirió reintervención con angioplastía primaria y administración de tirofiban, un agente bloqueador del receptor IIb/IIIa diferente. Se realizaron estudios diagnósticos para investigar otras causas de trombocitopenia en estos pacientes que reciben heparina, antiplaquetarios como ácido acetilsalicílico y clopidogrel, asociados a bloqueadores del receptor IIb/IIIa. Se realizó una revisión de publicaciones con reporte de esta complicación.

We present the case-report of a patient with instable angina who submitted to percutaneous coronary intervention and stent place for revascularization who developed purpura and groin hematoma associated to acute profound thrombocytopenia induced by abciximab infusion with nadir platelet counts 1 x 10(9)/L (1,000 platelets/mm³), his platelet recovery with the instituted treatment and the outcome with subacute intra-stent thrombosis that was associated with functionally platelet counts that required a primary angioplasty and administration of tirofiban, a platelet glycoprotein IIb/IIIa receptor antagonist. Laboratory confirmation to exclude other causes of thrombocytopenia and its association of glycoprotein IIb/IIIa receptor antagonist with heparin, acetylsalicylic acid and clopidogrel were obtained. We perform in literature trials with this complication.
Descritores: Anticorpos Monoclonais/efeitos adversos
Fragmentos Fab das Imunoglobulinas/efeitos adversos
Inibidores da Agregação Plaquetária/efeitos adversos
Trombocitopenia/induzido quimicamente
-Doença Aguda
Índice de Gravidade de Doença
Limites: Idoso
Humanos
Masculino
Tipo de Publ: Relatos de Casos
Responsável: MX1.1 - CENIDSP - Centro de Información para Decisiones en Salud Pública


  6 / 18 LILACS  
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Id: lil-661947
Autor: de Roodt, Adolfo Rafael; Litwin, Silvana; Estevez, Judith; Gould, Eduardo G; Dolab, Jorge A; Gould, Jorge.
Título: Comparación entre dos métodos de producción para la elaboración de antivenenos ofídicos / Snake antivenin: Comparison between two production methods
Fonte: Acta toxicol. argent;18(1):10-20, June 2010. ilus, tab.
Idioma: es.
Resumo: Las mordeduras producidas por serpientes venenosas son un serio problema médico en varias regiones del mundo y sobre las cuales los sistemas de salud actúan en diferentes grados en lo referente a tratamiento y prevención. Sin embargo, el tratamiento de las mordeduras de serpientes venenosas en animales domésticos puede resultar difícil por diversos motivos, siendo uno de estos la baja oferta o ausencia de antivenenos para uso veterinario. Las presiones comerciales en la industria farmacéutica han llevado a una reducción en la producción de antivenenos en varias partes del mundo, su disponibilidad es, a veces, bastante limitada y en algunos casos, son imposibles de conseguir. En este trabajo, inmunizamos caballos con veneno de serpientes Sudamericanas para obtener el plasma hiperinmune que fue procesado para obtener IgG entera o fragmentos F(ab´)2 usando dos métodos convencionales (fraccionamiento por ácido caprílico o doble precipitación salina y digestión con pepsina). Los antivenenos así obtenidos fueron probados en sus características bioquímicas e inmunoquímicas, así como en su potencia neutralizante. El SDS-PAGE de los antivenenos mostró bandas en el orden de los 150 y 100 kDa en los antivenenos conteniendo IgG entera o fragmentos F(ab´)2, respectivamente. La presencia de albúmina o contaminantes de alto o bajo peso molecular no fue detectada en ninguna de las preparaciones. No se observaron diferencias importantes en la potencia neutralizante de los antivenenos, aunque el costo de producción fue mucho más bajo en la obtención de IgG completa. A partir de esto, se sugiere que los bajos costos de producción en la obtención de antivenenos de IgG entera para uso veterinario, hacen a esta tecnología adecuada y rentable cuando la producción de F(ab´)2 no es posible.

Bites by venomous snakes are a serious medical problem in several regions of the world, on which the different health systems act with different modalities. Nevertheless, the treatment of venomous snakebites in domestic animals can turn difficult due several problems among which, the conspicuous, is the low availability or lack of antivenoms for veterinary use. As commercial pressures on the pharmaceutical industry have led to a reduction in the production of antivenins in several parts of the world, their availability is sometimes rather limited and sometimes these products are impossible to obtain. In this work, we immunized horses with venom of South American vipers to obtain hyperimmune plasma. The plasma was processed to separate whole IgG of F(ab´)2 fragments using two conventional methods (caprylic acid fractionation or double saline precipitation and pepsin digestion). The obtained antivenins were tested for their biochemical and immunochemical characteristics and neutralizing potency. The SDS-PAGE of the antivenins showed, in the processed antivenin, bands in the order of 150 and 100 kDa in the whole IgG or F(ab´)2 fragments, respectively. The presence of albumin or contaminants of high or low molecular weight was not detected in any of the preparations. No important differences were observed in the neutralizing potency of the antivenins, although production cost was very low with the method used to obtain pure IgG. The low production cost makes the production of antivenins for veterinary use profitable when the production of F(ab´)2 fragments is not possible.
Descritores: Antivenenos/uso terapêutico
Fragmentos Fab das Imunoglobulinas/farmacologia
Mordeduras de Serpentes
Venenos de Serpentes
-Caprilatos
Fracionamento Químico/métodos
Cavalos
Limites: Animais
Responsável: AR1.1 - Biblioteca Rafael Herrera Vegas


  7 / 18 LILACS  
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Id: lil-568612
Autor: Exaire, J. Emilio; Fathi, Robert F; Brener, Sorin J; Karha, Juhana; Ellis, Stephen G; Bhatt, Deepak L.
Título: Impaired myocardial perfusion score and inflammatory markers in patients undergoing primary angioplasty for acute myocardial infarction
Fonte: Arch. cardiol. Méx;76(4):376-382, oct.-dic. 2006.
Idioma: en.
Resumo: BACKGROUND: Microcirculatory dysfunction during acute myocardial infarction is mediated by various mechanisms including inflammation, thrombus, or plaque embolization. We hypothesize that patients with acute myocardial infarction and admission Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion grade (TMP) < 2 had increased inflammatory status as measured by high sensitivity C-reactive protein (hs-CRP). METHODS: From January 2002 to December 2003, 166 patients (178 lesions) were referred for primary percutaneous coronary intervention. Patients were stratified based on pre-PCI TMP < 2 or TMP 2. Univariate and multivariate predictors of in-hospital and 30-day death were determined with logistic regression. RESULTS: Pre-PCI TMP < 2 was found in 66% vs 34% with TMP 2 (P < .001). Hs-CRP levels were high in both groups but not significantly different (37.9 +/- 6 vs 33.7 +/- 6 mg/L, P = .63). Patients with TMP < 2 had higher WBC (12.83 +/-4.55 x 10(-3) vs 10.83 +/- 3.00 x 10(-3), P = .04), lower ejection fraction (40 +/- 11% vs 46 +/- 12%, P < .001), and higher admission CK-MB levels (116 +/- 13 ng/mL vs 55 +/- 13 ng/mL, P = .006). Death occurred in 12% in the poorTMP group vs 1.8% in the good TMP group (P = .03). Advanced age, use of an intra-aortic balloon pump, and elevated admission WBC were independently associated with in-hospital and 30-day death. CONCLUSIONS: High hs-CRP levels were not associated with impaired myocardial perfusion score. Microcirculatory impairment may be related to an increased inflammatory process, independent from high hs-CRP levels.
Descritores: Angioplastia Coronária com Balão
Anticorpos Monoclonais
Anticoagulantes
Aspirina
Circulação Coronária
Fibrinolíticos
Fragmentos Fab das Imunoglobulinas
Inflamação
Infarto do Miocárdio
Infarto do Miocárdio
Inibidores da Agregação Plaquetária
Complexo Glicoproteico GPIIb-IIIa de Plaquetas
Ticlopidina/análogos & derivados
-Anticorpos Monoclonais
Anticoagulantes
Aspirina
Biomarcadores
Proteína C-Reativa
Interpretação Estatística de Dados
Eletrocardiografia
Seguimentos
Fibrinolíticos
Balão Intra-Aórtico
Fragmentos Fab das Imunoglobulinas
Modelos Logísticos
Infarto do Miocárdio
Infarto do Miocárdio/mortalidade
Inibidores da Agregação Plaquetária
Fatores de Risco
Fatores de Tempo
Ticlopidina
Ticlopidina
Limites: Idoso
Feminino
Humanos
Masculino
Pessoa de Meia-Idade
Tipo de Publ: Estudo Comparativo
Estudo de Avaliação
Responsável: BR1.1 - BIREME


  8 / 18 LILACS  
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Id: lil-503616
Autor: Gomollón, Fernando; García López, Santiago.
Título: Tratamiento con agentes anti-TNFα en la enfermedad de Crohn: ¿qué fármaco debemos utilizar y cuándo?: [revisión] / Treatment with anti-TNFα agents in Crohn's disease: what drug we have to use and when?: [revision]
Fonte: Acta gastroenterol. latinoam;38(2):133-145, jun. 2008. tab.
Idioma: es.
Resumo: Crohn's disease (CD) is often very difficult to treat. Almost ten years ago "biologic" agents were introduced in the armamentarium to control CD. Although there are many new drugs in the pipeline, only two antiTNF agents have been released to the market (infliximab and, recently, adalimumab) and probably in 2008 certolizumab will be approved. A review of available evidence suggests that the three antibodies are effective in the induction and maintenance of response, and (to a lesser extent) remission. Infliximab has been very useful in fistulizing disease, and preliminary data do suggest that adalimumab and certolizumab will be also. Cost and long-term safety limit the use of these agents in daily practice. To maximize benefits and minimize risks, good patient selection and strict adherence to Clinical Guidelines seem the key points. It has been suggested that these drugs should be used in early disease to avoid progression, but current data are very scarce to generalize this recommendation. In anycase, we think that the use of "biologics" will provoke a dramatic change in CD treatment in the next 10 years.

Crohn's disesae (CD) is often very difficult to treat. Almost ten years ago "biologic" agents were introduced inthe armamentarium to control CD. Although there are many new drugs in the pipeline, only two antiTNF agents have been released to the market (infliximab and, recently, adalimumab) and probably in 2008 certolizumabwill be approved. A review of available evidence suggests that the three antibodies are effective in the induction and maintenance of response, and (to alesser extent) remission. Infliximab has been very useful in fistulizing disease, and preliminary data do suggest that adalimumab and certolizumab will be also. Cost and long-term safety limit the use of these agents in daily practice. To maximize benefits and minimize risks, good patient selection and strict adherence to Clinical Guidelines seem the key points. It has been suggestedthat these drugs should be used in early disease to avoid progression, but current data are very scarce to generalize this recommendation. In anycase, we think that the use of "biologics" will provoke a dramaticchange in CD treatment in the next 10 years.
Descritores: Anti-Inflamatórios
Anticorpos Monoclonais/uso terapêutico
Doença de Crohn/tratamento farmacológico
Fator de Necrose Tumoral alfa/antagonistas & inibidores
Fragmentos Fab das Imunoglobulinas/uso terapêutico
Polietilenoglicóis/uso terapêutico
Limites: Humanos
Tipo de Publ: Revisão
Responsável: BR1.1 - BIREME


  9 / 18 LILACS  
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Id: lil-502158
Autor: Grosso, D. M; Ferderbar, S; Wanschel, A. C. B. A; Krieger, M. H; Higushi, M. L; Abdalla, D. S. P.
Título: Antibodies against electronegative LDL inhibit atherosclerosis in LDLr-/- mice
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;41(12):1086-1092, Dec. 2008. ilus, graf.
Idioma: en.
Projeto: FAPESP; . Instituto do Milênio Redoxoma; . CNPq.
Resumo: In order to determine the effect of antibodies against electronegative low-density lipoprotein LDL(-) on atherogenesis, five groups of LDL low receptor-deficient (LDLr-/-) mice (6 per group) were immunized with the following antibodies (100 µg each): mouse anti-LDL(-) monoclonal IgG2b, rabbit anti-LDL(-) polyclonal IgG or its Fab fragments and mouse irrelevant monoclonal IgG and non-immunized controls. Antibodies were administered intravenously one week before starting the hypercholesterolemic diet (1.25 percent cholesterol) and then every week for 21 days. The passive immunization with anti-LDL(-) monoclonal IgG2b, polyclonal antibody and its derived Fab significantly reduced the cross-sectional area of atherosclerotic lesions at the aortic root of LDLr-/- mice (28.8 ± 9.7, 67.3 ± 17.02, 56.9 ± 8.02 µm² (mean ± SD), respectively) compared to control (124.9 ± 13.2 µm²). Vascular cell adhesion molecule-1 protein expression, quantified by the KS300 image-analyzing software, on endothelium and the number of macrophages in the intima was also decreased in aortas of mice treated with anti-LDL(-) monoclonal antibody (3.5 ± 0.70 per field x 10) compared to controls (21.5 ± 3.5 per field x 10). Furthermore, immunization with the monoclonal antibody decreased the concentration of LDL(-) in blood plasma (immunized: 1.0 ± 1.4; control: 20.5 ± 3.5 RLU), the amount of cholesterol oxides in plasma (immunized: 4.7 ± 2.7; control: 15.0 ± 2.0 pg COx/mg cholesterol) and liver (immunized: 2.3 ± 1.5; control: 30.0 ± 26.0 pg COx/mg cholesterol), and the hepatic content of lipid hydroperoxides (immunized: 0.30 ± 0.020; control: 0.38 ± 0.15 ng/mg protein). In conclusion, antibodies against electronegative LDL administered intravenously may play a protective role in atherosclerosis.
Descritores: Anticorpos Monoclonais/administração & dosagem
Aterosclerose/terapia
Imunização Passiva/métodos
Imunoglobulina G/administração & dosagem
Lipoproteínas LDL/administração & dosagem
Receptores de LDL/imunologia
-Anticorpos Monoclonais/imunologia
Aterosclerose/imunologia
Aterosclerose/metabolismo
Imuno-Histoquímica
Fragmentos Fab das Imunoglobulinas/administração & dosagem
Fragmentos Fab das Imunoglobulinas/imunologia
Imunoglobulina G/imunologia
Peroxidação de Lipídeos/imunologia
Lipoproteínas LDL/imunologia
MICE, INBRED CABDOMENABDOMINAL INJURIESBL
Receptores de LDL/metabolismo
Molécula 1 de Adesão de Célula Vascular/imunologia
Limites: Animais
Feminino
Camundongos
Coelhos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Brígido, M. M
Maranhão, A. Q
Texto completo
Id: lil-445298
Autor: Dantas-Barbosa, C; Brígido, M. M; Maranhão, A. Q.
Título: Construction of a human Fab phage display library from antibody repertoires of osteosarcoma patients
Fonte: Genet. mol. res. (Online);4(2):126-140, 30 jun. 2005. tab, graf, ilus.
Idioma: en.
Resumo: Osteosarcoma is the commonest type of primary malignant bone tumor, frequently found in adolescents at sites of rapid bone growth. Despite current management protocols, up to half of the patients succumb to this disease. Moreover, there is no well-characterized molecular marker for diagnosis and prognosis. Since phage display methodology allows the selection of human antibody fragments with potential use in clinical applications, we applied this procedure to construct a recombinant Fab (antigen binding fragment) library from patients with osteosarcoma. We used peripheral blood lymphocyte total RNA from 11 osteosarcoma patients and cloned recombinant Fab representing the micro, gamma and kappa chain antibody repertoires of these individuals. The resulting library was cloned in the pComb3X vector and attained 1.45 x 10(8) different functional forms. BstO I fingerprinting and DNA sequencing analysis of randomly selected clones revealed the diversity of the library, demonstrating that Fab harbors Vkappa chains from subgroups I to V, biased towards the A27 fragment, as normally reported for the human repertoire. Analysis of the VH repertoire revealed that our library has a slight bias towards the VH4 family, instead of the usually reported VH3. This is the first description of a phage display library from osteosarcoma patients. We believe these human Fab fragments will provide a valuable tool for the study of this neoplasia and could also contribute to improvements in the diagnosis of this disease.
Descritores: Fragmentos Fab das Imunoglobulinas/genética
Neoplasias Ósseas/genética
Osteossarcoma
Biblioteca de Peptídeos
RNA Neoplásico/genética
Sítios de Ligação de Anticorpos/genética
-Fragmentos Fab das Imunoglobulinas
Linfócitos/química
Marcadores Genéticos/genética
Neoplasias Ósseas/diagnóstico
Osteossarcoma
Reação em Cadeia da Polimerase
RNA Neoplásico/sangue
RNA Neoplásico/isolamento & purificação
Análise de Sequência de DNA
Limites: Humanos
Masculino
Feminino
Criança
Adulto
Responsável: BR1.1 - BIREME



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