RESUMO
Ligneous conjunctivitis is a rare form of chronic and recurrent bilateral conjunctivitis, in which thick membranes develop on the tarsal conjunctiva and on other mucosae. We report the case of a 55-year old female patient with bilateral ligneous conjunctivitis who was successfully treated with 50% heterologous serum. There was no recurrence or side effects after one-year follow-up. We suggest the use of 50% heterologous serum should be further studied to better determine its efficacy as a treatment option for ligneous conjunctivitis.
Assuntos
Plasminogênio/deficiência , Soro , Conjuntivite/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Plasminogênio/uso terapêutico , Dermatopatias Genéticas/patologia , Resultado do TratamentoRESUMO
ABSTRACT Ligneous conjunctivitis is a rare form of chronic and recurrent bilateral conjunctivitis, in which thick membranes develop on the tarsal conjunctiva and on other mucosae. We report the case of a 55-year old female patient with bilateral ligneous conjunctivitis who was successfully treated with 50% heterologous serum. There was no recurrence or side effects after one-year follow-up. We suggest the use of 50% heterologous serum should be further studied to better determine its efficacy as a treatment option for ligneous conjunctivitis.
RESUMO A conjuntivite lenhosa é uma forma rara de conjuntivite bilateral crônica e recorrente, na qual há formação de membranas espessas na conjuntiva tarsal e em outras mucosas. Relatamos o caso de uma paciente de 55 anos com conjuntivite lenhosa bilateral, que obteve sucesso no tratamento com soro heterólogo em concentração de 50%. Não houve recorrência após um ano de seguimento e nem efeitos colaterais ao tratamento. Dessa forma, o uso de soro heterólogo a 50% poderia ser mais estudado para melhor avaliação de sua eficácia como opção de tratamento para a conjuntivite lenhosa.
Assuntos
Humanos , Feminino , Plasminogênio/deficiência , Soro , Plasminogênio/uso terapêutico , Dermatopatias Genéticas/patologia , Resultado do Tratamento , Conjuntivite/patologia , Pessoa de Meia-IdadeRESUMO
Introduction: obesity, characterized by adiposity excess, is associated with endothelial dysfunction and possible inflammatory state with release of cytokines that determine endothelial function and can trigger chronic diseases. The dietary pattern are associated with the synthesis these cytokines. Fruits as the acai, which is rich in flavonoids, have a direct and beneficial effect on the control of this inflammatory process through the exercised antioxidant capacity. Objective: to evaluate the effect of acai pulp consumption on the inflammatory markers, anthropometric measurements, body composition, biochemical and dietary parameters in healthy women. Methods: forty women, were divided in 25 eutrophic and 15 with overweight. They intaked 200 g of acai pulp during 4 weeks. Anthropometric measurements, body composition, inflammatory markers, biochemical data, dietary intake and dietary antioxidants capacity were evaluated before and after the intervention. Results and discussion: after the intervention, there was significant increase of EGF (p=0.021) and PAI- 1(p=0.011) in overweight women. Moreover, there was increase in body weight (p=0.031), body mass index (p=0.028), percentage of truncal fat (p=0.003) and triceps skinfold thickness (p=0.046) in eutrophic women. However, the skinfold thickness (p=0.018) and total body fat (p=0.016) decreased in overweight women. There was reduction of total protein (p=0.049) due to the globulin reduction (p=0.005), but the nutritional status was maintained in eutrophic group. Conclusion: the intake of 200g acai pulp, modulated the EGF and PAI-1 expression, possibly by modulation of acai on the parameters of body composition, dietary, clinical, biochemical and inflammatory, led to a redistribution and resizing of body fat of the trunk area, and presumably increased visceral fat (AU)
Introducción: la obesidad, que se caracteriza por el exceso de adiposidad, se asocia con disfunción endotelial y posible estado inflamatorio con liberación de citoquinas que determinan la función endotelial y pueden desencadenar enfermedades crónicas. El patrón de dieta está asociado con la síntesis de estas citoquinas. Los frutos del acai, que es rico en flavonoides, tienen un efecto directo y positivo en el control de este proceso inflamatorio a través de los ejercicios de la capacidad antioxidante. Objetivo: evaluar el efecto del consumo de pulpa de acai en los marcadores inflamatorios, las medidas antropométricas, la composición corporal y los parámetros bioquímicos y dietéticos en mujeres sanas. Métodos: cuarenta mujeres fueron divididas en 25 eutróficas y 15 con sobrepeso. Se las administró 200 g de pulpa de acai durante 4 semanas. Antes y después de la intervención se evaluaron: medidas antropométricas, composición corporal, marcadores inflamatorios, datos bioquímicos, ingesta dietética y antioxidantes en la dieta. Resultados y discusión: después de la intervención, hubo un aumento significativo de EGF (p=0,021) y PAI-1 (p=0,011) en las mujeres con sobrepeso. Por otra parte, en las mujeres eutróficas hubo aumento del peso corporal (p=0,031), el índice de masa corporal (p=0,028), el porcentaje de grasa del tronco (p=0,003) y el espesor del pliegue cutáneo del tríceps (p=0,046). Sin embargo, el espesor del pliegue cutáneo (p=0,018) y la grasa corporal total (p=0,016) se redujeron en las mujeres con sobrepeso. Hubo una reducción de la proteína total (p=0,049) debida a la disminución de globulina (p=0,005), pero el estado nutricional se mantuvo en el grupo eutrófico. Conclusión: la ingesta de 200 g de pulpa de acai modula el EGF y PAI-1 de expresión, posiblemente por la modulación del acai en los parámetros de la composición corporal, la dieta, clínicos, bioquímicos e inflamatorios, lo que dio lugar a una redistribución y modificación del tamaño de la grasa corporal de la zona del tronco, y, presumiblemente, un aumento de la grasa visceral (AU)
Assuntos
Adulto , Feminino , Humanos , Euterpe/metabolismo , Plasminogênio/metabolismo , Plasminogênio/uso terapêutico , Ativadores de Plasminogênio/uso terapêutico , Fator de Crescimento Epidérmico/análise , Fator de Crescimento Epidérmico , Voluntários Saudáveis/estatística & dados numéricos , Obesidade/dietoterapia , Fitoterapia/organização & administração , Composição Corporal/fisiologia , Antropometria/métodos , Antioxidantes/uso terapêutico , Inflamação/dietoterapia , Inflamação/prevenção & controleRESUMO
The institution of combined modality therapy for unresected solid tumors has resulted in significant improvements in tumor control and survival benefit compared with radiotherapy (RT) alone. A number of chemotherapy agents that can enhance the effectiveness of RT, such as cisplatin and 5-fluorouracil, are now considered standard treatment for patients with a number of cancer types. There is growing interest in a number of additional agents that have also been found to have radiosensitizing ability. These include paclitaxel, docetaxel, irinotecan, gemcitabine, and vinorelbine, as well as biologic agents. Other agents may be of value because they act to counter dose-limiting toxicities associated with RT. This article provides an update of some important, recently completed and ongoing clinical trials evaluating novel chemoradiation protocols, with examples taken primarily from studies conducted by the Radiation Therapy Oncology Group (RTOG). Theoretical approaches to the development of new agents and combined modality regimens are also discussed.
Assuntos
Antineoplásicos/uso terapêutico , Drogas em Investigação/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Alquil e Aril Transferases/antagonistas & inibidores , Inibidores da Angiogênese/uso terapêutico , Angiostatinas , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimioterapia Adjuvante , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/uso terapêutico , Fracionamento da Dose de Radiação , Fatores de Crescimento Endotelial/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Farnesiltranstransferase , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Indóis/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Isoenzimas/antagonistas & inibidores , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Linfocinas/uso terapêutico , Masculino , Proteínas de Membrana , Fragmentos de Peptídeos/uso terapêutico , Plasminogênio/uso terapêutico , Prostaglandina-Endoperóxido Sintases , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Pirróis/uso terapêutico , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
PURPOSE: The etiology of ligneous conjunctivitis is now known to be due to an underlying type 1 plasminogen deficiency. We hereby report the clinical features of three cases and their response to topically administered plasminogen. DESIGN: Observational case series. METHODS: Two Caucasian females aged 5 years and an 18-month male of north African descent presented with a membranous conjunctivitis, which recurred after surgical excision. Case 1 presented before the association with plasminogen deficiency was known with a bilateral chronic membranous mucopurulent conjunctivitis from the age of 14 months associated with bronchiolitis and gingival hyperplasia. A diagnosis of ligneous conjunctivitis was entertained and a number of drops were instituted. At the age of 4 years plasminogen levels were ordered. Case 2 presented at the age of 4 years with a unilateral chronic membranous conjunctivitis. Plasminogen levels were requested as soon as a diagnosis of ligneous conjunctivitis was suspected. Case 3 was born with congenital hydrocephalus. Conjunctivitis was treated with antibiotics from the age of 1 month. He presented to the eye clinic at the age of 5 months when a clinical diagnosis of ligneous conjunctivitis was entertained and treated with a number of medications. Plasminogen levels were available at 9 months of age. RESULTS: The two female patients returned plasminogen levels of 0.25 U/ml and 0.3 U/ml, well below the normal level of 0.7-1.0 U/ml. Functional plasminogen levels in the male infant were not recordable with plasminogen antigen levels of 0.125 U/ml (normal range, 0.52-1.82). All cases have responded well to excision of the membranes and institution of topical plasminogen drops. There has been no recurrence with more than 12 months' follow-up. CONCLUSIONS: With the knowledge of the etiology of ligneous conjunctivitis, efforts are underway to identify the best method of delivery of plasminogen. Topical plasminogen concentrate from fresh frozen plasma holds promise as the definitive treatment for this chronic membranous conjunctivitis
Assuntos
Conjuntivite/tratamento farmacológico , Plasminogênio/uso terapêutico , Administração Tópica , Pré-Escolar , Conjuntivite/enzimologia , Conjuntivite/genética , Feminino , Humanos , Lactente , Masculino , Soluções Oftálmicas , Plasminogênio/deficiência , Plasminogênio/genéticaRESUMO
The use of angiogenesis inhibitors may offer novel strategies in brain tumor therapy. In contrast to traditional cancer treatments that attack tumor cells directly, angiogenesis inhibitors target at the formation of tumor-feeding blood vessels that provide continuous supply of nutrients and oxygen. With respect to brain tumor therapy, inhibitors of angiogenesis display unique features that are unknown to conventional chemotherapeutic agents. The most important features are independence of the blood-brain barrier, cell type specificity, and reduced resistance. Malignant brain tumors, especially malignant gliomas, are among the most vascularized tumors known. Despite multimodal therapeutic approaches, the prognosis remains dismal. Thus, angiogenesis inhibitors may be highly effective drugs against these tumors. In a clinical setting, they could be applied in the treatment of multiple tumors or postsurgically as an adjuvant therapy to prevent recurrence. This article provides an overview of current anti-angiogenic treatment strategies with emphasis on substances already in clinical trials or candidate substances for clinical trials. The cellular and molecular basis of these substances is reviewed.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Angiopoietina-1 , Angiopoietina-2 , Angiostatinas , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/cirurgia , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Colágeno/química , Colágeno/uso terapêutico , Terapia Combinada , Cicloexanos , Endostatinas , Fatores de Crescimento Endotelial/antagonistas & inibidores , Fatores de Crescimento Endotelial/fisiologia , Ácidos Graxos Insaturados/uso terapêutico , Glioma/irrigação sanguínea , Glioma/cirurgia , Humanos , Integrinas/antagonistas & inibidores , Integrinas/fisiologia , Linfocinas/antagonistas & inibidores , Linfocinas/fisiologia , Metaloproteinase 2 da Matriz/química , Inibidores de Metaloproteinases de Matriz , Metaloproteinases da Matriz/fisiologia , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/fisiologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/fisiologia , Fragmentos de Peptídeos/uso terapêutico , Plasminogênio/uso terapêutico , Proteínas/antagonistas & inibidores , Proteínas/fisiologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/fisiologia , Receptor TIE-2 , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/fisiologia , Receptores de Fatores de Crescimento/antagonistas & inibidores , Receptores de Fatores de Crescimento/fisiologia , Receptores de TIE , Receptores de Fatores de Crescimento do Endotélio Vascular , Sesquiterpenos , Suramina/uso terapêutico , Talidomida/uso terapêutico , Trombospondinas/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
The poor prognosis of patients with malignant brain tumors in spite of aggressive multimodality therapy has led to the search for novel therapeutic strategies. Among the targets for such treatment approaches, tumor angiogenesis has captured the attention of not only the medical field but also of the lay public because of its conceptual departure from traditional methods of cancer therapy. Angiogenesis and vascular proliferation are particularly important in the growth and progression of malignant gliomas and are used as indicators of the degree of malignancy. Recent studies have helped us gain a better understanding of the molecular mediators of this process. It is now evident that after the initial formation of malignancy the continued growth of a glioma is critically dependent on its angiogenic potential. Hence, several approaches to control angiogenesis are being developed and tested. In the present review, we examine some of these approaches from a therapeutic perspective and summarize the findings from early human trials of such agents.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Angiostatinas , Neoplasias Encefálicas/irrigação sanguínea , Hipóxia Celular , Movimento Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Colágeno/uso terapêutico , Cicloexanos , Endostatinas , Fatores de Crescimento Endotelial/antagonistas & inibidores , Endotélio Vascular/efeitos dos fármacos , Terapia Genética , Glioma/irrigação sanguínea , Humanos , Integrinas/antagonistas & inibidores , Interferons/uso terapêutico , Linfocinas/antagonistas & inibidores , Inibidores de Metaloproteinases de Matriz , Proteínas de Neoplasias/antagonistas & inibidores , O-(Cloroacetilcarbamoil)fumagilol , Fragmentos de Peptídeos/uso terapêutico , Plasminogênio/uso terapêutico , Prognóstico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptor TIE-2 , Retinoides/uso terapêutico , Sesquiterpenos/uso terapêutico , Estilbenos/uso terapêutico , Talidomida/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
The effects of the angiogenic inhibitors endostatin, angiostatin, and TNP-470 on tumor growth dynamics are experimentally and theoretically investigated. On the basis of the data, we pose a quantitative theory for tumor growth under angiogenic stimulator/inhibitor control that is both explanatory and clinically implementable. Our analysis offers a ranking of the relative effectiveness of these inhibitors. Additionally, it reveals the existence of an ultimate limitation to tumor size under angiogenic control, where opposing angiogenic stimuli come into dynamic balance, which can be modulated by antiangiogenic therapy. The competitive influences of angiogenically driven growth and inhibition underlying this framework may have ramifications for tissue size regulation in general.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/patologia , Modelos Biológicos , Neovascularização Patológica/patologia , Angiostatinas , Animais , Colágeno/uso terapêutico , Cicloexanos , Endostatinas , Cinética , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/prevenção & controle , O-(Cloroacetilcarbamoil)fumagilol , Fragmentos de Peptídeos/uso terapêutico , Plasminogênio/uso terapêutico , Sesquiterpenos/uso terapêutico , Transdução de SinaisAssuntos
Conjuntivite/genética , Fragmentos de Peptídeos/uso terapêutico , Plasminogênio/deficiência , Plasminogênio/uso terapêutico , Fatores de Coagulação Sanguínea/análise , Conjuntivite/tratamento farmacológico , Meia-Vida , Homozigoto , Humanos , Hidrocefalia/genética , Recém-Nascido , Masculino , Fragmentos de Peptídeos/farmacocinética , Plasminogênio/análise , Plasminogênio/genética , Plasminogênio/farmacocinética , Mutação Puntual , Sistema Respiratório/metabolismo , Mapeamento por Restrição , Análise de Sequência de DNA , Viscosidade , Cicatrização/genéticaAssuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Endotélio Vascular/efeitos dos fármacos , Metaloendopeptidases/antagonistas & inibidores , Neovascularização Patológica/tratamento farmacológico , Compostos Orgânicos , Angiostatinas , Animais , Compostos de Bifenilo , Colágeno/uso terapêutico , Endostatinas , Humanos , Ácidos Hidroxâmicos/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Fenilbutiratos , Plasminogênio/uso terapêuticoAssuntos
Antineoplásicos/uso terapêutico , Jornalismo Médico , Neovascularização Patológica/tratamento farmacológico , Jornais como Assunto , Angiostatinas , Animais , Ensaios Clínicos como Assunto , Colágeno/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Indústria Farmacêutica/economia , Endostatinas , Humanos , Investimentos em Saúde , Camundongos , Neoplasias/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Plasminogênio/uso terapêuticoRESUMO
The efficacy of thrombolytic therapy may be limited by local availability of plasminogen near a poorly perfused thrombus. The purpose of this study was to determine if the local (i.e., clot site) administration of 0.5 mg glu-plasminogen (glu-plg) or 0.5 mg lysplasminogen (lys-plg) could safely increase the thrombolytic efficacy of a 30-min intraarterial injection of 3,500 U kg-1 of two-chain urokinase plasminogen activator (UK) in a dog model of arterial thrombosis. Thrombolysis was measured by monitoring the continuous decrement of 125I-gamma emissions from a radiolabeled thrombus. Reflow was evaluated by a distally placed flowmeter and by direct visual examination. Forty-two dogs (mean weight 10.1 +/- 1.9 kg) were randomly sorted into six groups of 7 each. The dogs in each group were given either saline plus saline (group 1), saline plus UK (group 2), glu-plg plus saline (group 3), glu-plg plus UK (group 4), lys-plg plus saline (group 5), or lys-plg plus UK (group 6) by selective arterial catheterization 60 min after formation of an occlusive thrombus. Ninety minutes following drug administration, all groups which received UK (groups 2, 4, and 6) showed greater lysis (p less than 0.05) than the groups which received only saline or either glu- or lys-plg plus saline. Group 6, which received lys-plg plus UK, showed significantly greater lysis (34 +/- 4%) than both group 2 (23 +/- 2%), which received saline plus UK, and group 4 (19 +/- 3%), which received glu-plg plus UK (p less than 0.05). All dogs (7/7) in group 6 had reflow at 90 min whereas only 3/7 dogs had reflow in both groups 2 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Fragmentos de Peptídeos/uso terapêutico , Plasminogênio/uso terapêutico , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Animais , Testes de Coagulação Sanguínea , Cães , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Ativação Enzimática/efeitos dos fármacos , Injeções Intra-Arteriais , Fragmentos de Peptídeos/farmacologia , Plasminogênio/farmacologia , Distribuição Aleatória , Ativador de Plasminogênio Tipo Uroquinase/farmacologiaRESUMO
Short-term systemic thrombolytic treatment with 1.5 million I.U. streptokinase or 1.8 million I.U. urokinase or APSAC was carried out in 13 patients with acute myocardial infarction (11 men, 2 women, mean age 61 [44-73] years) after cardiopulmonary resuscitation (n = 11) or transvenous electrostimulation (n = 2). In seven of the patients the infarct vessel was found to be patent after the course of thrombolytic therapy. No haemorrhagic complications occurred. Two patients died: one of a reinfarct at 3 months and the other suddenly at home at 6 months. These results show that short-term high dosage systemic thrombolytic treatment can be successfully performed in individual cases even after resuscitation or central venous catheterization, provided that any serious traumatic lesions or inadvertent arterial punctures have been avoided.
Assuntos
Cardioversão Elétrica , Fibrinolíticos/uso terapêutico , Plasminogênio/uso terapêutico , Ressuscitação , Estreptoquinase/uso terapêutico , Terapia Trombolítica , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Idoso , Anistreplase , Terapia Combinada , Avaliação de Medicamentos , Feminino , Massagem Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , RecidivaRESUMO
Anisoylated plasminogen streptokinase activator complex (APSAC) was developed as a second generation thrombolytic agent in an attempt to overcome some of the limitations to the intravenous application of streptokinase for coronary artery thrombolysis. Temporary protection of the active site on the plasminogen molecule by acylation allows APSAC to be given by rapid injection, confers semiselectivity for clot (at lower doses) and prolonged fibrinolytic action. These properties may simplify intravenous administration, improve coronary reperfusion response and reduce reocclusion potential. Clinical trials with APSAC, still ongoing, allow the following tentative conclusions: the efficacy of intravenous APSAC appears to be equivalent to that of intracoronary streptokinase, when given within 4 hours of the onset of symptoms of myocardial infarction, and superior to that of intravenous streptokinase, but it is easier to administer. Early APSAC therapy leads to reperfusion rates of 60 to 65% and patency rates of 70 to 80%. Early reocclusion rates (within 24 hours) appear to be as low as or lower than those obtained with other agents. Bleeding complications and allergic manifestations after APSAC are acceptably low and comparable with those of equivalent doses of streptokinase. The potential for mortality benefit after APSAC appears to be high and is undergoing additional study. Thus, APSAC therapy, which can be given by simple injection over 2 to 5 minutes, appears promising as a future first line approach to reperfusion therapy in acute myocardial infarction.