RESUMO
This study aimed to evaluate the susceptibility of Brazilian isolates of Trypanosoma evansi to suramin sodium. For this purpose, three isolates of T. evansi (LPV-2005, LPV-2009 and LPV-2010) and seventy mice were used, with the animals divided in 10 groups (A, B, C, D, E, F, G, H, I and J) with seven animals each group. Mice of groups A, B, and C were infected with LPV-2005; Groups D, E and F with LPV-2009 and the groups G, H and I with LPV-2010. The group J was composed by healthy mice or uninfected. The parasitemia was monitored daily through blood smear, and the treatment of all groups was performed three days post-infection (PI), when all mice showed increased parasitemia. Groups A, D and G represented the positives controls, while groups B, E and H received a single dose of suramin sodium at 10 mgkg(-1) intramuscularly. Groups C, F and I were treated with three doses of suramin sodium at 10 mgkg(-1), respecting an interval of 24 h between each dose. Negative blood smears from all animals were obtained 24 h after treatment (AT), status maintained until the end of the experiment (50 days PI). The specific PCR for T. evansi was carried out from blood, showing negative results AT. Therefore, this study showed that a single dose of suramin sodium at 10 mgkg(-1) has the same efficacy of three doses, as recommended by the therapeutic literature. Furthermore, we observed that Brazilian isolates did not show resistance to the drug.
Assuntos
Suramina/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma/efeitos dos fármacos , Tripanossomíase/tratamento farmacológico , Animais , Brasil , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Camundongos , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Suramina/administração & dosagem , Suramina/farmacologia , Tripanossomicidas/administração & dosagem , Tripanossomicidas/farmacologia , Tripanossomíase/parasitologiaRESUMO
INTRODUCTION: The purpose of this study was to determine the effects of suramin, an antifibrotic agent, on cardiac function and remodeling in mdx mice. METHODS: mdx mice (8 months old) received intraperitoneal injections of suramin twice a week for 3 months. Control mdx mice (8 months old) were injected with saline. RESULTS: Suramin improved the electrocardiography profile with the main corrections seen in S- to R-wave ratio, PR interval, and Q amplitude, and a significant decrease in the cardiomyopathy index. Suramin decreased myocardial fibrosis, inflammation, and myonecrosis. CONCLUSIONS: These findings suggest that suramin may be a new adjunctive therapy to help improve cardiomyopathy in DMD.
Assuntos
Antineoplásicos/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/etiologia , Distrofina/deficiência , Distrofia Muscular de Duchenne/complicações , Suramina/uso terapêutico , Fatores Etários , Análise de Variância , Animais , Cardiomiopatias/sangue , Creatina Quinase/sangue , Modelos Animais de Doenças , Eletrocardiografia , Eletroencefalografia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Fibras Musculares Esqueléticas/patologia , Distrofia Muscular de Duchenne/sangue , Distrofia Muscular de Duchenne/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
Fibrosis is a pathological feature observed in patients with Duchenne muscular dystrophy (DMD) and in mdx mice, the experimental model of DMD. We evaluated the effect of suramin, a transforming growth factor-beta 1 (TGF-ß1) blocker, on fibrosis in mdx mice. mdx mice (6 months old) received suramin for 7 weeks. Suramin- and saline-treated (control) mdx mice performed exercise on a treadmill to worsen disease progression. Immunoblotting showed an increase of TGF-ß1 in mdx diaphragm, limb, and cardiac muscles. Suramin decreased creatine kinase in mdx mice and attenuated fibrosis in all muscles studied, except for cardiac muscle. Suramin protected limb muscles against damage and reduced the exercise-induced loss of strength over time. These findings support a role for TGF-ß1 in fibrinogenesis and myonecrosis during the later stages of disease in mdx mice. Suramin might be a useful therapeutic alternative for the treatment of dystrophinopathies.
Assuntos
Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Condicionamento Físico Animal , Suramina/farmacologia , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Animais , Creatina Quinase/metabolismo , Modelos Animais de Doenças , Feminino , Fibrose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Necrose , Condicionamento Físico Animal/efeitos adversos , Suramina/uso terapêutico , Fator de Crescimento Transformador beta1/fisiologiaRESUMO
Trypanosomiasis, a group of diseases including sleeping sickness in humans and Nagana in cattle in Africa, and Chagas' disease in South America, remains a considerable problem in the 21(st) century. The therapies that are available, however, usually have their roots in the "dye therapy" of a century ago, knowledge gained at the microscope from parasite staining procedures and converted to chemotherapy based on compounds closely related to the laboratory reagents. Dyes such as trypan red and trypan blue led to the development of suramin, while cationic nitrogen heterocyclic dyes furnished examples of the phenanthridinium class, such as ethidium (homidium) and isometamidium. Both suramin and isometamidium remain in use. Owing to mutagenicity issues, the presence of ethidium among the phenanthridinium dyes has led to concerns over the clinical use of related derivatives. There are several mechanisms for dye-DNA interaction, however, including possible hydrogen bonding of dye to the polymer, and these are discussed together with structure-activity relations and cellular localization of the phenanthridine and isomeric acridines involved. Better understanding of nucleic acid binding properties has allowed the preparation of more effective phenanthridinium analogues intended for use as anticancer/antiviral therapy.
Assuntos
Doença de Chagas/tratamento farmacológico , DNA/química , Fenantridinas/química , Fenantridinas/uso terapêutico , Tripanossomicidas/história , Tripanossomíase Africana/tratamento farmacológico , Acridinas/química , Acridinas/história , Acridinas/uso terapêutico , África , Animais , Compostos Azo/uso terapêutico , Bovinos , História do Século XIX , História do Século XX , Humanos , Ligação de Hidrogênio , Substâncias Intercalantes/química , Substâncias Intercalantes/história , Substâncias Intercalantes/uso terapêutico , Fenantridinas/história , América do Sul , Suramina/química , Suramina/uso terapêutico , Azul Tripano/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma congolense/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Avaliar o efeito do suramin na migração, proliferação e formação de tubo vascular em células endoteliais coroidianas (CECs) in vitro e em neovascularização coroidiana (NC) in vivo. Foi avaliada a migração através do experimento de Boyden Chamber. Foi avaliada a proliferação através do experimento MTT. Foi avaliada a formação de tubo vascular através do experimento gel colágeno 3D. As CECs foram estimuladas por fatores de crescimento (FC) e tratadas com suramin.O efeito sistêmico do suramin foi avaliado em NC induzidos por laser em olhos de ratos. O suramin inibiu a migração, proliferação e formação de tubo vascular estimulada por FC de forma dose dependente / This study evaluated the effects of suramin on choroidal endothelial cell (CEC) migration, proliferation and tube formation in vitro and choroidal neovascularization (CNV) in vivo. Migration was evaluated using Boyden chamber assay. Proliferation was evaluated by an MTT assay. Tube formation was evaluated using a 3D-tube formation assay. CECs were stimulated by growth factor (GF) treated with suramin. The effect of systemic administration of Suramin was evaluated on laser induced CNV in rats eyes. Suramin inhibited CEC migration, proliferation, and tube formation induced by GF in a dose dependent manner. CNV in rats was inhibited by systemic administration of Suramin 30mg/Kg. These studies indicate that suramin inhibits Angiogenesis in vitro and in vivo...
Assuntos
Técnicas In Vitro , Neovascularização de Coroide/patologia , Suramina/uso terapêutico , Técnicas de Cultura de Células/métodos , Degeneração Macular/patologia , Fatores de Crescimento Endotelial/fisiologiaAssuntos
Oncocercose , Animais , Dietilcarbamazina/uso terapêutico , Filaricidas/uso terapêutico , Guatemala , História do Século XX , Humanos , Insetos Vetores , Oncocercose/complicações , Oncocercose/tratamento farmacológico , Oncocercose/história , Oncocercose/transmissão , Simuliidae , Suramina/uso terapêuticoRESUMO
Protamine inhibits angiogenesis and blocks endothelial, fibroblast and platelet growth factors. Human and experimental gliomas spread and grow in response to both paracrine and autocrine release of these factors. Our objective was to study the effect of protamine administration on cell proliferation, angiogenesis and tumoral growth of C6 glioma. Additionally, we compared the antitumoral effect of protamine with that of another inhibitor of angiogenesis, suramin, and investigated a potential synergistic antitumoral action of low doses of protamine combined with the antineoplastic carmustine. C6 glioma cells were implanted subcutaneously in Wistar rats. A highly malignant glioma developed in 80% of animals; when the tumour reached a diameter of 1.5 cm, either protamine, suramin, carmustine or protamine plus carmustine were administered in various doses. Tumour parameters were measured and compared between groups. In a dose-dependent manner, protamine reduced tumour volume (P < 0.001), mitotic index (P < 0.05), vascular density (P < 0.05) and cell viability (P < 0.005) of C6 glioma. An ultrastructural study demonstrated membranous inclusions in the cytoplasm of 28% of tumoral and endothelial cells of tumours from animals treated with protamine. The inhibition of tumoral growth produced by moderate doses of protamine was similar to that produced by toxic doses of suramin. The combination of protamine and carmustine had a synergistic curtailing effect on tumoral growth (P < 0.001). Our results indicate that protamine is an effective agent against glioblastoma; in non-toxic doses it could potentiate the antineoplastic effect of nitrosoureas for the treatment of glial tumours.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Carmustina/uso terapêutico , Glioma/tratamento farmacológico , Antagonistas de Heparina/uso terapêutico , Neovascularização Patológica/prevenção & controle , Protaminas/uso terapêutico , Animais , Divisão Celular , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Glioblastoma/irrigação sanguínea , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioma/irrigação sanguínea , Glioma/patologia , Transplante de Neoplasias , Ratos , Ratos Wistar , Suramina/uso terapêuticoRESUMO
Se realiza una revisión del tema edema angioneurótico hereditario. Después de una introducción histórica se considera el sistema del complemento, el sistema de las cininas, los inhibidores de las proteasas hemáticas derivadas del plasminógeno y la vinculación entre ambos. Se consideran también los avances últimos en lo que a citogenética molecular se refiere. Se presentan las diferentes formas clínicas de los edemas angioneuróticos hereditarios, así como sus diferencias clínico-laboratoriales. Se hace una valoración de los tratamientos sustitutivos y profilácticos. Se expone el estudio de tres casos clínicos observados en el lapso de 30 años de práctica dermatológica.
Assuntos
Humanos , Masculino , Feminino , Adulto , Angioedema/genética , /administração & dosagem , /uso terapêutico , Androgênios/uso terapêutico , Angioedema/complicações , Angioedema/fisiopatologia , Calicreínas/efeitos adversos , Calicreínas/fisiologia , Cinarizina/administração & dosagem , Cinarizina/uso terapêutico , Complemento C1s , Complemento C1s/deficiência , Proteínas do Sistema Complemento , Diagnóstico Diferencial , Código Genético , Cininas/efeitos adversos , Plasma , Prognóstico , Estanozolol/administração & dosagem , Estanozolol/uso terapêutico , Suramina/administração & dosagem , Suramina/uso terapêuticoRESUMO
Se realiza una revisión del tema edema angioneurótico hereditario. Después de una introducción histórica se considera el sistema del complemento, el sistema de las cininas, los inhibidores de las proteasas hemáticas derivadas del plasminógeno y la vinculación entre ambos. Se consideran también los avances últimos en lo que a citogenética molecular se refiere. Se presentan las diferentes formas clínicas de los edemas angioneuróticos hereditarios, así como sus diferencias clínico-laboratoriales. Se hace una valoración de los tratamientos sustitutivos y profilácticos. Se expone el estudio de tres casos clínicos observados en el lapso de 30 años de práctica dermatológica. (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Angioedema/genética , Estanozolol/administração & dosagem , Estanozolol/uso terapêutico , Cinarizina/administração & dosagem , Cinarizina/uso terapêutico , Ácido Aminocaproico/administração & dosagem , Ácido Aminocaproico/uso terapêutico , Suramina/administração & dosagem , Suramina/uso terapêutico , Plasma , Diagnóstico Diferencial , Angioedema/complicações , Angioedema/fisiopatologia , Proteínas do Sistema Complemento , Cininas/efeitos adversos , Complemento C1s/deficiência , Complemento C1s/diagnóstico , Calicreínas/efeitos adversos , Calicreínas/fisiologia , Código Genético , Prognóstico , Androgênios/uso terapêuticoRESUMO
The sensitivity of an antigen detection enzyme immunoassay (Ag-ELISA) based on a Trypanosoma brucei group-specific monoclonal antibody was evaluated to detect circulating Trypanosoma evansi antigen in horse sera. Three horses and 2 mules were experimentally infected with T. evansi. Circulating antigens were detected on 7 and 21 days postinfection. Antigen levels increased during the course of the illness and remained high even when parasitemia was low or when parasites could not be detected. Antigens were cleared from serum when drug treatment was effective but persisted when it was not. In 6 outbreaks of "mal de caderas" involving 125 horses, T. evansi was found in 78 horses using standard parasite detection methods and antigenemia was detected in 58 of them (74%). The Ag-ELISA sensitivity rate varied between 63% and 100% for the 6 different outbreaks. A combination of Ag-ELISA and parasitologic methods diagnosed a total of 93 infected animals. These results show that the Ag-ELISA test is useful both to diagnose T. evansi and to assess the efficacy of drug treatment in horses.