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1.
Inflammation ; 42(3): 1071-1081, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30715690

RESUMO

The exact etiology and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still unknown, as a result, available therapeutic options for patients are far from satisfactory. Therefore, there is a need to develop a valid therapeutic approach that can ameliorate the manifestations of CP/CPPS. Fifty male C57BL/6 mice were randomly divided into five groups of ten mice each. All groups except naïve were subcutaneously injected with 0.2 ml of T2 plus complete Freund adjuvant (CFA) on day 0 and 14 to generate valid CP/CPPS model. After successful CP/CPPS induction, model group was injected with 0.2 ml of normal saline while PLGA, PLGA-OVA, and PLGA-T2 groups were administered intravenously with 0.2 ml mixture of PLGA, PLGA-OVA, and PLGA-T2, respectively. Voiding behavior, pain threshold, and hematoxylin and eosin staining were used to assess micturition habits, pain intensity as well as prostate inflammation. Additionally, TNF-α, CRP, and IL-10 levels in plasma were measured by using ELISA kits. Mice administered with PLGA-T2 showed higher pain threshold, lower urine frequencies, mild edema, and inflammation in prostate tissue in comparison to other groups. Moreover, the expression of TNF-α and CRP levels was markedly decreased while IL-10 expression was increased in the PLGA-T2 treatment group as compared to the other groups. Our results showed that nanoparticles conjugated with autoantigen novel peptide T2 could successfully alleviate or even heal CP/CPPS to some extent in mice. This study provides an easy, useful, and economic tool for ameliorating the manifestations of CP/CPPS that will improve the therapeutic approaches.


Assuntos
Antígenos CD2/uso terapêutico , Nanopartículas/uso terapêutico , Prostatite/tratamento farmacológico , Animais , Autoantígenos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Proteína C-Reativa/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Modelos Animais de Doenças , Interleucina-10/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
2.
Pain ; 160(3): 712-723, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30699097

RESUMO

Electroacupuncture (EA) is widely used in clinical settings to reduce inflammatory pain. Islet-cell autoantigen 69 (ICA69) has been reported to regulate long-lasting hyperalgesia in mice. ICA69 knockout led to reduced protein interacting with C-kinase 1 (PICK1) expression and increased glutamate receptor subunit 2 (GluR2) phosphorylation at Ser880 in spinal dorsal horn. In this study, we evaluated the role of ICA69 in the antihyperalgesic effects of EA and the underlying mechanism through regulation of GluR2 and PICK1 in spinal dorsal horn. Hyperalgesia was induced in mice with subcutaneous plantar injection of complete Freund adjuvant (CFA) to cause inflammatory pain. Electroacupuncture was then applied for 30 minutes every other day after CFA injection. When compared with CFA group, paw withdrawal frequency of CFA+EA group was significantly decreased. Remarkable increases in Ica1 mRNA expression and ICA69 protein levels on the ipsilateral side were detected in the CFA+EA group. ICA69 expression reached the peak value around day 3. More importantly, ICA69 deletion impaired the antihyperalgesic effects of EA on GluR2-p, but PICK1 deletion could not. Injecting ICA69 peptide into the intrathecal space of ICA69-knockout mice mimicked the effects of EA analgesic and inhibited GluR2-p. Electroacupuncture had no effects on the total protein of PICK1 and GluR2. And, EA could increase the formation of ICA69-PICK1 complexes and decrease the amount of PICK1-GluR2 complexes. Our findings indicate that ICA69 mediates the antihyperalgesic effects of EA on CFA-induced inflammatory pain by regulating spinal GluR2 through PICK1 in mice.


Assuntos
Autoantígenos/metabolismo , Proteínas de Transporte/metabolismo , Eletroacupuntura/métodos , Regulação da Expressão Gênica/genética , Proteínas Nucleares/metabolismo , Receptores de AMPA/metabolismo , Medula Espinal/metabolismo , Animais , Autoantígenos/química , Autoantígenos/genética , Autoantígenos/uso terapêutico , Proteínas de Transporte/genética , Proteínas de Ciclo Celular , Modelos Animais de Doenças , Adjuvante de Freund/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Imunoprecipitação , Inflamação/induzido quimicamente , Inflamação/complicações , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Nucleares/genética , Dor/complicações , Dor/etiologia , Manejo da Dor , Fosforilação/fisiologia , RNA Mensageiro/metabolismo , Fatores de Tempo
3.
Mol Pharm ; 16(2): 607-617, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30615457

RESUMO

Contemporary approaches to treating autoimmune diseases like multiple sclerosis broadly modulate the immune system and leave patients susceptible to severe adverse effects. Antigen-specific immunotherapies (ASIT) offer a unique opportunity to selectively suppress autoreactive cell populations but have suffered from marginal efficacy even when employing traditional adjuvants to improve delivery. The development of immunologically active antigen delivery vehicles could potentially increase the clinical success of antigen-specific immunotherapies. An emulsion of the antioxidant tocopherol delivering an epitope of proteolipid protein autoantigen (PLP139-151) yielded significant efficacy in mice with experimental autoimmune encephalomyelitis (EAE). In vitro studies indicated tocopherol emulsions reduced oxidative stress in antigen-presenting cells. Ex vivo analysis revealed that tocopherol emulsions shifted cytokine responses in EAE splenocytes. In addition, IgG responses against PLP139-151 were increased in mice treated with tocopherol emulsions delivering the antigen, suggesting a possible skew in immunity. Overall, tocopherol emulsions provide a functional delivery vehicle for ASIT capable of ameliorating autoimmunity in a murine model.


Assuntos
Autoantígenos/uso terapêutico , Emulsões/química , Encefalomielite Autoimune Experimental/tratamento farmacológico , Tocoferóis/química , Tocoferóis/uso terapêutico , Animais , Autoantígenos/administração & dosagem , Citocinas/metabolismo , Feminino , Tolerância Imunológica/efeitos dos fármacos , Imunoterapia/métodos , Camundongos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Baço/citologia
4.
Rev. cuba. cir ; 57(1): 49-57, ene.-mar. 2018. tab
Artigo em Espanhol | CUMED | ID: cum-72072

RESUMO

Introducción: las fisuras anales son un problema de salud importante en la población cubana, incluso con la supresión de los factores desencadenantes, muchas de ellas tienden a la cronicidad; su evolución es tórpida, y es elevado el riesgo de complicación de las mismas. Objetivo: evaluar la cicatrización de las fisuras anales mediante lisado plaquetario en el Hospital General Docente Comandante Pinares de San Cristóbal. Método: se realizó un estudio cuasi experimental en el servicio de cirugía general del Hospital General Docente Comandante Pinares desde enero 2015 hasta junio 2017. Se incluyeron en el estudio todos los pacientes adultos, de ambos sexos, atendidos por el diagnóstico de fisura anal con inadecuada respuesta al tratamiento convencional y sin otras enfermedades de base que impidieran el uso de la terapia regenerativa. A todos los pacientes se les solicitó el consentimiento informado previa explicación de las características del estudio. Resultados: la hemorroidectomía fue el proceder más frecuente asociado a las fisuras anales. El dolor fue el síntoma predominante antes del tratamiento. La reducción del área de la fisura fue evidente en los tratados con lisado. El efecto final en los pacientes tratados con el método fue positivo. Conclusiones: se comprobó que el lisado plaquetario usado para la cicatrización de la fisura anal crónica fue efectivo con un resultado de satisfacción por parte de los pacientes, con un mínimo de reacciones adversas. Puede representar un futuro promisorio en el tratamiento de esta enfermedad(AU)


Introduction: Anal fissures are an important health problem in the Cuban population, even with the suppression of the triggering factors, many of them tend to chronicity; its evolution is torpid, and their risk for complication is high. Objective: To evaluate the healing of anal fissures by platelet lysate in Comandante Pinares General Teaching Hospital in San Cristóbal. Method: A quasi-experimental study was performed in the general surgery service of Comandante Pinares General Teaching Hospital, from January 2015 to June 2017. All adult patients, of both sexes, were attended upon diagnosis of anal fissure and were included in the study. with inadequate response to conventional treatment and without other underlying diseases that could prevent the use of regenerative therapy. All patients were asked for their informed consent prior explanation of the study characteristics. Results: Hemorrhoidectomy was the most frequent procedure associated with anal fissures. Pain was the predominant symptom before treatment. The reduction in the area of ​​the fissure was evident in those patients treated with the lysate. The final effect in patients treated with the method was positive. Conclusions: The usage of the platelet lysate for the healing of chronic anal fissure proved effective, with a result of patient satisfaction, with a minimum of adverse reactions. It may represent a promising future in the treatment of this disease(AU)


Assuntos
Humanos , Masculino , Feminino , Autoantígenos/uso terapêutico , Fatores Desencadeantes , Medicina Regenerativa/métodos , Fissura Anal/diagnóstico , Coleta de Dados
5.
Rev. cuba. cir ; 57(1): 49-57, ene.-mar. 2018. tab
Artigo em Espanhol | LILACS | ID: biblio-960346

RESUMO

Introducción: las fisuras anales son un problema de salud importante en la población cubana, incluso con la supresión de los factores desencadenantes, muchas de ellas tienden a la cronicidad; su evolución es tórpida, y es elevado el riesgo de complicación de las mismas. Objetivo: evaluar la cicatrización de las fisuras anales mediante lisado plaquetario en el Hospital General Docente Comandante Pinares de San Cristóbal. Método: se realizó un estudio cuasi experimental en el servicio de cirugía general del Hospital General Docente Comandante Pinares desde enero 2015 hasta junio 2017. Se incluyeron en el estudio todos los pacientes adultos, de ambos sexos, atendidos por el diagnóstico de fisura anal con inadecuada respuesta al tratamiento convencional y sin otras enfermedades de base que impidieran el uso de la terapia regenerativa. A todos los pacientes se les solicitó el consentimiento informado previa explicación de las características del estudio. Resultados: la hemorroidectomía fue el proceder más frecuente asociado a las fisuras anales. El dolor fue el síntoma predominante antes del tratamiento. La reducción del área de la fisura fue evidente en los tratados con lisado. El efecto final en los pacientes tratados con el método fue positivo. Conclusiones: se comprobó que el lisado plaquetario usado para la cicatrización de la fisura anal crónica fue efectivo con un resultado de satisfacción por parte de los pacientes, con un mínimo de reacciones adversas. Puede representar un futuro promisorio en el tratamiento de esta enfermedad(AU)


Introduction: Anal fissures are an important health problem in the Cuban population, even with the suppression of the triggering factors, many of them tend to chronicity; its evolution is torpid, and their risk for complication is high. Objective: To evaluate the healing of anal fissures by platelet lysate in Comandante Pinares General Teaching Hospital in San Cristóbal. Method: A quasi-experimental study was performed in the general surgery service of Comandante Pinares General Teaching Hospital, from January 2015 to June 2017. All adult patients, of both sexes, were attended upon diagnosis of anal fissure and were included in the study. with inadequate response to conventional treatment and without other underlying diseases that could prevent the use of regenerative therapy. All patients were asked for their informed consent prior explanation of the study characteristics. Results: Hemorrhoidectomy was the most frequent procedure associated with anal fissures. Pain was the predominant symptom before treatment. The reduction in the area of ​​the fissure was evident in those patients treated with the lysate. The final effect in patients treated with the method was positive. Conclusions: The usage of the platelet lysate for the healing of chronic anal fissure proved effective, with a result of patient satisfaction, with a minimum of adverse reactions. It may represent a promising future in the treatment of this disease(AU)


Assuntos
Humanos , Masculino , Feminino , Autoantígenos/uso terapêutico , Fatores Desencadeantes , Medicina Regenerativa/métodos , Fissura Anal/diagnóstico , Coleta de Dados/estatística & dados numéricos
6.
Curr Opin Immunol ; 49: 44-50, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28992525

RESUMO

Studies with immunologics have shown that the natural history of Type 1 diabetes can be modified. These studies have targeted key mediators of the disease and recent analyses, together with studies in preclinical models have identified mechanisms that may be involved in the clinical effects. Several issues remain including specificity of the interventions, adverse effects of the treatments, and duration of their effects. Future studies are likely to include more specific approaches with agents such as cell therapies with selected immune regulatory subsets, antigen specific therapies, and combinations of agents with complementary mechanisms of activity.


Assuntos
Autoantígenos/uso terapêutico , Produtos Biológicos/uso terapêutico , Diabetes Mellitus Tipo 1/terapia , Imunoterapia/métodos , Células Secretoras de Insulina/patologia , Animais , Autoantígenos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Modelos Animais de Doenças , Humanos , Tolerância Imunológica , Células Secretoras de Insulina/efeitos dos fármacos , Terapia de Alvo Molecular
7.
Mediators Inflamm ; 2017: 3916519, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28751821

RESUMO

Citrullinated peptides are used for measuring anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). Accumulation of citrullinated proteins in the inflamed synovium suggests that they may be good targets for inducing peripheral tolerance. In view of the multiplicity of citrullinated autoantigens described as ACPA targets, we generated a multiepitope citrullinated peptide (Cit-ME) from the sequences of major citrullinated autoantigens: filaggrin, ß-fibrinogen, vimentin, and collagen type II. We assessed the ability of Cit-ME or the citrullinated ß60-74 fibrinogen peptide (ß60-74-Fib-Cit) which bears immunodominant citrullinated epitopes (i) to modify cytokine gene expression and (ii) to modulate Treg and Th17 subsets in PBMC derived from newly diagnosed untreated RA patients. RA patient's PBMC incubated with Cit-ME or ß60-74-Fib-Cit, showed upregulation of TGF-ß expression (16% and 8%, resp.), and increased CD4+Foxp3+ Treg (22% and 19%, resp.). Both peptides were shown to downregulate the TNF-α and IL-1ß expression; in addition, Cit-ME reduced CD3+IL17+ T cells. We showed that citrullinated peptides can modulate the expression of anti- and proinflammatory cytokines in PBMC from RA patients as well as the proportions of Treg and Th17 cells. These results indicate that citrullinated peptides could be active in vivo and therefore might be used as immunoregulatory agents in RA patients.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Autoantígenos/imunologia , Autoantígenos/uso terapêutico , Adulto , Idoso , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Autoantígenos/química , Citrulinação , Colágeno Tipo II/metabolismo , Epitopos , Feminino , Fibrinogênio/metabolismo , Humanos , Imunomodulação/fisiologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Vimentina/metabolismo , Adulto Jovem
8.
Nanomedicine (Lond) ; 12(11): 1231-1242, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28593827

RESUMO

AIM: Based on the ability of apoptosis to induce immunological tolerance, liposomes were generated mimicking apoptotic cells, and they arrest autoimmunity in Type 1 diabetes. Our aim was to validate the immunotherapy in other autoimmune disease: multiple sclerosis. MATERIALS & METHODS: Phosphatidylserine-rich liposomes were loaded with disease-specific autoantigen. Therapeutic capability of liposomes was assessed in vitro and in vivo. RESULTS: Liposomes induced a tolerogenic phenotype in dendritic cells, and arrested autoimmunity, thus decreasing the incidence, delaying the onset and reducing the severity of experimental disease, correlating with an increase in a probably regulatory CD25+ FoxP3- CD4+ T-cell subset. CONCLUSION: This is the first work that confirms phosphatidylserine-liposomes as a powerful tool to arrest multiple sclerosis, demonstrating its relevance for clinical application.


Assuntos
Autoantígenos/administração & dosagem , Imunoterapia/métodos , Lipossomos/química , Esclerose Múltipla/terapia , Glicoproteína Mielina-Oligodendrócito/administração & dosagem , Peptídeos/administração & dosagem , Fosfatidilserinas/química , Animais , Autoantígenos/imunologia , Autoantígenos/uso terapêutico , Feminino , Camundongos Endogâmicos C57BL , Esclerose Múltipla/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Glicoproteína Mielina-Oligodendrócito/uso terapêutico , Peptídeos/imunologia , Peptídeos/uso terapêutico , Linfócitos T Reguladores/imunologia
9.
Biomaterials ; 118: 51-62, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27940382

RESUMO

Autoimmune diseases occur when the immune system incorrectly recognizes self-molecules as foreign; in the case of multiple sclerosis (MS), myelin is attacked. Intriguingly, new studies reveal toll-like receptors (TLRs), pathways usually involved in generating immune responses against pathogens, play a significant role in driving autoimmune disease in both humans and animal models. We reasoned polyplexes formed from myelin self-antigen and regulatory TLR antagonists might limit TLR signaling during differentiation of myelin-specific T cells, inducing tolerance by biasing T cells away from inflammatory phenotypes. Complexes were formed by modifying myelin peptide with cationic amino acids to create peptides able to condense the anionic nucleic-acid based TLR antagonist. These immunological polyplexes eliminate synthetic polymers commonly used to condense polyplexes and do not rely on gene expression; however, the complexes mimic key features of traditional polyplexes such as tunable loading and co-delivery. Using these materials and classic polyplex analysis techniques, we demonstrate condensation of both immune signals, protection from enzymatic degradation, and tunable physicochemical properties. We show polyplexes reduce TLR signaling, and in primary dendritic cell and T cell co-culture, reduce myelin-driven inflammation. During mouse models of MS, these tolerogenic polyplexes improve the progression, severity, and incidence of disease.


Assuntos
Autoantígenos/imunologia , Autoantígenos/uso terapêutico , Autoimunidade/imunologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/terapia , Ácidos Nucleicos Peptídicos/uso terapêutico , Receptores Toll-Like/imunologia , Animais , Autoantígenos/farmacologia , Autoimunidade/efeitos dos fármacos , Células Cultivadas , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Ácidos Nucleicos , Ácidos Nucleicos Peptídicos/imunologia , Ácidos Nucleicos Peptídicos/farmacologia , Transdução de Sinais , Receptores Toll-Like/antagonistas & inibidores , Resultado do Tratamento
10.
Exp Neurol ; 286: 50-60, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27693617

RESUMO

Previous work by our group showed that transferring bone marrow cells transduced with a self-antigen induced immune tolerance and ameliorated experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). We also found that following retroviral transduction of murine bone marrow (BM) cells, the majority of cells generated and transduced were myeloid-derived suppressor cells (MDSCs). Here, we aimed to determine whether purified antigen-expressing MDSCs have similar therapeutic effects than those of unfractionated BM, and to investigate their potential mechanisms. We performed phenotypic and functional analyses in these cells using the same animal model, and we used purified antigen-expressing MDSCs in preventive and therapeutic approaches. These cells exerted therapeutic effects similar to those of BM cells, which depended upon self-antigen expression. The majority of monocytic (M)-MDSCs expressed the immunosuppressive molecule programmed death ligand-1 (PD-L1), CD80, CD86 and MHC class II molecules. Additionally, the animals infused with antigen-expressing cells exhibited lower percentages of activated T cells and higher percentages of B cells with a regulatory phenotype (B220+CD1dhigh CD5+) in the spleen than their respective controls. MDSCs expressing self-antigens, alloantigens or therapeutic transgenes are tolerogenic and can be exploited therapeutically in autoimmune diseases, transplantation and in gene therapy, respectively.


Assuntos
Autoantígenos/uso terapêutico , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/terapia , Células Supressoras Mieloides/fisiologia , Transferência Adotiva , Animais , Apoptose/fisiologia , Células da Medula Óssea/fisiologia , Sistema Nervoso Central/patologia , Citocinas/metabolismo , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/fisiopatologia , Feminino , Humanos , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides/efeitos dos fármacos , Retroviridae/genética , Índice de Gravidade de Doença , Baço/patologia , Canais de Ânion Dependentes de Voltagem
12.
J Neuroinflammation ; 13(1): 113, 2016 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-27207486

RESUMO

BACKGROUND: Tolerogenic dendritic cells (tolDC) have been postulated as a potent immunoregulatory therapy for autoimmune diseases such as multiple sclerosis (MS). In a previous study, we demonstrated that the administration of antigen-specific vitamin D3 (vitD3) tolDC in mice showing clinical signs of experimental autoimmune encephalomyelitis (EAE; the animal model of MS) resulted in abrogation of disease progression. With the purpose to translate this beneficial therapy to the clinics, we have investigated the effectivity of vitD3-frozen antigen-specific tolDC pulsed with myelin oligodendrocyte glycoprotein 40-55 peptide (f-tolDC-MOG) since it would reduce the cost, functional variability and number of leukapheresis to perform to the patients. METHODS: Mice showing EAE clinical signs were treated with repetitive doses of f-tolDC-MOG. Tolerogenic mechanisms induced by the therapy were analysed by flow cytometry and T cell proliferation assays. RESULTS: Treatment with f-tolDC-MOG was effective in ameliorating clinical signs of mice with EAE, inhibiting antigen-specific reactivity and inducing Treg. In addition, the long-term treatment was well tolerated and leading to a prolonged maintenance of tolerogenicity mediated by induction of Breg, reduction of NK cells and activation of immunoregulatory NKT cells. CONCLUSIONS: The outcomes of this study show that the use of antigen-specific f-tolDC promotes multiple and potent tolerogenic mechanisms. Moreover, these cells can be kept frozen maintaining their tolerogenic properties, which is a relevant step for their translation to the clinic. Altogether, vitD3 f-tolDC-MOG is a potential strategy to arrest the autoimmune destruction in MS patients.


Assuntos
Autoantígenos/uso terapêutico , Colecalciferol/uso terapêutico , Células Dendríticas/fisiologia , Células Dendríticas/transplante , Encefalomielite Autoimune Experimental/terapia , Animais , Transplante de Células/métodos , Criopreservação , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Seguimentos , Células Matadoras Naturais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito/imunologia , Fragmentos de Peptídeos/imunologia , Polissacarídeos/farmacologia , Fatores de Tempo
13.
Rev. esp. enferm. dig ; 108(3): 123-128, mar. 2016. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-148604

RESUMO

Objetivo: este estudio tiene como objetivo demostrar la efectividad y seguridad de un gel de fibrina autóloga rico en factores de crecimiento plaquetario para el tratamiento de las fístulas perianales complejas. Material y métodos: estudio epidemiológico prospectivo descriptivo. Se incluyen pacientes que presentan fístula perianal compleja o fístula perianal simple con alteración de la continencia. Se realiza identificación de ambos orificios y del trayecto, legrado del mismo e instilación del Vivostat PRF® en el trayecto hasta observar exceso de material por el OFE. Las variables a analizar son: edad, sexo, uso de setón previo, clínica prevalente, tipo de fístula, complicaciones postoperatorias, cierre de la fístula y alteraciones en la calidad de vida mediante el test sf-36(v2). Resultados: desde enero del 2011 hasta mayo del 2013 se ha intervenido a 23 pacientes, 12 hombres y 11 mujeres, con una media de edad de 49 años y un seguimiento mínimo de 12 meses. Dos abandonaron el estudio. 17 pacientes presentaban fístula transesfinteriana baja; 2, transesfinteriana alta, y 2, interesfinteriana con alteración de la continencia. El síntoma más frecuente es la supuración. Doce pacientes llevaban un setón laxo (62%), de los cuales curaron nueve. De todos los pacientes que hemos intervenido el porcentaje de éxitos es de un 62%. Ningún paciente desarrolló incontinencia después del tratamiento. Sólo dos refieren una peor calidad de vida después de la intervención. Conclusión: este estudio demuestra que hay un claro beneficio con el uso de Vivostat PRF® como tratamiento para las fístulas perianales complejas. Es una técnica altamente reproductible con resultados aceptables y que no produce alteraciones de la continencia (AU)


Objective: This study aims to demonstrate the effectiveness and safety of autologous fibrin gel rich in platelet growth factors for the treatment of complex perianal fistulas. Material and Methods: Prospective epidemiological study. Patients with complex perianal fistula or perianal fistula mere alteration of continence are included. identification of both holes and the journey, curettage of it and instillation of Vivostat PRF® in the way it is done to observe excess material by OFE. The variables analyzed were: age, sex, use of prior Seton clinic prevalent type of fistula, postoperative complications, fistula closure and impaired quality of life using the SF-36 test (v2). Results: From January 2011 to May 2013 have involved 23 patients, 12 men and 11 women, with an average age of 49 years and a minimum follow-up of 12 months. Two dropped out. 17 patients had low transsphincteric fistulas, 2 and 2 high transsphincteric intersphincteric with impaired continence. The most common symptom is the discharge. Twelve patients had a loose seton (62%), of which nine cured. Of all the patients we have operated the success rate is 62%. No patient developed incontinence after treatment. Only two reported a worse quality of life after surgery. Conclusion: This study demonstrates that there is a clear benefit to the use of Vivostat PRF® as a treatment for complex perianal fistulas. It is a highly reproducible technique with acceptable results and does not produce impairment of continence (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Autoantígenos/uso terapêutico , Glândulas Perianais , Glândulas Perianais/cirurgia , Complicações Pós-Operatórias/terapia , Fístula/tratamento farmacológico , Fístula/cirurgia , Avaliação de Eficácia-Efetividade de Intervenções , Qualidade de Vida , Receptores de Fatores de Crescimento/uso terapêutico , Estudos Prospectivos
14.
J Control Release ; 223: 178-187, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26739548

RESUMO

Antigen specific immunotherapy mediated via the sustained generation of regulatory T cells arguably represents the ideal therapeutic approach to preventing beta cell destruction in type 1 diabetes. However, there is a need to enhance the efficacy of this approach to achieve disease modification in man. Previous studies suggest that prolonged expression of self-antigen in skin in a non-inflammatory context is beneficial for tolerance induction. We therefore sought to develop a dry-coated microneedle (MN) delivery system and combine it with topical steroid to minimise local inflammation and promote prolonged antigen presentation in the skin. Here we show that a combination of surface-modified MNs coated with appropriate solvent systems can deliver therapeutically relevant quantities of peptide to mouse and human skin even with hydrophobic peptides. Compared to conventional "wet" intradermal (ID) administration, "dry" peptide delivered via MNs was retained for longer in the skin and whilst topical hydration of the skin with vehicle or steroid accelerated loss of ID-delivered peptide from the skin, MN delivery of peptide was unaffected. Furthermore, MN delivery resulted in enhanced presentation of antigen to T cells in skin draining lymph nodes (LNs) both 3 and 10days after administration. Repeated administration of islet antigen peptide via MN was effective at reducing antigen-specific T cell proliferation in the pancreatic LN, although topical steroid therapy did not enhance this. Taken together, these data show auto-antigenic peptide delivery into skin using coated MNs results in prolonged retention and enhanced antigen presentation compared to conventional ID delivery and this approach may have potential in individuals identified as being at a high risk of developing type 1 diabetes and other autoimmune diseases.


Assuntos
Autoantígenos/administração & dosagem , Cromogranina A/administração & dosagem , Diabetes Mellitus Tipo 1/terapia , Imunoterapia/métodos , Fragmentos de Peptídeos/administração & dosagem , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Apresentação do Antígeno/efeitos dos fármacos , Autoantígenos/uso terapêutico , Betametasona/administração & dosagem , Betametasona/uso terapêutico , Cromogranina A/uso terapêutico , Diabetes Mellitus Tipo 1/imunologia , Feminino , Humanos , Camundongos Transgênicos , Microinjeções , Pessoa de Meia-Idade , Agulhas , Fragmentos de Peptídeos/uso terapêutico , Pele/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Adulto Jovem
15.
Tumour Biol ; 36(8): 5753-5, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26234767

RESUMO

Protein phosphatase 2A (PP2A) is a well-known tumor suppressor frequently inhibited in human cancer. Alterations affecting PP2A subunits together with the deregulation of endogenous PP2A inhibitors such as CIP2A and SET have been described as contributing mechanisms to inactivate PP2A in prostate cancer. Moreover, recent findings highlight that functional inactivation of PP2A could represent a key event in the acquisition of castration-resistant phenotype and a novel molecular target with high impact at both clinical and therapeutic levels in prostate cancer.


Assuntos
Autoantígenos/metabolismo , Chaperonas de Histonas/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias de Próstata Resistentes à Castração/genética , Proteína Fosfatase 2/genética , Fatores de Transcrição/metabolismo , Apoptose/genética , Autoantígenos/genética , Autoantígenos/uso terapêutico , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Chaperonas de Histonas/genética , Chaperonas de Histonas/uso terapêutico , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/uso terapêutico , Terapia de Alvo Molecular , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/terapia , Proteína Fosfatase 2/antagonistas & inibidores , Proteína Fosfatase 2/uso terapêutico , Receptores Androgênicos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/uso terapêutico
16.
Can Vet J ; 56(7): 709-14, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26130832

RESUMO

The purpose of this retrospective case series was to assess the outcome of an autologous vaccination procedure on single and multiple sarcoid lesions, determine complication rate, and report owner satisfaction. Medical records (18 cases) from January 2009 through May 2014 were evaluated to identify horses undergoing the procedure. Signalment, number, size, anatomic location of lesions, and type of historical treatment were recorded. Follow-up was obtained via standardized owner survey, veterinary examination, and digital images. Data recorded and analyzed included ancillary therapies post-procedure, decrease in number and/or size of sarcoid lesions, sarcoid regrowth, complications, and owner satisfaction. There was a decrease in number of lesions observed by owners in 75% of cases and a decrease in size of sarcoids in 93.8% of cases. Clinical regression observed by owners was noted in 68.8% of cases. There were complications in 43.8% of cases and owner satisfaction in 75% of cases.


Assuntos
Autoantígenos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Doenças dos Cavalos/terapia , Neoplasias Cutâneas/veterinária , Animais , Feminino , Cavalos , Masculino , Estudos Retrospectivos , Neoplasias Cutâneas/terapia
17.
Mult Scler ; 21(5): 651-5, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25200502

RESUMO

We have recently demonstrated the safety and tolerability of a novel therapeutic regimen employing autologous blood cells chemically coupled with seven myelin peptides to induce antigen-specific tolerance in MS (ETIMS study). The aim of the current study was an extended safety analysis to assess the effect of the ETIMS approach on antibodies to common autoantigens, the myelin peptides used and common recall antigens. None of the patients showed induction of autoantibody responses. One patient had a measurable myelin peptide-specific response at baseline, which was reduced after treatment. Total immunoglobulins and recall antibody responses showed no significant change.


Assuntos
Formação de Anticorpos/efeitos dos fármacos , Autoantígenos/uso terapêutico , Células Sanguíneas/imunologia , Tolerância Imunológica , Esclerose Múltipla/terapia , Vacinas/uso terapêutico , Adulto , Autoanticorpos/análise , Autoantígenos/efeitos adversos , Relação Dose-Resposta Imunológica , Feminino , Humanos , Imunoglobulina G/análise , Masculino , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/imunologia , Vacinas/efeitos adversos
18.
Vestn Ross Akad Med Nauk ; (4): 63-7, 2013.
Artigo em Russo | MEDLINE | ID: mdl-24003724

RESUMO

Neovascular diseases of visual organ such as age-related macular degeneration, retinopathy of prematurity, diabetic retinopathy, thrombosis of central retina vein and its branches, neovascular glaucoma, choroid and retina tumors have the leading positions in the list of ophtalmopatologies that result in blindness and incapacity. The variety of angiostatic medications of applied ophtalmology is scant. The aim of work was to study the possibile approaches to angiogenesis regulation in vitro with the help of recombinant fragments of natural inhibitors of angiogenesis such as endostatin, tumstatin and PEDF (pigment epithelial derived factor), and also theirability to be the base of potentially feasible and pharmacologically active substances. It is determined that endostatin, tumstatin and PEDF, as well as the comparison medication Bevacizumab in vitro have pro-or antiangiogenic influence. The direction of the biological effect depends on the cultivation conditions, peptide concentration in the cultural fluid and stage of angiogenesis.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Autoantígenos/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Colágeno Tipo IV/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Endostatinas/uso terapêutico , Proteínas do Olho/uso terapêutico , Degeneração Macular/tratamento farmacológico , Fatores de Crescimento Neural/uso terapêutico , Serpinas/uso terapêutico , Células Cultivadas , Neovascularização de Coroide/patologia , Retinopatia Diabética/patologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Epitopos , Humanos , Inibidores de Proteases/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento
19.
Arch. Soc. Esp. Oftalmol ; 88(8): 302-306, ago. 2013. tab, ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-116519

RESUMO

Objetivo: Evaluar la efectividad del colirio de suero autólogo al 20% como tratamiento en la queratopatía neurotrófica. Material y métodos: Estudio longitudinal, observacional y descriptivo a partir de 19 pacientes (22 ojos) diagnosticados de queratopatía neurotrófica en distintos estadios según la clasificación de Mackie. Las variables evaluadas, tanto en la primera visita como a los 4 meses de seguimiento, fueron: agudeza visual mejor corregida, sintomatología subjetiva del paciente (escala de caras), test de Schirmer sin anestesia (mm), tiempo de rotura de la película lagrimal (BUT) (sg) así como el tiempo de curación del defecto epitelial (semanas). Para el análisis estadístico de los datos empleamos la prueba de rangos de Wilcoxon. Resultados: Se observó una mejoría sintomática en el 100% de los casos y del 71% en la agudeza visual mejor corregida, siendo ambas mejorías estadísticamente significativas. También observamos una mejoría en el test de Schirmer y en el BUT, pero estas no fueron estadísticamente significativas. La curación del defecto epitelial fue en el 71% de los casos antes de 6 semanas de tratamiento y en el 91% antes de las 12 semanas. El 9% restante, que no presentó curación, correspondía a queratopatías neurotrópicas en estadio 3. Conclusiones: El colirio de suero autólogo al 20% representa un tratamiento efectivo en las queratopatías neurotróficas grados 1 y 2, siendo un tratamiento insuficiente en las queratopatías de grado 3. En estos casos, en los que existe una importante pérdida tisular, la aplicación de suero autólogo a una mayor concentración, o de los derivados plaquetarios o del plasma rico en factores de crecimiento, podría resultar más efectiva que la aplicación de suero autólogo al 20%, debido a su mayor efecto sobre la proliferación celular (AU)


Objective: To evaluate the effectiveness of 20% autologous serum as a treatment for neurotrophic keratopathy. Material and methods: A longitudinal, observational and descriptive study was performed on 19 patients (22 eyes) with neurotrophic keratopathy in different stages of Mackie's classification. The following variables were evaluated on the first visit, and then 4 months later: best corrected visual acuity (BCVA), subjective patient symptomatology (faces scale), Schirmer's test without anesthesia (mm), tear film break-up time (BUT) (sg) and healing of the epithelial defect (weeks). The Wilcoxon signed-rank test was used for the statistical analysis of the data. Results: A symptomatic improvement was observed in 100% of the cases, and a 71% improvement in best corrected visual acuity (P < 0.05). There was also a statistically significant improvement in the Schirmer's test and BUT (P <0 .05). Healing of epithelial defect occurred in 71% of the cases within 6 weeks, and in 91% of the cases within 12 weeks of treatment. The remaining 9% of the cases that did not heal had a grade 3 neurotrophic keratopathy. Conclusions: The use of 20% autologous topical serum represents an effective treatment for grades 1 and 2 neurotrophic keratopathy, but is an insufficient treatment for a grade 3 keratopathy. In cases where there is a significant loss of tissue, the application of a higher concentration of autologous serum, or platelet-rich derivatives, or plasma rich in growth factors, may be more effective than the application of 20% autologous serum, due to their greater effect on cell proliferation (AU)


Assuntos
Humanos , Ceratite/tratamento farmacológico , Autoantígenos/uso terapêutico , Úlcera da Córnea/tratamento farmacológico , Soros Imunes/administração & dosagem , Resultado do Tratamento
20.
Diabetes Technol Ther ; 15 Suppl 2: S2-13-S2-20, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23786294

RESUMO

Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic ß-cells, and as such it should respond to immunotherapy. George Eisenbarth gave many significant contributions to this field. He has been involved at some level in most immunotherapy trials during the past three decades. He was among the pioneers who attempted immunotherapy approaches in patients with recent-onset T1D. In the early 1980s he began studying relatives of those with the disease, leading to the concept that T1D was a chronic autoimmune disease, in which islet autoimmune responses would silently destroy ß-cells and cause progressive impairment of insulin secretion, years to months before a diagnosis was made. Consequently, he was one of the first to attempt immune intervention in people at high risk of T1D. Throughout his career he developed autoantibody assays and predictive models (which included metabolic testing and later genetics) to identify individuals at risk of T1D. He provided seminal intellectual contributions and critical tools for prevention trials. His focus on insulin as a critical autoantigen led to multiple prevention trials, including the Diabetes Prevention Trial-Type 1 (DPT-1), which studied both parenteral and oral insulin. In the DPT-1 Oral Insulin Trial, a cohort with higher levels of insulin autoantibodies was identified that appeared to have delayed disease progression. Type 1 Diabetes TrialNet is conducting a new trial to verify or refute this observation. Moreover, George identified and tested in the mouse small molecules that block or modulate presentation of a key insulin peptide and in turn prevent the activation of insulin-specific T-lymphocytes. Thus, we believe his greatest contribution is yet to come, as in the near future we should see this most recent work translate into clinical trials.


Assuntos
Autoanticorpos/efeitos adversos , Diabetes Mellitus Tipo 1/imunologia , Hipoglicemiantes/uso terapêutico , Imunoterapia , Insulina/uso terapêutico , Abatacepte , Animais , Anticorpos Monoclonais Murinos/uso terapêutico , Autoanticorpos/sangue , Autoantígenos/imunologia , Autoantígenos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Complexo CD3/efeitos dos fármacos , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/prevenção & controle , Modelos Animais de Doenças , Feminino , História do Século XX , História do Século XXI , Humanos , Imunoconjugados/uso terapêutico , Imunoterapia/métodos , Imunoterapia/tendências , Insulina/metabolismo , Anticorpos Anti-Insulina/imunologia , Secreção de Insulina , Células Secretoras de Insulina/imunologia , Masculino , Camundongos , Rituximab
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