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2.
Lupus ; 19(2): 213-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19965944

RESUMO

The objective of this study was to investigate the efficacy and safety of anti-CD20 treatment in Hispanic patients with refractory systemic lupus erythematosus and to determine whether baseline parameters predict disease flare. Fifty-two patients with systemic lupus erythematosus, 13 with active lupus nephritis, eight with thrombocytopenia, three with leukocytopenia, 25 with severe musculoskeletal involvement and three with skin involvement) refractory to conventional therapy were treated with anti-CD20 treatment (rituximab; MabThera, Roche) plus ongoing immunosuppressive treatment. Disease activity was assessed monthly using the SLEDAI validated for the Mexican population with a follow-up period of 6 months. At 6 months of follow-up, significant clinical improvements were detected, with a reduction in the global SLEDAI validated for the Mexican population score. Five of the 13 patients with lupus nephritis (38.4%) had a complete renal response and five (38.4%) had a partial response. Rituximab was also effective in patients with autoimmune thrombocytopenia, inducing a significant increase in platelet counts (p = 0.012). Nineteen of 25 patients with severe musculoskeletal involvement had remission of arthritis. Only one of the three patients with skin involvement had no lesions at 6 months. Rituximab treatment also allowed a reduction of the oral prednisone dose in the majority of patients. No baseline predictors of flare were found. Treatment was discontinued after the first infusion in two patients due to serum sickness and in another due to pulmonary infection. In conclusion, the addition of rituximab to conventional immunosuppressive therapy may be an effective strategy for lupus nephritis, autoimmune thrombocytopenia and inflammatory polyarthritis in patients with refractory systemic lupus erythematosus.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD20/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Murinos , Antígenos CD20/imunologia , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacologia , Imunossupressores/uso terapêutico , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
3.
Histol Histopathol ; 24(6): 789-99, 2009 06.
Artigo em Inglês | MEDLINE | ID: mdl-19337976

RESUMO

Cell migration and adhesion are cytoskeleton- dependent functions that play a key role in epithelial physiology. Specialized epithelial cells in water transport have specific microfilament rearrangements that make these cells adopt a polyhedral shape, forming a sealed monolayer which functions as permeability barrier. Also, specific polarized microfilament phenotypes are formed at the front and the rear of migratory epithelial cells. In pathological processes such as cancer, increased migration occurs in invasive cells driven by the formation of polarized and differential microfilament phenotypes. Melatonin, the main product secreted by the pineal gland during dark phase of the photoperiod, acts as a cytoskeletal modulator in normal and cancer cells. In this paper we will summarize evidence supporting that melatonin acts as a microfilament modulator in epithelial MDCK cells, and we will describe its effects on cytoskeleton organization involved in the mechanism by which melatonin synchronizes water transport. In addition, we will review recent data that indicate that melatonin is able to switch microfilament phenotypes in MCF-7 human mammary cancer cells, from invasive migratory cells to dormant microfilament phenotypes that occur in non- migratory cells. Moreover, we will discuss the implications of the cytoskeleton as therapeutic target for cancer cells.


Assuntos
Citoesqueleto de Actina/metabolismo , Adesão Celular/fisiologia , Movimento Celular/fisiologia , Células Epiteliais/metabolismo , Melatonina/metabolismo , Invasividade Neoplásica , Animais , Citoesqueleto/metabolismo , Humanos , Neoplasias/metabolismo , Fenótipo
4.
Lupus ; 15(9): 600-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17080916

RESUMO

CD55 and CD59 are glycophosphatidylinositol-anchored proteins with complement inhibitory properties. Lymphopenia in systemic lupus erythematosus (SLE) has been associated with autoantibodies targeting nuclear antigens. The aim of this study was to evaluate the surface density of CD55 and CD59 in T and B lymphocytes from patients with SLE and lymphopenia and its possible correlation with the presence of common SLE autoantibodies. Flow cytometric analyses were performed on CD55 and CD59 stained CD3+ and CD19+ cells from 40 SLE patients, 30 with lymphopenia and 10 without it, and 25 healthy controls. Autoantibodies were detected in the sera by enzyme linked immunosorbent assay. The mean fluorescence intensity of CD55 and CD59 in T and B cells was significantly diminished in SLE patients with lymphopenia when compared with healthy subjects. Interestingly, the opposite was found in T and B cells from non-lymphopenic SLE patients. Although there was no correlation between CD55 and CD59 surface density and the presence of any specificity of the autoantibodies tested, higher titres of anti-dsDNA, anti-SM and anti-ribosomal p antibodies were significantly associated with lymphopenia. The deficiency of CD55 and CD59 expression may play a role in the pathophysiology of lymphopenia, most likely by increasing the susceptibility of cells to complement mediated cytolysis.


Assuntos
Linfócitos B/metabolismo , Antígenos CD55/biossíntese , Antígenos CD59/biossíntese , Lúpus Eritematoso Sistêmico/metabolismo , Linfopenia/metabolismo , Linfócitos T/metabolismo , Adulto , Anticorpos Antinucleares/metabolismo , Antígenos CD19/metabolismo , Complexo CD3/metabolismo , Estudos de Casos e Controles , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Testes Sorológicos
5.
Reumatol. clín. (Barc.) ; 1(2): 121-128, jul.-ago. 2005. ilus
Artigo em Inglês | IBECS | ID: ibc-77504

RESUMO

El sistema inmunitario se caracteriza principalmente por la capacidad de distinguir lo propio de lo extraño. En el intestino, el sistema inmunitario no sólo comparte esta propiedad, sino que es, además, apto para seleccionar los componentes nutritivos y/o benéficos de aquellos que pueden ser nocivos. Si se considera que el intestino es colonizado por bacterias comensales que contribuyen a la digestión y al control del crecimiento de microorganismos patógenos, no es sorprendente que sea la superficie mucosa el más extenso y, acaso, el más sofisticado de los compartimientos del sistema inmunitario. Así, las respuestas innata y adaptativa se suman a estructuras, células y mecanismos exquisitamente especializados, tales como el epitelio intestinal, las placas de Peyer, las células M, entre otros, que en conjunto son responsables del control dinámico de la homeostasis entre el intestino y su flora. La presente revisión versa sobre algunos conceptos populares sobre el aparato digestivo y hace hincapié en el papel del intestino como órgano inmunitario(AU)


The immune system is characterized by the ability to distinguish self from non-self. The intestinal immune system bears this latter property but, furthermore, it must discriminate among nutritious and beneficial substances from toxic or harmful ones. Considering that the gut has to be colonized by commensal bacteria participating in digestion as well as in the control of pathogen microorganisms, it is not surprising that mucosal surfaces are the largest and probably the most exquisitely specialized immune system’s compartment. This means that not only innate and adaptive immunity are present, but further, particular structures, cells, and mechanisms such as physical barrriers, epithelia, Peyer’s patches, M cells among others, which together are involved in the dynamic control of the homeostasis between gut and its flora. The present review deals with some popular conceptions about the digestive system with particular emphasis on the gut’s immunology(AU)


Assuntos
Humanos , Intestinos/imunologia , Sistema Imunitário/fisiologia , Mucosa Intestinal/imunologia , Probióticos/análise , Nódulos Linfáticos Agregados/imunologia
6.
Reumatol Clin ; 1(2): 121-8, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21794247

RESUMO

The immune system is characterized by the ability to distinguish self from non-self. The intestinal immune system bears this latter property but, furthermore, it must discriminate among nutritious and beneficial substances from toxic or harmful ones. Considering that the gut has to be colonized by commensal bacteria participating in digestion as well as in the control of pathogen microorganisms, it is not surprising that mucosal surfaces are the largest and probably the most exquisitely specialized immune system's compartment. This means that not only innate and adaptive immunity are present, but further, particular structures, cells, and mechanisms such as physical barrriers, epithelia, Peyer's patches, M cells among others, which together are involved in the dynamic control of the homeostasis between gut and its flora. The present review deals with some popular conceptions about the digestive system with particular emphasis on the gut's immunology.

7.
Transplant Proc ; 36(6): 1661-3, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15350444

RESUMO

UNLABELLED: The aim of this study was to explore differences in the cytokine profile among de novo kidney transplant recipients treated with either Rapamycin (Rapa) + cyclosporine (CsA) + prednisone (P) or CsA + azathioprine (Aza) + P. PATIENTS AND METHODS: Among the 13 adult kidney transplant recipients studied, seven received Rapa + CsA + P while the remaining six received CsA + Aza + P with their living donors serving as controls (n = 13). Spontaneous production of IL-2, IFNgamma, IL-10, and TGF-beta were measured by ELISA in supernatants from 24-hour cultured unstimulated peripheral blood mononuclear cell (PBMC) at time zero (the day before the transplant), and at 3 and 6 months posttransplant. Cytokines were also measured 1 month after CsA withdrawal in the Rapa + CsA + P group. RESULTS: From time zero to the end of the study, IL-2, IFNgamma, and IL-10 were present at low or undetectable levels in all three groups. TGF-beta tended to increase in supernatants from patients under Rapa + CsA + P at 6 months posttransplant and at 1 month after CsA withdrawal without correlation to Rapa blood levels. TGF-beta remained stable throughout the study period for patients included in the CsA + Aza + P group. There was no difference in this cytokine level between these study groups at any given time. CONCLUSIONS: This study showed no differences in the spontaneous cytokine profiles evaluated in patients treated with both therapeutic schemes.


Assuntos
Citocinas/sangue , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Sirolimo/uso terapêutico , Adulto , Azatioprina/uso terapêutico , Ciclosporina/sangue , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Humanos , Imunossupressores/sangue , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-2/sangue , Prednisona/uso terapêutico , Sirolimo/sangue , Fator de Crescimento Transformador beta/metabolismo
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