Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
1.
Clin Exp Med ; 8(3): 171-3, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18791691

RESUMEN

Good syndrome (GS) is a rare adult-onset immunodeficiency disease characterised by hypogammaglobulinaemia and thymoma. Here we describe a 72-year-old male patient who was diagnosed with GS when he was 62, after a two-year history of recurrent respiratory infections. A chest CT scan showed a mediastinal mass which was surgically removed; its histology revealed a thymoma. The patient was hypogammaglobulinaemic and his clinical condition dramatically improved after starting an appropriate dosage of IVIG. Two years ago he developed a normochromic normocytic anaemia requiring several transfusions. A bone marrow biopsy revealed a myelodysplastic syndrome. The patient started cyclosporine and the anaemia gradually improved, achieving transfusion independence.


Asunto(s)
Síndromes de Inmunodeficiencia/diagnóstico , Síndromes Mielodisplásicos/diagnóstico , Anciano , Ciclosporina/uso terapéutico , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Masculino , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/tratamiento farmacológico
2.
Clin Exp Rheumatol ; 26(4): 574-81, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18799087

RESUMEN

OBJECTIVE: To verify whether synthetic cannabinoids (CP55,940 and WIN55,212-2) are able to exert an anti-inflammatory effect on rheumatoid fibroblast-like synoviocytes (FLS) by down-regulating cytokine production, and determine whether this effect could be mediated by CB1/CB2 cannabinoid receptors. METHODS: Interleukin-6 (IL-6) and interleukin-8 (IL-8) were assayed in the supernatant from cultured FLS by ELISA method before and after 3 hours of incubation with CP55,940 (10 microM) and WIN55,212-2 (10 microM). Co-stimulation of cells with the cannabinoid receptor antagonists was performed to evaluate receptor involvement in cytokine modulation. All the experiments were conducted in basal conditions and after 1 hour pre-incubation with 0.1 ng/ml IL-1beta. FLS expression of CB1 and CB2 receptor was studied by Western Blot analyses. RESULTS: Both CP55,940 and WIN55,212-2 induced a potent and significant reduction in IL-6 and IL-8 secretion from IL-1beta. stimulated FLS. Although FLS express CB1 and CB2 receptor, cannabinoid receptor antagonists did not significantly modify the inhibition of cytokines secretion induced by CP55,940 and WIN55,212-2. CONCLUSIONS: In vitro, CP55,940 and WIN55,212-2 exert a potent anti-inflammatory effect on rheumatoid FLS via a non-CB1/CB2 receptor mediated mechanism.


Asunto(s)
Antiinflamatorios/farmacología , Artritis Reumatoide/inmunología , Benzoxazinas/farmacología , Ciclohexanoles/farmacología , Fibroblastos/efectos de los fármacos , Morfolinas/farmacología , Naftalenos/farmacología , Membrana Sinovial/efectos de los fármacos , Anciano , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Estudios de Cohortes , Femenino , Fibroblastos/inmunología , Fibroblastos/metabolismo , Humanos , Técnicas In Vitro , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/metabolismo , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB2/metabolismo , Membrana Sinovial/inmunología , Membrana Sinovial/metabolismo
3.
Clin Exp Med ; 6(1): 38-44, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16550343

RESUMEN

The aim of this study was to evaluate the presence of an imbalance between proinflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We considered two groups of 26 and 28 patients with acute myocardial infarction (AMI) and unstable angina (UA) respectively, compared with a group of 30 patients with stable angina and 30 healthy volunteers. We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)gamma and tumour necrosis factor (TNF)alpha, which are well known to possess proinflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity. We also assessed the clinical characteristics of groups and, particularly, we evaluated the circulating levels of C-reactive protein (hs-CRP). We found a significant increase of IFNgamma and TNFalpha production (P<0.01) and a significant decrease of IL10 production (P<0.05) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes where found between AMI and UA patients and SA patients and controls. Circulating levels of hs-CRP were significantly increased (P<0.01) in patients with ACS compared with the other control groups. Our data showed an increased production of proinflammatory mediators in ACS that may be detectable both in circulating blood and in cell cultures where it is possible to evaluate in a better way the functional state of cells; this finding was associated with a reduced production of the antiinflammatory cytokine IL10. In conclusion, a relevant imbalance is present in ACS and this fact could contribute to plaque instability and clinical manifestations.


Asunto(s)
Angina Inestable/inmunología , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Monocitos/inmunología , Infarto del Miocardio/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Enfermedad Aguda , Anciano , Angina Inestable/metabolismo , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Infarto del Miocardio/metabolismo
4.
Artículo en Inglés | MEDLINE | ID: mdl-16095891

RESUMEN

Iloprost, a stable prostacyclin analogue, regulates expression of genes that are involved in inflammation and in cell growth and inhibits the in vitro production of cytokines. We evaluated the effect of an in vivo weekly iloprost treatment on TNF-alpha and IL6 monocyte production (evaluated by ELISA), on monocyte apoptosis (Annexin V/uptake of propidium iodide by flow cytometry) and on peripheral blood mononuclear cell (PBMC) TNF-alpha receptors (TNF-RI and TNF-RII) mRNA expression (RT-PCR) in 14 atherosclerotic critical limb ischemia patients. PBMC were stimulated with LPS for 24h. TNF-alpha production was significantly reduced by iloprost whereas IL6 production was not affected. Iloprost did not accelerate monocyte apoptosis. TNF-RI mRNA expression was not modified by iloprost, whereas TNF-RII mRNA expression was significantly reduced. Our data show that iloprost may have anti-inflammatory effects in addition to the well-known vasodilatatory and anti-aggregant ones.


Asunto(s)
Iloprost/uso terapéutico , Interleucina-6/metabolismo , Isquemia/tratamiento farmacológico , Extremidad Inferior/irrigación sanguínea , Receptores Tipo II del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa , Anciano , Anciano de 80 o más Años , Antiinflamatorios/uso terapéutico , Apoptosis/efectos de los fármacos , Células Cultivadas , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Isquemia/metabolismo , Masculino , Monocitos/efectos de los fármacos , Monocitos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Receptores Tipo II del Factor de Necrosis Tumoral/antagonistas & inhibidores , Receptores Tipo II del Factor de Necrosis Tumoral/genética , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo
5.
Br J Dermatol ; 153(1): 59-65, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16029327

RESUMEN

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation. Extracorporeal photopheresis (ECP) has recently been introduced as an alternative treatment for cases of cGVHD refractory to conventional immunosuppressive treatment, but its mechanism of action is not yet clear. OBJECTIVES: To investigate in seven patients with cGVHD the effects of ECP on resistance of monocytes to apoptosis and on monocyte cytokine production. METHODS: We designed an in vitro model that could mimic the potential in vivo effect of reinfusion of peripheral blood mononuclear cells treated by ECP. The model was based on coculture of ECP-treated lymphocytes with untreated monocytes from the same patient. RESULTS: ECP did not accelerate spontaneous apoptosis of monocytes. However, ECP-treated monocytes produced increased amounts of interleukin (IL)-12. In contrast, IL-12 production by monocytes did not increase in cocultures, but IL-10 production was upregulated. CONCLUSIONS: These results suggest that reinfusion of large numbers of autologous apoptotic lymphocytes is significant for the therapeutic outcome of ECP through upregulation of IL-10, which is an immunosuppressive cytokine.


Asunto(s)
Enfermedad Injerto contra Huésped/tratamiento farmacológico , Interleucina-10/biosíntesis , Interleucina-12/biosíntesis , Monocitos/inmunología , Fotoféresis , Adulto , Apoptosis , Células Cultivadas , Enfermedad Crónica , Técnicas de Cocultivo , Femenino , Enfermedad Injerto contra Huésped/inmunología , Humanos , Linfocitos/inmunología , Masculino , Monocitos/patología
6.
Arch Dermatol Res ; 295(5): 175-82, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12883827

RESUMEN

Chronic graft-versus-host disease (cGVHD) is a severe and frequent complication of allogenic bone marrow transplantation which is often treated with extracorporeal photochemotherapy (ECP) with a positive clinical outcome in patients resistant to conventional protocols. The mechanism of action of ECP has not been fully elucidated, although several authors have reported that it is able to induce apoptosis. Using samples obtained from ten cGVHD patients, we sought to determine whether lymphocytes treated with ECP underwent apoptosis and, above all, the mechanisms involved. Lymphocytes at four stages were isolated: immediately before ECP, from the last buffy coat collected, after UV irradiation prior to reinfusion, and the day after ECP. When cultured for 48 h, lymphocytes treated with ECP underwent accelerated apoptosis (tested as annexin V binding cells and as intracellular histone-associated DNA fragments) in comparison with lymphocytes from the other samples. This enhanced programmed cell death could not be prevented by IL-2. Immediately after isolation, there was no difference in Bcl-2 or bax expression among the four different samples, or in Fas and FasL mRNA. However, when cultured, lymphocytes treated with ECP showed a rapid downregulation of Bcl-2, an upregulation of bax with an increased bax/Bcl-2 ratio, a decrease in bcl-2 mRNA and an increase in Fas. No changes were detectable in lymphocytes from the other samples. IL-2 and TNF-alpha production was not significantly different among lymphocytes from the four samples. In conclusion, in patients affected by cGVHD, ECP induced apoptosis of lymphocytes with the involvement of both the Fas/FasL system and the Bcl-2 protein family.


Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/terapia , Linfocitos/citología , Glicoproteínas de Membrana/metabolismo , Fotoféresis , Receptor fas/metabolismo , Adulto , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Células Cultivadas , Enfermedad Crónica , Regulación hacia Abajo/efectos de los fármacos , Proteína Ligando Fas , Femenino , Expresión Génica/efectos de los fármacos , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/metabolismo , Humanos , Interleucina-2/metabolismo , Linfocitos/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Proteína X Asociada a bcl-2
7.
Clin Exp Med ; 3(1): 37-44, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12748878

RESUMEN

Recent studies have shown that inflammation plays a major role in coronary plaque destabilization and in the induction of thrombosis in acute coronary syndromes. The aim of this study was to evaluate circulating lymphocyte activation and apoptosis in patients with non-ST elevation myocardial infarction (NSTEMI) in comparison with subjects with stable angina and with age-matched healthy controls. We considered T cell subpopulations, T cell surface HLA-DR and CD69 expression (evaluated by flow cytometry), lymphomonocyte spontaneous apoptosis (evaluated by ELISA), and IL2 production (evaluated by ELISA) in peripheral blood within 6 hours of onset of NSTEMI. We also investigated Fas expression on T cells (evaluated by flow cytometry) and FasL mRNA (evaluated by RT-PCR), as well as Fas functionality. In NSTEMI patients we found a significant increase of HLADR+ CD3+ and CD69+CD4+ cells. Spontaneous apoptosis was significantly increased in NSTEMI patients in comparison with the two control groups and was associated with an increased expression of Fas, an increased susceptibility to Fas agonist (CH11), and a normal production of IL2 in cell cultures. These data suggest that the enhanced apoptosis is due to a mechanism of "active" antigen-driven death, induced by the expression of death cytokines and not by the failure of cell growth factors. We conclude that peripheral lymphocytes are activated in NSTEMI and undergo an enhanced programmed cell death due to activation mechanisms. It is likely that lymphocyte activation occurs before the onset of acute ischemia and contributes to the plaque rupture and to the myocardial ischemic insult.


Asunto(s)
Apoptosis/inmunología , Activación de Linfocitos , Infarto del Miocardio/inmunología , Linfocitos T/inmunología , Secuencia de Bases , Cartilla de ADN , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Inmunofenotipificación , Infarto del Miocardio/fisiopatología , Receptor fas/inmunología
8.
Transpl Immunol ; 10(4): 269-75, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12507398

RESUMEN

Apoptosis plays a major role in tissue transplantation because intact T-cell-apoptosis pathways are required for the induction of tolerance to allografts. Moreover, immunosuppressive agents commonly used in clinical transplantation medicine promote lymphocyte apoptosis inhibiting the expression and production of cytokines involved in lymphocyte survival. The aim of our study was to evaluate peripheral blood mononuclear cells (PBMC) spontaneous apoptosis in patients undergoing chronic immunosuppressive treatment after cardiac transplantation. PBMC obtained from patients (n = 31) and controls matched for age and sex (n = 25) were cultured for 72 h and apoptosis was evaluated by quantification of fragmented DNA, staining with Hoechst 33258 dye and annexin V binding. We also investigated Fas expression and FasL mRNA expression as well as the ability of an IgM anti-Fas antibody to induce apoptosis. Finally, we evaluated IL2 production induced by PHA and the ability of IL2 to prevent apoptosis. In patients, PBMC underwent enhanced spontaneous apoptosis in comparison with controls. However, we could not find any difference between patients and normals as regards the expression of Fas and of FasL mRNA, even if the cross-linking of the Fas molecule induced apoptosis in PBMC from patients, whereas it failed to induce cell death in normals. We also found that IL2 production was significantly decreased in patients and that the addition of IL2 to the culture medium reduced PBMC spontaneous apoptosis. Our findings suggest that in cardiac transplanted patients PBMC undergo enhanced spontaneous apoptosis, which may contribute to prevent allograft rejection.


Asunto(s)
Apoptosis/efectos de los fármacos , Trasplante de Corazón , Inmunosupresores/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Adulto , Anciano , Supervivencia Celular , Proteína Ligando Fas , Humanos , Interleucina-2/biosíntesis , Leucocitos Mononucleares/fisiología , Glicoproteínas de Membrana/fisiología , Persona de Mediana Edad , ARN Mensajero/análisis , Receptor fas/fisiología
11.
Nutr Metab Cardiovasc Dis ; 10(3): 137-42, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11006922

RESUMEN

BACKGROUND AND AIM: Inflammatory and lipid factors share an important role in atherosclerosis. This study evaluates their relations in dyslipidemic subjects. METHODS AND RESULTS: We compared the complement system (serum hemolytic activity CH50, C3 and C4 fractions and terminal complex sC5b-9) in 30 hypercholesterolemic patients with elevated cholesterol and decreased HDL-cholesterol levels, 30 normolipemic patients with clinical atherosclerosis and 30 matched normal subjects. In addition we evaluated the circulating immune complexes containing cholesterol (chol-CIC) on the assumption that they might be important in complement activation, and the circulating levels of the adhesion molecule ICAM-1 (sICAM-1) as a sign of endhotelial dysfunction. We found a significant increase of sC5b-9 (but not of CH50 and C3, C4) in the hypercholesterolemics compared with the other groups. The plasma sC5b-9 level was inversely and significantly related to HDL-chol (regression analysis), whereas no direct significant relation was found between sC5b-9 and cholesterol. Chol-CIC were also significantly increased in this group. The atherosclerosis patients also presented a significant increase of sC5b-9. Lastly, both patient groups displayed a significant increase of sICAM-1. CONCLUSIONS: We suggest that complement activation in dyslipidemics may be induced by their increased immune complexes. However, the decrease of complement regulatory proteins carried by HDL is another important factor, while complement changes may be related to variations of other humoral and cell systems (endothelium, coagulative/fibrinolytic system), whose involvement is suggested in our study by the changes of sICAM-1.


Asunto(s)
Arteriosclerosis/sangre , Activación de Complemento , Hipercolesterolemia/sangre , Adulto , Anciano , Arteriosclerosis/inmunología , Arteriosclerosis/fisiopatología , Colesterol/sangre , Femenino , Humanos , Hipercolesterolemia/inmunología , Hipercolesterolemia/fisiopatología , Masculino , Persona de Mediana Edad
12.
Int J Clin Lab Res ; 30(3): 147-56, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11196073

RESUMEN

Thrombosis is a complication of atherosclerosis and monocytes play a determinant role either in the progression of atherosclerotic plaque or in blood coagulation by way of tissue factor expression. Platelets play a direct role in thrombosis and a hyperfunctional state has been described in hypercholesterolemic subjects. Moreover, platelets seem to be able to enhance monocyte activity. Cholesterol-lowering molecules (statins) are reported to reduce cardiovascular risk, either by decreasing the circulating level of cholesterol or by non-lipidic actions such as the reduction of monocyte and platelet activity. The aim of our study was to investigate the influence of platelets on the expression of tissue factor by monocytes and the effect induced by cerivastatin. We measured tissue factor levels by ELISA and the procoagulant activity of stimulated monocytes by a clotting assay on cellular preparations and whole blood in 40 hypercholesterolemic subjects (22 male, 18 female, mean age 52.7 +/- 12 years, total cholesterol 251.6 +/- 19.9 mg/dl) before and after cerivastatin addition. Tissue factor expression was enhanced in hypercholesterolemic subjects compared with normal subjects (31.6 +/- 7.6 vs. 23 +/- 5.8 pg/cells, P < 0.01). The presence of platelets increased the amount of tissue factor (55.3 +/- 7.3 pg/cells, P < 0.001) and cerivastatin reduced the expression of tissue factor in isolated monocytes, in the mixed cellular system, and in whole blood (19.6 +/- 4.1 pg/cells, P < 0.001). In conclusion, tissue factor expression by monocytes is enhanced in hypercholesterolemic subjects compared with normal controls. Platelets enhance monocyte production of tissue factor, and cerivastatin is able to counteract this prothrombotic mechanism.


Asunto(s)
Plaquetas/efectos de los fármacos , Hipercolesterolemia/sangre , Monocitos/efectos de los fármacos , Piridinas/farmacología , Tromboplastina/metabolismo , Adulto , Plaquetas/fisiología , Colesterol/sangre , HDL-Colesterol/sangre , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hipercolesterolemia/tratamiento farmacológico , Técnicas In Vitro , Lipopolisacáridos/farmacología , Masculino , Persona de Mediana Edad , Monocitos/fisiología , Tromboplastina/inmunología , Triglicéridos/sangre
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA