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1.
Reumatismo ; 76(3)2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39282775

RESUMO

OBJECTIVE: The aim of the current study was to compare the clinical and treatment characteristics and dimensions of health-related quality of life between female and male patients with axial spondyloarthritis (SpA) and psoriatic arthritis (PsA). METHODS: The present study is cross-sectional and comprises 119 patients with axial SpA and 198 patients with PsA. Clinical data were collected by standardized and self-reported instruments. Disease activity was evaluated by the Ankylosing Spondylitis Disease Activity Score with C-reactive protein and the Disease Activity in PSoriatic Arthritis (for SpA and PsA, respectively). Health-related quality of life was assessed with the Medical Outcomes Study 36-item Short Form Survey. Patients were stratified by gender, and the socio-demographic, clinical, and quality-of-life data were compared. RESULTS: Women with axial SpA and PsA had significantly lower education (p<0.001, p=0.004, respectively) and higher disease activity (p<0.001, p=0.003, respectively). Female patients with axial SpA were more frequently under second-line therapy (p=0.026) and glucocorticoid treatment (p=0.005), while women with PsA had more radiographic progression (p=0.006). Female patients with axial SpA and PsA had worse scores in the dimensions of quality of life regarding physical role, bodily pain, vitality, and mental health. Women with axial SpA had lower scores in general health, while women with PsA had lower scores in physical and social functioning. CONCLUSIONS: Women with axial SpA and PsA had worse scores than men in most clinical and treatment characteristics and health-related quality of life dimensions.


Assuntos
Artrite Psoriásica , Espondiloartrite Axial , Qualidade de Vida , Humanos , Feminino , Masculino , Artrite Psoriásica/psicologia , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Fatores Sexuais , Índice de Gravidade de Doença
2.
Reumatismo ; 75(1)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37154254

RESUMO

Psoriatic arthritis (PsA) is an inflammatory disease characterized by peripheral and axial involvement. Biological disease-modifying antirheumatic drugs (bDMARDs) are the mainstream treatment for PsA and bDMARDs retention rate is a proxy for the drug's overall effectiveness. However, it is unclear whether IL-17 inhibitors can have a higher retention rate than tumor necrosis factor (TNF) inhibitors, in particular in axial or peripheral PsA. A real-life observational study was conducted on bDMARD naïve PsA patients initiating TNF inhibitors or secukinumab. Time-to-switch analysis was carried out with Kaplan-Meyer curves (log-rank test) truncated at 3 years (1095 days). Sub-analyses of Kaplan-Meyer curves between patients presenting with prevalent peripheral PsA or prevalent axial PsA were also conducted. Cox regression models were employed to describe predictors of treatment switch/swap. Data on 269 patients with PsA naïve to bDMARD starting either TNF inhibitors (n=220) or secukinumab (n=48) were retrieved. The overall treatment retention at 1 and 2 years was similar for secukinumab and TNF inhibitors (log-rank test p NS). We found a trend towards significance in the Kaplan-Meyer at 3 years in favor of secukinumab (log-rank test p 0.081). Predominant axial disease was significantly associated with a higher chance of drug survival in secukinumab users (adjusted hazard ratio 0.15, 95% confidence interval = 0.04-0.54) but not in TNF inhibitor users. In this real-life, single-center, study on bDMARD naïve PsA patients, axial involvement was associated with longer survival of secukinumab but not of TNF inhibitors. Drug retention of secukinumab and TNF inhibitors were similar in predominantly peripheral PsA.


Assuntos
Antirreumáticos , Artrite Psoriásica , Humanos , Artrite Psoriásica/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Resultado do Tratamento
3.
Reumatismo ; 62(4): 253-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21253618

RESUMO

OBJECTIVE: Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. The -174G>C interleukin-6 (IL-6) promoter polymorphism was investigated in RA patients treated with rituximab (RTX), being IL-6 a key cytokine for B cell survival and proliferation, thus possibly implicated in rituximab efficacy. METHODS: The study was conducted in a real-life retrospective cohort of 142 unselected RA patients (120F/22M) treated with RTX and referred to 7 rheumatologic centres in the north of Italy. One hundred and thirteen (79.6%) patients were rheumatoid factor (RF)-positive and 112 (78.9%) were anti-CCP antibodies positive. The response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR criteria (DAS28) and the ACR criteria. The IL-6 -174G>C promoter polymorphism was analyzed by RFLP following previously reported methods. RESULTS: Lack of response to RTX at month +6 by EULAR criteria was more prevalent in RA patients with the IL-6 -174 CC genotypes (9/21, 42.8%), than in the GC/GG patients (23/121, 19.0%) (OR 3.196, 95% CI=1.204-8.485; p=0.0234). Similar results were found when evaluating the response by ACR criteria. No differences were found in RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status according to the different IL-6 -174 genotypes. CONCLUSION: IL-6 promoter genotyping may be useful to better plan treatment with RTX in RA. Larger replication studies are in course to confirm these preliminary results.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Interleucina-6/genética , Polimorfismo Genético , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab
4.
Reumatismo ; 60(3): 221-3, 2008.
Artigo em Italiano | MEDLINE | ID: mdl-18854885

RESUMO

The authors report two cases of active seropositive rheumatoid arthritis who were treated in an early phase of the disease with infliximab plus methotrexate obtaining a clinical remission. The benefit was maintained after the discontinuation of the anti-TNF alpha inhibitor for adverse events, indicating that the early administration of the drug may be followed by a sustained remission.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adulto , Anticorpos Monoclonais/administração & dosagem , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Indução de Remissão
5.
Reumatismo ; 60(2): 136-40, 2008.
Artigo em Italiano | MEDLINE | ID: mdl-18651059

RESUMO

Chikungunya is an arboviral disease transmitted by Aedes mosquitoes. The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia, that can persist for months. Chikungunya virus, a member of the genus Alphavirus, has recently caused a large outbreak on islands in the Indian Ocean and on the Indian subcontinent. The ongoing outbreak has involved more than 1.5 million patients, including travellers who have visited these areas. We describe our casistic of six travellers with Chikungunya arthropathy. All patients experienced fever and rash of short term during a travel in areas of epidemicity. All patients had peripheral poliarthralgias, which duration was >2 months in 4 cases (66%) and >6 months in 1 case (16%).


Assuntos
Infecções por Alphavirus , Artrite/virologia , Vírus Chikungunya , Adulto , Infecções por Alphavirus/diagnóstico , Artrite/diagnóstico , Feminino , Humanos , Masculino , Viagem
6.
Clin Rheumatol ; 37(2): 315-321, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28980085

RESUMO

To assess the long-term effectiveness and safety of tocilizumab, abatacept, and tumor necrosis factor-α inhibitors (TNFi), in the Italian real-world setting of rheumatoid arthritis (RA). The records of adult RA patients from the Italian biologics' registry Gruppo Italiano Studio Early Arthritis (GISEA) were analyzed. Demographic and clinical data were obtained at entry. The disease remission rate (28-joint disease activity score calculated using the erythrocyte sedimentation rate [DAS28-ESR] ≤ 2.6) and frequency of adverse events (AEs) were evaluated at 2 years. From 1999 to 2014, 7539 patients were treated with biologics (61.3% in first- and 22.6% in second-line), 68% of cases received TNFi, 9.1% tocilizumab, and 8.6% abatacept. Treatment groups showed a similar DAS28 at entry. As first-line, tocilizumab induced a significantly higher remission rate than abatacept or TNFi at 6 (51 vs 23.3 and 26.2%, respectively; p < 0.0001) and 24 months (52.3 vs 33.3 and 34.4%, respectively; p < 0.01). A similar pattern was observed in later lines. The most common AEs reported were infections, reactions to biologics (more frequent among TNFi-treated patients), increased transaminase (more frequent among TCZ-treated patients), and cardiovascular events. In clinical practice, TCZ induced a rapid and long-lasting remission and in a higher percentage of patients compared to abatacept and TNFi, with a good safety profile.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Abatacepte/efeitos adversos , Abatacepte/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Indução de Remissão/métodos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
8.
ACS Appl Mater Interfaces ; 8(33): 21832-8, 2016 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-27505445

RESUMO

Click thiol-ene chemistry is demonstrated for the reaction of thiol containing molecules with surface alkene bonds during electrical discharge activation. This plasmachemical reaction mechanism is shown to be 2-fold for allyl mercaptan (an alkene and thiol group containing precursor), comprising self-cross-linked nanolayer deposition in tandem with interfacial cross-linking to the surface alkene bonds of a polyisoprene base layer. A synergistic multilayer structure is attained which displays high wet electrical barrier performance during immersion in water.

9.
J Hypertens ; 16(5): 585-92, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9797169

RESUMO

BACKGROUND: We recently demonstrated that arachidonic:linoleic acid ratio of erythrocytes of essential hypertension patients is greater than normal. OBJECTIVE: To investigate fatty acid composition, capability for adhesion to biological substrate and expression of beta2 integrins of leucocytes obtained from peripheral blood and skin window exudate of essential hypertension patients. DESIGN: Neutrophil activation state was evaluated by reproducing the various conditions occurring in vivo during the life of the cell (i.e. under the 'resting' condition, such as in peripheral blood, and 'primed' condition, such as after transmigration through the endothelium and after administration of specific chemo-attractants). Because both peripheral blood and skin window leucocytes of the subjects were obtained on the same day, we could be sure that there had been no dietary influences on changes in levels of fatty acid. Thus, the observed changes should reliably reflect the metabolic rate of utilization of fatty acids coupled to the activation and migration of cells. RESULTS: Leucocytes from essential hypertension patients were richer in arachidonic acid than were the corresponding cells from normotensive subjects; this difference was also evident for functionally activated skin window leucocytes, in spite of there having been a greater loss of poly-unsaturated fatty acids and arachidonic acid after migration. Moreover, a greater than normal arachidonic acid:linoleic acid ratio was shown for the first time to apply for leucocytes of essential hypertension patients, so extending our previous findings on the erythrocytes. Leucocytes from essential hypertension patients, collected both from peripheral blood and from skin window exudate, proved far more adhesive than the corresponding cells from age-matched and sex-matched controls, but this was not associated with a quantitative hyperexpression of beta2 integrins. CONCLUSIONS: The results suggest that an increase in availability of arachidonic acid in leucocytes could be a further expression of the generalized disturbance of fatty acid levels associated with essential hypertension and that a condition of hyperadhesion of neutrophils could occur spontaneously in vivo during the course of hypertension.


Assuntos
Ácido Araquidônico/metabolismo , Hipertensão/sangue , Ativação de Neutrófilo , Neutrófilos/metabolismo , Neutrófilos/patologia , Adulto , Idoso , Adesão Celular , Células Cultivadas , Humanos , Pessoa de Meia-Idade
10.
Thromb Haemost ; 82(5): 1522-7, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10595648

RESUMO

To investigate the possible regulating role of omega-6 and of omega-3 fatty acids on platelet adhesiveness, we randomised 60 volunteers into three groups to take 20 ml (equivalent to 0.3 g omega-6, 3.6 g omega-3; omega-6/omega-3 ratio 0.1) per day of a fish oil supplement, or to take 25 g (equivalent to 1.5 g omega-6, 0.5 g omega-3; omega-6/omega-3 ratio 3) per day of a soy lecithin supplement, or to continue on their usual diet without any supplement (control group) for a period of 15 days. Platelet adhesion on fibrinogen-coated 96-well microtitre plates was evaluated in the resting condition and after stimulation with 2 microM ADP or 0.02 U/ml thrombin. Compared to the values before the experimental period, the fish oil group showed a significant reduction in stimulated adhesion (with ADP: from 18.8% to 15.6%, p<0.01; with thrombin: from 24.4% to 20.8%, p<0.005), whereas no difference was noted in the resting condition (from 3.6% to 3.5%, NS). In the soy lecithin group, platelet adhesion was increased in all test conditions (with ADP: from 18.7% to 23.2%, p<0.001; with thrombin: from 24.0% to 29.9% p<0.001; resting: from 3.5% to 6.6%, p<0.001). No significant changes were observed in the control group. A good correlation was found between platelet adhesion data and the changes in the platelet fatty acid omega-6/omega-3 ratio caused by the different supplementations. Our results indicate an inhibitory effect of fish oil rich in omega-3 fatty acids on stimulated human platelet adhesiveness and a stimulatory effect of soy lecithin rich in omega-6 fatty acids on resting and stimulated adhesion. They suggest moreover that the omega-6/omega-3 ratio is a determinant of platelet adhesion.


Assuntos
Gorduras na Dieta/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/farmacologia , Fosfatidilcolinas/farmacologia , Adesividade Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Difosfato de Adenosina/farmacologia , Adulto , Registros de Dieta , Ácidos Graxos Ômega-6 , Ácidos Graxos Insaturados/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Trombina/farmacologia
11.
Clin Exp Rheumatol ; 14(3): 243-7, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8809437

RESUMO

OBJECTIVE: To evaluate the modifications in the mechanical properties of the middle ear in rheumatoid arthritis by assessing its resonance frequency. METHODS: Thirty patients with rheumatoid arthritis (RA) aged 20 to 68 years (mean age 45.8 +/- 12.4 yrs) were investigated by multiple frequency tympanometry and their data were compared with those obtained in a control group of 48 subjects aged from 19 to 65 years. RESULTS: Normal values, calculated at the 95th percentile from the control group, ranged from 800 to 1250 Hz. Eleven RA patients (36.6%) displayed abnormal resonance values. These findings were monolateral in 9 patients and bilateral in 2 (in all a total of 13 ears). Nine out of 13 ears with abnormal multiple frequency tympanometry data were characterized by an increase in resonance and 4 by a decrease. CONCLUSION: These findings were attributed to abnormal acoustic impedence of the middle ear and indicate a possible involvement of the ossicular diarthroses in RA. Our study suggests that RA may involve the incudo-malleolar and incudo-stapedial joints, altering the ossicular mechanisms in response to static air pressure modifications.


Assuntos
Testes de Impedância Acústica , Artrite Reumatoide/fisiopatologia , Orelha Média/fisiopatologia , Adulto , Idoso , Audiometria de Tons Puros , Fenômenos Biomecânicos , Ossículos da Orelha/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Valores de Referência , Reflexo Acústico , Estatísticas não Paramétricas
12.
Clin Exp Rheumatol ; 13(5): 623-7, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8575141

RESUMO

OBJECTIVES: Several hypotheses have been proposed regarding the role of HLA-B27 antigen in the pathogenesis of the spondylarthropathies. METHODS: We studied some neutrophil functions in vivo in patients affected by ankylosing spondylitis or by reactive arthritis, with or without HLA-B27, and in healthy control subjects. In vivo neutrophil migration was investigated by Senn's skin window technique. An adhesion assay was also conducted and superoxide production was measured in circulating and migrating neutrophils after different stimuli. RESULTS: Neutrophil migration in vivo was higher in the HLA-B27 positive patients than in the controls, while no difference was found between the HLA-B27 negative patients and controls. Our data showed an increased response to formyl-methionyl-leucyl-phenylalanine by circulating neutrophils in the patients with ankylosing spondylitis, both HLA-B27 positive and negative, in comparison with all the other subjects. CONCLUSIONS: Our results revive the question of the role of HLA-B27 in the regulation of neutrophil migration; the reported in vivo priming of circulating neutrophils seems to be related to ankylosing spondylitis rather than to HLA-B27.


Assuntos
Movimento Celular/fisiologia , Antígeno HLA-B27/sangue , Neutrófilos/fisiologia , Espondilite Anquilosante/imunologia , Superóxidos/sangue , Adulto , Artrite Reativa/imunologia , Adesão Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/metabolismo , Estudos Retrospectivos , Espondilite Anquilosante/sangue
13.
Inflammation ; 17(1): 13-23, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7679371

RESUMO

Human neutrophils were isolated from blood and aseptic inflammatory exudates. The respiratory burst response was measured as superoxide (O2-) production by a microplate assay system and polarographically as oxygen consumption. Exudate cells exhibited a respiratory burst in response to n-formyl-methionyl-leucyl-phenyl-alanine (FMLP) that was two- to threefold higher than the burst exhibited by peripheral blood cells. The O2- production induced by substance P was also found to be fivefold higher in exudate cells, while the metabolic response to other stimulants such as concanavalin A (con A), phorbol-myristate acetate (PMA), NaF, and immunocomplexes was not primed. Serum-treated zymosan (STZ)-stimulated activity was primed by only 11%. In contrast, superoxide production in response to tumor necrosis factor-alpha (TNF) was decreased in exudate versus blood cells by about 50%. Therefore, the skin-window cells, compared to blood cells, appear to be at the same time primed, unmodified, and desensitized, according to the different stimulants employed.


Assuntos
Exsudatos e Transudatos/citologia , Neutrófilos/efeitos dos fármacos , Explosão Respiratória/efeitos dos fármacos , Concanavalina A/farmacologia , Humanos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/metabolismo , Consumo de Oxigênio , Técnica de Janela Cutânea , Fluoreto de Sódio/farmacologia , Substância P , Superóxidos/análise , Acetato de Tetradecanoilforbol/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Zimosan/farmacologia
14.
Inflammation ; 18(6): 575-87, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7843801

RESUMO

Human neutrophils were isolated both from peripheral blood (PB) and from aseptic inflammatory exudates obtained by the Senn's skin-window (SW) technique. The respiratory burst (O2- release) and the adherence to serum-coated wells of culture microplates was investigated using a simultaneous assay. Unstimulated PB resting neutrophils did not produce a significant amount of O2- and were incapable of adhering to serum-coated plastic surfaces, while unstimulated SW neutrophils showed augmented adhesion to serum-coated culture wells. SW neutrophils were primed to enhanced FMLP-dependent O2- release in response to n-formyl-methionyl-leucylphenylalanine (FMLP). Adhesion of SW neutrophils was significantly decreased by addition of low doses (10(-10)-10(-8) M) of FMLP (from 17.1% to 8.4%, P < 0.01, N = 12), while fully activating doses (> 5 x 10(-8) M) of FMLP induced a marked increase of the cell adhesion, more pronounced in SW (39.2%) than in PB cells (27.2%). Low (5 x 10(-9) M) and high (5 x 10(-7) M) FMLP doses induced morphological changes (polarization) and actin polymerization in the neutrophils from both sources. Biphasic dose-response curves of SW neutrophil adherence were observed using FMLP, but not using concanavalin A or phorbol myristate acetate as stimulatory agents. Therefore, the adherence of SW cells appears to be regulated in a complex fashion, nonlinearly dependent on the chemotactic peptide doses and specifically regulated according to the receptors involved.


Assuntos
Adesão Celular/efeitos dos fármacos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Ativação de Neutrófilo/fisiologia , Neutrófilos/fisiologia , Citoesqueleto/fisiologia , Humanos , Microscopia de Contraste de Fase , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Técnica de Janela Cutânea , Espectrometria de Fluorescência , Superóxidos/metabolismo
15.
Inflammation ; 26(4): 143-52, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12184627

RESUMO

Polymorphonuclear granulocytes (PMN) are commonly considered short-lived cells playing an efficient role in primary host defense via phagocytosis and release of cytotoxic compounds and inflammatory cytokines. Purified PMN do not express HLA-DR and CD69 molecules on cell surface, but they can be induced to do so by co-culture with peripheral blood derived mono-lymphocytes. De novo cell-surface expression of HLA-DR was also induced in PMN by co-culture with cell lines of lymphoid phenotype, but not with cell lines of myeloid phenotype. CD69 expression was not induced by co-culture with any of the cell lines used in the present study. In addition, we have observed induction of HLA-DR surface expression on PMN by culture in presence of culture supernatant of one of the cell lines of lymphoid origin, RPMI-8866. Quantitative analysis of HLA-DR and CD69 expression in stimulated PMN allowed us to divide PMN donors in two main groups, one with low expression and the other with high expression of the two molecules. HLA-DR surface expression was not altered by treatment with CHX and BFA, and RT-PCR analysis of total RNA from resting and stimulated PMN with RPMI-8866 supernatant did not detect the presence of any specific HLA-DR and CIITA transcript. Flow-cytometry and fluorescence microscopy analysis of resting PMN revealed the presence of HLA-DR molecules localized in intracellular vesicular-tubular structures. These data show that a reservoir of HLA-DR molecules is stored in the cytoplasm of human resting PMN and can be released to reach cell surface by a mobilization mechanism induced by cell surface interactions with selected cell types and sometimes with molecules released in culture supernatants.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Comunicação Celular , Antígenos HLA-DR/metabolismo , Linfócitos/fisiologia , Neutrófilos/fisiologia , Linhagem Celular , Técnicas de Cocultura , Humanos , Lectinas Tipo C
16.
Inflammation ; 21(2): 191-203, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9187962

RESUMO

Human neutrophils were isolated both from peripheral blood (PB) and from aseptic inflammatory exudates obtained by the Senn's skin window technique (SW). The respiratory burst (O2- production) induced by in response to n-formyl-methionyl-lencyl-phenylalanine (fMLP) and by serum-treated zymosan (STZ) was investigated using a microplate assay. SW neutrophils were primed to enhanced fMLP-dependent O2- production in response to fMLP but not to STZ. Pentoxifylline, a cAMP-elevating drug, dose-dependently inhibited the respiratory burst in any experimental condition, but the dose-effect curves were markedly different according the stimulant used and the source of the cells. With fMLP as stimulant, a significant inhibition of the O2- production by PB neutrophils was obtained using doses of 10 micrograms/ml, while SW neutrophils were inhibited only by doses equal or higher than 100 micrograms/ml. With STZ as stimulant, the inhibition of the respiratory burst of PB neutrophils and of SW neutrophils was obtained only with doses higher than 400 micrograms/ml and 1 mg/ml respectively. Pentoxifylline dose-dependently (10 micrograms/ml to 1 mg/ml) increased the intracellular adenosine 3'-5'-cyclic monophosphate (cAMP) to the same extent in SW and in PB neutrophils. These data indicate that the priming of neutrophil oxidative metabolism by in vivo inflammation is associated with an increase in the resistance to the regulating effect of cAMP on the fMLP-dependent activation pathway of NADPH oxidase. The fact that therapeutic doses of pentoxifylline do not inhibit the respiratory burst of primed neutrophils may have relevance in the interpretation of the clinical effects of this drug.


Assuntos
Inflamação/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Pentoxifilina/farmacologia , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Humanos , Técnicas In Vitro , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Pentoxifilina/administração & dosagem , Explosão Respiratória/efeitos dos fármacos , Técnica de Janela Cutânea , Superóxidos/metabolismo , Zimosan/farmacologia
17.
Inflammation ; 20(6): 673-81, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8979154

RESUMO

OBJECTIVE: To evaluate neutrophil functions in the elderly. METHODS: We investigated the PMN migration in vivo and PMN superoxide production and adhesion in response to a variety of compounds; PMN have been isolated both from blood and from a skin experimental exudate (obtained by Senn's skin window technique) of 25 normal elderly and of 25 normal young control subjects. RESULTS: No difference was found in PMN migration in vivo (62.9 +/- 21.3 x 10(6) and 65.5 +/- 9.1 x 10(6) PMN/cm2/24 hours in elderly and young subjects respectively), neither were different the adhesion under basal condition and after some stimuli and the superoxide production in basal condition and in response to STZ and PMA in two groups. In elderly subjects superoxide production, in response to fMLP, markedly resulted lower than in young controls both by circulating PMNs (3.6 +/- 2.7 and 9.3 +/- 3.3 nMOLES O2-/10(6) PMN respectively, p < 0.0001) and by exudate PMNs (13.6 +/- 4.3 and 19.4 +/- 6 nMOLES O2-/10(6) PMNs respectively, p < 0.005). CONCLUSION: Many PMN functions in the elderly do not differ from young people, suggesting that the overall defense function of these cells is not affected by aging. The only parameter that we have found to be different between the two groups is the poor superoxide production after fMLP stimulus of PMNs. The stimulus- and function-specificity of this defect in PMNs from elderly subjects indicates the existence of a dysregulation of the signal transduction pathway distal to fMLP receptor and proximal to NADPH oxidase activation.


Assuntos
Envelhecimento/imunologia , Neutrófilos/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Adesão Celular , Quimiotaxia de Leucócito , Feminino , Humanos , Masculino , N-Formilmetionina Leucil-Fenilalanina/farmacologia , NADPH Oxidases/metabolismo , Neutrófilos/efeitos dos fármacos , Receptores de Formil Peptídeo , Receptores Imunológicos/efeitos dos fármacos , Receptores de Peptídeos/efeitos dos fármacos , Explosão Respiratória , Superóxidos/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Zimosan/farmacologia
18.
Inflammation ; 22(4): 381-91, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9675609

RESUMO

Fifty-seven healthy volunteers matched for sex and age were subdivided in 3 groups and their usual Western diets were supplemented according to three different protocols: group 1, fish oil supplement (20 ml/day); group 2, soybean phosphatidylcholine (PC) (25 g/day) and group 3, no supplementation (control group). After 2 weeks several important modifications of neutrophil fatty acid composition were observed: fish oil induced a significant decrease of linoleic (LA) and arachidonic acid (AA) and a significant increase of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), while soy PC induced significant increases of LA, total polyunsaturated fatty acid (PUFA) and PUFA/SFA ratio. Neutrophil superoxide generation and adhesion were not modified by fish oil diet, on the contrary a slight but significant increase of O2.- production in response to fMLP was measured after soy PC diet. Our study confirms the possibility of changing neutrophil fatty acid composition in vivo by dietary means, but also suggests that the manipulation of cell functions, like superoxide anion generation and adhesion, is not easily and directly achieved by controlling membrane lipid environment.


Assuntos
Óleo de Fígado de Bacalhau/administração & dosagem , Ácidos Graxos/sangue , Neutrófilos/metabolismo , Fosfatidilcolinas/administração & dosagem , Adolescente , Adulto , Ácido Araquidônico/sangue , Adesão Celular/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Humanos , Técnicas In Vitro , Ácido Linoleico/sangue , Masculino , Pessoa de Meia-Idade , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Explosão Respiratória/efeitos dos fármacos , Glycine max , Superóxidos/sangue
19.
Inflammation ; 22(5): 533-43, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9793799

RESUMO

The aim of this study is to determine some functions of neutrophil in patients affected by psoriatic arthritis and to compare them to those of patients affected by cutaneous psoriasis and to normal controls. We used a model of experimental cutaneous inflammation allowing to separate a cluster of purified and viable PMN cells. Then we analyzed, within the three groups, the IL-8 concentration in serum and in the supernatant obtained from the inflammatory site to gather data on the possible pathogenic role played by this cytokine in psoriatic arthritis. We studied neutrophil functions in patients with cutaneous psoriasis and psoriatic arthritis, in acute phase, in comparison with healthy control subjects. We investigated in vivo neutrophil migration by Senn's skin window technique and measured adhesion assay and superoxide production in circulating and migrating neutrophils after different stimuli. We also measured IL-8 concentration in serum and in the supernatant obtained from the inflammatory site, artificially created through the skin window scrape. Neutrophil migration in vivo was significantly higher in both groups of patients than in controls. In the presence of fMLP, blood cells showed a burst of superoxide release, which was significantly more pronounced in patients when compared to healthy controls. Neutrophils from skin window scrape showed a much higher response to fMLP as compared to blood cells of all subject groups, but no differences were observed between patients and controls. No correlation was found between the three groups in adhesion ability under basal condition or in response to different stimuli by circulating and migrating neutrophils. Our results also show a great increase of IL-8 in the exudate from patients compared to controls. Our study shows that there is no difference in neutrophil functions between patients with psoriatic arthritis and cutaneous psoriasis; moreover we suggest that the source of high IL-8 levels are neutrophils rather than the keratinocytes.


Assuntos
Artrite Psoriásica/imunologia , Interleucina-8/metabolismo , Neutrófilos/imunologia , Psoríase/imunologia , Adulto , Artrite Psoriásica/etiologia , Estudos de Casos e Controles , Adesão Celular , Movimento Celular , Feminino , Humanos , Técnicas In Vitro , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Superóxidos/metabolismo
20.
Inflammation ; 23(5): 471-9, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10466583

RESUMO

CD23, the low affinity receptor for IgE, is a 45 kilodalton molecule belonging to the C-type lectin family, some members of which have been identified as adhesion molecules. Since it has been described upregulated in different cells in chronic inflammatory diseases and in rheumatoid arthritis in particular, where neutrophils are directly involved in tissue damage, our interest, in this work, has been focused on the expression and regulation of this antigen on neutrophil membrane. We studied 22 patients suffering from rheumatoid arthritis and 22 healthy control subjects. CD23 expression on neutrophil membrane was analyzed by immunofluorescence. Neutrophils of 9 out of 22 patients expressed CD23 molecules, neutrophils of 11 out of 22 patients expressed CD23 only after 24 h of incubation in RPMI; only 2 out of 22 patients did not express the CD23 antigen on neutrophil membrane either after isolation or after a 24 h incubation. On the contrary neutrophils isolated from healthy subjects did not express CD23 molecules upon isolation. Only in 7/22 control subjects neutrophils resulted positive after 24 h of incubation in RPMI. Moreover, we found that in our experimental conditions the presence of IFN-g or GM-CSF alone or in combination with IL-4 inhibited CD23 expression during the 24 h incubation. Our results show that there is a strong association between neutrophil ability to express CD23 and rheumatoid arthritis, and that such expression may be regulated by GM-CSF, IFN-gamma and IL-4.


Assuntos
Artrite Reumatoide/imunologia , Neutrófilos/imunologia , Receptores de IgE/biossíntese , Adulto , Artrite Reumatoide/sangue , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ativação de Neutrófilo , Receptores de IgE/imunologia
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