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1.
Rheumatol Int ; 37(2): 293-298, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27873008

RESUMO

Systemic lupus erythematosus (SLE) is associated with increased cardiovascular risk. We aimed to evaluate arterial stiffness and the ankle brachial index (ABI), two markers of subclinical cardiovascular disease, in SLE. We studied 55 patients with SLE (12.7% males, age 53.3 ± 15.3 years) and 61 age- and gender-matched controls. Arterial stiffness was evaluated by measuring pulse wave velocity (PWV), augmentation index (AIx) and central systolic, diastolic, pulse and mean blood pressure (BP). Peripheral arterial disease was defined as ABI ≤ 0.90. Regarding markers of arterial stiffness, patients with SLE had lower PWV and AIx than controls (p < 0.01 and p < 0.05, respectively). However, after adjusting for differences in cardiovascular risk factors between patients with SLE and controls, PWV and AIx did not differ between the two groups. Central systolic, diastolic, pulse and mean BP also did not differ between the two groups. In patients with SLE, PWV correlated independently with systolic BP (B = 0.05, p < 0.001) and waist/hip ratio (B = 6.72, p < 0.05). Regarding ABI, the lowest ABI was lower in patients with SLE than in controls (p < 0.005). However, after adjusting for differences in cardiovascular risk factors between patients with SLE and controls, the lowest ABI did not differ between the two groups. The prevalence of PAD also did not differ between patients with SLE and controls (10.0 and 5.4%, respectively; p = NS). Markers of arterial stiffness and the ABI do not appear to differ between patients with SLE and age- and gender-matched controls. However, given the small sample size, larger studies are needed to clarify whether SLE promotes arterial stiffness and PAD.


Assuntos
Pressão Sanguínea/fisiologia , Lúpus Eritematoso Sistêmico/complicações , Doença Arterial Periférica/complicações , Rigidez Vascular/fisiologia , Adulto , Idoso , Índice Tornozelo-Braço , Velocidade do Fluxo Sanguíneo/fisiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/fisiopatologia , Análise de Onda de Pulso
2.
Crit Rev Immunol ; 34(5): 389-97, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25404046

RESUMO

T regulatory cells (Tregs) comprise the cardinal mechanism of peripheral immune tolerance by modulating the function of virtually each immune cell. Given that atherosclerosis is a chronic inflammation of the arterial wall, certain components of the immune system have been proven to have a central role in its pathogenesis. Consequently, various clinical and experimental studies have been conducted to elucidate the role of Tregs in suppressing this immune-mediated inflammation. In this review, current experimental and clinical knowledge on the role of Tregs in the atherogenic process is presented after a short introduction to their generation and function. Based on these data, Treg-targeted therapeutic approaches are discussed in regard to their potential for clinical application.


Assuntos
Aterosclerose/imunologia , Aterosclerose/terapia , Linfócitos T Reguladores/imunologia , Animais , Artérias/imunologia , Humanos , Terapia de Imunossupressão , Inflamação/imunologia
3.
Clin Exp Rheumatol ; 32(5): 630-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25197969

RESUMO

OBJECTIVES: Several studies have reported low numbers of T regulatory cells (Tregs) in active systemic lupus erythematosus (SLE). However, it is not evident if these cells may be utilised as a biomarker in assessing disease activity. METHODS: Tregs (CD4+CD25highFOXP3+) were prospectively assessed by flow cytometry in 285 separate blood samples from 100 white Caucasian SLE patients and 20 healthy controls. Patients were divided, according to disease activity (as measured by SLEDAI) into groups A (n=39, samples=94, SLEDAI=0), B (n=33, samples=92, SLEDAI=1-5), C (n=10, samples=53, SLEDAI=6-10) and D (n=18, samples=46, SLEDAI>10). Longitudinal measurements were performed in 131 cases (37 relapses, 44 remissions and 50 cases with stable disease activity) during three years. Statistics were performed by Student's t-test or one-way ANOVA; correlations with Pearson co-efficient, while p<0.05 was considered significant. RESULTS: Tregs were found significantly lower in severely active disease (group D), compared to healthy controls, inactive disease, mild and moderate disease activity (0.57±0.16% vs. 1.49±0.19%, 1.19±0.34% and 1.05±0.36%, 0.72±0.21%, p<0.05, respectively). There was a strongly inverse correlation between Tregs and SLEDAI (r=-0.644, p<0.001). Alterations in disease activity were characterised by inverse alterations in Tregs: relapse (from 1.23±0.44% to 0.64±0.19%, p<0.001, mean change 0.59±0.41%), remission (from 0.65±0.27% to 1.17±0.30%, p<0.001, mean change 0.52±0.35%). In cases with unaltered disease activity, Treg numbers remained stable (from 0.98±0.35% to 1.03±0.34%, p=0.245). Tregs were practically halved during relapse (mean reduction 42.6±22.2%), and doubled during remission (mean increment 113±120.9%). Mean change of Tregs in stable disease was significantly lower (7.3±20.6%, p<0.001). A clinically significant change in SLEDAI (sum of cases with relapse and remission, n=81) was followed by a significant (>20%) inverse change in Tregs in 71/81 cases (sensitivity 87.7%). In 50 cases of stable disease activity, Tregs were significantly changed (>20%) in 13 cases (specificity 74%). Positive predictive value (PPV) was 84.5% and negative predictive value (NPV) was 78.7%. CONCLUSIONS: CD4+CD25highFOXP3+ T regulatory cells displayed a strongly inverse correlation to disease activity in the long term. Treg alterations reflected changes in SLEDAI with high sensitivity. These cells may be a reliable biomarker for the assessment of disease activity in SLE by longitudinal measurements.


Assuntos
Fatores de Transcrição Forkhead/sangue , Subunidade alfa de Receptor de Interleucina-2/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Recidiva , Indução de Remissão , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
4.
ACS Appl Mater Interfaces ; 16(12): 15043-15049, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38477897

RESUMO

The operation of oxide-based memristive devices relies on the fast accumulation and depletion of oxygen vacancies by an electric field close to the metal-oxide interface. Here, we show that the reversible change of the local concentration of oxygen vacancies at this interface also produces a change in the thermal boundary resistance (TBR), i.e., a thermal resistive switching effect. We used frequency domain thermoreflectance to monitor the interfacial metal-oxide TBR in (Pt,Cr)/SrTiO3 devices, showing a change of ≈20% under usual SET/RESET operation voltages, depending on the structure of the device. Time-dependent thermal relaxation experiments suggest ionic rearrangement along the whole area of the metal/oxide interface, apart from the ionic filament responsible for the electrical conductivity switching. The experiments presented in this work provide valuable knowledge about oxide ion dynamics in redox-based memristive devices.

5.
Epileptic Disord ; 15(2): 203-6, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23773932

RESUMO

Hypohidrosis is an uncommon and reversible side effect of topiramate treatment, reported mainly in children. This report presents an adult patient with complex partial seizures who was treated with topiramate and developed hypohidrosis coupled with hyperthermia, related to high environmental temperature and physical exercise. Reduced sweat response was confirmed using the Neuropad test. Signs and symptoms ceased after drug discontinuation. During topiramate treatment, it is important to recognise this side effect, although the exact causal mechanism has not yet been clarified.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia Parcial Complexa/tratamento farmacológico , Frutose/análogos & derivados , Hipo-Hidrose/induzido quimicamente , Adulto , Febre/etiologia , Frutose/efeitos adversos , Humanos , Hipo-Hidrose/complicações , Masculino , Topiramato
6.
BMC Infect Dis ; 11: 358, 2011 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-22206235

RESUMO

BACKGROUND: Immunocompromised patients, such as systemic lupus erythematosus (SLE) sufferers have an increased risk of mortality, following influenza infection. In the recent pandemic, influenza A H1NI virus caused 18449 deaths, mainly because of adult respiratory distress syndrome or bacterial co-infections. CASE PRESENTATION: In this case report, an SLE patient with viral-induced septic shock, without overt pulmonary involvement, is discussed. The patient was administered oseltamivir and supportive treatment, including wide-spectrum antibiotics, vasopressors and steroids, according to the guidelines proposed for bacterial sepsis and septic shock. She finally survived and experienced a lupus flare soon after intensive care unit (ICU) discharge. CONCLUSIONS: To our knowledge, this is the first case to report severe septic shock from influenza A/H1N1 virus, without overt pulmonary involvement.


Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/complicações , Influenza Humana/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Choque Séptico/complicações , Choque Séptico/diagnóstico , Antibacterianos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antivirais/administração & dosagem , Feminino , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/patologia , Lúpus Eritematoso Sistêmico/patologia , Pessoa de Meia-Idade , Oseltamivir/administração & dosagem , Radiografia Torácica , Choque Séptico/patologia , Esteroides/administração & dosagem , Tomografia Computadorizada por Raios X , Vasoconstritores/administração & dosagem
7.
9.
Clin Dev Immunol ; 2008: 327346, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19190764

RESUMO

Chronic brucellosis patients display a defective Th1 response to PHA. We have previously shown that heat-killed B. abortus (HKBA) can downregulate the PHA-induced increase of CD4+/CD25+ and CD14+/CD80+ cells of brucellosis patients. In the present study, we investigate the effect of E. coli LPS, as a potent stimulant of monocytes and autologous T-lymphocytes, on the PHA-cultured PBMCs of the same groups of patients. Thirteen acute brucellosis (AB) patients, 22 chronic brucellosis (CB) patients, 11 "cured" subjects, and 15 healthy volunteers were studied. The percentage of CD4+/CD25+ and CD4+/CD28+ T-lymphocytes as well as CD14+/CD80+ monocytes were analyzed by flow cytometry after PBMCs culture with PHA plus E. coli LPS. A significant decrease in the percentage of CD4+/CD25+ and CD4+/CD28+ T-lymphocytes was observed in CB compared to AB. In HKBA cultures, compared to E. coli LPS-cultures, there was a significant reduction of CD4+/CD25+ T-lymphocytes in all groups and CD14+/CD80+ in patients groups. We suggest that Brucella can modulate host immune response, leading to T-cell anergy and chronic infection.


Assuntos
Brucella abortus/imunologia , Brucelose/imunologia , Linfócitos T CD4-Positivos/metabolismo , Lipopolissacarídeos/imunologia , Antígeno B7-1/metabolismo , Brucelose/sangue , Antígenos CD28 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Células Cultivadas , Doença Crônica , Citocinas/metabolismo , Escherichia coli/imunologia , Humanos , Imunofenotipagem , Subunidade alfa de Receptor de Interleucina-2 , Lipopolissacarídeos/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Fito-Hemaglutininas/imunologia , Fito-Hemaglutininas/farmacologia
11.
Case Rep Rheumatol ; 2014: 809629, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25349765

RESUMO

Environmentally induced systemic sclerosis is a well-recognized condition, which is correlated with exposure to various chemical compounds or drugs. However, development of scleroderma-like disease after exposure to silicone has always been a controversial issue and, over time, it has triggered spirited debate whether there is a certain association or not. Herein, we report the case of a 35-year-old female who developed Raynaud's phenomenon and, finally, systemic sclerosis shortly after silicone breast implantation surgery.

12.
Int J Rheum Dis ; 17(7): 790-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25430593

RESUMO

BACKGROUND: Cyclophosphamide efficacy in lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE) is probably mediated by a non-specific ablation of reactive lymphocytes. However, little is known in regard to its effect on T regulatory cells (Tregs) in such patients, which was the aim of this study. PATIENTS AND METHODS: Ten Caucasian lupus patients were included, six with LN classes IV-V (mean age 33.8 ± 8.8 years) and four with NPSLE (mean age 35.5 ± 8.8 years, clinical manifestations: 1/4 acute confusional state, 1/4 psychosis, 2/4 refractory seizures). Cyclophosphamide was administered at monthly pulses (500 mg/m(2) /month for 6 months); doses of other administered drugs, including steroids, remained stable or lower. CD4(+) CD25(high) FOXP3(+) Tregs were assessed by flow-cytometry at baseline and before every subsequent pulse and 3-6 months after the final pulse. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). RESULTS: In LN patients, Tregs were significantly increased even after the fourth pulse (0.54 ± 0.20% vs. 1.24 ± 0.29%, P < 0.001). Likewise, in NPSLE, Tregs were significantly expanded after the fourth pulse (0.57 ± 0.23% vs. 1.41 ± 0.28%, P < 0.001). SLEDAI was significantly reduced in all patients. CONCLUSIONS: Cyclophosphamide pulse therapy was associated with a significant increase of the CD4(+) CD25(high) FOXP3(+) Tregs in patients with active LN and NPSLE. This effect is probably indirect and may partially explain the beneficial role of cyclophosphamide in such cases.


Assuntos
Ciclofosfamida/administração & dosagem , Fatores Imunológicos/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/tratamento farmacológico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Feminino , Fatores de Transcrição Forkhead/sangue , Humanos , Subunidade alfa de Receptor de Interleucina-2/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/sangue , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Masculino , Pulsoterapia , Indução de Remissão , Linfócitos T Reguladores/imunologia , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
13.
World J Hepatol ; 5(7): 387-92, 2013 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-23898372

RESUMO

AIM: To present the characteristics and the course of a series of anti-hepatitis B virus core antibody (HBc) antibody positive patients, who experienced hepatitis B virus (HBV) reactivation after immunosuppression. METHODS: We retrospectively evaluated in our tertiary centers the medical records of hepatitis B virus surface antigen (HBsAg) negative patients who suffered from HBV reactivation after chemotherapy or immunosuppression during a 3-year period (2009-2011). Accordingly, the clinical, laboratory and virological characteristics of 10 anti-HBc (+) anti-HBs (-)/HBsAg (-) and 4 anti-HBc (+)/antiHBs (+)/HBsAg (-) patients, who developed HBV reactivation after the initiation of chemotherapy or immunosuppressive treatment were analyzed. Quantitative determination of HBV DNA during reactivation was performed in all cases by a quantitative real time polymerase chain reaction kit (COBAS Taqman HBV Test; cut-off of detection: 6 IU/mL). RESULTS: Twelve out of 14 patients were males; median age 74.5 years. In 71.4% of them the primary diagnosis was hematologic malignancy; 78.6% had received rituximab (R) as part of the immunosuppressive regimen. The median time from last chemotherapy schedule till HBV reactivation for 10 out of 11 patients who received R was 3 (range 2-17) mo. Three patients (21.4%) deteriorated, manifesting ascites and hepatic encephalopathy and 2 (14.3%) of them died due to liver failure. CONCLUSION: HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving.

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