RESUMO
The aims of the present study were to evaluate biomarkers of oxidative and nitrosative stress in systemic lupus erythematosus (SLE) patients, in particular products of DNA/RNA oxidative damage and their correlation with disease activity. This study included 188 controls and 203 patients; 153 with inactive SLE (SLEDAI < 6) and 50 with active SLE (SLEDAI ≥ 6) without renal impairment. Oxidative stress was assessed by tert-butyl hydroperoxide-initiated by chemiluminescence, advanced oxidation protein products (AOPP), total radical-trapping antioxidant parameter (TRAP), nitric oxide metabolites (NOx), and DNA/RNA oxidation products. Patients with SLE showed increased oxidative stress, as demonstrated by the augmentation of lipid hydroperoxides ( p < 0.0001) and AOPP ( p < 0.001) and reduced total antioxidant capacity ( p < 0.0001), without differences between patients with active disease and in remission. NOx levels and DNA/RNA oxidation products were inversely and independently associated with disease activity ( p < 0.0001 and p = 0.021, respectively), regardless of BMI and prednisone use. The linear regression analysis showed that about 5% of the SLEDAI score can be explained by the levels of DNA/RNA oxidation products ( r2:0.051; p = 0.002) and about 9% of this score by the levels of NOx ( r2:0.091; p < 0.0001). This study provides evidence for an inverse association between serum NOx levels and DNA/RNA oxidation products and SLE disease activity, suggesting that oxidative/nitrosative stress markers may be useful in evaluating SLE disease activity and progression of the disease.
Assuntos
Lúpus Eritematoso Sistêmico/fisiopatologia , Óxido Nítrico/metabolismo , Estresse Nitrosativo/fisiologia , Estresse Oxidativo/fisiologia , Adulto , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , DNA/metabolismo , Progressão da Doença , Feminino , Glucocorticoides/uso terapêutico , Humanos , Modelos Lineares , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Oxirredução , Prednisona , RNA/metabolismo , Índice de Gravidade de DoençaRESUMO
This study evaluated the association of tumor necrosis factor beta (TNF-ß) NcoI polymorphism with the presence of multiple sclerosis (MS), disability, and HLA-DRB1 alleles in 208 Brazilian MS patients. As controls, 147 healthy individuals were included. The disability was evaluated at baseline and 5-year follow-up using the Expanded Disability Status Scale (EDSS). The TNF-ß genotypes were determined using PCR and restriction fragment length polymorphism and serum TNF-α level was determined using enzyme-linked immunosorbent assay. Among the MS patients, 166 (79.8 %) were white, 39 (18.7 %) were brown, and three (1.4 %) were Asian descents (those were excluded from the further analysis). Among the 205 MS patients, 149 (72.6 %) presented remitting-relapsing MS. The baseline and 5-year follow-up EDSS ranged from 0.0 to 3.0 and from 1.0 to 5.7, respectively. The TNFB2/B2 genotype was associated with the presence of MS among the white patients (p = 0.0443). Brown patients presented higher disability (p = 0.0234) and higher TNF-α levels (p = 0.0463) than white patients. White and brown patients carrying TNFB2/B2 genotype exhibited higher TNF-α levels (p = 0.0354 and p = 0.0309, respectively) than those with other geotypes. Association between TNF-ß NcoI genotypes and HLA-DRB1 alleles was not observed among the MS patients (p > 0.05). Taken together, TNFB2 allele was associated with the presence of MS independently of HLA-DRB1 in white patients and the TNFB2/B2 genotype was associated with increased TNF-α levels in white and brown patients, which could be an important genetic factor candidate for the susceptibility and pathogenesis of MS.
Assuntos
Cadeias HLA-DRB1/genética , Linfotoxina-alfa/genética , Esclerose Múltipla/genética , Polimorfismo de Fragmento de Restrição , Adulto , Brasil , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/etnologia , Fator de Necrose Tumoral alfa/sangue , População BrancaRESUMO
OBJECTIVES: To determine whether disease activity verified by laboratorial parameters is associated with a higher frequency of hypertension in patients with systemic lupus erythematosus (SLE) without renal impairment and to investigate factors that could influence this hypertension. METHOD: This study included 102 controls, 70 patients with inactive SLE, and 53 patients with active SLE without renal impairment. We evaluated T helper type 1 (Th1)/Th2 lineage cytokines, nitric oxide (NO), insulin resistance (IR), and oxidative stress. RESULTS: Patients with active SLE had a higher probability of developing hypertension compared to controls [odds ratio (OR) 3.833, 95% confidence interval (CI) 1.806-8.137, p < 0.0003] and patients with inactive SLE (OR 2.215, 95% CI 1.032-4.752, p = 0.0394). Active SLE patients had a higher interleukin (IL)-12/IL-4 ratio (p < 0.05) than both controls and inactive SLE patients. Protein oxidation was significantly higher in patients with active SLE than in the control group and in patients with inactive SLE (p < 0.01 and p < 0.05, respectively). Multivariate analysis revealed an association between the presence of hypertension and he levels of glucose (p = 0.0276), insulin (p = 0.0498), hydroperoxides (p = 0.0221), IFN-γ (p = 0.0494), IL-17 (p = 0.0272), IL-12/IL-10 (p = 0.0373), IFN-γ/IL-10 (p = 0.0142), IFN-γ/IL-4 (p = 0.0320), and adiponectin (p = 0.0433). CONCLUSIONS: Patients with active SLE without renal impairment had an increased frequency of high blood pressure (43.4%) compared with patients with inactive SLE (25.7%) and controls (16.7%). Hypertension was associated with serologically active disease and was influenced by an increased Th1/Th2 ratio and oxidative stress.
Assuntos
Hipertensão/complicações , Lúpus Eritematoso Sistêmico/complicações , Estresse Oxidativo/fisiologia , Células Th1/metabolismo , Células Th2/metabolismo , Adulto , Glicemia/metabolismo , Citocinas/sangue , Feminino , Humanos , Hipertensão/imunologia , Hipertensão/metabolismo , Insulina/sangue , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Pessoa de Meia-Idade , Células Th1/imunologia , Células Th2/imunologiaRESUMO
The aims of the present study were to report the frequency of metabolic syndrome in systemic lupus erythematosus (SLE); to verify differences in inflammatory biomarkers and oxidative stress in SLE patients with or without metabolic syndrome; and to assess which metabolic syndrome components are associated with oxidative stress and disease activity. The study included 58 SLE patients and 105 controls. SLE patients were divided in two groups, with and without metabolic syndrome. 41.4% patients met the criteria for metabolic syndrome compared with 10.5% controls. Patients with SLE and metabolic syndrome had significantly raised serum uric acid, C-reactive protein (CRP), lipid hydroperoxides, and protein oxidation when compared with patients with SLE without metabolic syndrome. Lipid hydroperoxides were correlated with CRP, whereas protein oxidation was associated with waist circumference and uric acid. There was a positive association between serum C3 and C4 and glucose and between C3 and CRP. SLE disease activity index (SLEDAI) scores were positively correlated with body mass index (BMI) and waist circumference (WC). In conclusion, SLE patients have a high prevalence of metabolic syndrome and this syndrome directly contributes to increase inflammatory status and oxidative stress. Inflammatory processes, being overweight/obese, and uric acid may favor oxidative stress increases in patients with SLE and metabolic syndrome. C3 and C4 may have a positive acute-phase protein behavior in patients with SLE.
Assuntos
Biomarcadores/metabolismo , Inflamação , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Síndrome Metabólica/sangue , Síndrome Metabólica/imunologia , Estresse Oxidativo , Proteínas de Fase Aguda/metabolismo , Adulto , Proteína C-Reativa/metabolismo , Comorbidade , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Peroxidação de Lipídeos , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade , Sobrepeso , Fatores de Risco , Ácido Úrico/sangueRESUMO
Oxidative stress exerts an important role on the pathophysiological mechanisms of systemic lupus erythematosus (SLE). This study investigated oxidative stress in patients with SLE and its correlation with disease activity, corticosteroid therapy, and liver function biomarkers. The study included 58 patients with SLE and 105 healthy volunteers. Patients showed oxidative stress increase evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), advanced oxidation protein products (AOPP), and nitric oxide metabolites. C-reactive protein (CRP) was associated with CL-LOOH and with AOPP. Aspartate aminotransferase correlated significantly with CL-LOOH and with AOPP. Patients with disease activity showed an inverse significant correlation of daily prednisone doses and CL-LOOH and a direct correlation with total antioxidant capacity. In conclusion, patients with SLE have persistent lipoperoxidation and protein oxidation even with inactive disease or mild disease activity. The significant correlation between oxidative stress and CRP suggests that, despite clinical remission, the persistence of an inflammatory condition favors oxidative stress. Oxidative stress was associated with liver enzymes, and this relationship seems to support the hypothesis of drug-induced oxidative stress with consequent liver injury. In relation to non-active disease, patients with active SLE did not present oxidative stress and antioxidant capacity changes, due to the antioxidant drugs used in SLE treatment, especially prednisone.
Assuntos
Lúpus Eritematoso Sistêmico/metabolismo , Estresse Oxidativo , Corticosteroides/uso terapêutico , Adulto , Antioxidantes/uso terapêutico , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos , Fígado/lesões , Fígado/fisiopatologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismoRESUMO
The aim of this study was to evaluate associations between seropositivity for IgG and IgM anti-Toxoplasma gondii antibodies and socio-economic and environmental variables in pregnant women of Londrina, state of Paraná, Brazil. We interviewed 492 pregnant women, each of whom answered an epidemiological questionnaire, and collected blood samples for measurement of IgG and IgM anti-T. gondii antibodies by chemiluminescence. A confirmatory diagnosis of acute infection was made by an IgG avidity test. Titres of specific IgG anti-T. gondii were obtained by IFAT. Seropositivity for IgG anti-T. gondii antibodies was observed in 242 women (49.2%) and, of these, six pregnant women (1.2%) showed seropositivity for IgM. Age group, level of education, per capita income, presence of a cat in the house and a habit of eating green vegetables were all factors associated with a greater chance of infection with T. gondii. This study showed that 250 (50.8%) pregnant women were susceptible to T. gondii and considered to be at high risk for toxoplasmosis during pregnancy. Based on the results obtained, is critical to establish a program of health surveillance for toxoplasmosis, in order to contribute to diagnosis and early treatment during the prenatal period. It is also necessary to introduce measures to prevent the Toxoplasma infection in seronegative pregnant women.
Assuntos
Anticorpos Antiprotozoários/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Complicações Parasitárias na Gravidez/epidemiologia , Toxoplasmose/epidemiologia , Adolescente , Adulto , Animais , Brasil/epidemiologia , Gatos , Feminino , Humanos , Gravidez , Complicações Parasitárias na Gravidez/diagnóstico , Primeiro Trimestre da Gravidez , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Toxoplasmose/diagnóstico , Adulto JovemRESUMO
Antiretroviral therapy advances have proportioned to AIDS patients a survival increase. At the same time, the permanence of the seropositive people in the nosocomial environment becomes common not only by the adverse reactions caused by this therapy, but also by several opportunistic diseases that take them into and out of hospital environment. During the hospital permanence, the patients expose their impaired immune system to the nosocomial virulent microorganisms, and acquire destructive nosocomial infections that sometimes can be lethal. Among several hospital syndromes described, little is known about infections in immunocompromised patients and how their immune system is able to determine the course of the infection. The objective of this study was to describe the major microorganisms involved in the nosocomial infections of HIV-1 seropositive patients associated with their immunological status. The survey was carried out with the Hospital Infection Control Service records, from University Hospital, Londrina, Paraná, Southern of Brazil, during the period from July 2003 to July 2004. From all the cases studied (n=969), 24 patients (2.5%) had AIDS diagnosis and a half of them was women with the mean of CD4+ T cells counts of 158/mm³. The main topography of the infection was pulmonary (50.0%) and the main isolated microorganisms were Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. A major incidence of infection was observed in patients with CD4+ T cells counts lower than 50/mm³. The study of the relationship between the impairment of the immune system and infectious agents could provide a better healthcare of people living with HIV/AIDS and advances into the nosocomial infection control systems.
Avanços na terapia anti-retroviral têm proporcionado aos pacientes com AIDS um aumento na sobrevida. Ao mesmo tempo, a permanência de pacientes soropositivos no ambiente nosocomial torna-se comum não só pelos efeitos colaterais desta terapia, mas também pelas diversas doenças oportunistas que acometem estes indivíduos dentro e fora do ambiente hospitalar. Durante o período de internação, a fragilidade do sistema imunológico é exposta à virulência da microbiota nosocomial, adquirindo infecções hospitalares graves e muitas vezes fatais. Dentre as diversas síndromes de infecções hospitalares descritas, pouco se sabe sobre estas infecções em pacientes imunocomprometidos e sobre como o estado imunológico é capaz de determinar o curso destas infecções. Este trabalho teve como objetivo determinar os principais microrganismos envolvidos nas infecções hospitalares de pacientes soropositivos para a infecção pelo HIV-1 e descrever a associação com seu perfil imunológico. Realizou-se análise de dados de notificações do Serviço de Controle de Infecção Hospitalar do Hospital Universitário, Londrina, Paraná, na região sul do Brasil, no período de julho de 2003 a julho de 2004. Do total de casos estudados (n=969), 24 pacientes (2,5%) tinham o diagnóstico de AIDS, sendo metade do gênero feminino, com contagem média de células T CD4+ de 158,4/mm³. A principal topografia foi o sítio pulmonar (50,0%), sendo Staphylococcus aureus, Pseudomonas aeruginosa e Escherichia coli os principais microrganismos isolados. Observou-se maior incidência de infecção em pacientes com contagem de células T CD4+ menor que 50/mm³. O estudo da relação entre sistema imunológico e microrganismos causadores de infecções poderá contribuir para melhorias nos cuidados de pacientes com AIDS e avanços nos sistemas de controle de infecção hospitalar.
Assuntos
Humanos , Síndrome da Imunodeficiência Adquirida , Infecção Hospitalar , HIV-1 , Sistema Imunitário , Métodos , Pacientes , Técnicas e Procedimentos DiagnósticosRESUMO
Antiretroviral therapy advances have proportioned to AIDS patients a survival increase. At the same time, the permanence of the seropositive people in the nosocomial environment becomes common not only by the adverse reactions caused by this therapy, but also by several opportunistic diseases that take them into and out of hospital environment. During the hospital permanence, the patients expose their impaired immune system to the nosocomial virulent microorganisms, and acquire destructive nosocomial infections that sometimes can be lethal. Among several hospital syndromes described, little is known about infections in immunocompromised patients and how their immune system is able to determine the course of the infection. The objective of this study was to describe the major microorganisms involved in the nosocomial infections of HIV-1 seropositive patients associated with their immunological status. The survey was carried out with the Hospital Infection Control Service records, from University Hospital, Londrina, Paraná, Southern of Brazil, during the period from July 2003 to July 2004. From all the cases studied (n=969), 24 patients (2.5%) had AIDS diagnosis and a half of them was women with the mean of CD4(+) T cells counts of 158/mm(3). The main topography of the infection was pulmonary (50.0%) and the main isolated microorganisms were Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. A major incidence of infection was observed in patients with CD4(+) T cells counts lower than 50/mm(3). The study of the relationship between the impairment of the immune system and infectious agents could provide a better healthcare of people living with HIV/AIDS and advances into the nosocomial infection control systems.
RESUMO
Antiretroviral therapy advances have proportioned to AIDS patients a survival increase. At the same time, the permanence of the seropositive people in the nosocomial environment becomes common not only by the adverse reactions caused by this therapy, but also by several opportunistic diseases that take them into and out of hospital environment. During the hospital permanence, the patients expose their impaired immune system to the nosocomial virulent microorganisms, and acquire destructive nosocomial infections that sometimes can be lethal. Among several hospital syndromes described, little is known about infections in immunocompromised patients and how their immune system is able to determine the course of the infection. The objective of this study was to describe the major microorganisms involved in the nosocomial infections of HIV-1 seropositive patients associated with their immunological status. The survey was carried out with the Hospital Infection Control Service records, from University Hospital, Londrina, Paraná, Southern of Brazil, during the period from July 2003 to July 2004. From all the cases studied (n=969), 24 patients (2.5%) had AIDS diagnosis and a half of them was women with the mean of CD4+ T cells counts of 158/mm³. The main topography of the infection was pulmonary (50.0%) and the main isolated microorganisms were Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. A major incidence of infection was observed in patients with CD4+ T cells counts lower than 50/mm³. The study of the relationship between the impairment of the immune system and infectious agents could provide a better healthcare of people living with HIV/AIDS and advances into the nosocomial infection control systems.
Avanços na terapia anti-retroviral têm proporcionado aos pacientes com AIDS um aumento na sobrevida. Ao mesmo tempo, a permanência de pacientes soropositivos no ambiente nosocomial torna-se comum não só pelos efeitos colaterais desta terapia, mas também pelas diversas doenças oportunistas que acometem estes indivíduos dentro e fora do ambiente hospitalar. Durante o período de internação, a fragilidade do sistema imunológico é exposta à virulência da microbiota nosocomial, adquirindo infecções hospitalares graves e muitas vezes fatais. Dentre as diversas síndromes de infecções hospitalares descritas, pouco se sabe sobre estas infecções em pacientes imunocomprometidos e sobre como o estado imunológico é capaz de determinar o curso destas infecções. Este trabalho teve como objetivo determinar os principais microrganismos envolvidos nas infecções hospitalares de pacientes soropositivos para a infecção pelo HIV-1 e descrever a associação com seu perfil imunológico. Realizou-se análise de dados de notificações do Serviço de Controle de Infecção Hospitalar do Hospital Universitário, Londrina, Paraná, na região sul do Brasil, no período de julho de 2003 a julho de 2004. Do total de casos estudados (n=969), 24 pacientes (2,5%) tinham o diagnóstico de AIDS, sendo metade do gênero feminino, com contagem média de células T CD4+ de 158,4/mm³. A principal topografia foi o sítio pulmonar (50,0%), sendo Staphylococcus aureus, Pseudomonas aeruginosa e Escherichia coli os principais microrganismos isolados. Observou-se maior incidência de infecção em pacientes com contagem de células T CD4+ menor que 50/mm³. O estudo da relação entre sistema imunológico e microrganismos causadores de infecções poderá contribuir para melhorias nos cuidados de pacientes com AIDS e avanços nos sistemas de controle de infecção hospitalar.
RESUMO
The natural history and pathogenic processes of infection by the human immunodeficiency virus type 1 (HIV-1) are complex, variable, and dependent upon a multitude of viral and host factors and their interactions. The CCR5-Delta32 allele remains the most important genetic factor known to be associated with host resistance to the HIV-1 infection. However, other mutations in the CCR5, CCR2, CX(3)CR1, CXCL12 (SDF1), and CCL5 (RANTES) genes have been identified and associated with host resistance and/or susceptibility to HIV-1 infection and disease progression. Some studies have also suggested that chemokine receptor gene polymorphisms may affect response to potent antiretroviral therapy. This article reviews the polymorphisms already described in the mutant chemokine receptors or ligands and their impact on the host susceptibility to HIV-1 infection and on the clinical course of the disease, as well as the development of new anti-HIV therapies that takes into account these potential targets in the host. These genetic polymorphisms could be used as genetic markers to detect individuals at higher risk of developing either a faster disease progression or therapeutic failure. Once these individuals are identified, therapeutic strategies based on either different, more aggressive drugs or combinations of drugs can be used, either alone or in combination with shorter intervals for therapeutic monitoring. Pharmacogenetics is very likely to underlie future therapies for HIV-1 infection, and current patients with multi-resistance to the existing antiretroviral agents could also benefit from this approach. These developments also underscore the importance of continuing the investigation of new therapies targeted to the host in order to inhibit the HIV-1 entry into the host cells.