Tumor necrosis factor beta (TNF-ß) NcoI polymorphism is associated with multiple sclerosis in Caucasian patients from Southern Brazil independently from HLA-DRB1.

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.

Hypertension is associated with serologically active disease in patients with systemic lupus erythematosus: role of increased Th1/Th2 ratio and oxidative stress.

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.

Clinical insights from adiponectin analysis in breast cancer patients reveal its anti-inflammatory properties in non-obese women.

Adiponectin is a cytokine reported as a determinant of poor prognosis in women with breast cancer. However, because data regarding its role in breast cancer have been obtained primarily from studies employing overweight or obese women, the adiponectin profile in non-obese women is poorly understood. In this study, we determined adiponectin levels in plasma from non-obese women with breast cancer and investigated a possible correlation with systemic inflammatory status. We determined the plasma adiponectin levels as well as biochemical and oxidative stress parameters in 80 women. Our results revealed that plasma adiponectin levels were affected by chemotherapy, estrogen receptor status, and disease progression. Adiponectin was positively correlated with antioxidant levels, without affecting either the metastatic behavior of disease or patient outcome. These findings highlight adiponectin as a novel player in the endocrine signaling that modulates the oxidative inflammatory response in human breast cancer, and contribute to the understanding of the role of adiponectin in pathological conditions in non-obese women.

Oxidative stress is associated with liver damage, inflammatory status, and corticosteroid therapy in patients with systemic lupus erythematosus.

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.

Inflammatory biomarkers and oxidative stress measurements in patients with systemic lupus erythematosus with or without metabolic syndrome.

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.

Factors associated with seropositivity for anti-Toxoplasma gondii antibodies in pregnant women of Londrina, Paraná, Brazil.

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.

Genetic polymorphisms in the chemokine and chemokine receptors: impact on clinical course and therapy of the human immunodeficiency virus type 1 infection (HIV-1).

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.

Stromal cell-derived factor 1 (SDF1) genetic polymorphism in a sample of healthy individuals, seronegative individuals exposed to human immunodeficiency virus type 1 (HIV-1) and patients infected with HIV-1 from the Brazilian population.

The interaction of viral and host factors is believed to determine not only the risk for initial human immunodeficiency virus type 1 (HIV-1) acquisition but also the course of the infection. Genetic polymorphisms in the chemokine receptors and their ligands were related to the susceptibility and resistance to HIV-1 infection. A polymorphism in the conserved 3' untranslated region of the stromal cell-derived factor-1 (SDF1) gene, which encodes a ligand of the CXCR4 receptor, has been related either to delayed progression to AIDS or to rapid disease progression and death. Global, regional, and ethnic distributions of frequencies of SDF1 genotypes and of the SDF1-3'A allele vary significantly. Although the HIV-1 epidemic is increasing in Brazil, little information about the frequencies of host genetic mutations related to HIV/AIDS resistance in the Brazilian population has been reported. To address this question, this study was carried out in order to determine the frequencies of the SDF1 polymorphism and the SDF1-3'A allele on 1061 genomic DNA samples purified from peripheral blood cells of 136 healthy individuals (group 1), 147 HIV-1-exposed seronegative individuals (group 2), 161 HIV-1-infected asymptomatic individuals and with CD4(+) T-cells count 350 mm(-3) (group 3), and 617 HIV-1-infected individuals with AIDS and/or CD4(+) T-cells count < 350 mm(-3) (group 4). The frequencies of the SDF1-3'A homozygous mutation were 3.7%, 6.1%, 4.3%, and 5.3% among groups 1, 2, 3, and 4, respectively (P = 0.5120). The overall frequency of the SDF1-3'A allele was 0. 1984 and did not differ among the four groups (P = 0.2744). The results underscore the global distribution of the SDF1 polymorphism and the hypothesis that the SDF1-3'A allele, itself, may not be sufficient to prevent the risk of HIV-1 infection and may be not related to the progression of the disease in the Brazilian population.

Immune and hormonal activity in adults suffering from depression.

An association between depression and altered immune and hormonal systems has been suggested by the results of many studies. In the present study we carried out immune and hormonal measurements in 40 non-medicated, ambulatory adult patients with depression determined by CID-10 criteria and compared with 34 healthy nondepressed subjects. The severity of the condition was determined with the Hamilton Depression Rating Scale. Of 40 depressed patients, 31 had very severe and 9 severe or moderate depression, 29 (72.5%) were females and 11 (27.5%) were males (2.6:1 ratio). The results revealed a significant reduction of albumin and elevation of alpha-1, alpha-2 and beta-globulins, and soluble IL-2 receptor in patients with depression compared to the values obtained for nondepressed subjects (P<0.05). The decrease lymphocyte proliferation in response to a mitogen was significantly lower in severely or moderately depressed patients when compared to control (P<0.05). These data confirm the immunological disturbance of acute phase proteins and cellular immune response in patients with depression. Other results may be explained by a variety of interacting factors such as number of patients, age, sex, and the nature, severity and/or duration of depression. Thus, the data obtained should be interpreted with caution and the precise clinical relevance of these findings requires further investigation.

Immune and hormonal activity in adults suffering from depression

An association between depression and altered immune and hormonal systems has been suggested by the results of many studies. In the present study we carried out immune and hormonal measurements in 40 non-medicated, ambulatory adult patients with depression determined by CID-10 criteria and compared with 34 healthy nondepressed subjects. The severity of the condition was determined with the Hamilton Depression Rating Scale. Of 40 depressed patients, 31 had very severe and 9 severe or moderate depression, 29 (72.5 percent) were females and 11 (27.5 percent) were males (2.6:1 ratio). The results revealed a significant reduction of albumin and elevation of alpha-1, alpha-2 and beta-globulins, and soluble IL-2 receptor in patients with depression compared to the values obtained for nondepressed subjects (P<0.05). The decrease lymphocyte proliferation in response to a mitogen was significantly lower in severely or moderately depressed patients when compared to control (P<0.05). These data confirm the immunological disturbance of acute phase proteins and cellular immune response in patients with depression. Other results may be explained by a variety of interacting factors such as number of patients, age, sex, and the nature, severity and/or duration of depression. Thus, the data obtained should be interpreted with caution and the precise clinical relevance of these findings requires further investigation

[Prevalence of American trypanosomiasis, syphilis, toxoplasmosis, rubella, hepatitis B, hepatitis C, human immunodeficiency virus infection, assayed through serological tests among pregnant patients, from 1996 to 1998, at the Regional University Hospital Norte do Paraná]. / Prevalência de tripanossomíase americana, sífilis, toxoplasmose, rubéola, hepatite B, hepatite C e da infecçao pelo vírus da imunodeficiência humana, avaliada por intermédio de testes sorológicos, em gestatantes atendidas no período de 1996 a 1998 no Hospital Universitário Regional Norte do Paraná (Universidade Estaduaal de Londrina, Paraná, Brasil).

In order to evaluate the seroprevalence of the american trypanosomiasis, syphilis, toxoplasmosis, rubella, hepatitis B infection, hepatitis C infection and human immunodeficiency virus infection among pregnant women attended at the Hospital Universitário Regional Norte do Paraná, Londrina State University, Paraná, a retrospective study of the serologic results performed in the prenatal routine during the period of June 1996 to June 1998 was carried out. The rates of seropositivity were as follows: american trypanosomiasis = 0.9%, syphilis = 1.6%, toxoplasmosis = 67% (IgG) and 1.8% (IgM), rubella = 89% (IgG) and 1.2% (IgM), hepatitis B surface antigen = 0.8%, hepatitis C virus = 0.8% and human immunodeficiency virus infection = 0.6%. An association between the increase in the seroprevalence of Chagas' disease and patient age was detected (p=0.006). The results underscore the importance of the serological tests in perinatal care, to prevent both the congenital and perinatally transmitted forms of theses infectious diseases.

Capacidade fagocítica de polimorfonucleares (PMN) humanos frente a várias partículas: Candida albicans, Zymosan, Staphylococcus aureus, Micrococcus, Escherichia coli / Phagocytosis capacity of the human neutrophils (PMN) against some particles

O processo de fagocitose envolve a ligação de partículas a receptores de superfície, resultando em indução de sinais intracitoplasmáticos e internalização de partículas, tendo importante papel na evolução das moléstias infecciosas, principalmente das bacterianas. Neste trabalho, nos propusemos a estudar a fagocitose “in vitro”, por meio do isolamento de PMN do sangue periférico de 17 amostras provenientes de doadores do Hemocentro do HURNP colocados em contato com as diversas partículas acima citadas. Com o objetivo de se obter a indicação da partícula mais adequada para uso na rotina laboratorial, as características avaliadas foram a capacidade fagocítica e a facilidade de leitura ao microscópio ótico. Os resultados obtidos indicam maior capacidade fagocítica (em porcentagem de células que apresentaram fagocitose) quando se faz uso da partícula de Zymosan (77 por cento) seguido de C. albicans (70 por cento) e o maior índice de partículas fagocitadas (em porcentagem de células que fagocitaram acima de 4 partículas) quando se fez uso de Zymozan (50 por cento) seguido de S. aureus (37 por cento) permitindo concluir que destas partículas a mais adequada para uso na rotina laboratorial é o Zimosan.

Seropositivity for anti-trypanosoma cruzi antibodies among blood donors of the "Hospital Universitário Regional do Norte do Paraná", Londrina, Brazil.

The most frequent form of acquisition of Chagas' disease in endemic areas was the transmission through the feces of contaminated triatominae. However, special attention should be paid in urban areas to transmission by blood transfusion, justifying the compulsory screening of blood donors. Early investigations at blood banks in the town of Londrina, Brazil, demonstrated that the seroprevalence of anti-Trypanosoma cruzi antibodies among blood donors was approximately 7.0% in the fifties. Further studies demonstrated practically the same seroprevalence until the eighties. In an attempt to obtain data about the real dimension of the seropositivity for anti-Trypanosoma cruzi antibodies in the region, the authors carried out a large-scale study on 45,774 serum samples from blood donors of the Hemocentro of Hospital Univesitário Regional do Norte do Paraná (HURNP), Universidade Estadual de Londrina. The immunological tests were done at the Division of Clinical Immunology of HURNP from May 1990 to December 1994. The serum samples were studied by the indirect hemagglutination assay (IHA, using kits commercially obtained from EBRAM) and by indirect immunofluorescence (IFI, using kits from LIO SERUM) with anti-human IgG conjugate (LABORCLIN). The results demonstrated that 643 serum samples were positive in both assay corresponding to a seroprevalence of 1.4%, i.e., a significant decrease in anti-Trypanosoma cruzi antibodies in the region in comparison with the previously mentioned rates. Data correlating sex and age of seropositive blood donors are presented, as well as the possible factors that may have contributed to the results observed.

Soropositividade para Doença de Chagas em pacientes com infecção pelo vírus da imunodeficiência humana (HIV) no Hospital Universitário Regional do Norte do Paraná (HURNP), Londrina, Paraná / Soropositivity to Chagas disease in patients with human immunodeficient virus infection attended at Hospital Universitário Regional do Norte do Paraná (HURNP), Londrina, Brazil

A reativação das formas indeterminadas e crônicas da Doença de Chagas (DC) tem sido associada com leucemias, linfomas, transplantes e infecção pelo vírus da imunodeficiência humana (HIV), segundo Rocha et al; Pitella; Uip et ai. Devido à disseminação da síndrome da imunodeficiência adquirida (SIDA) na América Latina, onde o DC continua sendo uma importante endemia, há um presente e crescente risco de co-infecção com o HIV e o Trypanossoma Cruzi, afirmam Amato e Neto et al. O objetivo deste trabalho é determinar a freqüência desta associação nos pacientes atendidos no HURNP, Londrina Paraná. Os resultados das reações sorológicas para DC (HAI, IFI, E ELISA) realizados em 181 soros randomicamente selecionados de pacientes com testes anti-HIV reagentes (Elisa e Western Blot) foram analisados. Entre eles, 4 (2,20%) mostraram resultados positivos em, pelo menos, duas reações sorológicas para DC; 4 (2,20%) somente na HAI; 2 (1,10% somente na IFI e 1 (0,55%) mostrou resultados duvidosos na HAI; 2 (1,10%) somente na IFI e 1 (0,55%) mostrou resultados duvidosos na HAI E IFI. O fato de que a migração tem levado a DC a novas regiões geográficas e de que a DC tem sido crescentemente diagnosticada em populações urbanas, onde há uma alta prevalência de infecção pelo HIV, segundo Rocha et al, reforça a importância de se considerar o T.cruzi outro importante patógeno oportunista associado com a SIDA, especialmente em regiões endêmicas para o T.cruzi.

Anticorpo anti-Trypanosoma cruzi como fator de reatividade cruzada na pesquisa de anticorpos anti-DNA por imunofluorescência indireta / Anti-Trypanosoma cruzi antibodies as a factor of cross-reactivity in the research of anti-DNA antibodies by indirect immunofluorescence

Na pesquisa de anticorpos anti-DNA podem ser utilizadas várias metodologias como a imunofluorescência indireta (IFI), enzimaimunoensaio (ELISA) ou radioimunoensaio (RIE) com DNA marcado com 14C, sendo que a IFI empregando Crithçidia luciliae como substrato é a mais utilizada. Sendo este um parasita flagelado da família dos tripanosomatídeos, apresenta estruturas antigênicas comuns ao Trypanosoma cruzi. Portanto, soros de pacientes com sorologia positiva para Doença de Chagas (DC) podem apresentar uma reatividade cruzada entre estes parasitas, constituindo um fator interferente na reação de IFI para pesquisa de anticorpos anti-DNA. Com o objetivo de verficar a freqüência com que esta inferência ocorre na rotina laboratorial, analisou-se os resultados obtidos na pesquisa de anti-DNA por IFI realizadas no período de junho de 1994 a julho de 1995 no Setor de Imunologia Clínica do Hospital Universitário Regional do Norte do Paraná, Londrina-Paraná. Das 927 reações realizadas, 60 (6,47%) foram reagentes, 832 (89,75%) não reagentes e 35 (3,77%) apresentaram um padrão inespecífico de fluorescência. Suspeitando-se de reatividade cruzada, foram realizadas reações sorológicas para DC (HAI e IFI) nestas amostras, sendo que 100% apresentaram resultados reagentes para ambas as reações. Estes dados confirmam a interferência dos anticorpos anti-Trypanosoma cruzi na pesquisa de anticorpos anti-DNA por IFI e alertam para a necessidade da confirmação de resultados falsos-positivos, principalmente em regiões onde a DC é endêmica.