Heat shock protein bystander antigens for peptide immunotherapy in autoimmune disease.

Mucosal administration of an antigen eliciting bystander suppression at the site of inflammation results in effective antigen-specific immunotherapy for autoimmune diseases. Heat shock proteins are bystander antigens that are effective in peptide-specific immunotherapy in both experimental and human autoimmune disease. The efficacy of preventive peptide immunotherapy is increased by enhancing peptide-specific immune responses with proinflammatory agents. Combining peptide-specific immunotherapy with general suppression of inflammation may improve its therapeutic effect.

Risk Factors for Relapse in Childhood Nephrotic Syndrome.

Minimal change nephrotic syndrome is the most common cause of the glomerular disease in children. Despite its high initial response to corticosteroids, relapses are common leading to increased morbidity. Therefore, appraisal of common triggers of relapse becomes an imperative for successful management of childhood nephrotic syndrome. The objective of the study was to identify the risk factors for frequent relapse in childhood nephrotic syndrome. This descriptive cross-sectional study was conducted in the department of Paediatrics, Rangpur Medical College Hospital, Bangladesh from January 2013 to December 2014. A total of 60 patients with relapsed idiopathic childhood nephrotic syndrome fulfilling the selection criteria were enrolled into the study. Serum total protein, serum albumin and urine culture were done. The following potential risk factors for relapse were analyzed using Chi-square test: age at onset of NS, sex, socioeconomic status, atopy, short duration of initial therapy with steriod, serum total protein, serum albumin level and infection. Among 60 patients, short duration of therapy with steriod (<8 weeks) for first attack was significantly higher among frequent relapse (FRNS) cases compared with infrequent relapse (IFRNS) group (63% vs. 27.27%). FRNS group had initial brief period of remission of <6 months, (p=0.04). Difference in mean serum albumin and that of serum total protein between FRNS and IFRNS cases was (1.0±0.66 vs. 2.66±1.6gm/dl) (p<0.0001) and (3.5±1.2 vs. 6.5±2.12gm/dl) (p<0 .0001) respectively. This study concluded that short initial therapy with corticosteroid, brief duration of initial remission; low serum total protein and decreased serum albumin were the risk factors for frequent relapses.

Artificial antigen-presenting cells as a tool to exploit the immune 'synapse'.

Recent progress in molecular medicine has provided important tools to identify antigen-specific T cells. In most cases, the approach is based on oligomeric combinations of recombinant major histocompatibility complex-peptide complexes fixed to various rigid supports available for binding by the T-cell receptor. These tools have greatly increased our insight into mechanisms of immune responses mediated by CD8+ T cells. Examples of the diverse fields of application for this technology include immunization, viral infections and oral tolerance induction.

Positive selection in autoimmunity: abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis.

A novel 'multistep molecular mimicry' mechanism for induction of rheumatoid arthritis (RA) by bacterial antigens that activate T lymphocytes previously 'educated' by peptides derived from a class of human histocompatibility antigens is reported here. These antigens have the amino acid sequence QKRAA, which is also present on the Escherichia coli heat-shock protein dnaJ. Synovial fluid cells of early RA patients have strong immune responses to the bacterial antigen, but cells from normal subjects or controls with other autoimmune diseases do not. The activated T cells may cross-react with autologous dnaJ heat-shock proteins that are expressed at synovial sites of inflammation. Our findings may have direct relevance to new strategies for the immune therapy of RA.

Comparison of WHO Clinical Criteria and Radiological Findings of Pneumonia in Children Aged 02-59 Months.

Despite recent advances, pneumonia contributes substantially to childhood mortality in low and middle-income countries. To reduce case fatality, World Health Organization (WHO) adopted a working formula to identify pneumonia clinically in resource constrained setting. Chest X-ray is the gold standard test to diagnose pneumonia but this tool is not readily available or affordable in primary health facility in developing countries even when it is indicated. Objective of the study was to compare WHO clinical criteria and radiological findings of pneumonia in children aged 02-59 months. This cross-sectional observational study was conducted at inpatient department of Paediatrics of Rangpur Medical College Hospital from July 2015 to June 2017. Total 112 patients aged 2 to 59 months fulfilling selection criteria were enrolled into this study. Data were collected and chest X-ray was done for each patient. Data were analyzed through SPSS software (version 16.0). Minimum level of significance was predetermined as p<0.05. Among 112 patients, mean age of chest radiograph positive cases of pneumonia was 7.64±7.08 months and that of negative cases 10.75±10.95 months. There was no statistically significant difference of age (p=0.083) between chest radiography positive and negative cases. Radiological findings were positive in 52(46.43%) cases and negative in 60(53.57%). Fever, cough and fast breathing were present in all patients with sensitivity 100%. Chest indrawing was significantly more (p=0.003) among 52(46.43%) cases who demonstrated positive radiological findings with sensitivity 63.46% (95% CI = 48.96% to 76.37%). There was no statistically significant difference of fever, cough and fast breathing between radiograph positive and negative cases. Chest indrawing was significantly more in radiograph positive cases. The results highlighted the importance of adoption of positive radiograph of WHO guideline to identify pneumonia.

Multiple metals and agricultural use affects oxidative stress biomarkers in freshwater Aegla crabs.

Metals and agrochemicals are among the main aquatic contaminants, being able to trigger oxidative stress in exposed organisms. The objective of this work was to evaluate the correlation between the level of oxidative stress biomarkers in Aegla crabs (Crustacea, Anomura) with (i) the set of metals present in the streams sediment and (ii) with land uses of three hydrographic basins. The study was carried out in streams (≤ 2nd order) of hydrographic basins in southern Brazil (Basins of Rio Suzana, Rio Ligeirinho-Leãozinho and Rio Dourado). In these streams were quantified the land uses and Cu, Cr, Cd, Fe, Mn and Zn concentrations in the sediment. The enzymes Catalase (CAT) and Glutathione Reductase (GR), as well as the level of membrane lipid peroxidation (TBARS), were analyzed in adult females. The PCA analysis showed that the distribution of metals was different between the basins. Cd, Cr and Fe were correlated positively with CAT and negatively with TBARS and GR. The Dourado basin had the lowest concentrations of these three metals and the highest levels of TBARS. However, in Dourado basin there is predominance of agriculture land use, and TBARS was positively correlated with agricultural land use. Besides in Dourado basin, GR activity was higher than in the others basins, indicating a compensatory response in relation to CAT inhibition. The basins of Suzana and Ligeirinho-Leãozinho rivers had lower TBARS values, which may be due to the induction of CAT in response to metals accumulated in sediment. In summary, this work indicates that in the basins with a higher concentration of toxic metals there is an adaptive response of CAT induction, which reduces TBARS in Aegla. On the other hand, in the basin with lower metallic contamination, TBARS occurrence was primarily influenced by agricultural land use.

Efficacy of F-75 & F-100 Recipes in theTreatment of Severe Acute Malnutrition: A Randomized Controlled Trial.

Severe malnutrition is an important cause of death in children. According to new WHO-growth chart 2006, the proportion of children with severe wasting is 3.1% thus the total number being 4, 65000 (BDHS 2014). Overall risk of death among children with severe acute malnutrition (SAM) is 9 times more than well nourished children. The death rate among hospitalized children of SAM was as high as 15%. Once properly treated, severely malnourished children would grow up leading a normal life. Severe malnutrition in children can be successfully treated by using WHO guidelines that have been shown to be feasible and sustainable even in small district hospital with limited resources. A randomized controlled trial was conducted at department of Pediatrics, Dhaka Medical College Hospital, Dhaka, Bangladesh from July 2014 to September 2015. The trial enrolled 92 SAM patients (46 cases + 46 controls) aged 06 months to 59 months of either sex who meet the inclusion criteria consecutively. Enrolled children were randomized by lottery method into two groups, Group I and Group II. Patients in Group I was treated with F-75 and F-100 recipes and managed in two phases, initial stabilization phase with F-75 recipes then subsequently rehabilitation phase by F-100 recipes. Patients in Group II was treated with prepackaged F-75 & F-100 formulae and feeding was given in two phases i.e. initial stabilization phase and subsequently rehabilitation phase according to national guidelines for the management of severe malnourished children. Then play therapy was given for half an hour daily with red colored toy in Ashic play centre Dhaka Medical College Hospital for patients of both groups. The time (days) taken to return of appetite (mean±SD) was 5.1±1.16 and 4.8±1.34 in Group I and Group II respectively, disappearance of edema (mean±SD) 4.8±1.53 in and 4.9±1.05 for Group I Group II respectively, to gain target weight (mean±SD) 13.8±2.20 days and 13.5±1.74 days in Group I and Group II respectively, rate of weight gain (mean±SD) 17.70±7.07gm/kg/day for Group I and 16.20±4.63gm/kg/day for Group II. The side effects, diarrhea was equal in both group, vomiting was more in Group II, combined diarrhea and vomiting was more in Group I but the differences were not statistically significant. The treatment cost (mean±SD) was higher in Group II (97.2±78.24 BDT/child/day) than in Group I (58.5±54.36 BDT/child/day). Return of appetite and disappearance of oedema and target weight gain were similar in both groups but treatment cost was higher in Group II than Group I, which was statistically significant.

Diagnostic Performance of RBC Indices in Beta Thalassaemia Trait.

Beta thalassaemia trait is one of the most common forms of thalassaemia in Bangladesh. This clinical entity usually remains undiagnosed because they present with mild anaemia or sometimes no anaemia. Determination of trait is the mainstay of prevention of thalassaemia. RBC indices can provide valuable diagnostic tool for beta thalassaemia trait. This was a hospital based cross-sectional, analytical study, done at Department of Paediatrics, Rangpur Medical College Hospital, Rangpur, Bangladesh from July 2014 to June 2016. A total of 150 anaemic children, aged 1-15 years from inpatient and outpatient department were included by purposive sampling. Blood samples were collected and sent to the Department of Biochemistry, Rangpur Medical College to determine the value of RBC indices. Out of 150 anaemic children 37(24.66%) children were diagnosed as E-trait, 9(9%) E-disease 6(4%) as E-Beta thalassaemia, 1(0.66%) had error in the report, a total of 53 children were excluded from the study. Finally, 32(21.3%) children, diagnosed as beta thalassaemia trait and 65(43.33%) children, diagnosed as normal Hb variant, so a total of 97 children were enrolled in this study. Age of the children was 1-15 years. Their mean age was 6.4 years. Male female ratio was 1.15:1. There was significant difference of HbA2 between BTT and non BTT group of participants (p value <0.001). Value of MCV and MCH were significantly greater in BTT than non BTT group (p value <0.05). Sensitivity, Specificity, Positive predictive value, Negative predictive value and Youden index of MCV were 81.25%, 90.76%, 81%, 90% and 71 respectively. Sensitivity, Specificity, Positive predictive value, Negative predictive value and Youden index of MCH were 84.37%, 92.30%, 84%, 92% and 76 respectively.

Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis.

By using a sandwich ELISA, soluble human IL-6 receptor (sIL-6 R) levels were measured in the sera of 20 healthy children and of 25 patients with systemic juvenile rheumatoid arthritis (JRA). In patients with systemic JRA, serum sIL-6 R levels (114.6 +/- 37.7 ng/ml) were significantly lower (P < 0.01) than those of healthy children (161.2 +/- 45.5 ng/ml). Serum sIL-6 R levels were negatively correlated (r = -0.610, P < 0.001) with serum IL-6 levels measured with the B9 cells. The serum IL-6/sIL-6 R complex was detected using an ELISA based on a monoclonal antibody to IL-6 for capture and on a monoclonal antibody to human sIL-6 R for detection. Healthy controls had little, if any, detectable serum IL-6/sIL-6 R complex (OD 0.024 +/- 0.027), while the majority of patients with systemic JRA presented measurable serum IL-6/sIL-6 R complex (OD 0.492 +/- 0.546). IL-6 levels estimated in the circulating IL-6/sIL-6 R complexes were in the range of nanograms per milliliter and approximately 20-fold higher than those measured by the B9 cells. Since serum C-reactive protein concentrations were much more correlated with serum levels of IL-6/sIL-6 R complexes (r = 0.713, r2 = 0.51, P < 0.0001) than with the serum IL-6 levels measured with the B9 cells (r = 0.435, r2 = 0.19, P = 0.05), the large quantities of serum IL-6 present in IL-6/sIL-6 R complexes appear to be biologically relevant in vivo, at least as far as the induction by IL-6 of acute phase protein production.

The susceptibility sequence to rheumatoid arthritis is a cross-reactive B cell epitope shared by the Escherichia coli heat shock protein dnaJ and the histocompatibility leukocyte antigen DRB10401 molecule.

Immunological responses to bacterial heat shock proteins have been implicated in the pathogenesis of arthritis in animals and humans. The predicted amino acid sequence of dnaJ, a heat shock protein from Escherichia coli, contains an 11-amino acid segment that is homologous to the third hypervariable region of the human histocompatibility antigen (HLA) DRB10401 (formerly known as HLA Dw4), the part of the molecule that carries susceptibility to rheumatoid arthritis. To test the biological significance of this finding, we expressed and purified recombinant dnaJ (rdnaJ), and determined its immunologic cross-reactivity with HLA DRB10401. A rabbit antipeptide antiserum raised against the sequence of the third hypervariable region of HLA DRB10401 specifically bound to 'dnaJ, thus confirming that a similar sequence is expressed on the bacterial protein. Of greater consequence, an antiserum to the 'dnaJ protein recognized not only a peptide from the third hypervariable region of HLA DRB10401, but also the intact HLA DRB10401 polypeptide. Furthermore, the antibody to 'dnaJ reacted with HLA DRB10401 homozygous B lymphoblasts, but not with HLA DRB11501, DRB10101, DRB10301, and DRB10701 (formerly known as HLA Dw2, DR 1, DR 3, and DR 7, in the same order) homozygous cells. These results demonstrate that exposure to a bacterial heat shock protein can elicit antibodies against the rheumatoid arthritis susceptibility sequence in the third hypervariable region of HLA DRB10401.

Genetic bias in immune responses to a cassette shared by different microorganisms in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease associated with HLA-DRbeta1 alleles which contain the QKRAA amino acid sequence in their third hypervariable region(s). The QKRAA sequence is also expressed by several human pathogens. We have shown previously that an Escherichia coli peptide encompassing QKRAA is a target of immune responses in RA patients. Here we address two questions: first, whether QKRAA may function as an "immunological cassette" with similar, RA-associated, immunogenic properties when expressed by other common human pathogens; and second, what is the influence of genetic background in the generation of these responses. We find that early RA patients have enhanced humoral and cellular immune responses to Epstein-Barr virus and Brucella ovis and Lactobacillus lactis antigens which contain the QKRAA sequence. These results suggest that the QKRAA sequence is an antigenic epitope on several different microbial proteins, and that RA patients recognize the immunological cassette on different backgrounds. ANOVA of immune responses to "shared epitope" antigens in monozygotic twin couples shows that, despite significantly elevated responses in affected individuals, a similarity between pairs is retained, thus suggesting a role played either by hereditary or shared environmental factors in the genesis or maintenance of these responses.

Multiple metals and agricultural use affects oxidative stress biomarkers in freshwater Aegla crabs / Presença de múltiplos metais e agricultura afetam biomarcadores de estresse oxidativo em caranguejos de água doce (Aegla)

Metals and agrochemicals are among the main aquatic contaminants, being able to trigger oxidative stress in exposed organisms. The objective of this work was to evaluate the correlation between the level of oxidative stress biomarkers in Aegla crabs (Crustacea, Anomura) with (i) the set of metals present in the streams sediment and (ii) with land uses of three hydrographic basins. The study was carried out in streams (≤ 2nd order) of hydrographic basins in southern Brazil (Basins of Rio Suzana, Rio Ligeirinho-Leãozinho and Rio Dourado). In these streams were quantified the land uses and Cu, Cr, Cd, Fe, Mn and Zn concentrations in the sediment. The enzymes Catalase (CAT) and Glutathione Reductase (GR), as well as the level of membrane lipid peroxidation (TBARS), were analyzed in adult females. The PCA analysis showed that the distribution of metals was different between the basins. Cd, Cr and Fe were correlated positively with CAT and negatively with TBARS and GR. The Dourado basin had the lowest concentrations of these three metals and the highest levels of TBARS. However, in Dourado basin there is predominance of agriculture land use, and TBARS was positively correlated with agricultural land use. Besides in Dourado basin, GR activity was higher than in the others basins, indicating a compensatory response in relation to CAT inhibition. The basins of Suzana and Ligeirinho-Leãozinho rivers had lower TBARS values, which may be due to the induction of CAT in response to metals accumulated in sediment. In summary, this work indicates that in the basins with a higher concentration of toxic metals there is an adaptive response of CAT induction, which reduces TBARS in Aegla. On the other hand, in the basin with lower metallic contamination, TBARS occurrence was primarily influenced by agricultural land use.

Os metais e agroquímicos estão entre os principais contaminantes aquáticos, podendo desencadear estresse oxidativo em organismos expostos. O objetivo deste trabalho foi avaliar uma possível correlação entre o nível de biomarcadores de estresse oxidativo em Aegla (Crustacea, Anomura) com (i) o conjunto de metais presentes no sedimento e (ii) com os usos da terra, em três bacias hidrográficas distintas. O estudo foi realizado em riachos (≤ 2ª ordem) de bacias hidrográficas do Sul do Brasil (Bacias do Rio Suzana, do Rio Ligeirinho-Leãozinho e do Rio Dourado), as quais foram caracterizadas em função do percentual de usos da terra e do nível de Cu, Cr, Cd, Fe, Mn e Zn no sedimento. As enzimas Catalase (CAT) e Glutationa Redutase (GR), bem como o nível de peroxidação lipídica das membranas (TBARS), foram analisadas em fêmeas adultas. Uma análise de PCA mostrou que a distribuição de metais foi distinta entre as bacias. Cd, Cr e Fe no sedimento correlacionaram positivamente com a CAT e negativamente com TBARS e GR. Entretanto, a bacia do Dourado apresentou os menores níveis destes três metais e os maiores níveis de TBARS, o que pode ser justificado pelo predomínio da agricultura nesta bacia, já que o TBARS correlacionou positivamente com o percentual de uso agrícola. Nesta bacia, a atividade da GR foi mais alta do que nas outras, indicando uma resposta compensatória em relação a inibição da CAT. As bacias do rio Suzana e rio Ligeirinho-Leãozinho apresentaram valores menores de TBARS, o que pode decorrer da indução da CAT em função dos metais acumulados no sedimento. Em síntese, este trabalho indica que nas bacias com maior concentração de metais tóxicos ocorre uma resposta adaptativa de indução da CAT, o que reduz os níveis de TBARS em Aegla. Por outro lado, na bacia com menor contaminação metálica os níveis de TBARS foram primariamente influenciados pelo uso agrícola.

Multiple metals and agricultural use affects oxidative stress biomarkers in freshwater Aegla crabs / Presença de múltiplos metais e agricultura afetam biomarcadores de estresse oxidativo em caranguejos de água doce (Aegla)

Metals and agrochemicals are among the main aquatic contaminants, being able to trigger oxidative stress in exposed organisms. The objective of this work was to evaluate the correlation between the level of oxidative stress biomarkers in Aegla crabs (Crustacea, Anomura) with (i) the set of metals present in the streams sediment and (ii) with land uses of three hydrographic basins. The study was carried out in streams (≤ 2nd order) of hydrographic basins in southern Brazil (Basins of Rio Suzana, Rio Ligeirinho-Leãozinho and Rio Dourado). In these streams were quantified the land uses and Cu, Cr, Cd, Fe, Mn and Zn concentrations in the sediment. The enzymes Catalase (CAT) and Glutathione Reductase (GR), as well as the level of membrane lipid peroxidation (TBARS), were analyzed in adult females. The PCA analysis showed that the distribution of metals was different between the basins. Cd, Cr and Fe were correlated positively with CAT and negatively with TBARS and GR. The Dourado basin had the lowest concentrations of these three metals and the highest levels of TBARS. However, in Dourado basin there is predominance of agriculture land use, and TBARS was positively correlated with agricultural land use. Besides in Dourado basin, GR activity was higher than in the others basins, indicating a compensatory response in relation to CAT inhibition. The basins of Suzana and Ligeirinho-Leãozinho rivers had lower TBARS values, which may be due to the induction of CAT in response to metals accumulated in sediment. In summary, this work indicates that in the basins with a higher concentration of toxic metals there is an adaptive response of CAT induction, which reduces TBARS in Aegla. On the other hand, in the basin with lower metallic contamination, TBARS occurrence was primarily influenced by agricultural land use.

Os metais e agroquímicos estão entre os principais contaminantes aquáticos, podendo desencadear estresse oxidativo em organismos expostos. O objetivo deste trabalho foi avaliar uma possível correlação entre o nível de biomarcadores de estresse oxidativo em Aegla (Crustacea, Anomura) com (i) o conjunto de metais presentes no sedimento e (ii) com os usos da terra, em três bacias hidrográficas distintas. O estudo foi realizado em riachos(≤ 2ª ordem) de bacias hidrográficas do Sul do Brasil (Bacias do Rio Suzana, do Rio Ligeirinho-Leãozinho e do Rio Dourado), as quais foram caracterizadas em função do percentual de usos da terra e do nível de Cu, Cr, Cd, Fe, Mn e Zn no sedimento. As enzimas Catalase (CAT) e Glutationa Redutase (GR), bem como o nível de peroxidação lipídicadas membranas (TBARS), foram analisadas em fêmeas adultas. Uma análise de PCA mostrou que a distribuição de metais foi distinta entre as bacias. Cd, Cr e Fe no sedimento correlacionaram positivamente com a CAT e negativamente com TBARS e GR. Entretanto, a bacia do Dourado apresentou os menores níveis destes três metais e os maiores níveis de TBARS, o que pode ser justificado pelo predomínio da agricultura nesta bacia, já que o TBARS correlacionou positivamente com o percentual de uso agrícola. Nesta bacia, a atividade da GR foi mais alta do que nas outras, indicando uma resposta compensatória em relação a inibição da CAT. As bacias do rio Suzana e rio Ligeirinho-Leãozinho apresentaram valores menores de TBARS, o que pode decorrer da indução da CAT em função dos metais acumulados no sedimento. Em síntese, este trabalho indica que nas bacias com maior concentração de metais tóxicos ocorre uma resposta adaptativa de indução da CAT, o que reduz os níveis de TBARS em Aegla. Por outro lado, na bacia com menor contaminação metálica os níveis de TBARS foram primariamente influenciados pelo uso agrícola.

Multiple metals and agricultural use affects oxidative stress biomarkers in freshwater Aegla crabs

Abstract Metals and agrochemicals are among the main aquatic contaminants, being able to trigger oxidative stress in exposed organisms. The objective of this work was to evaluate the correlation between the level of oxidative stress biomarkers in Aegla crabs (Crustacea, Anomura) with (i) the set of metals present in the streams sediment and (ii) with land uses of three hydrographic basins. The study was carried out in streams ( 2nd order) of hydrographic basins in southern Brazil (Basins of Rio Suzana, Rio Ligeirinho-Leãozinho and Rio Dourado). In these streams were quantified the land uses and Cu, Cr, Cd, Fe, Mn and Zn concentrations in the sediment. The enzymes Catalase (CAT) and Glutathione Reductase (GR), as well as the level of membrane lipid peroxidation (TBARS), were analyzed in adult females. The PCA analysis showed that the distribution of metals was different between the basins. Cd, Cr and Fe were correlated positively with CAT and negatively with TBARS and GR. The Dourado basin had the lowest concentrations of these three metals and the highest levels of TBARS. However, in Dourado basin there is predominance of agriculture land use, and TBARS was positively correlated with agricultural land use. Besides in Dourado basin, GR activity was higher than in the others basins, indicating a compensatory response in relation to CAT inhibition. The basins of Suzana and Ligeirinho-Leãozinho rivers had lower TBARS values, which may be due to the induction of CAT in response to metals accumulated in sediment. In summary, this work indicates that in the basins with a higher concentration of toxic metals there is an adaptive response of CAT induction, which reduces TBARS in Aegla. On the other hand, in the basin with lower metallic contamination, TBARS occurrence was primarily influenced by agricultural land use.

Resumo Os metais e agroquímicos estão entre os principais contaminantes aquáticos, podendo desencadear estresse oxidativo em organismos expostos. O objetivo deste trabalho foi avaliar uma possível correlação entre o nível de biomarcadores de estresse oxidativo em Aegla (Crustacea, Anomura) com (i) o conjunto de metais presentes no sedimento e (ii) com os usos da terra, em três bacias hidrográficas distintas. O estudo foi realizado em riachos ( 2ª ordem) de bacias hidrográficas do Sul do Brasil (Bacias do Rio Suzana, do Rio Ligeirinho-Leãozinho e do Rio Dourado), as quais foram caracterizadas em função do percentual de usos da terra e do nível de Cu, Cr, Cd, Fe, Mn e Zn no sedimento. As enzimas Catalase (CAT) e Glutationa Redutase (GR), bem como o nível de peroxidação lipídica das membranas (TBARS), foram analisadas em fêmeas adultas. Uma análise de PCA mostrou que a distribuição de metais foi distinta entre as bacias. Cd, Cr e Fe no sedimento correlacionaram positivamente com a CAT e negativamente com TBARS e GR. Entretanto, a bacia do Dourado apresentou os menores níveis destes três metais e os maiores níveis de TBARS, o que pode ser justificado pelo predomínio da agricultura nesta bacia, já que o TBARS correlacionou positivamente com o percentual de uso agrícola. Nesta bacia, a atividade da GR foi mais alta do que nas outras, indicando uma resposta compensatória em relação a inibição da CAT. As bacias do rio Suzana e rio Ligeirinho-Leãozinho apresentaram valores menores de TBARS, o que pode decorrer da indução da CAT em função dos metais acumulados no sedimento. Em síntese, este trabalho indica que nas bacias com maior concentração de metais tóxicos ocorre uma resposta adaptativa de indução da CAT, o que reduz os níveis de TBARS em Aegla. Por outro lado, na bacia com menor contaminação metálica os níveis de TBARS foram primariamente influenciados pelo uso agrícola.

Shape and size constraints on dust optical properties from the Dome C ice core, Antarctica.

Mineral dust aerosol (dust) is widely recognized as a fundamental component of the climate system and is closely coupled with glacial-interglacial climate oscillations of the Quaternary period. However, the direct impact of dust on the energy balance of the Earth system remains poorly quantified, mainly because of uncertainties in dust radiative properties, which vary greatly over space and time. Here we provide the first direct measurements of the aerosol optical thickness of dust particles windblown to central East Antarctica (Dome C) during the last glacial maximum (LGM) and the Holocene. By applying the Single Particle Extinction and Scattering (SPES) technique and imposing preferential orientation to particles, we derive information on shape from samples of a few thousands of particles. These results highlight that clear shape variations occurring within a few years are hidden to routine measurement techniques. With this novel measurement method the optical properties of airborne dust can be directly measured from ice core samples, and can be used as input into climate model simulations. Based on simulations with an Earth System Model we suggest an effect of particle non-sphericity on dust aerosol optical depth (AOD) of about 30% compared to spheres, and differences in the order of ~10% when considering different combinations of particles shapes.

Antibody reactivity against single stranded DNA of various species in normal children and in children with diffuse connective tissue diseases.

The aim of this work was to study possible differences in the humoral response against autologous and heterologous (bacterial and mammalian) ssDNA in children with diffuse connective tissue diseases (DCTD) compared with age matched controls. We found that IgM anti ssDNA were significantly increased in systemic lupus eritematosus (SLE) and in juvenile arthritis (JA), but not in juvenile dermatomyositis (JDM). IgG anti ssDNA were significantly elevated only in children with SLE. We next evaluated the binding specificity to human and bacterial ssDNA by inhibition assays. We found that SLE and JA sera recognised epitopes shared in common to endogenous and bacterial ssDNA. In contrast, in normal subjects IgG binding to bacterial DNA was not inhibited by human DNA, while IgG anti human ssDNA were cross reactive with the bacterial antigen. These data suggest that natural antibodies (IgM) producing cells are activated in some but not all DCTD, and that normal children have different reactivity against autologous and heterologous ssDNA with respect to SLE and JA patients.

Genetic and environmental factors in the immune pathogenesis of rheumatoid arthritis.

Our experiments have led us to conclude that the rheumatoid arthritis shared epitope may act as a peptide that is important for positive and negative selection of T lymphocytes, that T lymphocytes are skewed by positive selection to recognize epitopes that are similar but not identical to self, and that peptide sequences that are similar to the RA-shared epitope are abundantly expressed by microorganisms that chronically infect most people. This combination of events could partly explain the association of the shared epitope with the severe forms of RA. The hypothesis cannot be tested directly, because we do not postulate that any unique population of autoreactive T cells is expanded in RA; however, the role of positive selection in molding the human T-cell repertoire to exogenous antigens can be tested by mapping T-cell antigenic determinants on the E. coli dnaJ protein or the gp110 protein of EBV in people with different HLA-DR types. Moreover, positive selection models imply that maternal antigens that cross the placenta can influence the T-cell repertoire. Thus, one might expect to find that the frequency of HLA-DR4 in the mothers of patients with RA who themselves lack the DR4 antigen, would be more frequent than predicted by chance alone. As the principles of positive selection are more precisely delineated in animal systems, it should become possible to ascertain more clearly how the shared epitope on HLA-DR molecules enhances the severity of autoimmune reactions; however, RA only occurs in humans; possibly because of the unique inability of human macrophages to replicate. Thus, only the direct analysis of patients can directly reveal the mechanisms of disease pathogenesis.

Molecular basis for the association between HLA DR4 and rheumatoid arthritis. From the shared epitope hypothesis to a peptidic model of rheumatoid arthritis.

Susceptibility to rheumatoid arthritis (RA) maps to residues QKRAA/QRRAA in the third hypervariable region of the HLA DR beta 1 chain. Peptides from the same area of MHC class II molecules are able to modulate the T-cell repertoire by deleting self-reactive T-cells. The Epstein Barr virus glycoprotein gp110 and the dna J heat-shock protein from E. coli mimic the third hypervariable region of HLA-Dw4DR beta 1. Thus, the same area of HLA DR beta 1 carries susceptibility to RA, modulates the T-cell repertoire and is mimicked by human pathogens. RA may originate from a particular shape imposed on the T-cell repertoire by the QKRAA/QRRAA sequence in the third hypervariable region of HLA DR beta 1.

Infection and molecular mimicry in autoimmune diseases of childhood.

The etiopathogenesis of childhood chronic autoimmune disease is, in most cases, unknown. Most likely, several factors overlap in determining the loss of tolerance toward certain autoantigens that become the target of the disease and the main cause of its perpetuation. Infectious agents have often been implicated in the pathogenesis of these diseases, but, to date, compelling evidence for a horizontal transmission or for localized epidemics is lacking. Human pathogens may nevertheless play a role in determining the loss of tolerance toward certain self-antigens by means of mechanisms other than classic infection. It is common knowledge that human pathogens often express proteins with high antigenic potential with important homologies with human proteins. Evolutionary pressures based upon the necessity of escaping the host's specific immune responses may have determined this phenomenon, called "molecular mimicry". It is reasonable to assert that certain individuals can develop abnormal immune responses upon contact with an antigen that mimics a self-protein. These responses may ultimately lead to self-reactivity and autoimmune disease. In this model of molecular mimicry, self-reactivity is triggered by cross-recognition of a self and an exogenous protein that bear the same sequence. A disease triggered by such a mechanism should present with: i) some form of an acute or chronic autoimmune clinical manifestation; ii) a documented clinical correlation between contact with a human pathogen and the autoimmune disease; iii) immune cross-reaction between a protein from a pathogen and a homologous human protein. Acute rheumatic fever, Reiter's syndrome and the other reactive arthritides fulfill the above conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-double stranded DNA, anti-histone, and anti-nucleosome IgG reactivities in children with systemic lupus erythematosus.

In this study we evaluated the presence of anti-nucleosome reactivity in children with systemic lupus erythematosus (SLE), and assessed its clinical correlations in comparison with anti-dsDNA and anti-histone IgG levels. Reactivities to nuclear substrates were determined by enzymatic immunoassays in 80 sera from 22 children with SLE, and solid phase adsorption experiments were performed. In children with active SLE, the anti-dsDNA, anti-histone, and anti-nucleosome IgG levels were elevated, and were significantly correlated with disease severity; during remission anti-histone (but not anti-dsDNA and anti-nucleosome) antibodies, although reduced, were still significantly elevated. The results of adsorption studies showed that anti-dsDNA antibodies contributed to anti-nucleosome reactivity, while anti-histone antibodies did not. The recognition of the H3H4-DNA nucleosome subparticle, rather than H2AH2B-DNA, may be related to the nucleosome reactivity. In children with SLE anti-nucleosome reactivity is present; it is in part due to anti-dsDNA antibodies and in part to antibodies recognizing conformational epitopes that may be related to the H3H4-DNA nucleosome subparticle. Its clinical significance for diagnosis is not greater than that of the anti-dsDNA antibodies.