Germinal center architecture disturbance during Plasmodium berghei ANKA infection in CBA mice

<p>Abstract</p> <p>Background</p> <p>Immune responses to malaria blood stage infection are in general defective, with the need for long-term exposure to the parasite to achieve immunity, and with the development of immunopathology states such as cerebral malaria in many cases. One of the potential reasons for the difficulty in developing protective immunity is the poor development of memory responses. In this paper, the potential association of cellular reactivity in lymphoid organs (spleen, lymph nodes and Peyer's patches) with immunity and pathology was evaluated during <it>Plasmodium berghei </it>ANKA infection in CBA mice.</p> <p>Methods</p> <p>CBA mice were infected with 1 × 10⁶<it>P. berghei </it>ANKA-parasitized erythrocytes and killed on days 3, 6–8 and 10 of infection. The spleen, lymph nodes and Peyer's patches were collected, fixed in Carson's formalin, cut in 5 μm sections, mounted in glass slides, stained with Lennert's Giemsa and haematoxylin-eosin and analysed with bright-field microscopy.</p> <p>Results</p> <p>Early (day 3) strong activation of T cells in secondary lymphoid organs was observed and, on days 6–8 of infection, there was overwhelming activation of B cells, with loss of conventional germinal center architecture, intense centroblast activation, proliferation and apoptosis but little differentiation to centrocytes. In the spleen, the marginal zone disappeared and the limits between the disorganized germinal center and the red pulp were blurred. Intense plasmacytogenesis was observed in the T cell zone.</p> <p>Conclusion</p> <p>The observed alterations, especially the germinal center architecture disturbance (GCAD) with poor centrocyte differentiation, suggest that B cell responses during <it>P. berghei </it>ANKA infection in mice are defective, with potential impact on B cell memory responses.</p

Embryonic desiccation resistance in Aedes aegypti: presumptive role of the chitinized Serosal Cuticle

<p>Abstract</p> <p>Background</p> <p>One of the major problems concerning dengue transmission is that embryos of its main vector, the mosquito <it>Aedes aegypti</it>, resist desiccation, surviving several months under dry conditions. The serosal cuticle (SC) contributes to mosquito egg desiccation resistance, but the kinetics of SC secretion during embryogenesis is unknown. It has been argued that mosquito SC contains chitin as one of its components, however conclusive evidence is still missing.</p> <p>Results</p> <p>We observed an abrupt acquisition of desiccation resistance during <it>Ae. aegypti </it>embryogenesis associated with serosal cuticle secretion, occurring at complete germ band extension, between 11 and 13 hours after egglaying. After SC formation embryos are viable on dry for at least several days. The presence of chitin as one of the SC constituents was confirmed through Calcofluor and WGA labeling and chitin quantitation. The <it>Ae. aegypti </it>Chitin Synthase A gene (<it>AaCHS1</it>) possesses two alternatively spliced variants, <it>AaCHS1a </it>and <it>AaCHS1b</it>, differentially expressed during <it>Ae. aegypti </it>embryonic development. It was verified that at the moment of serosal cuticle formation, <it>AaCHS1a </it>is the sole variant specifically expressed.</p> <p>Conclusion</p> <p>In addition to the peritrophic matrix and exoskeleton, these findings confirm chitin is also present in the mosquito serosal cuticle. They also point to the role of the chitinized SC in the desiccation resistance of <it>Ae. aegypti </it>eggs. <it>AaCHS1a </it>expression would be responsible for SC chitin synthesis. With this embryological approach we expect to shed new light regarding this important physiological process related to the <it>Ae. aegypti </it>life cycle.</p

Obesity and disease activity in juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>Children with physical disabilities may have an increased risk for obesity and obesity might be a risk factor for inflammatory arthritis. The aims of this study were: to determine the prevalence of obesity in children and adolescents with juvenile idiopathic arthritis (JIA), and to examine the association between obesity and disease activity in this population.</p> <p>Findings</p> <p>A cross-sectional analysis of all patients with JIA attending a pediatric rheumatology clinic, between October 2009 and September 2010, was performed. A linear regression model was used to explore the association between obesity and disease activity in patients with JIA. A total of 154 subjects were included in the analysis; median age was 10.6 years, 61% were female, and 88% were white. Obesity was found in 18%, 12% were overweight, and 3% were underweight. There was no association between obesity and JADAS-27 (Juvenile Arthritis Disease Activity Score 27), physician's assessment of disease activity, parent's assessment of child's well-being, erythrocyte sedimentation rate, number of active joints, or C-reactive protein (p-value range 0.10 to 0.95).</p> <p>Conclusions</p> <p>Although 18% of patients with JIA were obese, we did not find an association between obesity and disease activity. As obesity confers an additional health risk in children with arthritis, addressing this co-morbidity should be a health priority in patients with JIA. Future studies are necessary to further explore potential associations between obesity, development of JIA, and disease activity.</p

Peripheral blood biomarkers in multiple sclerosis.

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heteroge-neity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpre-dictable response to therapies. The major focus of the research on MS is the identification of biomarkers inbiologicalfluids, such as cerebrospinalfluid or blood, to guide patient management reliably. Because of the diffi-culties in obtaining spinalfluid samples and the necessity for lumbar puncture to make a diagnosis has reduced,the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However,currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkerscould radically alter the management of MS at critical phases of the disease spectrum, allowing for interventionstrategies that may prevent evolution to long-term neurological disability. This article provides an overview ofthis researchfield and focuses on recent advances in blood-based biomarker researc

Omental and pleural milky spots: different reactivity patterns in mice infected with Schistosoma mansoni reveals coelomic compartmentalisation

In vertebrate animals, pleural and peritoneal cavities are repositories of milky spots (MS), which constitute an organised coelom-associated lymphomyeloid tissue that is intensively activated by Schistosoma mansoni infection. This study compared the reactive patterns of peritoneal MS to pleural MS and concluded from histological analysis that they represent independent responsive compartments. Whole omentum, lungs and the entire mediastinum of 54 S. mansoni-infected mice were studied morphologically. The omental MS of infected animals were highly activated, modulating from myeloid-lymphocytic (60 days of infection) to lymphomyeloid (90 days of infection) and lymphocytic or lymphoplasmacytic (160 days of infection) types. The non-lymphoid component predominated in the acute phase of infection and was expressed by monocytopoietic, eosinopoietic and neutropoietic foci, with isolated megakaryocytes and small foci of late normoblasts and mast cells. Nevertheless, pleural or thoracic MS of infected mice were monotonous, consisting of small and medium lymphocytes with few mast and plasma cells and no myeloid component. Our data indicate that compartmentalisation of the MS response is dependent on the lymphatic vascularisation of each coelomic cavity, limiting the effects or consequences of any stimulating or aggressive agents, as is the case with S. mansoni infection

Adherence to secondary prophylaxis and disease recurrence in 536 Brazilian children with rheumatic fever

<p>Abstract</p> <p>Background</p> <p>More than 15 million people worldwide have rheumatic fever (RF) and rheumatic heart disease due to RF. Secondary prophylaxis is a critical cost-effective intervention for preventing morbidity and mortality related to RF. Ensuring adequate adherence to secondary prophylaxis for RF is a challenging task. This study aimed to describe the rates of recurrent episodes of RF, quantify adherence to secondary prophylaxis, and examine the effects of medication adherence to the rates of RF in a cohort of Brazilian children and adolescents with RF.</p> <p>Methods</p> <p>This retrospective study took place in the Pediatric Rheumatology outpatient clinic at a tertiary care hospital (Instituto de Puericultura e Pediatria Martagão Gesteira) in Rio de Janeiro, Brazil, and included patients with a diagnosis of RF from 1985 to 2005.</p> <p>Results</p> <p>536 patients with RF comprised the study sample. Recurrent episodes of RF occurred in 88 of 536 patients (16.5%). Patients with a recurrent episode of RF were younger (p < 0.0001), more frequently males (p = 0.003), and less adherent (p < 0.0001) to secondary prophylaxis than patients without RF recurrence. Non-adherence to medication at any time during follow-up was detected in 35% of patients. Rates of non-adherence were higher in the group of patients that were lost to follow-up (42%) than in the group of patients still in follow-up (32%) (p = 0.027). Appointment frequency was inadequate in 10% of patients. Higher rates of inadequate appointment frequency were observed among patients who were eventually lost to follow-up (14.5%) than in patients who were successfully followed-up (8%) (p = 0.022). 180 patients (33.5%) were lost to follow up at some point in time.</p> <p>Conclusions</p> <p>We recommend implementation of a registry, and a system of active search of missing patients in every service responsible for the follow-up of RF patients. Measures to increase adherence to secondary prophylaxis need to be implemented formally, once non-adherence to secondary prophylaxis is the main cause of RF recurrence. Detection of irregularity in secondary prophylaxis or in appointments should be an alert about the possibility of loss of follow-up and closer observation should be instituted.</p

Physiological and Morphological Aspects of Aedes aegypti Developing Larvae: Effects of the Chitin Synthesis Inhibitor Novaluron

Population control of the dengue vector mosquito, Aedes aegypti, is difficult due to many reasons, one being the development of resistance to neurotoxic insecticides employed. The biosynthesis of chitin, a major constituent of insect cuticle, is a novel target for population control. Novaluron is a benzoylphenylurea (BPU) that acts as a chitin synthesis inhibitor, already used against mosquitoes. However, information regarding BPU effects on immature mosquito stages and physiological parameters related with mosquito larval development are scarce. A set of physiological parameters were recorded in control developing larvae and novaluron was administered continuously to Ae. aegypti larvae, since early third instar. Larval instar period duration was recorded from third instar until pupation. Chitin content was measured during third and fourth instars. Fourth instars were processed histochemically at the mesothorax region, stained with hematoxylin and eosin (HE) for assessment of internal tissues, and labeled with WGA-FITC to reveal chitinized structures. In control larvae: i) there is a chitin content increase during both third and fourth instars where late third instars contain more chitin than early fourth instars; ii) thoracic organs and a continuous cuticle, closely associated with the underlying epidermis were observed; iii) chitin was continuously present throughout integument cuticle. Novaluron treatment inhibited adult emergence, induced immature mortality, altered adult sex ratio and caused delay in larval development. Moreover, novaluron: i) significantly affected chitin content during larval development; ii) induced a discontinuous and altered cuticle in some regions while epidermis was often thinner or missing; iii) rendered chitin cuticle presence discontinuous and less evident. In both control and novaluron larvae, chitin was present in the peritrophic matrix. This study showed quantitatively and qualitatively evidences of novaluron effects on Ae. aegypti larval development. To our knowledge, this is the first report describing histological alterations produced by a BPU in immature vector mosquitoes