The signal transducer and activator of transcription 6 (STAT-6) mediates Th2 inflammation and tissue damage in a murine model of peanut-induced food allergy.

INTRODUCTION: Food allergies are inflammatory conditions mediated by Th2 and probably STAT-6 dependent immune responses. OBJECTIVE AND DESIGN: Here we investigated the role of Signal Transducer and Activator of Transcription 6 (STAT-6) in development of inflammation in peanut allergy. METHODS: To induce food allergy, wild-type (WT) and mice deficient for STAT-6 (Stat6-/-) were sensitized with peanut proteins and challenged with peanut seeds. RESULTS: WT animals lost weight and refused the peanut diet, in contrast to Stat6-/- mice, which had a better maintenance of body weight and more regular seeds' consumption. The augmented peanut-specific IgG, IgG1 and IgE in the allergic WT was abolished in Stat6-/- animals that also presented increased IgG2a. There was an overall reduction in the gut mediators in the absence of STAT-6, including those related to inflammatory and Th2 responses, in contrast to a rising counter regulatory and Th1 reaction in Stat-6-/- mice. These animals had IFN-γ and IL-10 similar to WT after the four-week challenge. Most interestingly, Stat-6-/- mice had no intestinal damage, in contrast to WT animals, which had inflammatory infiltrate, tissue destruction, epithelial exulceration, edema, congestion and loss of villous architecture in the small gut segments. CONCLUSIONS: STAT-6 plays an important role in the establishment of the Th2 inflammatory responses and intestinal damage in peanut allergy.

Dual-task effects on postural sway during sit-to-stand movement in children with Down syndrome.

BACKGROUND: Cognitive and postural tasks require common cognitive mechanisms, resulting in conflicts when both tasks are simultaneously performed. The presence of neuromotor dysfunctions, such as Down syndrome, may impair coordination processes required to perform dual-tasks. The objective of this study was to investigate the dual-task effects on postural sway during sit-to-stand movements in typical children and children with Down syndrome in a cross-sectional study. METHODS: Twenty six typical children (10.2 ± 2.4 years) and 21 with Down syndrome (10.3 ± 2.3 years) performed sit-to-stand in the following conditions: (1) simple task; (2) dual-task bimanual activity (DT-Bim): sit-to-stand while carrying a tray using both hands; (3) dual-task unimanual dominant activity (DT-Uni-Dom): sit-to-stand while holding a plastic cup simulating water using the dominant hand; (4) dual-task unimanual non-dominant activity (DT-Uni-Nondom): sit-to-stand movement while holding a plastic cup simulating water. For data analysis, sit-to-stand was divided into three phases: preparation (phase 1), rising (phase 2), and stabilisation (phase 3). The following variables were calculated for each phase: anterior-posterior and medial-lateral amplitude of centre-of-pressure displacement, anterior-posterior and medial-lateral velocity of centre-of-pressure sway and area of centre-of-pressure sway. RESULTS: Children with Down syndrome showed greater sway than typical children in all sit-to-stand phases. Typical children showed greater anterior-posterior amplitude in phase 2 of sit-to-stand during DT-Uni Nondom compared with DT-Uni Dom. Children with Down syndrome during simple task condition showed greater and faster values sway in phases 2 and 3 of sit-to-stand movement than in DT-Bim activity, DT-Uni Dom activity and DT-Uni Nondom activity. During the condition of DT-Bim activity, these children showed lower anterior-posterior velocity of sway in phase 2 than during DT-Uni Dom activity. CONCLUSIONS: Children with Down syndrome showed greater postural sway during sit-to-stand than typical children. The addition of a concurrent motor task to sit-to-stand impacted postural sway in different intensities and in different ways across groups. Dual-tasks increased body sway in typical children in the DT-Uni Nondom condition compared with dominant one. In children with Down syndrome, dual-tasks decreased body sway, apparently resulting in a postural strategy of stiffness.

Urolitíase por cistina em cães no Brasil / Canine cystine urolithiasis in Brazil

O presente trabalho tem como objetivo relatar três casos de urolitíase canina por cistina, atendidos no Hospital Veterinário da Universidade Estadual de Londrina entre o período de 2007 a 2009. O diagnóstico de urolitíase foi baseado na anamnese, no exame físico e nos exames laboratoriais e radiográficos, e a confirmação do tipo de urólito envolvido foi realizada no Centro de Urólitos de Minnesota-USA, por meio de análise quantitativa, revelando cálculos puros de cistina. A terapia instituída incluiu a remoção cirúrgica dos urólitos e a prevenção de recidivas, por meio do aumento da solubilidade da cistina na urina com dieta comercial própria, aumento da ingestão hídrica e alcalinização medicamentosa da urina.

Three cases of canine cystine urolithiasis were reported at the Veterinary Hospital of Londrina State University in the period from 2007 to 2009. The diagnosis of urolithiasis was based on clinical history, physical examination, laboratory tests and radiographs, and the confirmation of the urolith type was performed at the Minnesota Urolith Center - USA, trough quantitative analysis, showing pure cystine uroliths. The therapy administered in both cases included surgical removal of the uroliths and prevention of recurrence by increasing the solubility of cystine in the urine with a commercial diet, increased fluid intake and alkalinization of the urine.

Hematopoietic SCT modulates gut inflammation in experimental inflammatory bowel disease.

Hematopoietic SCT (HSCT) and high-dose chemotherapy are being explored as therapy for various human refractory immune-mediated conditions, including inflammatory bowel diseases (IBD). Nevertheless, the exact immunological mechanisms by which the BM cells (BMCs) or immunosuppression provide remission from these diseases is not yet clear. In this work, we investigated the role of these therapies in the modulation of gut mucosal inflammation in an experimental model of IBD. Colitis was induced in mice by 2,4,6-trinitrobenzenesulfonic acid and after CY was administered (200 mg/kg) alone (CY group) or followed by BMCs infusion (HSCT group). Animals were followed for 60 days. Both HSCT and CY reduced the histopathological features of colitis significantly. Infused cells were localized in the gut, and a marked decrease of CD4(+) leukocytes in the inflammatory infiltrate on days +7 and +14 and of CD8(+) cells on day +7 was found in both treatments allied to impressive reduction of proinflammatory Th1 and Th17 cytokines. Although chemotherapy alone was the best treatment regarding the induction of immunosuppressive molecules, only HSCT resulted in increased survival rates compared with the control group. Our findings indicate that high-dose CY followed by HSCT is effective in the modulation of mucosal immunity and in accelerating immune reconstitution after BMT, thus providing valuable tools to support the development and understanding of novel therapeutic strategies for IBD.

B cells are involved in the modulation of pathogenic gut immune response in food-allergic enteropathy.

Food enteropathies involve uncontrolled or hypersensitivity reactions to ingested nutrients and may result in IgE and T-helper type 2 (Th2) responses as in food allergy. However, the precise role of B cells in the development of food enteropathies remains uncertain. In this work, we used B cell-deficient mice (B KO) and a model of peanut sensitization to examine the involvement of B lymphocytes in the pathogenesis of food allergy. Results showed that priming of wild-type (WT) mice with peanut proteins induced specific IgG1 and IgE responses in serum, with edema, tissue destruction, epithelial exulceration and inflammatory infiltrate in the gut of sensitized and challenged (S + Peanut) WT animals. In contrast, there was no sera immunoglobulin detection and absence of tissue destruction in the gut of B KO mice, which presented moderate inflammatory infiltrate and villous enlargement after peanut challenge. These animals presented marked decrease in IL-4 and TNF-alpha and high levels of IL-10, TGF-beta, IL-12p40 and IFN-gamma mRNA in the gut. Moreover, the expression of CCL5, CCL11 and CXCL1 was reduced in the gut of B KO mice, in contrast to elevated messages of CCL2 or similar detection of Th1-related chemokines in S + Peanut WT mice. Finally, we provided evidence that B cells are necessary to the development of food-related enteropathies and induction of gut inflammation during allergic reactions to food.

Modulation of mucosal immunity in a murine model of food-induced intestinal inflammation.

BACKGROUND: Hypersensitivity or uncontrolled responses against dietary antigens can lead to inflammatory disorders like food allergy and current models reflect a variety of causes but do not reveal the detailed modulation of gut immunity in response to food antigens after breakdown in mucosal tolerance. OBJECTIVE: To develop and characterize a murine model for food-induced intestinal inflammation and to demonstrate the modulation of gut immune response by dietary allergenic antigens. METHODS: C57BL/6 mice were sensitized with peanut proteins, challenged with peanut seeds and their sera and gut segments were collected for subsequent analyses. RESULTS: Sensitization and challenged with peanut seeds led to alterations in gut architecture with inflammatory response characterized by oedema in lamina propria and cell infiltrate composed mainly by eosinophils, mast cells, phagocytes, natural killer and plasma cells, together with low percentage of gammadelta+ and CD4+CD25+Foxp3+ cells in Peyer's patches. These animals also presented high levels of specific IgE and IgG1 in sera and modulation of mucosal immunity was mediated by increased expression of GATA-3, IL-4, IL-13 and TNF-alpha in contrast to low IFN-gamma in the gut. CONCLUSION: A murine model for food-induced intestinal inflammation was characterized in which modulation of gut immunity occurs by peanut antigens in consequence of T-helper type 2 (Th2) allergic response and failure of regulatory mechanisms necessary for mucosa homeostasis, resembling food allergy. This work shed some light on the understanding of the pathogenesis of gastrointestinal disorders and intolerance in the gut and supports the development of therapies for food-related enteropathies like food allergy, focusing on gut-specific immune response.