Toxoplasma gondii promotes changes in VIPergic submucosal neurons, mucosal intraepithelial lymphocytes, and goblet cells during acute infection in the ileum of rats.

BACKGROUND: The intestinal mucosa plays an important role in the mechanical barrier against pathogens. During Toxoplasma gondii infection, however, the parasites invade the epithelial cells of the small intestine and initiate a local immune response. In the submucosal plexus, this response promotes an imbalance of neurotransmitters and induces neuroplasticity, which can change the integrity of the epithelium and its secretory function. This study evaluated the submucosal neurons throughout acute T. gondii infection and the relationship between possible alterations and the epithelial and immune defense cells of the mucosa. METHODS: Forty Wistar rats were randomly assigned to 8 groups (n = 5): 1 control group, uninfected, and 7 groups infected with an inoculation of 5000 sporulated T. gondii oocysts (ME-49 strain, genotype II). Segments of the ileum were collected for standard histological processing, histochemical techniques, and immunofluorescence. KEY RESULTS: The infection caused progressive neuronal loss in the submucosal general population and changed the proportion of VIPergic neurons throughout the infection periods. These changes may be related to the observed reduction in goblet cells that secret sialomucins and increase in intraepithelial lymphocytes after 24 hours, and the increase in immune cells in the lamina propria after 10 days of infection. The submucosa also presented fibrogenesis, characterizing injury and tissue repair. CONCLUSIONS AND INFERENCES: The acute T. gondii infection in the ileum of rats changes the proportion of VIPergic neurons and the epithelial cells, which can compromise the mucosal defense during infection.

Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells.

BACKGROUND: The increased susceptibility of patients with atopic dermatitis (AD) to disseminated viral skin infections such as eczema herpeticum (ADEH+) is poorly understood. OBJECTIVES: The primary goal of the current study was to determine whether ADEH+ subjects have identifiable defects in cell-mediated immunity that reduce their ability to control viral infections. MATERIALS AND METHODS: In this study, we evaluated cytokine expression by various subsets of peripheral blood mononuclear cells from ADEH+ (n = 24) compared with AD without a history of viral infections (ADEH-) (n = 20) before and after treatment with herpes simplex virus (HSV). RESULTS: We found that interferon (IFN)-γ expression after HSV treatment was lower in the CD8+ T cells and monocytes from patients with ADEH+ compared with patients who are ADEH- or nonatopic. Given the induction of CD8+ T cells as the result of antigen presentation by human leucocyte antigen (HLA) class I, consistent with the findings described above we also found that the HLA B7 allele was significantly associated with risk of the ADEH+ phenotype (odds ratio = 1·91, P = 0·02, 125 ADEH+ and 161 ADEH- subjects). CONCLUSIONS: These data suggest that defects in viral-induced IFN-γ from CD8+ T cells contribute to the ADEH+ phenotype.

Changes in antigen-specific T-cell number and function during oral desensitization in cow's milk allergy enabled with omalizumab.

Food allergy is a major public health problem, for which there is no effective treatment. We examined the immunological changes that occurred in a group of children with significant cow's milk allergy undergoing a novel and rapid high-dose oral desensitization protocol enabled by treatment with omalizumab (anti-immunoglobulin (Ig)E monoclonal antibodies). Within a week of treatment, the CD4(+) T-cell response to milk was nearly eliminated, suggesting anergy in, or deletion of, milk-specific CD4(+) T cells. Over the following 3 months while the subjects remained on high doses of daily oral milk, the CD4(+) T-cell response returned, characterized by a shift from interleukin-4 to interferon-γ production. Desensitization was also associated with reduction in milk-specific IgE and a 15-fold increase in milk-specific IgG4. These studies suggest that high-dose oral allergen desensitization may be associated with deletion of allergen-specific T cells, without the apparent development of allergen-specific Foxp3(+) regulatory T cells.

C1 esterase inhibitor concentrate in 1085 Hereditary Angioedema attacks--final results of the I.M.P.A.C.T.2 study.

BACKGROUND: The placebo-controlled study International Multicentre Prospective Angioedema C1-INH Trial 1 (I.M.P.A.C.T.1) demonstrated that 20 U/kg C1 esterase inhibitor (C1-INH) concentrate (Berinert®; CSL Behring, Marburg, Germany) is effective in treating acute abdominal and facial Hereditary Angioedema (HAE) attacks. METHODS: I.M.P.A.C.T.2 was an open-label extension study of I.M.P.A.C.T.1 to evaluate the safety and efficacy of long-term treatment with 20 U/kg C1-INH for successive HAE attacks at any body location. Efficacy outcomes included patient-reported time to onset of symptom relief (primary) and time to complete resolution of all symptoms (secondary), analysed on a per-patient and per-attack basis. Safety assessments included adverse events, vital signs, viral safety and anti-C1-INH antibodies. RESULTS: During a median study duration of 24 months, 1085 attacks were treated in 57 patients (10-53 years of age). In the per-patient analysis, the median time to onset of symptom relief was 0.46 h and was similar for all types of attacks (0.39-0.48 h); the median time to complete resolution of symptoms was 15.5 h (shortest for laryngeal attacks: 5.8 h; 12.8-26.6 h for abdominal, peripheral and facial attacks). Demographic factors, type of HAE, intensity of attacks, time to treatment, use of androgens and presence of anti-C1-INH antibodies had no clinically relevant effect on the efficacy outcomes. There were no treatment-related safety concerns. No inhibitory anti-C1-INH antibodies were detected in any patient. CONCLUSIONS: A single dose of 20 U/kg C1-INH concentrate is safe and provides reliable efficacy in the long-term treatment of successive HAE attacks at any body location.

Análise quali-quantitativa da influência das atividades físico-desportivas na saúde de crianças e jovens pertencentes a um programa de educação pelo esporte na Cidade do Natal - Brasil / Quali-quantitative analysis of influence of sports activities in the health of children and young people in a Program of Sports Education in Natal-Brasil

PURPOSE: Verify in a specific social totality of lower socioeconomical level, what would be the main interest for parents to place their children in an Educational Program Through Sport. To evaluate and classify children and young people as to physical aptitude related to health through scientifically validated indicators and to relate them to socioeconomical condition. To verify compatibility between qualitative and quantitative researches. METHODS: The sample of the qualitative study is composed of 22 subjects, characterizing itself as a non probabilistic sample of the causal type. Semi structured interview techniques in an individual situation and free evocation of words were used, based on the presuppositions of the Theory of Social Representations. A mixed sample, of the quantitative study, is composed of 67 children, where the possibility of relationship of the family income variable was confirmed with the variables: Body Composition and Flexibility, that compose the physical aptitude indicator related to health and the social representation of the parents. RESULTS: The qualitative results refer to biological aspects of health that constitute the central nucleus of the social representation of sport. In the quantitative aspect, it is verified that there was no correlation statistically, significant between the indexes of physical aptitude and the family income. CONCLUSION: The reason attributed to the physical-sport activities by the parents or relatives of the children, is based on the benefits to biological health and is shown by the children's good performance in the applied aptitude tests. There is not significant correlation between the index of physical aptitude applied to health, which reinforces the possibility of the parents social representation and the children's behavior.

Measurement of the flow properties of powders with special reference to die fill.

The flow behaviour of four pharmaceutical powders was investigated using a model shoe-die-filling system. The variation of mass delivered to the die as a function of shoe velocity provides a measure of flowability. The paper discusses the concept of critical velocity, above which incomplete filling is observed, in the context of pharmaceutical powders. The filling process was recorded using a high-speed video system, which allowed the different flow patterns to be observed, and how this influences the critical velocity to be evaluated. The influence of humidity, which was investigated in detail for one of the powders, was found to be small. The initial conditioning of the material, the die opening and if die filling takes place in air or in vacuum, however, were found to change the flow behaviour significantly.

A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO).

Hypohidrotic ectodermal dysplasia (HED), a congenital disorder of teeth, hair, and eccrine sweat glands, is usually inherited as an X-linked recessive trait, although rarer autosomal dominant and recessive forms exist. We have studied males from four families with HED and immunodeficiency (HED-ID), in which the disorder segregates as an X-linked recessive trait. Affected males manifest dysgammaglobulinemia and, despite therapy, have significant morbidity and mortality from recurrent infections. Recently, mutations in IKK-gamma (NEMO) have been shown to cause familial incontinentia pigmenti (IP). Unlike HED-ID, IP affects females and, with few exceptions, causes male prenatal lethality. IKK-gamma is required for the activation of the transcription factor known as "nuclear factor kappa B" and plays an important role in T and B cell function. We hypothesize that "milder" mutations at this locus may cause HED-ID. In all four families, sequence analysis reveals exon 10 mutations affecting the carboxy-terminal end of the IKK-gamma protein, a domain believed to connect the IKK signalsome complex to upstream activators. The findings define a new X-linked recessive immunodeficiency syndrome, distinct from other types of HED and immunodeficiency syndromes. The data provide further evidence that the development of ectodermal appendages is mediated through a tumor necrosis factor/tumor necrosis factor receptor-like signaling pathway, with the IKK signalsome complex playing a significant role.

Atopic diseases and upper respiratory infections.

This article reviews information on the topics of asthma, atopic dermatitis, food allergy, and upper respiratory infections. The asthma section provides an in-depth look at sociodemographic factors contributing to asthma morbidity and the barriers to asthma control. New findings on the triggers and therapies of atopic dermatitis and new articles on formula allergy and peanut allergy are presented. Recent publications in the areas of sinusitis and upper respiratory infections are also reviewed.

X-linked hyper IgM syndrome.

X-linked hyper IgM syndrome is largely caused by defects in the CD40L (CD154). The patients have low levels of IgG and have difficulty with respiratory infections as well as opportunistic infections. The morbidity of this syndrome is high; however, early diagnosis and therapy should reduce morbidity and mortality.

Atopic diseases and upper respiratory infections.

This article reviews information on the topics of asthma, allergic rhinitis, atopic dermatitis, food allergy, and upper respiratory infections. The asthma section includes a review of inhaled steroids and their potential side effects. New findings on the pathogenesis, triggers, and therapies of atopic dermatitis and new insights into food hypersensitivity reactions are presented. Recent publications in the areas of allergic rhinoconjunctivitis and upper respiratory infections are also reviewed.

Malignant spindle cell tumor arising in the mandible of a patient with florid osseous dysplasia.

Florid osseous dysplasia is a non-neoplastic condition of the alveolar processes of the jaws characterized by the replacement of multiple foci of bone by fibrous connective tissue, accompanied by gradual deposition of cementum, bone, or both. The lesions are not associated with inflammatory diseases of the dental pulp or periodontal tissues. In fully developed florid osseous dysplasia, there are multiple lobulated masses in the alveolar bone bilaterally in the mandible and sometimes in the maxilla. This is the first report of a malignancy originating within the jaws of a patient with florid osseous dysplasia. A spindle cell malignancy was diagnosed in the mandible of a 54-year-old black woman whose jaw was affected by florid osseous dysplasia bilaterally. Despite extensive surgery and radiotherapy, the patient died 20 months after diagnosis of the malignancy.

Effect of intravenous immunoglobulin on steroid consumption in patients with severe asthma: a double-blind, placebo-controlled, randomized trial.

BACKGROUND: There is a significant group of patients with severe asthma who require chronic use of systemic steroids for control of their disease. These patients are at risk for severe side effects from oral steroids. Intravenous immunoglobulin (IVIG) has immunomodulatory properties, and a few open-label trials have suggested its possible benefit in individuals with severe asthma. OBJECTIVE: This study was designed to assess the potential benefit of IVIG as a steroid-sparing agent in patients with severe asthma. METHODS: Thirty-eight immunocompetent steroid-requiring patients with severe asthma were randomly enrolled in a double-blind, placebo-controlled trial of IVIG. RESULTS: Of the 38 patients enrolled, 28 patients completed the study. A significant reduction in oral steroid requirement was observed in both the IVIG-treated (n = 16) and the placebo-treated (n = 12) patients. Further exploration of the results showed that IVIG, but not placebo, had a significant steroid-sparing effect in patients requiring high doses of oral steroids (ie, >2000 mg in the year before the study). Within this subgroup, IVIG treatment (n = 9) resulted in a significant decrease in oral steroid requirement, with a median of 16.4 mg/day during the pretreatment period to 3 mg/day during the treatment phase (P =. 0078). No significant decrease in oral steroid requirement was observed in placebo-treated patients (n = 8) within this subgroup. Objective and subjective parameters of the patients' asthma were unchanged in spite of the steroid tapering achieved in the group treated with IVIG. CONCLUSION: IVIG may be a useful steroid-sparing agent in patients with severe asthma requiring high doses of oral steroids.

Diagnosis of oral ulcers.

Ulcers commonly occur in the mouth. Their causes range from minor irritation to malignancies and systemic diseases. Innocent solitary ulcerations, which result from trauma and infections, must be distinguished from squamous cell carcinomas, which also typically present as solitary ulcers. Multiple oral ulcers may be classified as acute, recurrent and/or chronic. The most common causes of rapid-onset oral ulcers include acute necrotizing ulcerative gingivitis, allergies and erythema multiforme. The two common forms of acute (short-term) recurrent oral ulcers, "cold sores" or "fever blisters," which are caused by the herpes simplex virus, and recurrent aphthous ulcers ("canker sores"), may be distinguished largely on the basis of their location. Most types of multiple chronic oral ulcers are associated with disturbances of the immune system. They include erosive lichen planus, mucous membrane pemphigoid and pemphigus vulgaris. Clinical criteria which are most useful in identifying the cause of oral ulcers are vesicles or bullae, which may not be seen because they rupture rapidly in the oral environment; constitutional signs and symptoms; and lesions on the skin and/or other mucosa. In some cases, diagnosis depends upon culture or biopsy, particularly with the application of immunofluorescence to the surgical specimen.

Atopic disease, rhinitis and conjunctivitis, and upper respiratory infections.

This review highlights updated information on the topics of atopic dermatitis, food allergy, asthma, allergic rhinitis, and upper respiratory infections. Recent finding on the pathogenesis, triggers, and therapies of atopic dermatitis are discussed. New insights into peanut allergy and formula intolerance are presented. Topics highlighted in the section on asthma include quality of life and quality of care. Recent publications in the areas of allergic rhinoconjunctivitis and upper respiratory infections are also reviewed.

IgE-mediated allergy and desensitization to factor IX in hemophilia B.

BACKGROUND: We describe two patients with factor IX deficiency and high levels of inhibitors to factor IX who developed anaphylaxis to factor IX. OBJECTIVE: The aim of this study was to develop a skin test, RAST, and desensitization protocol for factor IX allergy. METHODS: The patients were evaluated by skin test and RAST to factor IX. They also underwent desensitization to factor IX. RESULTS: Both patients had positive skin test and RAST reactions to factor IX. Control subjects had negative reactions. Both patients were successfully desensitized to factor IX by using two different desensitization protocols. The patients' skin test and RAST reactions to factor IX converted to negative after desensitization. CONCLUSIONS: IgE-mediated reactions to factor IX do occur and may be diagnosed with the use of skin test and RAST. Patients with this type of reaction may be successfully desensitized to factor IX.