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Breakdown of mucosal immunity in the gut and resultant systemic sensitization by oral antigens in a murine model for systemic lupus erythematosus.

Secreted IgA plays a pivotal role in the mucosal immunity to maintain the front line of body defense. We found that the level of fecal IgA was dramatically decreased in aged (NZB x NZW)F(1) (BWF(1)) mice developing lupus nephritis, whereas levels in similarly aged New Zealand Black (NZB) and New Zealand White (NZW) mice remained unchanged compared with young mice. The number of cells obtained from Peyer's patches was markedly decreased in aged BWF(1) mice. Aged BWF(1) mice showed increased susceptibility to pathogenic bacterial infection. Furthermore, oral administration of OVA failed to inhibit secondary IgG response induced by systemic immunization, suggesting defective oral tolerance in aged BWF(1) mice. A significant amount of orally administered OVA was incorporated directly into the intestinal lamina propria in aged BWF(1) mice whereas it was mainly localized in subepithelial domes and interfollicular region in Peyer's patches in young mice. T cells obtained from renal and pulmonary lymph nodes of aged BWF(1) mice that had been orally administered with OVA showed an Ag-specific T cell proliferation, whereas those from young BWF(1), aged NZB, and aged NZW mice did not. Interestingly, aerosol exposure to OVA of aged BWF(1) mice, which had been orally administered with the same Ag, provoked an eosinophil infiltration in the lung. These results demonstrate that mucosal immunity in the gut is impaired and oral Ags induce systemic sensitization instead of oral tolerance in the development of murine lupus.

Administration, Inhalation↗

The medical complications of drug abuse.

There is a vast array of abused drugs, and only a few of the more commonly used substances have been discussed. Patients with drug abuse frequently present with atypical syndromes and diseases. These individuals usually have less social, medical and economic support, making them more susceptible to the diseases that are associated with poverty, such as tuberculosis, and the complications of diseases such as hypertension, congestive heart disease and diabetes that require long-term care. Our strategy in the evaluation of these patients should consider all these aspects of medicine. A meticulous assessment and comprehensive care are necessary to render quality care for these complicated human and toxicological problems.

Administration, Inhalation↗

A mouse model of aerosol-transmitted orthopoxviral disease: morphology of experimental aerosol-transmitted orthopoxviral disease in a cowpox virus-BALB/c mouse system.

OBJECTIVES: To determine the morphologic changes and disease progression of aerosolized cowpox virus infection in BALB/c mice and to ascertain the suitability of cowpox virus-infected BALB/c mice as a model of aerosol-transmitted, orthopoxviral respiratory disease. METHODS: BALB/c mice were inoculated with cowpox virus, Brighton strain, by aerosol or intranasal route. Mice were killed at specified times after inoculation, necropsied, and tissues were collected for routine histology, immunohistochemistry, and electron microscopy. RESULTS: Inoculation by both routes resulted in disease and death. Immunolabeled viral antigen and lesions predominated in the tissues associated with the inoculation route, that is, lungs, airways, trachea, and nasal passages and sinuses. Tracheitis was evident in the intranasally infected group only. Lesions were generally necrotizing and hemorrhagic, neutrophilic, and increased in extent and severity in a time-dependent fashion. Viral intracytoplasmic inclusion bodies, immunolabeled viral antigen, or virions were readily seen in epithelial tissues, smooth muscle cells of airways and vessels, fibroblasts, periosteal cells, perineural cells, and macrophages. Although the extension of infection appeared to be primarily direct, lesions suggesting hematogenous dissemination were occasionally noted in bone marrow and skin. Transmission electron microscopy demonstrated features of cell injury or death, virion assembly and maturation, and both A-type and B-type inclusions. CONCLUSIONS: Aerosol inoculation of BALB/c mice with cowpox virus provides a reliable and facilitative model of aerosol-transmitted, orthopoxviral respiratory disease.

Administration, Inhalation↗

Corticosteroids: implications for nursing practice.

Corticosteroids are essential in the management of various inflammatory conditions, but their adverse effects can be a problem. The authors describe the uses and effects of corticosteroids, and discuss the nursing role in minimising problems associated with their use.

Administration, Inhalation↗

[Diagnosis and management of asthma].

Asthma is a chronic inflammatory disorder of the airways with many inflammatory cells such as eosinophils, mast cells, T lymphocytes and basophils. This inflammation causes airflow limitation, airway hyperresponsiveness, respiratory symptoms and disease chronicity. Long-term-control medication are needed to prevent and control asthma symptoms.

Administration, Inhalation↗

Acute toxicity, primary irritancy, and genetic toxicity studies with 3-(methylthio)propionaldehyde.

Basic acute toxicity, primary irritancy, and genetic toxicity studies were conducted with 3-(methylthio)propionaldehyde (3-MTP). The acute rat peroral LD50 (with 95% confidence limits) for 3-MTP as a 25% (v/v) dilution in corn oil was 1.00 (0.59-1.70) ml/kg (males) and 1.68 (0.95-2.99) ml/kg (females); most deaths occurred 1.5 to 4 h postdosing. By 24-h occluded contact with undiluted 3-MTP, the rabbit acute percutaneous LD50 was 0.71 (0.43-1.15) ml/kg (males) and 0.79 (0.49-1.30) ml/kg (females): times to death ranged from 2 h to 2 d after the start of dosing. Exposure of rats to a statically generated saturated atmosphere killed all 5 males with a 40 min exposure and all 5 females with a 24 min exposure. In contrast, a 4-h exposure of rats to a dynamically generated saturated vapor atmosphere of 3-MTP did not produce any mortalities or signs of toxicity. A 4-hr occluded contact with 0.5 ml undiluted 3-MTP caused moderate to severe erythema and severe edema resolving by 7 to 17 d. Five/6 animals had necrosis apparent on removal of the occlusive dressing and persisting 10 to 17 d. On the rabbit eye, 0.1 ml undiluted 3-MTP produced moderate to severe corneal injury with iritis and moderate conjunctival inflammation which persisted 21 d in 3/6 animals; 0.01 ml caused moderate diffuse corneal injury and moderate conjunctival inflammation with healing by 7 d. 3-MTP did not produce mutagenic activity either in the absence or presence of metabolic activation with a Salmonella typhimurium reverse mutation assay using strains TA98, TA100, TA1535, TA1537 and TA1538. In a mouse lymphoma cell (L5178Y/tk +/-) assay, 3-MTP produced concentration-related increases in mutant colonies, both in the absence and presence of metabolic activation. Increases were mainly in the sigma (chromosomal damaging) colonies. In a mouse bone marrow micronucleus study, with vapor exposures to 37.4, 88.5 and 155.6 ppm for 1 h/d for 2 consecutive d, there were exposure concentration-related increases in micronucleated erythrocytes which were statically significant for male mice.

Administration, Cutaneous↗

Drugs for asthma.

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Acetates↗