A method for experimental reproduction of stages of chronic obstructive pulmonary disease formation (from acute inflammation to bronchopulmonary tissue restructuring characteristic of this disease) is presented. Lung injury and inflammation were induced by nitrogen dioxide. Hyperplasia and hypersecretion of goblet cells, squamous cell metaplasia of the ciliary epithelium, emphysema, and focal fibrosis served as the morphological substrate for the formation of bronchial obstruction. The adequacy of the model is confirmed by signs characteristic of chronic obstructive pulmonary disease: hyperexpression of CD3 lymphocytes in the bronchial wall and parenchyma, manifold increased production of TNFα and TGFβ, high concentrations of circulating pathogenic immune complexes. Persistence of the structural and functional shifts throughout 6 months after exposure to nitrogen dioxide indicated a chronic course of the resultant pathological process.

Chronic obstructive pulmonary disease (COPD) is among the leading causes of morbidity and mortality worldwide. Glucocorticoids are currently the most applicable anti-inflammatory treatment for COPD. However, a subset of COPD subjects is relatively insensitive to this treatment. Fenspiride, a non-corticosteroid anti-inflammatory drug, has been described to have beneficial effects in patients with COPD, although the mechanism of its action is not well known. The effect of fenspiride on contractile activity of bronchial smooth muscle was studied in a rat model of COPD induced by long-term exposure of the animals to nitrogen dioxide (NO2). Contractile activity of bronchial smooth muscle was evaluated in vitro. Isometric contraction of bronchial preparations was measured following electrical stimulation. Fenspiride administration to rats during the acute stage of COPD (15 days of NO2 exposure) prevented the bronchial constriction induced by NO2. The bronchodilator effect of a low-dose of fenspiride (0.15 mg/kg) was mediated by interaction with the nerve endings of capsaicin-sensitive C-fibers. Interaction of fenspiride with C-fibers was shown to prevent initiation of neurogenic inflammation, as evidenced by lack of COPD-like structural changes in the lungs. The bronchodilator effect of a high-dose of fenspiride (15 mg/kg) was mediated not only by the afferent component, but also involved a direct relaxing effect on smooth muscle cells. The anti-inflammatory and bronchodilator effects of a low-dose of fenspiride may be used for prevention of COPD development in individuals from high-risk cohorts exposed to aggressive environmental factors.

The authors found that the density of colostrum in cows with a homozygous genotype for the B allele of the kappa-casein gene was higher compared to the homozygous genotype for the A allele and had a greater amount of immunoglobulins by 29.5 mg/l, respectively. The formation of high colostral immunity in calves obtained from cows of mothers of genotypes AB and BB prevented the occurrence of diseases of the gastrointestinal tract, and in calves obtained from mothers of genotype AA genotype kappa-casein with a reduced amount of immunoglobulins in colostrum, it led to the development of diarrhea in 12% of newborn calves. The dynamics of the live weight of calves obtained from cows of mothers with the AA genotype of the kappa-casein gene, during the first 30 days of life, was 6.34 and 4.78 kg lower than in young cows with the BB and AB genotypes of the kappa-casein gene. At the age of one month, the leukocyte content in calves obtained from cows from mothers with a homozygous genotype for allele A of the kappa-casein gene was less by 10.8 and 16.2%, and hemoglobin by 10.5 and 10.7%.

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