Differential Influence of Pueraria lobata Root Extract and Its Main Isoflavones on Ghrelin Levels in Alcohol-Treated Rats

The study was carried out on alcohol-preferring male Wistar rats. The following drugs were repeatedly (28×) administered: acamprosate (500 mg/kg, p.o.), naltrexone (0.1 mg/kg, i.p), and Pueraria lobata (kudzu) root extract (KU) (500 mg/kg, p.o.) and its isoflavones: daidzin (40 mg/kg, p.o.) and puerarin (150 mg/kg, p.o.). Their effects on a voluntary alcohol intake were assessed. KU and alcohol were also given for 9 days in an experiment on alcohol tolerance development. Finally, total and active ghrelin levels in peripheral blood serum were measured by ELISA method. Acamprosate, naltrexone, daidzin, and puerarin, reducing the alcohol intake, caused an increase in both forms of ghrelin levels. On the contrary, though KU inhibited the alcohol intake and alcohol tolerance development, it reduced ghrelin levels in alcohol-preferring rats. The changes of ghrelin concentration could play a role as an indicator of the currently used drugs. The other effect on the KU-induced shift in ghrelin levels in the presence of alcohol requires further detailed study.

Can Gram-Negative Bacteria Develop Resistance to Antimicrobial Blue Light Treatment?

Antimicrobial blue light (aBL) treatment is considered low risk for the development of bacterial resistance and tolerance due to its multitarget mode of action. The aim of the current study was to demonstrate whether tolerance development occurs in Gram-negative bacteria. We evaluated the potential of tolerance/resistance development in Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa and demonstrated that representative Gram-negative bacteria may develop tolerance to aBL. The observed adaption was a stable feature. Assays involving E. coli K-12 tolC-, tolA-, umuD-, and recA-deficient mutants revealed some possible mechanisms for aBL tolerance development.

Exercise Reduces Morphine-Induced Hyperalgesia and Antinociceptive Tolerance

Chronic morphine intake for treating various pain is frequently concomitant with morphine-induced hyperalgesia and tolerance. The mechanisms can be explained by the activation of p38-MAPK proteins in microglia in the spinal cord horn. Exercise has been shown to prevent the development of microglia overactivation. Thus, we designed to test whether exercise prevents the morphine-induced hyperalgesia and tolerance as well as suppression of p38 phosphorylation. A p38 inhibitor SB203580, exercise, and exercise preconditioning were used for treating morphine-induced hyperalgesia and tolerance development in the present study. The behavior tests for hyperalgesia and tolerance were performed in male Wistar rats before and after morphine administration. Western blotting and immunostaining for examining phosphorylated-p38 expression were performed after the behavior tests. Our results showed that SB203580 and exercise, but not exercise preconditioning, prevented the occurrence of morphine-induced hyperalgesia and tolerance. Meanwhile, exercise decreased morphine-induced phosphorylated-p38 overexpression. In summary, exercise prevented the development of morphine-induced hyperalgesia and tolerance. The mechanism may be related to inhibition of p38 phosphorylation.

Active maintenance of proton motive force mediates starvation-induced bacterial antibiotic tolerance in Escherichia coli

Recent evidence suggests that metabolic shutdown alone does not fully explain how bacteria exhibit phenotypic antibiotic tolerance. In an attempt to investigate the range of starvation-induced physiological responses underlying tolerance development, we found that active maintenance of the transmembrane proton motive force (PMF) is essential for prolonged expression of antibiotic tolerance in bacteria. Eradication of tolerant sub-population could be achieved by disruption of PMF using the ionophore CCCP, or through suppression of PMF maintenance mechanisms by simultaneous inhibition of the phage shock protein (Psp) response and electron transport chain (ETC) complex activities. We consider disruption of bacterial PMF a feasible strategy for treatment of chronic and recurrent bacterial infections.

DIAGNOSTIC PREDICTORS OF TOLERANCE DEVELOPMENT IN THE ELIMINATION DIET IN CHILDREN WITH COW'S MILK PROTEIN ALLERGY

Background. Cow's milk protein allergy is a topical issue in pediatrics. This disease affects 2-3% of young children. Methods. The study included 30 children with a confirmed cow’s milk protein allergy and a prescribed milk elimination diet. The children were observed for 36 months. The molecular profile was evaluated by detecting the major components of milk (Bos d 8, Bos d 5, Bos d 4), minor (Bos d 6), and cross-reactive with serum albumin (Fel d 2, Can f 3). Results. The study group included 46.7% of boys. The mean age of the subjects was 14.5±3.18 months. Nine of the 25 analyzed factors were identified in the course of our work by the method of logistic regression with progressive selection, which in combined action affect the formation of tolerance to cow's milk proteins in allergic children. There are three clinical examples of calculating the prediction of the complete tolerance development in the elimination diet in children with cow's milk protein allergy. Conclusions. Independent predictors that reduce the likelihood of the tolerance development in the elimination diet, have identified: skin test to milk, Bos d 8, Bos d 5, Bos d 4, Bos d 6. Independent predictors of the tolerance development in the elimination diet are: milk-specific IgE, total IgE, Fel d 2, Can f 3. Low probability of tolerance development by elimination therapy is a recommendation for prescribing treatment to a patient by specific oral tolerance induction.

Development of Tolerance in University Students during Second Language Acquisition

The present research tested various technologies of pedagogical support of tolerance development in students of a technical university during foreign language acquisition. The paper reviews scientific approaches to the essence of tolerance and introduces the stages of its formation, the definitions of pedagogical technology and teaching technology, etc. The author focused on teaching a foreign language in a non-linguistic university and proved that the choice of forms, methods, and technologies depends on a number of circumstances. The research revealed substantive characteristics of tolerance in students and the positive effect of second language acquisition on the parameters of tolerance. The changes in the content characteristics of tolerance were registered on the basis of the corresponding indicators. The study made it possible to determine the effectiveness of the classroom and extracurricular conditions that contribute to the development of tolerance in students of technical universities.

Study of tolerance development in older pre-school-age children in the context of inclusive education

Based on theoretical and methodological and empirical research, to identify the specifics of tolerance manifestation in older pre-school-age children with normative development in the conditions of inclusive education. The following methodologies were used: "Diagnostics of tolerance of preschool children to peers with disabilities" by A.S. Sirotyuk, aimed at revealing the specifics of the cognitive component development; "Studying the understanding of emotional states of people" by G.A. Uruntaeva and Y.A. Afonkina, revealing the emotional and motivational component of tolerance in preschool children. To study the behavioral component, the following methodologies were used: "Two little houses" by T.D. Martsinkovskaya; “The method of studying children's tolerance” by Dominique de Saint Mars, aimed at studying the interaction of preschool children in the conditions of inclusive education. As a result of the sample examination of preschool children with normative development and children with disabilities in pre-school educational establishments in Yelets and Lipetsk, the relationship between the cognitive, behavioral, and emotional-motivational components of tolerance in older pre-school-age children was revealed.