The problem of acute osteomyelitis in children is of special importance among the inflammatory diseases of musculoskeletal system, due to infectious conditions arising in the body and spreading to the bone tissue caused by impaired immune regulation, first of all, concerning neutrophilic granulocytes. Of interest is studying the subsets of neutrophilic granulocytes arising when the cells are involved into the inflammatory process in acute pediatric osteomyelitis, and determining the opportinity to influence the level of receptor expression aiming for correction of their functions. The purpose of our study was to evaluate the effect of hexapeptide arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine on the altered phenotype of neutrophilic granulocytes in children with acute osteomyelitis using an in vitro experimental model. We examined the peripheral blood samples from children with acute hematogenous or post-traumatic osteomyelitis at the age of 10 to 17 years (n = 12) upon their admission to the hospital, and from healthy children (n = 7). Blood samples from children with acute osteomyelitis were incubated with hexapeptide (10-6 g/L) for 60 min, at 37 C. The content of neutrophilic granulocyte subsets (CD16+CD62L+CD11b+CD63- and CD16+CD62L+CD11b+CD63+), expression density of appropriate membrane receptors were assessed by flow cytometric technique (FC 500 Beckman Coulter, USA). Phagocytic function was studied by assessing the degree of completed phagocytosis of S. aureus. It was found that, in acute osteomyelitis, a 8.5-fold increased proportion of activated CD16+CD62L+CD11b+CD63+NG subset with the CD16brightCD62LbrightCD11bbrightCD63dimNG phenotype was revealed, along with a decrease in the CD16+CD62L+CD11b+CD63-NG subset and changes in the CD16dimCD62LbrightCD11bmidCD63- NG phenotype as compared with reference indexes of healthy children. At the same time, an increased number of actively phagocytic cells was noted, however, with decreased indexes characterizing capture and digestion of the bacterial antigen. In the in vitro experiments, the tested hexapeptide was shown to modulate the phenotypes of both studied subsets (CD16brightCD62LmidCD11bmidCD63- and CD16midCD62LmidCD11bmidCD63dimNG), thus promoting restoration of the receptor expression levels to the reference group values, as well as phagocytic activity, in terms of uptake and digestive capacity of microbial cells. Thus, the dominance of a diagnostically significant activated CD16+CD62L+CD11b+CD63+ neutrophil subset with the CD16brightCD62LbrightCD11bbrightCD63dimNG phenotype was found in acute osteomyelitis in children. The results of in vitro studies have shown that the hexapeptide caused phenotypic modulation of the CD16+CD62L+CD11b+CD63- neutrophils, and CD16+CD62L+CD11b+CD63+NG subsets, along with recovery of their phagocytic activity. In the future, our results may provide a basis for the development of new effective therapeutic regimens.
Aim. The research was carried out to create and evaluate the effectiveness of the rehabilitation algorithm of children who underwent a surgery on the colon and anorectal area.Materials and methods. We have experience in rehabilitation of 245 patients aged from 8 months to 15 years with anorectal agenesis and Hirschsprung's disease. To assess the effectiveness of the proposed algorithm of rehabilitation measures we formed 2 identical groups according to age, sex and nosology indicators. The main group consisted of 136 children with abovementioned pathology. Rehabilitation measures were carried out according to the developed algorithm. It included early bougienage, general and local physiotherapy, correction of intestinal dysbiosis by selective decontamination, relief of water-electrolyte and metabolic disorders. The control group consisted of 109 patients. Rehabilitation was carried out according to the traditional methods. Results. When comparing the results of rehabilitation, the following data were obtained: therapeutic and preventive bougienage was carried out for 18.34±1.29 months in patients of the control group and for 9.56±0.94 months in children of the main group. The duration of anal sphincter insufficiency treatment in the control group was 23.48±1.95 months and only 11.29±1.07 months in the main group. The timing of the correction of dysbiosis in patients of the control group was 36.25±2.17 months and 14.36±1.14 months in children of the main group. The duration of electrolyte disorders and metabolic disorders correction in the control group was 14.16±0.57 months and 6.34±0.28 months in the main group.Conclusion. The application of the developed algorithm of rehabilitation measures made it possible to reduce their duration by more than 2 times according to all the studied criteria. It allows us to recommend the created rehabilitation algorithm for wide clinical application.
Treatment of young children with atypical or recurrent purulent soft tissue infections (PSTD) that do not respond well to surgery and antibiotics is most challenging. PSTD occurs against the background of impaired functioning of the immune system and, first of all, the system of neutrophilic granulocytes (NG). The vector effect of immunotropic therapy on a specific NG subsets may allow the correction of NG dysfunctions without compromising host protection, including strategies to enhance, inhibit or restore their functions.The aim of study: to evaluate in vitro the modulating effects of arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine (HP) on the transformed phenotype of 4 NG subsets, as well as on the functional activity of NG in children with purulent-inflammatory soft tissue diseases.We studied samples of peripheral blood (PB) from young children 2-4 years old: 17 children with atypical acute PSTD and 10 apparently healthy children. At stage I, a comparative assessment of the content and phenotype of 4 NG subsets CD16+CD62L+СD63- , CD16+CD62L+СD63+, СD64- CD16+CD32+CD11b+, СD64+CD16+CD32+CD11b+, phagocytic and microbicidal functions of NG was carried out. At stage II, the in vitro system determined the effects of HP on NG in children with PSTD according to the studied parameters. By the method of flow cytometry (FC500 “Beckman Coulter” (USA), conjugates of MkAT “Beckman Coulter International S.A.” (France)), the relative number of NGs of the studied subsets and the density of receptor expression (MFI) were determined. To assess the phagocytic function of NG a microbiological method was used to assess the completeness of phagocytosis with S. aureus (strain 209). The activity of NG NADPH oxidase was investigated in the NBT-spontaneous test (NBTsp.) and in the in vitro NBT-induced test (NBTind.). A comparative study of PB samples from conventionally healthy children and children with PSTD made it possible to identify various variants of transformation of the phenotype of the studied NG subsets, associated with defects in their functional activity. In the in vitro system the effects of HP were demonstrated, manifested by a decrease in the amount of CD16+CD62L+CD63+NG and an increase in CD16+CD62L+CD63- NG, modulation of the negatively altered phenotype of subsets CD64- CD32+CD16+CD11b+NG and CD64+CD32+CD16+CD11b+NG, aimed at restoring phagocytic function and maintaining the tension of NADPH oxidases.As a result of the study it was found the immunomodulatory effects of HP, which is manifested in the reorientation of NG from the pro-inflammatory phenotype to the anti-inflammatory one, which can be used in the future when creating personalized targeted immunotherapy aimed at correcting defective functioning NG in early children, suffering from PSTD.
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