The aim of the study was to determine changes in the content of matrix metalloproteinases (MMP) and their tissue inhibitor in children with uncomplicated compression fractures of the spine (UCFS). Materials and methods. Eighty-five children, including 69 patients with UCFS (average age 12.3 ± 2.6 years), were comprehensively examined. The reference group consisted of 16 children (average age 11.8 ± 2.7 years) without spinal pathology. During the diagnostic period for 1-3 days, changes in the MMP content and their tissue inhibitor (TIMP-1) in blood serum were determined by the enzyme immunoassay method in all children after trauma. Results. It was found that in the acute period after spinal injury, the blood levels of gelatinases (MMP-2 and MMP-9), stromelysin (MMP-3), and collagenases (MMP-8) significantly increased compared to their levels in children of the reference group. At the same time, the levels of TIMP-1 and the ratio of MMP/TIMP-1 concentrations in the blood of patients with UCFS significantly decreased compared to the control, which indicates the predominance of the proteolytic effect of MMP. Analysis of changes in the content of MMP in the blood in UCFS boys and girls did not reveal significant differences in the levels of the studied MMP and TIMP-1, except for a significant increase in the concentrations of stromelysin (MMP-3) in the blood serum of boys compared with its level in girls and the control. With different severity of the course of UCFS in children, a significant increase in MMP concentrations associated with an increase in the severity of the injury was revealed, and a substantial decrease in the content of TIMP-1 in the blood of patients compared to its levels in children with 1-2 degrees of severity and control. Conclusion. The established patterns indicate that the determination of the content of MMR and TIMP-1 in the blood in UCFS children allows monitoring the course of the reparative process after injury to the vertebral bodies in children.
Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in preterm infants. The development of NEC is associated with changes in the expression of a number of acute phase proteins and cytokines, such as C-reactive protein (CRP), procalcitonin (PCT), calprotectin (CP). To determine their diagnostic and prognostic significance there were performed studies of the dynamics of the blood levels of CRP, PCT and CP in preterm infants with NEC. A total of 68 premature infants with conservative and surgical stages of the NEC were examined. In all patients at admission, 3rd and 7th day of the treatment there was determined the serum concentration of CRP, PCT and CP. The gradual significant decline in CRP, PCT and CP. Blood concentrations was established at the 7th day of the observation ofpatients with conservative stage of NEC, which was associated with a favorable outcome of the treatment of NEC in this group of preterm infants. More pronounced changes in these markers in the blood of patients with surgical stage of the SEC due to a sharp increase in concentration and a lack of the decline in their content in the course of treatment, are associated with severe NEC and are a formidable sign of unfavorable course of the NEC, which requires timely revision and optimization of the treatment of such patients.
N preterm infants with cerebral ischemia, the blood level of such mediators of endothelial dysfunction (MED), as endothelin-1, nitric oxide, angiotensin II, homocysteine, neurotrophic factors, tissue type plasminogen activator and von Willebrand factor was quantified. The established patterns of changes in the blood level of these mediators, depending on the degree of prematurity and severity of cerebral ischemia, reflect the severity of impairment of the functional state of the endothelial system. The quantitative data on the blood MED level in premature infants can be considered as criteria for the assessment of the degree of endothelial dysfunction, as in choosing modes for adequate timely correction of cerebrovascular disorders in newborns.
Twenty-nine children (mean age of 12.6 ± 2.3 years) with combined bone trauma were examined. The reference group consisted of 20 conditionally healthy children (mean age of 11.8 ± 2.7 years) without the pathology of the locomotor system. The content of bone biomarkers - osteoprotegerin (OPG), bone isoenzyme of alkaline phosphatase (AP), osteocalcin (OC), hyaluronic acid (HA), as well as matrix metalloproteinases (MMPs) and cytokines - TGF-β, MCP-1 and MIP-1β in serum was determined by the enzyme immunoassay in dynamics: on the 1-3rd, 7-th, 14-th and 30-th days after the trauma. Remodeling of bone tissue after a combined trauma at the stage of formation of the regenerate was established to be characterized by diverse changes in the serum content of bone biomarkers, which are not substantially dependent on the severity of the trauma. At the same time, a significant increase in the concentrations of OPG, AP and HA was combined with a pronounced decrease in the content of OC. At 7-14th days after the injury OC levels were lower by more than 3 times compared with the control, indicating a slowdown in the mineralization of the osteoid and a disturbance in the formation of bone tissue during this period. By 30 days after trauma serum concentrations of gelatinases (MMP-2, MMP-9) and collagenases (MMP-8) increased significantly, stromelysin levels (MMP-3) did not change. By 30th day after the injury serum concentrations of gelatinases (MMP-2, MMP-9) and collagenases (MMP-8) increased significantly, stromelysin levels (MMP-3) did not change, and the TIMP-1 content declined. Early detection of changes in blood levels of bone biomarkers during the process of the recovery after combined trauma in children makes it possible to ensure timely correction of disturbances and choice of optimal individual treatment tactics for the management of a particular patient, taking into account the peculiarities of his bone metabolism
There were comprehensively examined 55 children, including 35 children with combined bone injury (average age of 12.6 ± 2.3 years), reference group consisted of 20 apparently healthy children (average age of 11.8 ± 2.7 years) without pathology of the motor system. on the 1-3rd and 30th day after the combined bone injury, changes in the content of matrix metalloproteinases (MMP) and cytokines - transforming growth factor-beta (TGF-β), monocytic chemotactic factor (MCP-1) and macrophage inflammatory protein (MIP-1β) were followed in the dynamics by serum immunoassay determination. It was established that after combined bone injury at the stage of post-traumatic formation of the regenerate by 30th days the serum concentrations of gelatinases (MMP-2, MMP-9) and collagenases (MMP-8) significantly increased, the levels of stromelysins (MMP-3) did not change, and the content of TIMP-1 decreased. Early detection of changes in the blood content of bone biomarkers during the recovery process after a combined trauma in children allows the timely implementing the correction of disturbances and the choice of the optimal individual treatment tactics for a particular patient, taking into account the features of his bone metabolism.
Glycogen storage disease (GSD) is a rare form of the pathology in children caused by genetically determined pathological changes of the formation or cleavage of glycogen. Depending on the disorders of functions of enzymes involved in glycogen metabolism, there are known up to 15 GSD types, among them there are isolated liver, muscular and mixed forms. There are presented data of the immunoassay analysis of changes in concentrations of the array of proteins considered as biomarkers of apoptosis: sAPO-1/FAS receptor, sFAS-L, cytochrome C, annexin V, caspase-8, caspase-9 and TNF-α in the serum of GSD with the prevailed liver damage (I, III, VI and IX types). There was established the excess of the concentration of cytochrome C in the serum of GSD children by 2,7 times sAPO-1/FAS receptor - 8,9 times, sFAS-L - 2,5 times, annexin V - 4,8 times and TNF-α - 2,9 times in comparison with reference values. Whereby the excess in the cytochrome C content, sAPO-1/FAS receptor, sFAS-L annexin V and the serum was observed in all patients, that indicating to the higher activity of apoptosis in GSD. In this connection GSD in children can be considered as a form of pathology associated with the pronounced apoptosis that contributes to the progression of structural changes in the liver.
The data of examination of 80 in-patients with the mixed form of cystic fibrosis (CF) are presented. All cases were divided into 3 groups according to the severity of the course of the disease. 16 conditionally healthy children made up a reference group. Determination of blood serum concentrations of interleukins (IL4, IL6), transforming growth factor-β1 (TGF-β1), matrix metalloproteinases MMP-2, MMP-8, MMP-9 and tissue inhibitor-TIMP-1 was performed by immunoassay ELISA method. The changes in the content of MMP and TIMP-1 in the blood serum of patients with various severity of the course of CF were found to be characterized by a significant decrease in MMP-8 and TIMP-1 concentrations, an increase in MMP-2 levels in children with moderate СF and a significant increase in MMP-9 concentrations, especially pronounced in patients with severe CF. At the same time, no definite dependence of the changes in MMP and TIMP-1 concentrations in the blood serum of patients on the frequency of exacerbations in the CF course and the dominant microbiota was found. Changes in the content of IL and TGF-β1 in the blood serum of children with the various severity of the course of CF were characterized by an increase in the concentrations of IL4 and TGFβ1 by more than 9.8 times, and IL6 - by 4.6 times if compared with the reference group. However, there no direct correlation was found between the changes in their production and the severity of the course of CF. The authors believe elevated levels of MMP, TIMP, and altered relationships between them can be used as biomarkers of the exacerbation of CF course in children.
A total of 288 children with chronic inflammatory diseases of the lung (HIDL), including cystic fibrosis (CF), were examined comprehensively. Significant activation of neutrophilic elastase (NE) in the chronic pulmonary heart (CPH) and an increase in the activity of cathepsin G (according to the activation of anti-cathepsin-G) in CPH patients was established. An increase in the level of matrilysin - matrix metalloproteinase-7 (MMP-7) as the condition worsened was also found in patients with chronic leukemia; A significant increase in the content of MMP-7 is typical not so much for CPH patients, but for СF patients, in particular, during the formation of CPH in them. In СF patients, even without worsening the condition in the form of pulmonary arterial hypertension (PAH), the developing pulmonary heart (DPH) and CPH, the levels of MMP-7 were increased more significantly than in congenital lung malformations cases. In patients with pulmonary arterial hypertension (PAH) grade 1, the levels of IL-4 and IL-6 were 11.1 and 4.4 times higher than in controls, respectively. In PAH grade 2 children, the concentrations of IL-4 and IL-6 were 11.5 and 4.8 times higher than in controls. The dynamics of the content of endothelin-1 in the blood of patients was also characterized by an increase in its concentrations in HIDL patients by 4.5, 2.4 and 4.7 times, respectively, compared with the control. The content of nitric oxide in the blood of PAH patients was significantly lower than in the control and directly depended on the severity of PAH.
Hypoxic-ischemic brain damage of the newborn infant to date is the one of the major problems in neonatology. The comprehensive clinical, laboratory and neurological examination of newborns of different gestational ages with perinatal CNS disorder was executed with the use of informative diagnostic technologies. Structural and functional disorders caused by cerebral ischemia, were established to be accompanied by significant changes in brain activity, the severity of which increases with decreasing gestational age of newborns. Certain concentrations of plasma factors of hemostasis in newborns were shown to be markers of the severity of cerebral ischemia and efficiency of complex neuroprotective therapy. Positive neurotrophic effects of gliatilin in the treatment of infants with cerebral ischemia were established to manifest by normalization of the clinical state, neurological symptoms and stabilization of plasma hemostasis, which determined the rate of regenerative treatment of ischemic brain injuries.
Necrotizing enterocolitis (NEC) is a major cause of the morbidity and high mortality in preterm infants. With the ELISA method there were determined cytokine concentrations of the transforming growth factor-β (TGF-β), macrophage inflammatory protein1β (MIP-1β), matrix metalloproteinases (MMP-2, -3, -8, -9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in low birthweight (LBW) premature infants with NEC. There were examined 68 infants at the conservative and surgical stages of NEC. In all patients on admission at 3rd and 7th day of the treatment the concentration of these compounds was determined in blood serum and tissues from damaged ileum and colon. There were established divergent differences in TGF-β content (reduction by 1,9-3 times) and MIP-1β (1.3-1.5 fold increase) in serum as compared with the control. More pronounced changes in the blood concentrations of these biomarkers in patients at the surgical stage of the NEC due to a decrease in TGF-β content, a significant increase in MIP-1β concentrations, MMP-8, TIMP-1 and the lack of the decrease in their content in the course of treatment, are associated with the severe course of NEC in LBW premature infants and prove to be indices of the unfavorable course of NEC, which requires to revise and optimize the therapeutic approach timely in such patients.