Background: Chemotherapy-induced peripheral polyneuropathy is a major neurotoxicity of treatment for acute lymphoblastic leukemia (ALL) in children. Pathophysiological mechanisms of the injury of peripheral neural system are not fully investigated; however, some studies have shown the involvement of vascular endothelial growth factors. Aim: To evaluate plasma levels of angiogenic growth factors in children with ALL and to identify their association with the development of vincristine-induced peripheral polyneuropathy. Materials and methods: This single center prospective study included 41 patients with ALL aged 3 to 17 years. All patients were given the ALL-MB 2015 chemotherapy regimen. Depending on the vincristine-induced peripheral polyneuropathy, the patients were divided into two groups: the main group (n = 22) comprised of the patients with neurological signs and symptoms of peripheral neuropathy and the control group (n = 19), those without clinical signs of the peripheral nervous system involvement. The levels of angiogenic growth factors (VEGF-A, VEGF-D, PlGF-1, and PDGF-BB) were measured in plasma by multiparameter immunofluorescent analysis. Results: During 3 months of the follow up the chemotherapy-induced signs of peripheral polyneuropathy developed in 53.6% (n = 22) of the children. In 72.7% (n = 16) of the patients the chemotherapy-induced peripheral polyneuropathy was characterized by a combination of neurologic abnormalities with prevailing motor symptoms. The comparative analysis of plasma angiogenic growth factors in children with ALL depending on the presence or absence of the vincristine-induced peripheral polyneuropathy showed that there was a significant decrease of the VEGF-A in those with chemotherapy-induced peripheral polyneuropathy, compared to those without (Me [Q1; Q3]: 178.20 [138.40; 228.45] and 558.50 [160.10; 650.0], respectively, p 0.017). This parameter had diagnostic sensitivity of 77.7% and specificity of 76.9%. Conclusion: We have shown a high clinical value of plasma vascular endothelial growth factor (VEGF-A) level, which makes it possible to consider it as a significant biological marker of neurotoxicity in vincristine-induced peripheral polyneuropathy.
Introduction. Fractures of the maxilla are characterized by such features as the close location of vital anatomical structures, the visual organ, as well as the aesthetic importance of this area of the face and the presence of risk of serious complications. The aim of the work was to estimate the level of angiogenic factors in the oral fluid: vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor D (VEGF-D), placental growth factor (PIGF), platelet-derived growth factor BB (PDGF-BB) (VEGF-A, VEGF-D, PIGF, PDGF-BB) and neurotrophins: nerve growth factor (NGFb) and basic brain-derived neurotrophic factor (BDNF) in orbital maxilla fractures. Materials and methods. A single-center, open-label, prospective case-control study was conducted in which 10 patients an upper jaw fracture of the maxilla (study group) and 10 practically healthy volunteers (comparison group) were examined. Along with clinical-instrumental and laboratory examination, patients were also examined for the content of VEGF-A, VEGF-D, PIGF, PDGF-BB, NGFb and BDNF in oral fluid by multiparametric fluorescent analysis with magnetic microspheres (xMAP technology, Luminex 200, USA). Results. The content of VEGF-A, VEGF-D, NGFb did not differ significantly between trauma patients and healthy practically volunteers. The content of PIGF-1 and PDGF-BB was markedly elevated in maxillary fracture, with the latter concentration being 12-fold higher than in the comparison group. Discussion. The results suggest that such injuries are accompanies by an imbalance of angiogenic and neurogenic polypeptides, manifested by increased levels of placental growth factor, platelet-derived growth factor and basic brain-derived neurotrophic factor. Conclusions. The study of the vascular remodeling and neuroprotection is important not only for extensive skeletal and craniocerebral trauma, but also for relatively local trauma – skull bone fracture in the orbit.
Age-related changes in the oral cavity are accompanied by the development of age-related pathology, such as chronic periodontitis (CP). Although apoptosis plays a certain role in its pathogenesis, this fact, however, has not been evaluated clinically, and the diagnostic information content of biomarkers of apoptosis and aging has not been determined. The aim of the study was to evaluate the content of cleaved poly-(ADP-ribose)-polymerase (cPARP) and caspase-3 (Casp3) in mixed saliva of elderly patients with age-related dental diseases and in mature patients with mild to moderate CP. The study included 69 people. The control group included 22 healthy young volunteers aged 18 to 44 years. The main group included 22 elderly patients aged 60 to 74 years. They were divided into subgroups according to clinical manifestations: occlusion (comparison group), periodontal, and dystrophic syndromes. Additionally, a group of 25 patients of mature age from 45 to 59 years old with mild to moderate CP was analyzed. The content of salivary Casp3 in patients with occlusion syndrome was lower than in healthy young people (p=0.014). In patients with the periodontal syndrome, the content of cPARP was higher than in the comparison group (p=0.031). The group with dystrophic syndrome had the highest level of Casp3 in comparison with the control group and the comparison group (p=0.012, p=0.004, respectively). There were no statistically significant differences between patients of different age groups with mild to moderate CP. Evaluation of the correlation between cPARP and Casp3 levels revealed a direct relationship in the group of elderly patients and in patients with mild CP (r=0.69, r=0.81, respectively). We assessed the effect of Casp3 levels on changes in the cPARP levels by means of a simple linear regression analysis. The cPARP level correlated with the content of Casp3 (r2=0.555). According to the results of the ROC analysis, it was found that using the cPARP indicator it would be possible to distinguish between groups of elderly patients with periodontal and occlusion syndromes (AUC=0.71), while using Casp3 it would be possible to distinguish patients with the occlusion syndrome and the control group (AUC=0.78). Since the level of Casp3 in young people is significantly higher than in the elderly patients, its decrease can be considered as a potential salivary biomarker of aging. The level of studied cPARP in the elderly has clinical value in periodontal syndrome and low age dependence.
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