Динамика показателей роста после повторного введения ботулинического токсина типа А у пациентов с детским церебральным параличом

.

Substantiation of approaches to the correction of lipid metabolism disorders and non-alcoholic fatty liver disease in children with exogenous obesity

BACKGROUND: According to the involvement of oxidative stress in the pathogenesis of obesity, the plasma level of coenzyme q10 in the correlation relationship with lipid metabolism disorders and functional liver state is of interest to study.AIM: Substantiation of approaches to the correction of lipid metabolism disorders and non-alcoholic fatty liver disease in children with exogenous obesity based on the content of coenzyme Q10 and its relationship with lipid profile and liver enzymes.MATERIALS AND METHODS: The single-center cross-sectional study enlisted the control (n=32, -1.0≤BMI SD score ≤+2.0) and obese (n=40, BMI SD score>+2.0) groups of children with the mean age of 12 yr. In all children BMI, lipidogram, liver enzymes (ALT and AST), plasma coenzyme Q10 and liver ultrasound examination were assessed.RESULTS: Patients of both groups were comparable (p> 0.05) in age and gender. The level of coenzyme Q10 in the compared groups was comparable (p> 0.05) and did not differ in patients with different degrees of obesity. According to the results of the study of the lipid profile in the obese children, the level of HDL was lower, and the level of LDL was higher than that in control group. The highest value of HDL was obtained in the patients with the 1st degree of obesity and the highest level of triglycerides — in the patients with the 4th degree of obesity. The control group demonstrated moderate correlations between endogenous coenzyme Q10 and total cholesterol (r=0.474, p=0.009) which persists in patients with the first degree of obesity (r = 0.548, p = 0.035). There was no difference in AST in the study groups, however, the main group demonstrated elevated ALT and ALT/AST ratio (p <0.001). The highest ALT and ALT / AST ratio were observed in patients with greatest degree of obesity. Eighteen obese children (45%) had ALT / AST ratio ≥1 (in the control group –one patient (3%) (p <0.001), while fourteen patients showed liver enlargement and structure change according to ultrasound (80%). The control group demonstrated moderate correlations between endogenous coenzyme Q10 and total cholesterol (r=0.474, p=0.009) and between coenzyme Q10 and ALT / AST ratio (r=0.412, p=0.023) . In the obese group there was correlation between AI and ALT / AST (r = 0.436, p = 0.006) and in patients with the 1st degree of obesity — between also coenzyme Q10 and ALT (r = 0.875, p <0.001).CONCLUSION: The disturbances in adequate control of cholesterol by coenzyme Q10 in obese children possibly confirming the involvement of oxidative stress in the pathogenesis of dyslipidemia and non-alcoholic fatty liver disease can serve as indication to use coenzyme Q10 in order to correct these complications

Mandatory chromosomal segment balance in aneuploid tumor cells

Copyright: Copyright 2013 Elsevier B.V., All rights reserved.Background: Euploid chromosome balance is vitally important for normal development, but is profoundly changed in many tumors. Is each tumor dependent on its own structurally and numerically changed chromosome complement that has evolved during its development and progression? We have previously shown that normal chromosome 3 transfer into the KH39 renal cell carcinoma line and into the Hone1 nasopharyngeal carcinoma line inhibited their tumorigenicity. The aim of the present study was to distinguish between a qualitative and a quantitative model of this suppression. According to the former, a damaged or deleted tumor suppressor gene would be restored by the transfer of a normal chromosome. If so, suppression would be released only when the corresponding sequences of the exogenous normal chromosome are lost or inactivated. According to the alternative quantitative model, the tumor cell would not tolerate an increased dosage of the relevant gene or segment. If so, either a normal cell derived, or, a tumor derived endogenous segment could be lost. Methods: Fluorescence in Situ Hybridization based methods, as well as analysis of polymorphic microsatellite markers were used to follow chromosome 3 constitution changes in monochromosomal hybrids. Results: In both tumor lines with introduced supernumerary chromosomes 3, the copy number of 3p21 or the entire 3p tended to fall back to the original level during both in vitro and in vivo growth. An exogenous, normal cell derived, or an endogenous, tumor derived, chromosome segment was lost with similar probability. Identification of the lost versus retained segments showed that the intolerance for increased copy number was particularly strong for 3p14-p21, and weaker for other 3p regions. Gains in copy number were, on the other hand, well tolerated in the long arm and particularly the 3q26-q27 region. Conclusion: The inability of the cell to tolerate an experimentally imposed gain in 3p14-p21 in contrast to the well tolerated gain in 3q26-q27 is consistent with the fact that the former is often deleted in human tumors, whereas the latter is frequently amplified. The findings emphasize the importance of even minor changes in copy number in seemingly unbalanced aneuploid tumors.publishersversionPeer reviewe

Metformin as an Adjunctive Therapy for Pancreatic Cancer: A Review of the Literature on Its Potential Therapeutic Use

Pancreatic ductal adenocarcinoma has the worst prognosis of any cancer. New adjuvant chemotherapies are urgently required, which are well tolerated by patients with unresectable cancers. This paper reviews the existing proof of concept data, namely laboratory, pharmacoepidemiological, experimental medicine and clinical trial evidence for investigating metformin in patients with pancreatic ductal adenocarcinoma. Laboratory evidence shows metformin inhibits mitochondrial ATP synthesis which directly and indirectly inhibits carcinogenesis. Drug–drug interactions of metformin with proton pump inhibitors and histamine H2-receptor antagonists may be of clinical relevance and pertinent to future research of metformin in pancreatic ductal adenocarcinoma. To date, most cohort studies have demonstrated a positive association with metformin on survival in pancreatic ductal adenocarcinoma, although there are many methodological limitations with such study designs. From experimental medicine studies, there are sparse data in humans. The current trials of metformin have methodological limitations. Two small randomized controlled trials (RCTs) reported null findings, but there were potential inequalities in cancer staging between groups and poor compliance with the intervention. Proof of concept data, predominantly from laboratory work, supports assessing metformin as an adjunct for pancreatic ductal adenocarcinoma in RCTs. Ideally, more experimental medicine studies are needed for proof of concept. However, many feasibility criteria need to be answered before such trials can progress

Altered mRNA expression of genes related to nerve cell activity in the fracture callus of older rats: A randomized, controlled, microarray study

BACKGROUND: The time required for radiographic union following femoral fracture increases with age in both humans and rats for unknown reasons. Since abnormalities in fracture innervation will slow skeletal healing, we explored whether abnormal mRNA expression of genes related to nerve cell activity in the older rats was associated with the slowing of skeletal repair. METHODS: Simple, transverse, mid-shaft, femoral fractures with intramedullary rod fixation were induced in anaesthetized female Sprague-Dawley rats at 6, 26, and 52 weeks of age. At 0, 0.4, 1, 2, 4, and 6 weeks after fracture, a bony segment, one-third the length of the femur, centered on the fracture site, including the external callus, cortical bone, and marrow elements, was harvested. cRNA was prepared and hybridized to 54 Affymetrix U34A microarrays (3/age/time point). RESULTS: The mRNA levels of 62 genes related to neural function were affected by fracture. Of the total, 38 genes were altered by fracture to a similar extent at the three ages. In contrast, eight neural genes showed prolonged down-regulation in the older rats compared to the more rapid return to pre-fracture levels in younger rats. Seven genes were up-regulated by fracture more in the younger rats than in the older rats, while nine genes were up-regulated more in the older rats than in the younger. CONCLUSIONS: mRNA of 24 nerve-related genes responded differently to fracture in older rats compared to young rats. This differential expression may reflect altered cell function at the fracture site that may be causally related to the slowing of fracture healing with age or may be an effect of the delayed healing