[Functional characterization of two novel splicing mutations in glucokinase gene in monogenic diabetes MODY2].

Two novel mutations in glucokinase (GCK) gene-G to C substitution at -1 position of intron 7 acceptor splice site (c. 864-1G>C) and synonymous substitution c. 666C>G (GTC>GTG, p.V222V) in exon 6--were identified in patients with monogenic diabetes MODY2 (Maturity Onset Diabetes of Young). GCK minigenes with these mutations were constructed. Analysis of splicing products upon transfection of minigenes into human embryonic cell line HEK293 has shown that each of these nucleotide substitutions impair normal splicing. Mutation c.864-1G>C blocks the usage of normal acceptor site which activates cryptic acceptor splice sites within intron 7 and generates aberrant RNAs containing the portions ofintron 7. Synonymous substitution c.666C>G creates novel donor splice site in exon 6 that leads to formation of defective GCK mRNA with deletion of 16 nucleotides of exon 6. Analysis of in vitro splicing of minigenes confirms the inactivating action of novel mutations on glucokinase expression.

[Modern aspects of diabetic ketoacidosis treatment in children].

UNLABELLED: The aim of the research - the analysis of the regularities of diabetic ketoacidosis treatment in children and adolescents with type 1 diabetes mellitus, the explanation of the results obtained with the use of biological systems stability theory elements. MATHERIALS AND METHODS: The study included 90 children with type I diabetes mellitus in a state of diabetic ketoacidosis of different severity degree. With newly diagnosed type 1 diabetes mellitus - 56 children, with the "courced" diabetes - 34 children. In the evaluation of patients status was defined glucose, pH, and other indicators of acid-base status, using gas analyzer GEM Premier 3000 ("Instrumental laboratory", USA). RESULTS: All children received treatment under the Protocol, approved by the Moscow Health Department, withdrawn from the state of diabetic ketoacidosis without any complications. In the basis of this methodology is application of glucose solutions and "small" doses of insulin from the start of infusion therapy in spite of hyperglycemia. This therapy helps to prevent cerebral edema against the background of gradually reduce the blood glucose. pH recovery was explained by the existence of a common pathophysiology process. Given the qualitative description of this process on the basis of biological systems stability theory. Were determined 3 stationary state: pH = 7.4 and pH < 6,9; and one is unstable, called "the point of no return" - pH = 6.9. The conclusions of this theory substantiate the effectiveness of ketoacidosis treatment with offered method CONCLUSION: The offered technique for diabetic ketoacidosis treatment on the basis of the glucose solutions infusion throughout the treatment and "small" doses of insulin values pH and glucose in a safe range, even in patients with high risk of brain edema, which is confirmed by biological systems stability theory.

[Correlation of metabolic syndrome clinical signs and genetic determinants at children with obese].

UNLABELLED: The aim of the work was to study the clinical and genetic factors at children with obese that predispose to the development of MS, and the development of algorithm for generating risk of MS. MATERIALS AND METHODS: Two comparable age and sex groups of children--148 children with obesity and 46--with normal body weight. We assessed anthropometric indices, blood pressure (BP), lipid profile, carbohydrate metabolism, the level of uric acid. 83 children with obesity were genotyped for polymorphisms: I/D gene ACE, G-75A ApoA1, S19W ApoA5, Sstl ApoC3, E2/E3/E4 ApoE and W/R ADRB3. RESULTS: 98,0% of children had abdominal obesity. In 35,8% was identified high blood pressure. In 47,4% was diagnosed hypo-alpha cholesterolemia and/or hypertriglyceridemia (HTG). In 21,0% of children was identified hyperglycemia. 25,7%were suffered from hyperuricemia. Among the genotyped children 57,0% of homo-and heterozygous carriers of D allele ACE gene had high blood pressure. More than half of the holders of 19W-allele ApoA5 (68,5%),--75A-allele of ApoA1 (56,0%), 52-allele of the gene ApoC3 (53,0%), E4-ApoE gene (85,7%), in the heterozygous state had metabolic TG and/or HDL. In 60,3% of the carriers W/W genotype of ADRB3 gene revealed a combination of hyperglycemia with hyperinsulinemia and/or TG. CONCLUSION: As a result of, aiming aimed at early detection of the major manifestations of MS clinical and genetic study was revealed stable combination of constitutional, metabolic and molecular-genetic factors. Based on these data was developed algorithm for forming groups at risk of MS and individual tactics to prevent and/or therapy.