Aim of the study. To elucidate the association between the polymorphous marker A/del132 of the CCR5 gene with type 1 diabetes mellitus. Materials and methods. The study included 177 patients with type 1 diabetes mellitus (DM1) and 408 healthy subjects (ethnic Russians). CR5 alleles and genotypes were identified with the use of the real-time amplification technique. Results. It was shown that the CCR5 allele without 32 base pair deletion (allele A) predominated in both diabetic patients and diabetes-free subjects. The difference between their occurrence in the two groups was insignificant. At the same time, we documented a significant rise in the frequency of del132/del132 genotype in the diabetic patients compared with the healthy subjects (p=0.008). It is concluded that carriers of the CCR5-del32/del32 genotype in the Russian population of Moscow are at high risk of developing type 1 diabetes mellitus.

Aim. To estimate the degree of arterial calcinosis in the distal segments of the lower extremities in the patients presenting with diabetes mellitus (DM) and varying severity of distal diabetic polyneuropathy (DPN). Materials and methods. The study involved 61 patients with DM ( 21 men and 40 women, mean age 51.4 +- 11.68 years) of whom 27 suffered DM1 and 34 DM2. Group 1 was comprised of 37 patients with diabetic osteoarthropathy (DOAP), group 2 included 13 patients with severe DPN, and group 3 11 patients having moderate DPN. All the patients underwent comprehensive laboratory and instrumental examination including measurement of peripheral sensitivity and electromyography. The degree of arterial calcinosis in the distal segments of the lower extremities was determined using multispiral computed tomography (MSCT) with the calculation of the Agatston tibial artery calcification scores. Results. The groups were matched for the patients' age, duration of disease, total cholesterol and creatinin levels, and glomerular filtration rate. Moreover, the patients of groups 1 and 2 were matched for the functional state of nerve fibers in the lower extremities and were significantly different in respect to this characteristic from the patients of group 3. Median of the Agatston tibial artery calcification scores in group 1 was 365.4 (min - 0, max - 1600) and in group 2 2.7 (min - 0, max - 74.6). Groups 1 and 2 were comparable in terms of the degree of calcinosis and were significantly different from group 3 (p < 0.05 1 vs 3; p < 0.005 2 vs 3). The Agatston tibial artery calcification scores negatively correlated with the motor response (r = -0.3; p < 0.05) and vibrational sensitivity (r = -0.4, p < 0.01). Conclusion. Results of the study suggest the leading role of DPN in the development and progression of arterial calcinosis in the distal segments of the lower extremities in the patients with diabetes mellitus.

Congenital adrenal cortical hyperplasia (CAH) is one of the commonest endocrine pathologies in the children. Screening newborn infants for CAH is currently based on the measurement of 17-hydroxyprogesterone (17-OHP) levels in blood spots using the immunoenzymatic assay. However, this techniques is known to suffer relatively low specificity accounting for the high percentage of false-positive results. We compared two 17-OHP measurement tecniques, immunoenzymatic assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) employed for the additional examination of the children in whom screening for CAH revealed the enhanced blood 17-OHP levels. The study included 50 patients at the age from 7 days to 1.5 months born at different gestational ages. 17-OHP levels were measured in all of them using the immunoenzymatic assay and LC-MS/MS. The results of the study indicate that the latter technique should be regarded as the method of choice for the confirmation of diagnosis of CAH. The absence of clinical manifestations of 21-hydroxylase deficiency in the patients in whom the immunoenzymatic assay reveals the enhanced levels of 17-OHP whereas the LC-MS/MS method demonstrates the normal or only slightly elevated concentrations of 17-OHP allows to exclude diagnosis of CAH. The gestational age of the infant is the key factor in the choice of the upper threshold level of 17-OHP for the purpose of screening; the child's body weight is of low diagnostic value. The 17-OHP levels measured by LC-MS/MS in the boys may be slightly higher than the reference values compared with the girls.

Aim of the study. To estimate the effectiveness and safety of substitution therapy with growth hormone (GH) in children with various brain tumours. Materials and methods. The study involved 68 patients admitted to N.N. Burdenko Institute of Neurosurgery between 2001 and 2011 including 35 ones with craniopharyngioma, 18 with medulloblastoma, and 15 with germ cell tumours (GCT) in the chiasmosellar region. All patients suffered growth hormone insufficiency and received GH replacement therapy. Their antropometric characteristics (height and growth rate) and IGF-1 levels were measured before, 6 and 12 months after the onset of the treatment. The doses of GH varied from 0.03 to 0.034 mg/kg/day. Results. The substitution therapy with GH resulted in an increase of the growth rate in patients with craniopharyngioma from 2.3±1.6 to 9.4±1.9 cm/year (p<0.001), in those with GCT from 1.2±0.9 to 7.4±2.6 cm/year (p=0.01), and in patients with medulloblastoma from 2.3±1.5 to 6.2±2.6 cm/year (p<0.01). The growth rate in patients treated by spinal irradiation was lower than that in those given no such treatment (6.0±2.3 cm/year and 9.2±2.1 cm/year respectively; p<0.001). The tumour recurred in eight of 35 (23%) patients with craniopharyngioma during GH therapy. The frequency of relapses was not significantly different from that in patients who did not receive growth hormone. Patients with medulloblastoma and GCT did not develop relapses. No adverse reactions to GH therapy were documented in this study.

The objective of the present study was to analyse dynamics of the serum adiponectin levels during treatment of obesity in the adolescents. A total of 34 patients at the age varying from 12 to 17 years presenting with "simple" constitutional exogenous obesity were available for observation. All of them had metabolic complications, such as impaired glucose tolerance, insulin resistance, dyslipidemia, and arterial hypertension. A course of motivational education for the change of lifestyle was provided to 15 patients and their parents in combination with healthy diets, physical activities, and orlistat intake (120 mg, one capsule thrice daily) during 6 months. The patients of the control group (n=19) were given non-medicamental therapy alone. The effectiveness of therapy was estimated before, 6 and 12 months after its initiation. The combined treatment of complicated obesity in the adolescents was shown to promote a decrease of the body weight by 0.04-0.08 SDS of MBI within one year after the onset of therapy. Simultaneously, the degree of dyslipidemia, insulin resistance, and disturbances of carbohydrate metabolism was reduced whereas the serum adiponectin levels increased. The study failed to reveal advantages of orlistat treatment for the reduction of BMI. At the same time, the introduction of this medication into combined therapy of obesity in adolescents resulted in a clinically significant decrease of the frequency of dyslipidemia, largely due to lowering the total cholesterol and LDLP cholesterol levels. Orlistat therapy was well tolerated by the patients. Variations in the adiponectin level were in agreement with body weight dynamics and changes of insulin resistance. It is concluded that low serum adiponectin levels in association with the high frequency of complications may suggest high risk of progression of metabolic disturbances in obese adolescents towards adulthood.

This study has demonstrated high sensitivity and specificity of the low-dose (5 mcg) 1-24-ACTH stimulation test used for diagnostics of the non-classical form of congenital adrenal hyperplasia (21-hydroxilase deficiency).

The circadian rhythm of melatonin secretion was studied by measuring the amount of its decomposition product (6-sulfatoxymelatonin) in discrete urine sample collected during daytime and night-time periods. The study included a total of 29 subjects ten of whom suffered nocturnal sleep deprivation. 6-sulfatoxymelatonin in the patients of the latter group was measured twice throughout the study: during the 24-hour period with normal sleep and during the 24-hour period with nocturnal sleep deprivation. It was shown that nocturnal sleep deprivation resulted in the disturbances of the circadian rhythms of melatonin production. It sharply decreased at night-time to the levels characteristic of daytime secretion. In the subjects with the normal sleep regimen (i.e. without nocturnal deprivation) the daytime adiponectin levels amounted to 63-75% of the average daily value.

Defects in the insulin gene (INS) are one of the causes responsible for the development of permanent and sometimes transient diabetes mellitus (DM) in the children during the first year of life. Both autosomal dominant and autosomal recessive mutations in the INS gene have been described. Dominant mutations are responsible for the development of absolute insulin deficiency due to precocious apoptosis of pancreatic beta-cells and the formation of the symptomocomplex clinically identical with type 1 diabetes mellitus. Recessive mutations affect insulin biosynthesis and cause DM manifestations within a few first weeks of life of the child. The first case of DM manifestation in a 7-month old girl in Russia is described; it is attributable to a new heterozygous mutation in the insulin gene.

g15384delG(G133fsX15), c.215T⇒C(p.L72S), c.309C⇒A(p.N103K), c.313C⇒T(p.R105W), c.422C⇒G(p.S141C), c.104_106delTCA, c.481_482delC⇒T, and c.135del13bp mutations in LEP in the homozygous state are known to be associated with the early onset of severe obesity and disturbances of many physiological functions. Similar pathological changes are induced by mutations in LEPR, such as G⇒A substitution in the splicing donor site, deletions of 4 and 11 base pairs in the 5'-terminus of cDNA, deletion of 66 bp in the CRH domain of LEPR, compound deletion of 1 base pair in the 5'-terminus/p.R612H, and missense mutations P316T, A409E, W664R, and H684P. Disturbances in LEP and LEPR expression in homozygous subjects are associated with severe obesity, retarded sexual development, insulin resistance, disordered secretion of adenohypophyseal hormones, and immunodeficiency. Mutations in LEP cause more serious pathological changes than LEPR mutations. In the homozygous state, mutations in POMC, such as 3804C⇒A, 6906delC, 6922insC, and compound heterozygous mutations 7134delG/7013G⇒T, 6996del/6851A⇒T, 3804CA/7100insGG are associated in man with morbid obesity and acute adrenal cortical insufficiency. In the heterozygous state, these mutations predispose to obesity in the absence of concomitant disorders. Mutations in MC4R are the most common cause of obesity. They are known to induce severe pathology in homozygous subjects but significantly milder disturbances of adipose tissue metabolism in heterozygotes. In both cases, obesity is not accompanied by serious disturbances of other functions.