[Impairments of gastrointestinal tract in autism].

In the article the peculiarities of the gastrointestinal tract in children with autism. Presents the algorithm for evaluation of children with autism in KhSMGC, the statistical data about the frequency of lesions of the gastrointestinal tract. The main directions of correction of digestive disorders and its results.

[Gastrointestinal and metabolic impairments in cystic fibrosis].

This article is about the peculiarities of gastrointestinal lesions, and the nature of metabolic disorders in patients with cystic fibrosis. Presented statistical data abouth the frequency of various gastrointestinal disorders in cystic fibrosis, studied the spectrum of ultrasound changes and changes in the biochemical status of patients with cystic fibrosis.

Double blind placebo control trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine.

Large neutral amino acids (LNAA) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In an open-label study using LNAA, a surprising decline of blood Phe concentration was found in patients with PKU in metabolic treatment centres in Russia, the Ukraine, and the United States. To validate the data obtained from this trial, a short-term double-blind placebo control study was done using LNAA in patients with PKU, with the participation of three additional metabolic centres--Milan, Padua and Rio de Janeiro. The results of the short trial showed significant lowering of blood Phe concentration by an average of 39% from baseline. The data from the double-blind placebo control are encouraging, establishing proof of principle of the role of orally administered LNAA in lowering blood Phe concentrations in patients with PKU. Long-term studies will be needed to validate the acceptability, efficacy and safety of such treatment.

Large neutral amino acids in the treatment of phenylketonuria (PKU).

Large neutral amino acids (LNAAs) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In earlier studies on mice with PKU (ENU(2)/ENU(2)), LNAAs were given and a surprising decline in blood Phe concentrations was observed. The formula used in the mouse experiment (PreKUnil) lacked lysine. Therefore, a new formulation of LNAAs (NeoPhe) was developed, introducing changes in the concentration of some amino acids and adding lysine, so that such a mixture could be used in humans. The new formula was found to be effective in reducing blood Phe concentration in mice by about 50% of the elevated levels. Patients with PKU were given LNAAs and blood Phe concentrations were determined in an open-label study. Three centers--in Russia, the Ukraine and the USA--took part in the study. NeoPhe was given at 0.5 g/kg per day in three divided doses to eight subjects with PKU and at 1.0 g/kg per day to three patients, for one week. The NeoPhe resulted in decrease of elevated blood Phe by 50% in both groups. The preliminary data from this study are encouraging and a double blind placebo-controlled trial will be required to show long-term efficacy and tolerance of LNAAs in the treatment of PKU.

[Distribution of the HIV-1 resistance-conferring alleles (CCR5delta32, CCR2-64I, and SDF1 3'A) in Russian, Ukrainian, and Belarusian populations]. / Raspredelenie VICH-protektivnykh allelei (CCR5delta32, CCR2-64I i SDF1-3'A) v vyborkakh russkikh, ukrintsev i belorusov.

The frequencies of three alleles, CCR5delta32, CCR2-64I, and SDF1 3'A, known to decrease the risk of AIDS onset and the rate of the disease progression in HIV-infected individuals were determined in three native population samples from Russia, Ukraine, and Belarus. The frequencies of the alleles were 0.15, 0.12, 0.21; 0.12, 0.07, 0.20; and 0.12, 0.08, 0.26 for Russians, Ukrainians, and Belarussians, respectively. The proportion of the individuals without any of three protective alleles among Russians, Ukrainians, and Belarussians constituted 49, 65, and 61%, respectively. The genotype frequencies for the three loci studied were in Hardy-Weinberg equilibrium. Based on the three-locus genotype frequencies, the hazard ratios (relative hazards, RH) of AIDS onset in HIV-infected individuals in each sample were calculated as ranging from 0.79 to 0.88. In the samples of Eastern Slavs analyzed the estimated frequencies of the AIDS-protective alleles tested, as well as the frequencies of the corresponding genotypes and the relative hazards of AIDS onset were within the range of these parameters for the other European populations. The data on the allele frequencies and the relative hazard values in Russians, Ukrainians and Belarussians can be used as the predictors of AIDS onset and progression rate in HIV-1-infected individuals from the populations studied.

[Analysis of the DRD4 gene polymorphism in populations of Russia and neighboring countries]. / Issledovanie polimorfizma gena DRD4 v populiatsiiakh Rossia i sopredel'nykh stran.

Allele and genotype frequencies of the VNTR polymorphism in the third exon of human DRD4 gene were determined in 544 individuals living in Russia (Russians, Bashkirs, Tatars, and Mordovians) and in the neighboring countries (Kazakhs and Ukrainians). The data obtained were compared with the allele frequency distribution patterns reported for the populations of Eurasia. Similarly to other Eurasian populations, in our population samples R4 allele was prevalent (64 to 87%). The frequency of this allele in the populations of Western Europe constitute 61 to 71%, while in the populations of Asia it varies from 74 to 96%. In this respect, the populations studied occupied the intermediate position. In the samples examined the R7 allele frequency decreased from 7% in Ukrainians to 1% in Bashkirs, while in Kazakhs and Mordovians the allele was absent. This finding was consistent with the R7 allele distribution pattern in the populations of Eurasia, characterized by higher frequency in the West and lower frequency or absence of the allele in the East. In the group of 22 Eurasian populations, the R7 allele frequency negatively correlated with the frequency of the R4 allele (r = -0.86 at P < 0.001). Unlike the R4 and R7 alleles, the frequency of which changed in the eastward direction, the R2 allele frequency distribution displayed slightly expressed latitudinal increase southwards. The DRD4 genotype distribution deviated from the equilibrium in most of the samples examined. In some samples, statistically significant increase of the R2/R2 homozygotes frequency was demonstrated. One of the possible explanations of this phenomenon is assortative mating with respect to phenotypic (behavioral) allele manifestation. The data obtained can serve as the basis for the investigation of the possible role of the DRD4 alleles as the risk factors for the development of alcoholism and other types of addictions.

[Structure of the gene pool of eastern Ukrainians from Y-chromosome haplogroups]. / Struktura genofonda vostochnykh Ukraintsev po gaplogruppam Y-khromosomy.

Y chromosomes from representative sample of Eastern Ukrainians (94 individuals) were analyzed for composition and frequencies of haplogroups, defined by 11 biallelic loci located in non-recombining part of the chromosome (SRY1532, YAP, 92R7, DYF155S2, 12f2, Tat, M9, M17, M25, M89, and M56). In the Ukrainian gene, pool six haplogroups were revealed: E, F (including G and I), J, N3, P, and R1a1. These haplogroups were earlier detected in a study of Y-chromosome diversity on the territory of Europe as a whole. The major haplogroup in the Ukrainian gene pool, haplogroup R1a1 (earlier designated HG3), accounted for about 44% of all Y chromosomes in the sample examined. This haplogroup is thought to mark the migration patterns of the early Indo-Europeans and is associated with the distribution of the Kurgan archaeological culture. The second major haplogroup is haplogroup F (21.3%), which is a combination of the lineages differing by the time of appearance. Haplogroup P found with the frequency of 9.6%, represents the genetic contribution of the population originating from the ancient autochthonous population of Europe. Haplogroups J and E (11.7 and 4.2%, respectively) mark the migration patterns of the Middle-Eastern agriculturists during the Neolithic. The presence of the N3 lineage (9.6%) is likely explained by a contribution of the assimilated Finno-Ugric tribes. The data on the composition and frequencies of Y-chromosome haplogroups in the sample studied substantially supplement the existing picture of the male lineage distribution in the Eastern Slav population.

A case of Rett syndrome from Ukraine--clinical diagnosis confirmed by mutation analysis of the MECP2 gene.

Rett syndrome (RTT) is an X-linked disorder caused by mutations in the methyl-CpG-binding protein 2 gene (MECP2). The incidence is 1:10,000-1:15,000 females worldwide. To date, the mutational spectrum of MECP2 in the Ukrainian population is not known. Here we present first Ukrainian girl with classic clinical signs of RTT, in whom mutation of MECP2 gene was detected. Total genomic DNA was extracted from a dry blood spot using the QIAamp DNA Mini Kit (Qiagen) according to the manufacturer's protocol. Genomic DNA was used to amplify coding sequence and exon/intron borders of MECP2 gene. Products were examined by restriction analysis and automatic direct sequencing. The sequencing analysis of our patient revealed a small deletion of 4 bases AAAG at position 856-859 in exon 4 of MECP2 gene (856-859del4). This mutation leads to a frameshift (K286fs) and a premature stop codon. The creation of premature stop codon results in synthesis of truncated MeCP2 protein. Localization of the mutation into the transcription repression domain (TRD) probably affects the function of MECP2 protein in the process of transcriptional repression. To our knowledge this is the first case from Ukraine, in whom clinical diagnosis of RTT was confirmed by mutation analysis of MECP2 gene. Mutation analyses of further patients are needed to establish the spectrum of MECP2 mutations in the Ukrainian population. (Tab. 1, Fig. 3, Ref. 22.)

[Chromosomal syndromes in the autosomal system and the problems of differential diagnosis]. / Khromosomnye sindromy v sisteme autosom, problemy differentsial'nogo diagnoza.

The karyotype of 2715 patients suspected of chromosome pathology has been studied. Chromosomal aberrations in the system of autosomes has been revealed. A diagnostic programme promoting a selective screening of chromosome pathology in nonspecialized medical institutions is developed. Medical-social rehabilitation programme for patients with chromosome syndrome is worked out.

[Role of phenotype in liver function in adolescents with change of the tuberculin reaction during chemoprophylaxis]. / Znachenie fenotipa dlia funktsionalnogo sostoianiia pecheni u podrostkov s virazhom tuberkulinovykh reaktsii pri provedenii khimioprofilaktiki.

A total of 92 adolescents aged 13-17 with a turn in the tuberculin reactions underwent clinicomorphological and laboratory examinations at sanatorium where they received chemoprophylaxis for tuberculosis. The clinicomorphological examination involved description of phenotypical characteristics of dysembryogenetic stigmas by 22 anatomical units. Hepatic function was assessed before and during chemoprophylaxis by serum biochemistry: total and direct bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, cholesterol, triglycerides, urea, uric acid. High stigmatization of the phenotype, the presence of dysembryogenetic stigmas of the face and skull, nose, jaws, chest, abdomen and pelvis occurred more frequently in adolescents with changes in serum biochemistry reflecting hepatic condition.

[Possibilities of the prenatal diagnosis of congenital developmental disorders in the second trimester of pregnancy using ultrasound]. / Vozmozhnosti prenatal'noi diagnostiki vrozhdennykh porokov razvitiia vo II trimestre beremennosti s pomoshch'iu ul'trazvukovogo issledovaniia.

Ultrasonography was used in the second pregnancy trimester as a noninvasive method of prenatal diagnosis of congenital malformations (CM) in 1071 pregnant women. These were found in 1.2% of the examinees, were local and multiple with predominance of CNS anomalies. Key ultrasonic signs of CM are specified. It was noted that a fertilized egg presents valuable specific and nonspecific information. Ultrasonography is shown to be of high informative value in prenatal diagnosis of CM in the second trimester.