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.

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.

Objectives. To study the role of the ADRB2 gene polymorphism (rs1042713) in the impaired external respiratory function in children with bronchial asthma (BA). Material and methods. The study group included 60 children aged 3-17 years with allergic (n=37) and mixed form of BA (n=23). The genotyping of the investigated gene locus was performed by PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism), BA control was exercised using the Asthma Control Test (ACT). Results. The analysis of allele frequencies showed an association of allele A with normal spirogram parameters in patients with BA (p=0.042). In children under 12 years, there were statistically significant differences in spirogram indices when comparing patients with genotypes AA and GG (p=0.045). An association of allele A with the absence of pathological changes was revealed when evaluating the results of spirometry (p=0.021). There was a moderate positive correlation (r=0.615, p=0.011) between the assessment of nocturnal symptoms (Asthma Control Test) and the genotype of the ADRB2 gene polymorphism in children aged 12 years and older. Conclusions. An association of the ADRΒ2 gene polymorphism (rs1042713) with the external respiratory function was revealed in an objective study by spirometry and a subjective assessment of this indicator by the patient himself/herself or by his/her parents. This gene locus can be included in the BA target panel in order to determine the likelihood of uncontrolled course development of the disease with impaired external respiratory function and in the future to develop an individual program for dispensary observation of the patient.

Objective. The role of the GLCCI1 gene polymorphism (rs37973) analysis in children with bronchial asthma (BA). Methods. The study involved 60 children 3-17 years old with allergic (n=37) and mixed forms of BA (n=23). The genetic study included performing genotyping of the studied locus of the GLCCI1 gene (rs37973) by PCR-RFLP (polymerase chain reaction – restriction fragment length polymorphism). Results. Analysis of the frequency of genotypes and alleles occurrence established the predominance of heterozygotes (AG) and allele G in the study group. There were statistically significantly higher indices of VC, FVC, FEV1 and MEF75 (according to spirometry data) with a heterozygous genotype (AG) in comparison with a homozygous GG (p<0,05). At the same time, there was a statistically significantly greater number of children with a FEV1 level ≥80% (p=0,009) when comparing the same subgroups of genotypes. Conclusion. The study revealed the association of GLCCI1 gene polymorphism (rs37973) with the respiratory function according to spirometry data. The presence of a heterozygous gene variant (AG) determined higher indicators of the function of respiratory function (VC, FVC, FEV1, MEF75). The study with the establishment of the GLCCI1 gene (rs37973) genotype can be used to diagnose a prognostically favorable and unfavorable course of asthma in children, which should be taken into account when choosing various basic methods of therapy and rehabilitation.

An assessment of the modern methods of diagnosis of an allergy, the level of development of the modern technologies in medicine which can provide the complete diagnosis of allergic diseases is given, reveal type and the mechanism of a hypersensitivity, an organism sensitization to causal significantly allergen, by means of specific allergological inspection of in vivo. The role of the modern cell-like methods capable to reveal of an allergy and hypersensitivity, a possibility of their application in clinics and laboratories is shown.