ALPHA- AND BETA-GLOBIN GENE MUTATIONS IN GEORGIA AND ARMENIA.

Georgia and Armenia are situated at the northern rim of the thalassemia belt and bordering to countries with a known high prevalence of thalassemias. In this study we assessed the carrier frequency and potential spectrum of alpha- and beta-globin mutations among 202 and 190 unselected Georgian and Armenian subjects, respectively. We found four alpha-globin mutations (-3.7del, -4.2del, anti-3.7 triplication, poly-A2) in 9 Armenians (4.74%) and 4 Georgians (1.78%). The heterozygous beta-globin codon 8 [-AA] mutation was detected in one individual from Armenia only. Overall, carrier frequencies seem to be low in both countries, supporting the notion that thalassemias are not a major health problem there.

Familial Mediterranean fever in Georgia.

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder caused by mutations in the MEFV gene. Carrier rates are known to be particularly high among Sephardic Jews, Turks, Armenians and Arab populations. Our literature survey regarding FMF and MEFV mutations in Georgia revealed a lack of existing studies. We applied multiplex PCR and reverse-hybridization teststrips (FMF StripAssay) to simultaneously analyze twelve common MEFV mutations in DNA samples from dried blood on filter cards, which had been obtained from 202 unselected newborns at various hospitals in Tbilisi, Georgia. We found 30 samples to be heterozygous and one to be compound heterozygous or carrier of a complex allele (two mutations in cis). The carrier rate of MEFV mutations (15.3%) was remarkable. The most frequently observed variants were E148Q (15x), M680I G/C (5x) and M694V (4x). Five other MEFV mutations were found at lower prevalence (V726A, A744S, R761H: 2x each; P369S, F479L: 1x each). Based on these new findings, the awareness for FMF and the availability of appropriate testing should be further promoted in Georgia.

[Some immunological changes in children with bacterial infections treated with bacteriophages].

The aim of the study was to reveal the possible immunological changes in children with bacterial infections treated with commercial bacteriophage preparations administered per os. In case of medical indications (for treatment or diagnostic) blood sampling was carried out. In serum the antibodies against bacteriophage preparations - phage cocktail components (phages against Staphylococcus, Streptococcus, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa) were investigated. The neutralisation reaction was used. There were processed samples from 65 children with following diagnoses: sepsis, bacterial pneumonia, urinary tract infection, bacterial infections of upper respiratory ways, bacterial diarrhea. In samples taken in the first days of treatment antibodies were revealed in infants up to one month (I group) in 0/29 cases - 0%, in infants aged from one month till one year (II group)- 1/25 - 4.0%, in children aged from 1 till 15 years (III group) - 3/9 - 33.3%; data after 14-20 days from the beginning of treatment - I group - 0/9 - 0%, II group - 4/15 - 26.7%, III group - 5/5 - 100%; data after 30-60 days from the beginning of the treatment - I group - 1/5 - 20.0%, II group - 6/10 - 60.0%, III group - 3/3 - 100%. Bacteriophages neitralisation degree varied between 50,7% and 97.3%. Any regularity regarding different components of used phage preparations was not established. In case of inclusion of commercial phage preparations administered per os in the treatment of bacterial infections in children, the anti-phage neutralizing antibodies are produced by the macroorganism. This fact limits the duration of phage therapy and its usage in the treatment of future bacterial infections in treated patients. Production of anti-phage antibodies in young infants is substantially less expressed and this indicates to purposefulness and presumably higher efficacy of bacteriophage therapy in this age period.

[The congenital parcial erithroblastopenia--Diamond-Blackfan anemia].

The article presents twenty-five year observation on 5 patients with Diamond-Blackfan anemia. In 2010 the new case of this pathology in neonate was diagnosed. Research suggests that rarely, the Diamond-Blackfan anemia may be may be the result of an aplastic anemia. To find out what the real cause of anemia is the number of reticulocytes and qualitative and quantitative indicators bone marrow should be investigated in newborns and infants.

[University center on rare diseases, as a successful example of the integration of the clinical sector into the system of medical education].

There is substantiated appropriateness of the establishment of the University Center on Rare Diseases. It is indicated that the center could illustrate a successful integration of the clinical sector into the system of medical education. The model of the functioning of center and its regulations are presented. The main topics of the special teaching module on rare diseases for physicians are submitted as well.

[Purposefulness of using fuzzy logic approaches in the rare disease clinical trials].

Different methods being used in the rare diseases clinical trials are examined. There is shown the purposefulness of using fuzzy approaches for such studies. Some advantages of Fuzzy logic methods in comparison with Baysian approach are substantiated.

[What happens when the child gets bacteriophage per os?].

The aim of the work was to define the distribution of phages administered per os to children for medical reasons, and the immune response. 102 children aged from 5 days to 15 years with different diseases of bacterial etiology (pneumonia, sepsis, urinary infection, pharyngitis/sinusitis, enteral infection) were monitored. Pyobacteriophage was being included into the complex therapy. The drug was administered per os. In 6/7 of blood, 48/55 urine and 64/75 stool samples taken on the 3-5th day of treatment different components of pyobacteriophage were revealed. The titers varied from 103 to 105 pfu/ml. No age differences were seen. In two weeks after the onset of the phagotherapy the antibodies to phages were tested in the blood serum using the neutralization reaction method. The blood samples were taken from 31 patients. In 14 of them the antibodies neutralizing 52.5-97.3% of the phage activity were seen. A significant age-related peculiarity was determined: in newborns and infants the antibodies were not revealed or their activity was low. Obtained results confirm the reasonability to use of peroral phagotherapy in gastro-intestinal infections. At the same time it was ascertained that the phages taken per os can permeate into the internal environment of the organism and thus the peroral phagotherapy can be used to treat systemic infections and urinary tract infections as well. Absence or low production of the antiphage antibodies in newborns and infants suggests high efficacy of the phagotherapy in this age group.