Genetic Landscape of Nephropathic Cystinosis in Russian Children.

Nephropathic cystinosis is a rare autosomal recessive disorder characterized by amino acid cystine accumulation and caused by biallelic mutations in the CTNS gene. The analysis methods are as follows: tandem mass spectrometry to determine the cystine concentration in polymorphonuclear blood leukocytes, Sanger sequencing for the entire coding sequence and flanking intron regions of the CTNS gene, multiplex PCR to detect a common mutation-a 57 kb deletion, and multiplex ligation-dependent probe amplification to analyze the number of exon copies in the CTNS gene. Haplotype analysis of chromosomes with major mutations was carried out using microsatellite markers D17S831, D17S1798, D17S829, D17S1828, and D17S1876. In this study, we provide clinical, biochemical, and molecular genetic characteristics of 40 Russian patients with mutations in the CTNS gene, among whom 30 patients were selected from a high-risk group of 85 people as a result of selective screening, which was carried out through cystine concentration measurement in polymorphonuclear blood leukocytes. The most common pathogenic variant, as in most described studies to date, was the 57 kb deletion, which represented 25% of all affected alleles. Previously non-described variants represented 22.5% of alleles. The founder effect in the Karachay and Chechen ethnic groups was shown for the following major variants: c.1015G > A and c.518A > G.

BONE REPAIR AFTER THE GLASS-CERAMICS IMPLANTATION INTO THE RATS' FEMUR DEFECT.

The aim is to study the bone response to the implantation of two glass-ceramic materials into the distal metaphysis of the femur of rats. Experiment was carried out on 30 white 4-month-old laboratory male rats. Animals were randomly divided into two groups for the implantation of two types of calcium silicate-phosphate glasses (BS-11 or ASZ-5) into the defect of femur. Histology analysis was performed 7, 14 and 30 days (n=5 in each group) after the surgery. Estimate of bone-to-implant area (BIC%), fibrous-tissue-to-implant area (FIC%) and collagen distribution in polarization light was performed. 7daysafterimplantationthe fibrous tissue and new-formed woven bone tissue were found around BS-11 and ASZ-5. After 7daysFIC% was greater than BIC%: in BS-11 group by 2.2 times (p<0.001) and in ASZ-5 group by 2.5 times (р<0.001). 14daysafterimplantation BIC% increased compared to 7 days: in BS-11 groupby 2.2 times (р<0.001) and in ASZ-5 groupby 2.7 times (р<0.001). After 30 days, the lamellar bone tissue was found around the implanted BS-11 and ASZ-5 (100% of the perimeter). ASZ-5 microparticles were embedded in the newly formed lamellar bone at 14 and 30 days after implantation. The collagen fibers were oriented parallel to the implants surface of BS-11 and ASZ-5. Glass-ceramic ASZ-5 and BS-11 materials have high biocompatibility, good osteoconductive and osteoinductive properties and are incorporated into the bone. However, the rapid degradation of ASZ-5 makes it fragile, which may become a limitation for its use in loaded areas of the skeleton.

HISTOMORPHOMETRIC EVALUATION OF BONE REPAIR AFTER CARBON/CARBON COMPOSITE IMPLANTATION IN LUMBAR VERTEBRAE IN RATS.

The aim is to study the characteristics of bone regeneration under the conditions of implantation of carbon/carbon composite material with and without pyrocarbon coating in the vertebral bodies of rat. C/c composite (n=9) or c/c composite & PC (n=9) were implanted into hole defects in the LIII vertebral bodies of white laboratory male rats (6-7 months, weight 250-350 g). The material was made in the form of a cylinder (diameter 2 mm, height 2 mm). Histological and histomorphometric study were performed at 15, 30 and 90 days after implantation. After 15 days, bone and granulation tissues were found in the ratio of ½ along the perimeter of both materials. After 30 days, fibroreticular bone tissue and connective tissue of varying degrees of maturity formed around the implants. The relative content of new formed bone tissue near the c/c composite after 30 and 90 days was 1.4 times lower (p<0.001) compared with the c/c composite and PC group. The studied materials are biocompatible, do not interfere with bone regeneration, and do not cause inflammatory reactions. Osseointegration qualities are higher for the c/c composite & pyrocarbon coated.

Regulation of reactive oxygen species production by peripheral blood neutrophils from women with postpartum endometritis.

Production of reactive oxygen species in unfractionated peripheral blood increased in parturient women without postpartum infectious complications and patients with postpartum endometritis. The control group included nonpregnant women with normal reproductive function. Intergroup differences were revealed in the degree of respiratory burst activation with opsonized zymosan and response of isolated granulocytes to chemotactic peptide N-formyl-Met-Leu-Phen (1 muM). Production of reactive oxygen species tended to normal after therapy. We studied the effects of a specific mitogen-activated protein kinase p38MAPK inhibitor and inhibitors of tyrosine protein phosphatases and phosphatidylinositol-3-kinase. The role of p38MAPK in reactive oxygen species generation by cells changes significantly in parturient women.

Natural histidine-containing dipeptide carnosine as a potent hydrophilic antioxidant with membrane stabilizing function. A biomedical aspect.

A review on the distribution and biological effects of carnosine and a hypothesis for its biological mechanisms of action are presented. Carnosine and its structural and functional relative, anserine, were found in skeletal muscles at the beginning of the century. Their effects on muscle-working capacity, on the stability of membrane-bound enzymes, as well as their potent immunomodulating property, could not be explained by their pH-buffering capacity or formation of the secondary metabolites histidine and beta-alanine alone. This article suggests that the basis for the biological activities of carnosine and relative compounds is their potent antioxidant and membrane-protecting activity. The plausible chemical mechanism of this activity is discussed, and data regarding the usage of carnosine as a drug for treatment of immunodeficiency are summarized.

Pattern of changes in clinico-immunological indicators of patients with drug allergy during treatment with autologous blood.

An efficient method for the treatment of drug allergy was proposed and practically implemented. The method consists in autologous venous blood being lyzed with sterile bidistilled water at a ratio of 5:1 and injected subcutaneously and partially intradermally into the reflexogenic zones of the back 2-3 cm from the spinal column. During the first week of treatment, increasing doses were injected (3 to 10 ml), whereas during the second week the doses decreased from 10 to 3 ml. Following treatment the patients felt better and featured enhanced working ability as well as markedly declined susceptibility to common colds. The most informative immunological indicators were chosen to evaluate the efficiency of therapy.