FEATURES OF CLINICAL SYMPTOMS AND SIGNS, HEMATOLOGICAL AND BIOCHEMICAL PARAMETERS IN CHILDREN WITH JOINT HYPERMOBILITY IN A LATE PERIOD UPON THE CHORNOBYL NPP ACCIDENT. / OSOBLYVOSTI KLINIChNOÏ SYMPTOMATYKY, GEMATOLOGIChNYKh TA BIOKhIMIChNYKh POKAZNYKIV U DITEY̆ Z GIPERMOBIL'NISTIu SUGLOBIV U VIDDALENYY̆ PERIOD PISLIa AVARIÏ NA ChORNOBYL'S'KIY̆ AES.

OBJECTIVE: establishing the types and frequency of disembriogenetic stigma in children with joint hypermobility given the clinical and laboratory features, genetic component and endocrine regulation of these disorders in a late period upon the accident. MATERIALS AND METHODS: Children (n = 109) inhabiting the radiologically contaminated territories and having the connective tissue dysplasia (CTD) signs were involved in the study. Diseases in family history, ossalgia complaints, fractures in a personal history, bone disembriogenetic stigma, joint hypermobility, type of somatic diseases, blood serum biochemical parameters (namely calcium, alkaline phosphatase, total protein, cholesterol, creatinine, iron, ferritin content), serum cortisol, free thyroxine, pituitary thyroid-stimulating hormone (TSH) levels, free amino acid composition in urine and radiation dose were considered. RESULTS: Radiation doses in children having the CTD ranged from (0.37 ± 0.11) mSv to (0.56 ± 0.10) mSv with no difference from that in those without CTD. Joint hypermobility (JHM) correlated with cancer in family history (rs = 0.53) and lower extremity varicose vein disease (rs = 0.40) (p < 0.05). Incidence of ossalgia, easy fatigability, and bone fractures was higher in children with CTD. Anomalies of the dentofacial system were first in line (38.5 %) in these children. Proportion of children with grade II JHM and platypodia was lower (rs = 0.42), but with lower extremity deformations was higher (rs = 0.68) (p < 0.05) vs. in the control group. Iron and ferritin deficiencies both with lymphocytosis were more common in children with CTD than in the comparison group (p < 0.05). The increased content of oxyproline, lysine, proline both with glycine deficiency were detected in children having the CTD, i.e. an imbalance of amino acids from the collagen content was observed featuring a predominance of catabolic processes over anabolic ones. There was a direct correlation between the TSH level and the JHM grade (rs = 0.49), although the values of hormone concentration in these children did not exceed the reference range (maximum values were 3.3 µIU/ml). CONCLUSIONS: The revealed abnormalities in amino acid content, ferrokinetics, and thyroid function indices can affect the collagen formation, organic matrix structure of bone tissue and significantly deregulate the hemato- poiesis. The later can underlie the pathways of haematologic malignancy development.

Evaluation of median survival patients with acute lymphoblastic leukemia exposed to ionizing radiation by the Chornobyl accident, depending on the aminoacid composition of stromal fibroblasts bone marrow and indicators of myelogram. / OTsINKA MEDIANY VYZhYVANOSTI KhVORYKh NA GOSTRI LIMFOBLASTNI LEYKEMII, IaKI ZAZNALY VPLYVU IONIZUIu ChOGO VYPROMINENNIa VNASLIDOK AVARII NA ChAES, ZALEZh NO VID AMINOKYSLOTNOGO SKLADU STROMAL'NYKh FIBROBLASTIV KISTKOVOGO MOZKU TA POKAZNYKIV MIIeLOGRAMY.

OBJECTIVE: To investigate the aminoacid composition in the stromal fibroblasts of bone marrow and indexes of hemogram in children with acute lymphoblastic leukemias, which exposed to radiation from the Chornobyl accident, for evaluation of the median survival. MATERIALS AND METHODS: In the study 54 patients with acute lymphoblastic leukemia, residents of Kyiv, Zhytomyr and Chernihiv regions of Ukraine were involved. Effectiveness of stromal fibroblasts colony forming units of bone marrow and aminoacid composition of fibroblasts were studied. Bone marrow examination was conducted on day33 and after stop of chemotherapy, the median survival of patients and exposure dose were evaluated. RESULTS: In children with acute leukemias effectiveness of stromal fibroblasts of bone marrow was 2-2,3 times lower than normative. Correlation (rs = +0,83) between the number of erythroid progenitor cells in the bone marrow and proline content in stromal fibroblasts established . The correlation between patients median survival and number of granulocytes in myelogram (rs = + 0,82) was proven. Mean exposure doses in patients was (5,86 ± 1,11) mSv and it did not correlate with myelogram results, effectiveness of stromal fibroblasts of bone marrow and median survival. CONCLUSIONS: The median survival of patients with acute leukemias depends on the content of amino acids in stro mal fibroblasts of bone marrow and recover of hematopoiesis after chemotherapy.

[EFFECT OF BIOACTIVE ALDEHYDES ON GELATIN PROPERTIES].

Bioactive aldehydes are among main factors of proteins postsynthetic modifications, which are the cause and consequence of many diseases. Comparative study of some aldehydes modifying action on gelatin was carried out in vitro. Gelatin samples (20 mM) were incubated with: ribose, deoxyribose, glyoxal, methylglyoxal, formaldehyde, acrolein (20 mM each) and their combinations in 0.1 M Naphosphate buffer (pH 7.4) containing 0.02% sodium azide at 37 °C in the dark for 30 days. We investigated the fluorescent properties of these samples and their molecular weight distribution by electrophoresis. It has been revealed that formed adducts had different fluorescence spectra. According to fluorescence intensity these aldehydes were put in order: formaldehyde < methylglyoxal < acrolein

Rationale treatment and preventive measures for correction of bone structure in children with acute leukemia, exposed to ionizing radiation due to the Chornobyl accident. / Ocinka likuval''no-profilaktychnyh zahodiv dlja korekcii' struktury kistkovoi' tkanyny u ditej z gostrymy lejkemijamy, jaki zaznaly vplyvu ionizujuchogo vyprominennja vnaslidok avarii' na ChAES.

Objective. To justify and evaluate the effectiveness of treatment and preventive measures taken to correct the bio-chemical and biophysical changes in the structure of bone in children exposed to ionizing radiation due to Chornobyl accident in the dynamics of leukemic process. Materials and methods. The study involved 144 patients with acute lymphoid and myeloid leukemia. Serum calcium, total protein, alkaline phosphatase, cortisol and thyroid-stimulating hormone were investigated, as well as calcium and phosphate excretion, amino acids composition in the urine, acid-base balance and buffer systems of blood, bone density. Results. A reduction of bone densitometry, calcium and cortisol levels and increase of serum alkaline phosphatase and urine oxyproline were found in children with acute leukemia in acute I phase and during the chemotherapy. In the period of remission the majority of patients did not differ from the comparison group. The signs of osteopenic syndrome that require monitoring of the bone structure status were revealed in 10.0 % of children of the comparison group. Radiation doses of leukemia patients were 3.66 ± 0.11 mSv. No relationship between radiation dose and indicators that reflect the state of the bone tissue structures has been established. The use of complex health care measures in children with acute leukemia in remission, contributed to the positive effect of 62.0 %. Worser effect was observed in patients with an unfavorable course of the disease. Conclusions. Results of the study of bone tissue metabolism prove fore a change in the organic and mineral matrix in patients with acute leukemia exposed to ionizing radiation as a result of the Chonobyl NPP accident, and persons without hematologic diseases, and the need for treatment and prevention.

[DEFINITION OF INTERRELATION BETWEEN AMINOACID COMPOSITION OF URINE AND BONE TISSUE DENSITY AT CHILDREN WITH ACUTE LEUKAEMIA FOR ONCOHEMATOLOGICAL PATHOLOGY RISK GROUP FORMATION].

Age and sexual indexies of densitometry at patients with acute leukemia (AL) and healthy children are presented. 31% of children with AL during the initial period of disease had manifestations of the osteopenic syndrome. At patients with AL more often than at healthy children anomalies of development of front part of skull are defined. The partial contribution of free and peptides-connencted oxyproline in urine at AL patients differs in comparison with control group that is caused by modification or deficiency of the corresponding enzymes. 30% of patients with AL had raised concentration of free oxyproline in urine, and lowered glycine concentration that testifies to the increased disintegration of collagen and deficiency of tile plastic material necessary for collagene-forming processes. The obtained data should be considered for forming of risk group on oncohematological pathology at children.

[Altered collagene characteristics and lysyl oxidase activity in lathyrism].

Experiments were carried out on rats with lathyrism, which was induced by adding semicarbazide (0.075%) into drinking water for 45 days. The data obtained show a 30% reduction in the body weight and an increase in.organ weight coefficients. Semicarbazide intake led to the pelvic limb paralysis, scoliosis, bone tissue degradation, cartilage growth, 46% decrease of the calcium level in the femur. It has been detected essential structural changes in extracellular matrix based on the collagen cross-links reduction. The activity of lysyl oxidase, a key enzyme for the collagen development, showed 5-fold decrease in the aorta tissues. The level of formaldehyde, a nonenzymic cross-links developer, has been measured in the liver tissue by the aldehyde trap (5,5-dimethyleyclohexane-1,3-dione) administration and then fluorimetric determination of formaldimedone. Under semicarbazide load, the formaldehyde level in the liver tissue was reduced by 47%. Therefore, semicarbazide influences not only the enzymic development of aldehyde groups in collagen, but the level of other aldehydes, which can cause cross-links. This experimental model of lathyrism is appropriate for investigation of the lysyl oxidase inhibitors effect on extracellular matrix.

[State of bone structures in children with acute leukemia, experiencing unfavorable factors from Chernobyl accident].

The authors present an assessment of bone structure condition in children with acute leukemia. The changes in the collagen molecule, amino acid composition of urine and proteins reparation processes were revealed. Calcium phosphate excretion in the patients urine were increased. The serum osteocalcin level and colony formation efficiency of bone marrow fibroblasts in acute leukemia patients are lower than in control group. In the initial period of the disease 32% of patients have disturbancies in their endocrine status. The bone structure violation is combined with unfavorable disease outcome. The effectiveness of the treatment and prevention steps in acute leukemia patients depends on the leukemic process stage.

[Polyamines and collagenes interaction in different processes of extracellular matrix production and functioning in norm and with pathology].

A great file of experimental data on tight interrelations between polyamines and main components of extracellular matrix (collagenes, laminin, fibronectin, etc.) metabolisms has been accumulated in the recent twenty years. Consequences of such tight interaction of collagenes, polyamines, enzymes of their metabolisms during formation and functioning of extracellular matrix are realised not only at a cellular level (proliferation, differentiation, adhesion, apoptosis), but also at the level of the whole organism (immunity, connective tissues and skeleton formation, tumors). Search for the ways of cells behavior modulation via influence on the levels of polyamines and contents of extracellular matrix at present is new direction in pharmacology of antitumor preparations that enables regulation of organism-tumor relationships, inhibition of angiogenesis, tumor growth and metastasing.

[Modifying effect of low-molecular metabolities on the state of extracellular matrix of connective tissue of animals].

On the basis of complex approach to bone and haematopoetic tissue interaction the authors studied the influence of low weight metabolites on stromal fibroblasts and components of extacellular matrix of bone and skin (collagen and glycosaminoglycans). Specificity of different metabolites action on physico-chemical abilities of type I collagen, amino acid composition changes, surface charge, ratio of alpha- and beta-compounds, BrCN-fragments of alpha-1 component cross-links was shown. The dose dependence of formiate effect on processes of proteins glycosilation, cross-linking in bone and cartilage connective tissue and serum glycoproteins was established. The results obtained showed sensitivity of the bone tissue exstacellular matrix to influence of low-weight metabolites action at the level of post-synthetic modification of its components, their intermolecular interaction and process of osteogenesis.

[Role of formic acid in transformation of acetic and succinic acids in animal tissues]. / Rol' murashynoï kysloty v peretvorenni otstovoï i iantarnoï kyslot u tkanynakh tvaryn.

Acetic and succinate acids KoA acyl derivatives interacting with formate were displayed to produce alpha-ketoacids--pyruvate and alpha-ketoglutarate. These acids also interact with formate and make pyruvic and malate acids, while alpha-ketoglutarate, evidently, tricarboxy acids. Interaction of formate with acetic and succinate acids inspite of occurring out of the tricarbone cycle increases the latter metabolic functions.

[Cartilage collagen in health and in pathology]. / Kollagen khriashcha v norme i pri patologii.

The paper deals with the latest data on structure organization of collagen proteins--basic and minor components of the extracellular matrix of the animal cartilage tissue. Their genetic determination and tissue specificity, differences in the initial structure, sizes of spiral and globular domains, availability of --SH- and --S--S-bonds are emphasized. Data are presented which confirm that the change in the collagen state is one of the determining factors in pathogenesis of the cartilage tissue.

[Collagen from human joint cartilage in deforming arthritis]. / Kollagen sustavnogo khriashcha cheloveka pri deformiruiushchem artroze.

Type II collagen of human cartilage has been comparatively studied in norm and at deforming arthrosis. Collagen preparations are characterized by aminoacid composition and electrophoretic mobility in polyacrylamide gel. It is supposed that at deforming arthrosis the degenerative-dystrophic processes in the articular cartilage of man are caused by appearance of procollagen.

[Structure and properties of collagen in leukemia]. / Osobennosti struktury i svoistv kollagena pri leikoze.

Collagen I was isolated from human bone tissue and from mice bone tissue of the AKR-50 strain at the pronounced stage of leukosis. Dissimilarity of native and leukemic collagens was exhibited after evaluation of their amino acid composition, electrophoretic mobility in polyacrylamide gel containing SDS, content of the carbohydrate moiety as well as of isopoints, elution profiles in reverse-phase chromatography and gel filtration and electron microscopy of SLS-crystallites. Impairments of collagen processing in leukemia appear to be responsible for its alterations in structure and properties.

[Pathogenesis of arthrosis deformans of the knee joint]. / K voprosu o patogeneze deformiruiushchego artroza kolennogo sustava.

The authors have studied the biochemical characteristics (type, aminoacid composition, carbohydrate component content) of the collagene proteins in the articular cartilage in normal conditions and in various expression of deforming arthrosis of the knee joint. The results (collagen of the its type formation, disturbances in the aminoacid composition of collagen of the 1st and 2nd types, changes in the carbohydrate component content, accumulation of procollagen of type 2) allowed to suggest that already at the early stages of development of deforming arthrosis there are distortion of synthesis and disturbance in postsynthetic transformations of the collagen proteins of hyaline cartilaginous tissue which lead to disturbances in the structure and in the function of the matrix and progressive degradation of the articular cartilage.

[Type I collagen in rat skin in an excess of dietary amino acids]. / Kollagen tipa I kozhi krys pri izbytke otdel'nykh aminokislot v pishchevom ratsione.

Type I collagen in skin of rats who were given redundant amounts of leucin, valine, methionine or phenyl alanine differed essentially from the normal level in the amino acidic composition. Considerable shifts in the value of pI of the proteins under study as compared with the normal level are found during isofocusing. When studying subunits of collagen preparations by the reverse-phase chromatography certain differences typical of each studied state are revealed in the elution profiles in normalcy and under amino acid loadings.

[Acid-soluble collagen in the skin of rats who received a tryptophan load and were kept on a protein-free diet]. / Kislotorastvorimyi kollagen kozhi krys pri nagruzke triptofanom na fone bezbelkovogo ratsiona.

Crystalline preparations of acid-soluble collagen of rat skin in norm and with tryptophan load against a background of the protein-free diet were fractionated by differential salting out using NaCl in concentrations corresponding to precipitation zones of collagen 1,3 and 4. Amino acid composition, electrophoretic mobility in polyacrylamide gel, profiles of elution from CM-cellulose, content of the carbohydrate component and--S--S-bonds were studied in proteins of the mentioned fractions and in the precipitate insoluble after the pepsin action. Essential differences as compared to the normal level in the amino acid composition and elution profiles were detected in the fraction corresponding to collagen I. Quantitative changes in the carbohydrate component and--S--S-bonds occur due to the fraction inaccessible to the persin action.

[Crystalline preparations of acid-soluble collagen from rat skin]. / Kristallicheskie preparaty kislotorastvorimogo kollagena kozhi krys.

Crystalline preparations of rat skin acid-soluble collagen are a complex of collagen and glycoprotein of noncollagenic nature. Heat denaturation of the preparation, treatment with urea and DS-Na result in decomposition of this complex. Proteins composing it differ in amino acid composition, the presence of -S-S-bonds, the amount of a carbohydrate component, electrophoretic mobility in polyacrylamide gel and solubility in acid medium. Differential salting out by various NaCl concentrations permits separating the acid-soluble collagen preparations into fractions containing and noncontaining the accompanying noncollagen component. d

[Amino acid composition of preparations acid-soluble skin collagen and free amino acids in rat serum under loading with valine and methionine]. / Aminokislotnyi sostav preparatov kislotorastvorimogo kollagena kozhi i svobodnye aminokisloty syvorotki krovi krys pri nagruzke valinom i metioninom.

The valine and methionine loading against a background of protein-free diet evokes interrelated changes in amino acid composition of acid-soluble skin collagen preparations and free amino acids pool of blood serum in rats. The isolated collagen preparations also differ essentially from the normal preparations in the content of disulphide groups and elution profiles.

[Molecular heterogeneity of collagen in normal and pathologic states]. / Molekuliarnaia geterogennosy' kollagena v norme i pri patologii.

Collagen, the main protein of the connective tissue, is characterized by considerable heterogeneity. More than five types of collagen molecules, or seven types of subunits coded by different structural genes are studied. Both in the age aspects and under different pathologies the ratio of collagen types in some tissues changes, new types of collagen molecules are synthetized. Collagen not peculiar to the rat skin in normal state is synthetized in the unbalanced nitrogen nutrition with addition of amino acids, such as glycin and tryptophan.