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degree of MVP showed that the probability of arrhythmic disorders they may have in 6.3 times higher than in patients with I degree of MVP (OR = 6.3). On this base we select the group of patients with high risk of arrhythmic complications of idiopathic MVP: young men with II— III degree of MVP and the presence of 4 or more musculoskeletal dysembriogenesis stigmas.
Conclusions. Thus, UCTD syndrome is a unique abnormal background for the existence of various clinical conditions with a wide range of symptoms. Early detection and correction of phenotypic markers of UCTD from the side of the musculoskeletal system will improve the quality of life of such patients and reduce possibility of disability in a future.
PANASIUK Y., KORDA M.
Ternopil State Medical University named after
I.Ya. Horbachevsky, Ternopil, Ukraine
Using of Lovastatin Nanoparticles for the Osteoporosis Treatment and Fracture Risk Reduction (Experimental Study)
Introduction. A new published experimental data and clinical studies demonstrate the ability of lovastatin to affect osteoregeneration. This effect of statins is realized through the increased expression of bone morphogene-tic protein 2. However, current studies on the possibility of statins to reduce the risk of fractures are controversial. The positive effect of statins on bone metabolism was observed with oral administration of these drugs but in very high doses. That is why it is so important to develop the new ways of statins delivering to fracture zones, particularly in the form of nanoparticles.
Aim. To investigate the possibility of using lovastatin in nanoparticles to restore posttraumatic bone defects in rats.
Materials and methods. White mature male rats (n = 168) were used in experiment. All animals were divided into four groups: I — intact animals, II — control group (animals with simulated bone defect), III — animals with bone defect, which were administered with lovastatin transdermally, IV — animals with bone defect treated with lovastatin incorporated into polymeric nanoparticles. The bone defect (2.0 mm in diameter) was
made by dental drill in the upper third of the tibia. The
III group of animals received lovastatin in doses 0.1, 1.0, 5.0 mg/kg during the whole period of experiment. The
IV group of rats was injected with lovastatin incorporated into polymeric nanoparticles directly into the fracture zones in a dose 1.0 mg/kg. The animals were decapitated on the 3rd, 7th, 14th and 28th day. Biochemical (activity of alkaline and acid phosphatases, mineralization index, collagenolytic activity of plasma, oxyproline Ca and P levels in plasma), radiographic, histological, and statistical methods were used in the study.
Results. Our results showed a positive effect of transdermal sdministration of lovastatin only in dose 5 mg/kg, which is significantly higher than the average therapeutic dose. There was no effect of transdermal applying of lovastatin in dose 0.1 and 1.0 mg/kg. At the same time the using of lovastatin incorporated into polymeric nanoparticles resulted in a significant decrease of the bone resorption symptoms on the 3rd and 7th day of the experiment, which was confirmed by the biochemical markers and histological examination. Using of incorporated into polymeric nanopar-ticles lovastatin also resulted in the strengthening of osteo-regeneration on the 14th day of experiment and resumption of posttraumatic bone defect on the 28th day.
Conclusion. In our studies we have shown that the incorporated into polymeric nanoparticles lovastatin induces posttraumatic osteoregeneration. The obtained results require further extensive research in this area.
PANKIV I.
Institute of Gerontology named after D.F. Chebotarev AMS Ukraine, Kyiv, Ukraine
Hypovitaminosis D in Autoimmune Thyroiditis Patients with Subclinical and Overt Hypothyroidism
Introduction. There is increasing interest in the role of vitamin D deficiency in a number of chronic health problems including autoimmune diseases. A number of factors have been implicated in pathogenesis of most autoimmune disorders, one of the most recent agents found to be associated with autoimmunity is vitamin 25(OH)D. Serum 25(OH)D, the most abundant circulating precursor of active vitamin D, is the most widely accepted indicator of vitamin D status and reflects combined contributions from cutaneous synthesis. Importantly, both vitamin D and thyroid hormone bind to similar receptors called steroid hormone receptors. A different gene in the
vitamin D receptor was shown to predispose people to autoimmune thyroid disease including Graves' disease and Hashimoto's thyroiditis.
Aim: to investigate the total vitamin 25(OH)D in 70 autoimmune thyroiditis patients with subclinical (n = 21) and overt (n = 49) hypothyroidism.
Material and methods. 70 patients and 20 apparently healthy individuals with matched age and sex were underwent a detailed clinical examination, thyroid function tests (TSH, fT4, fT3, thyroid peroxidase antibodies) and serum total vitamin 25(OH)D. They were living in Kolomyja region and recruiting to outpatient clinic of Central Regional Hospital during the period from September 2013 to July 2014. Written consent was taken from all participants in this study. They were classified into three main groups: Group I. Patients with autoimmune thyroiditis and subclinical hypothyroidism. It included 21 patients (3 male (14.3 %) and 18 female (85.7 %)), their mean ages 46.36 ± 2.84 years. They were
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diagnosed as patients with subclinical hypothyroidism if TSH level was higher than 4.0 ^IU/ml with normal levels of fT3 and fT4. Group II. Patients with autoimmune thyroiditis and overt hypothyroidism. It included 49 patients (13 male (26.5 %) and 36 female (73.5 %)), their mean ages 48.16 ± 3.19 years. They were diagnosed as patients with overt hypothyroidism if TSH level was higher than 4.0 ^IU/ml with lower levels of fT3 and fT4 than normal value. Group III. Control group included 20 apparently healthy individuals (3 male (15 %) and 17 female (85 %)), their mean ages are 47.20 ± 2.78 years. They were not complaining from any chronic medical diseases with normal clinical examinations, no history of thyroid diseases or any chronic illness may interfere with our results. They were not on vitamin D supplements.
Results. Levels of serum TSH were significantly increased in subclinical (6.80 ± 1.84 ^IU/ml) and hypothyroid (10.24 ± 2.09 ^IU/ml) groups as compared to control group (2.16 ± 0.39 ^IU/ml) (p < 0.05). The thyroid peroxidase antibodies level was 312.83 ± 7.19 IU/ml in subclinical hypothyroid group and was 529.31 ±
± 9.62 IU/ml in the hypothyroid group. The levels of serum total 25(OH)D were significantly decreased in subclinical (21.9 ± 1.1 nmol/L) and overt hypothyroid groups (18.8 ± 1.2 nmol/L) as compared to control group (27.1 ± 1.2 nmol/L) (p < 0.05). A highly significant negative correlation was found between serum TSH, thyroid peroxidase antibodies and total 25(OH)D levels (p < 0.001). Also highly significant positive correlation was found between the levels of serum total 25(OH)D and serum fT4 (p < 0.001). There was significant positive correlation between TSH and thyroid peroxidase antibodies levels (p < 0.05).
Conclusions. We showed, that there was a highly significant decrease in (25OH)D levels in autoimmune thyroiditis patients both in the subclinical and overt hypothyroid groups as compared to control group. A highly significant negative correlation was found between serum TSH, thyroid peroxidase antibodies and total 25(OH)D levels. Also highly significant positive correlation was found between the levels of serum total 25(OH)D and serum fT4.
PASIEYSHVILI L.M., PASIEYSHVILI T.M.
Kharkiv National Medical University, Kharkiv, Ukraine
Allelic Polymorphism of FDPS Gene in Prognosis of Osteoporosis in Young Patients with Osteoarthritis
Introduction. The occurrence of osteoarthrosis (OA) in young people in most cases is the result of injuries (more often sports) or overweight. Also, one of the concepts of development is cell activation, which is accompanied by an increased destruction of cartilage and decreased of matrix synthesis. Cytokines and growth factors influence on chondrocytes through specific signaling pathways that regulate the synthesis of matrix metalloproteinases. Changes in chondrocytes can disrupt the processes of differentiation and lead to the synthesis of matrix cartilage is not enough high quality. A possible next step of the progression OA is the formation of osteoporosis (OP). One of the ways of OP development may be genetic deviation of the FDPS gene. Diphosphates, which structure includes nitrogen, are inhibitors of the enzyme FDPS, which plays a significant role in the synthesis of cholesterol and triggers apoptosis of osteoblasts. Changes in the given gene provoke decrease in bone mass and bone density.
Aim: To determine the frequency of pathological mutations of the FDPS gene in patients with osteoarthrosis as a marker of the formation of osteoporosis.
Materials and methods. Were examined 32 patients with OA at the age of 21 to 39 years and disease duration from 2 to 17 years. In 15 cases, it was preceded by the appearance of chronic rheumatism of the lower limbs (athletes), in 9 cases, it developed against the background of obesity 2—3 stage. All patients underwent clinical, radiological and densitometric study. DNA diagnostics were studied in blood leukocytes, which included a study of the insertion-deletion polymorphism of FDPS gene — method of
polymerase chain reaction with using a diagnostic test systems SNP-Express ACE Alu Ins/Del (Liteh, Russia).
The control group included 50 practically healthy persons of similar age and sex.
Results. The study showed that in 9 cases OA changes at densitometric study has not been identified; 11 patients (34.4 %) were diagnosed with osteopenia and 12 (37.5 %) — osteoporosis of different severity. In the study of polymorphism of FDPS gene was found that in patients with normal densitometry genotype A/A was found in 5 cases (55.6 %), genotype A/C was identified in 3 patients (33.3 %) and pathological C/C genotype in 1 (11.1 %). In the group of patients with osteopenia and OA — normal genotype was found in 2 cases (18.2 %); genotype A/C in 6 patients (54.5 %) and pathological genotype (C/C) of the FDPS gene in 3 patients (27.3 %). In the group of patients with OP has increased frequency of pathological mutations (C/C genotype) to 66.7 % (8 patients); and genotype A/C was set at 4 patients (33.3 %). In studying of the prevalence of the FDPS gene of the healthy patients were received the following results: A/A genotype was recorded in 68 % (34 patients), A/C — in 24 % (12) and C/C — 8 % (4 patients).
Thus, patients with OA and osteopenia in 3.4 times frequently were recorded pathological mutation of FDPS gene in comparison with those of the control group. In patients with OA and osteoporosis this indicator was in 8.3 times higher.
Conclusion. In young patients with OA often determined violation of the structure of bone tissue, leading to the formation of osteopenia (11 patients — 34.4 %) or osteoporosis (12 — 37.5 %). Development of such changes in bone tissue occurs against pathological mutation of the FDPS gene (genotype C/C).
Thus, the study variants of the FDPS gene in patients with OA can be used as a marker for the formation of osteoporosis, which allows to develop measures for its prevention.
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