The activity of proliferation and apoptosis of thyrocytes in the thyroid tissue of patients of nodular goiter with autoimmune thyroiditis considering the polymorphism of the BCL-2 (RS17759659), CTLA-4 (RS231775), APO-1/FAS (RS2234767) genes

Nodular goiter with autoimmune thyroiditis is one of the most important problems of modern endocrinology, with inadequately studied etiological and pathogenic mechanisms of development. It is characterized by the lack of objective and reliable diagnostic methods, effective treatment methods, uncertain therapy or indications for the choice of treatment methods. A total we have examined 125 patients who were operated for a nodular endemic goiter with autoimmune thyroiditis. Investigated the activity of proliferation and apoptosis of thyrocytes in the thyroid tissue of patients of nodular goiter with autoimmune thyroiditis considering the polymorphism of the bcl-2 (rs17759659), ctla-4 (rs231775), apo-1/fas (rs2234767) genes. The expression/density markers - Fas/ FasL, Bcl-2, p53 and Ki-67 on the thyrocytes in the lymphoid infiltration and destruction areas, as well as in normal thyroid tissue (as a control) were studied. The number of immunoreactive cells, which expressed the above-mentioned regulating apoptosis and proliferation markers in NGAIT patients, depending on the genes polymorphism BCL-2 (rs17759659), CTLA-4 (rs231775) and APO-1/Fas (rs2234767) were counted. It was found that in NGAIT patients a few links of programmable thyroid cell killing of Fas-induced apoptosis were activated, and associated with the polymorphic cite of BCL-2 (rs17759659) gene and almost 6 times weaker with CTLA-4 (rs231775) gene, through enhanced expression of Fas and Fas L on the cells surface in lymphoid infiltration and destruction areas (stronger in GG genotype carriers of BCL2 gene)

Drug therapy in autoimmune thyroiditis

Background. Autoimmune thyroiditis (AIT) is one of the unsolved problems of modern endocrinology, the etiology and pathogenesis being still insufficiently known. Objectives. To study the effects of substitution, antioxidant and lymph-drainage ther­apy on the structure and function of the thyroid gland in patients with AIT and hypothyroidism. Methods. We have identified 2 groups of patients with AIT and subclinical hypothyroid­ism. The first group – control group – included 20 patients who received substitution therapy with thyroxine. The second group included 33 patients who received a comprehensive treatment with thyroxine, alpha lipoic acid and Lymphomyosot. Results. The use of substitution therapy with thyroxine and the proposed an­tioxidant and lymph drainage therapy in patients with AIT led to the improve­ment of the structure of the gland, reduced the activity of peroxide oxidation pro­cesses and the activity of pro-inflammatory cytokines, increased the level of anti­oxidant defense enzymes, normalized the number of aniline-positive lymphocytes, improved the lymphatic drainage function of the gland. Our results sustain the effectiveness of the proposed method of complex treatment in patients with autoimmune thy­roiditis

Clinical markers of immune disorders in the pathogenesis of Escherichia coli enteritis

Background. Escherichia coli enteritis is one of the most common causes of diarrhea in developed countries and is caused usually by pathogenic strains of Escherichia coli. Objectives. To investigate the role of reactive response of polymorphonuclear neutrophilic granulocytes (NG) of peripheral blood in the systemic inflammatory response mechanisms of acute Escherichia enterocolitis (AEC), depending on genes polymorphism of heat shock proteins (HSP) family 70-2 (HSP70-2, 1267A®G) and interleukin 10 (IL-10, C-592A). Material and methods. The genes polymorphism was analysed by PCR based method in 95 patients with AEC and 30 healthy individuals. Clinical markers of immune disorders were evaluated after hematological indices, based upon an extended general clinical blood analysis, using verified formulas. Results. The endogenous intoxication severity did not depend reliably on genotypes of IL-10 gene (rs1800872), however it was significantly 23.68% (р=0.043) higher in GG-genotype carriers of HSP70-2 gene (rs1061581). The reduction of cellular reactivity by 14.71-19.08% (р<0.01) did not depend on the analyzed genes genotypes. But general non-specific immune reactivity decreases 3.49-4.24 times (р<0.001) was deeper in GG-genotype carriers of HSP70-2 gene and AA-genotype carriers of IL-10 gene by 17.78% (р=0.009) and 12.37% (р=0.023) respectively. The immunologic resistance index was lower by 18.75% (р=0.024) in GG-genotype carriers than in patients with А allele. Conclusions. Hematological indices, based upon an extended general clinical blood analysis, are indicative and reliable non-specific clinical markers of immune disorders in case of AEC

Evaluation of remote results of surgical treatment of nodular endemic goiter with autoimmune thyroiditis

Introduction. Autoimmune thyroiditis is one of the most important problems of modern endocrinology, with inadequately studied etiological and pathogenic mechanisms of development. It is characterized by the lack of objective and reliable diagnostic methods, effective treatment methods, uncertain therapy or indications for the choice of treatment methods. The aim of the study. Determination of markers for prediction of clinical course and choice of surgery’ volume in patients with nodular goiter and autoimmune thyroiditis, taking into account the oxidative, autoimmune and apoptotic processes. Material and methods. A total of 95 patients who were operated for a nodular endemic goiter on the background of autoimmune thyroiditis were examined. The status of pro- and antioxidant systems, the activity of proinflammatory cytokines, hormonal function of thyroid gland, the level of antibodies to thyroperoxidase, thyroglobulin antibodies and ultrasound structural changes in the thyroid gland have been evaluated in all patients, before and after surgery. Results. In patients with nodular endemic goiter and autoimmune thyroiditis, in the remote period after surgical treatment, there is a significant increase in the peroxide oxidation index and a decrease in the activity of antioxidant defense systems, against the suppression of apoptotic processes and the activation of pro-inflammatory cytokines. These processes lead to functional failure, hyperplasia and the progression of structural thyroid abnormalities, with progression of the functional incapacity of the thyroid gland and inadequate long-term outcome of treatment. Conclusions. The study allowed to clarify the indications and contraindications of different methods of treatment in patients with NGAIT, taking into account the parameters of severity of peroxide oxidation processes, the activity of apoptosis and functional capacity of the gland

FEATURES OF TREATMENT OF PATIENTS WITH GENERALIZED PERIODONTITIS WITH MANIFESTATIONS OF PSYCHOEMOTIONAL STRESS

Topicality. In the complex treatment of patients with generalized periodontitis, it is necessary to take into account the peculiarities of the etiology and pathogenesis of dystrophic-inflammatory periodontal diseases. Conditionally pathogenic microorganisms of the dental biofilm can exert their pathogenic effect only in case of a slight decrease in the local or systemic immune defense of the patient's body. The presence of stress has a significant impact on the resistance of the organism and, accordingly, on the development, course and treatment of periodontal diseases. This should be taken into account in the complex treatment of patients with generalized periodontitis. Considering this, a medical scheme for the preparation of patients with generalized periodontitis with the presence of psycho-emotional stress using a complex of adrenoblockers has been proposed. Aim of the study. To determine the clinical efficacy of the proposed complex of adrenoblockers in the complex treatment of patients with generalized periodontitis of the chronic course in the presence of psychoemotional stress. Material and methods. For this study, 40 patients were selected with a generalized chronic periodontitis with the presence of psychoemotional stress. Medicamental treatment was performed using the proposed premedication with a complex of adrenoblockers. A comprehensive survey of the condition of the periodontal tissues of patients before treatment and as soon as possible after treatment was carried out. To assess the clinical efficacy of treatment, a test of Schiller-Pisarev (1962), PMA index by C. Parma (1961), hygienic index OHI-S (1978), index PBI (H.R. Mühlemann, S. Son, 1971), periodontal index PI (A.L. Russel, 1956) were used. The level of psychological stress was assessed using the DASS-21 and Spielberger-Khanin questionnaires. Results. As a result of the investigation it was found that the usage of the proposed complex of adrenoblockers in the complex therapy of patients with chronic course of generalized periodontitis with the presence of psychoemotional stress can effectively inhibit the dystrophic-inflammatory process in periodontal tissues. This confirms by the decline in the index PMA, OHI-S, РВІ, PI at nearest observation terms. Conclusions. Usage of the proposed complex of adrenoblockers increases the effectiveness of treatment of chronic course of generalized periodontitis in patients with the presence of psychoemotional stress

CHARACTERISTICS AND FEATURES OF CLINICAL MANIFESTATIONS OF PRIMARY HYPERALDOSTERONISM (LITERATURE REVIEW)

Introduction. Primary hyperaldosteronism as a cause of secondary arterial hypertension ranges from 4.6 to 13.0%, and among patients with refractory hypertension to medication therapy is about 20%. Meanwhile, its detectability among patients with arterial hypertension in centers of primary health care is from 6 to 13%, and in secondary care centers – from 23 to 30%. The high frequency of life-threatening cardiovascular complications dictates the need for early and timely diagnosis of primary hyperaldosteronism in the stages of the primary and secondary units of medical care. In addition, studies conducted in German and Italian hospitals among general practitioners showed a low level of knowledge about primary hyperaldosteronism. Objective. To promote the knowledge of general practitioners about clinical symptoms and clinical features of primary hyperaldosteronism. Results. Therefore, the main task of the work is the systematization and dissemination of knowledge for general practitioners about the symptoms and peculiarities of the clinical course of primary hyperaldosteronism. Such signs as an inadequate response to hypotensive therapy of a combination of three drugs, a manifestation of arterial hypertension under the age of 30, a rapid increase in blood pressure even in the elderly and/or the loss of efficacy of antihypertensive therapy, apnea in dream are distinguished in its non-specific clinical picture, without indicating priority. In the literature, there are recommendations to separate classical and secondary clinical manifestations. Classical include arterial hypertension, hypokalemia, hypervolemia, metabolic alkalosis, and minor ones such as headache, retinopathy, neuromuscular symptoms (paresthesia’s, convulsions, general weakness), carbohydrate metabolism disorders, arrhythmias, early onset of hypertrophy and fibrosis of the heart muscle and smooth muscle vessels, hypokalemia and moderate hypernatremia. Conclusions. In the clinical course of the disease, the cardiovascular, neuromuscular, renal and metabolic syndromes are distinguished, or in combination of several of them, in each particular case, the primary hyperaldosteronism may appeared (or manifested)

MOLECULAR-GENETIC MECHANISMS IN DEVELOPMENT OF DEGREE OF FUNCTION AND HYPERPLASIA OF THYROID GLAND OF PATIENTS WITH NODULAR GOITER WITH AUTOIMMUNE THYROIDITIS AND THYROID ADENOMA

Introduction. Autoimmune thyroiditis affects in average 2% to 5% of the general population, with young adult females and the elderly being the most vul-nerable patients. Hashimoto's thyroiditis causing hypothyroidism is the most prevalent etiology. Although genetics is well known to cause and influence the progression of autoimmune diseases in approximately 79%, other environmental factors are known to be involved in the development of autoimmune thyroid dis-eases: quantity of ingested iodine, stress, drugs, pregnancy, and changes in sexual hormones. Autoimmune thyroiditis, as a background disease of nodular goiter, in which hypothyroidism usually develops, has been insufficiently studied. Material and methods. The BCL-2 (rs17759659), CTLA-4 (rs231775), Fas (rs2234767) genes' polymorphism were studied by Real-Time Polymerase Chain Reaction in 95 patients with NGAIT, 30 patients with thyroid adenoma (TA) and 25 healthy individuals. The thyroid gland (TG) functional activity changes (nor-mal function, subclinical and clinical hypothyroidism) and TG hyperplasia degrees (IB, II and III) were analyzed. Results. TA and NGAIT are more common in the minor G-allele carriers (GА- and GG-genotypes) of the BCL-2 gene and in homozygous G allele patients (GG-genotype) of the Fas gene by 11.5 and 4.34 times (р<0.01), with no signifi-cant interdependence between the CTLA4 gene's genotypes. TG hyperplasia in patients' general cohort as well as in those with NGAIT is associated with the wild A alleles of the CTLA-4 gene (АА- and AG-genotypes): the І and ІІІ degree hy-perplasia occurred reliably more frequently in the AA genotype carriers, and ІІ degree of the TG enlargement in the AG genotype patients. Conclusions. Pathology of the thyroid gland has unreliable chances to be inherited depending on the polymorphism of BCL-2 (rs17759659), CTLA-4 (rs231775) and Fas (rs2234767) genes in Bukovina region (Western Ukraine). We did not find any difference between the relative incidences of the genotypes of the analyzed genes in the patients with NGAIT and those with TA or depending on the TG function (euthyroid goiter, subclinical and clinical hypothyroidism).

Optical Absorption Imaging by Photothermal Expansion with 4 nm Resolution

For quite a long time, people thought of the diffraction limit of light as a fundamental unbreakable barrier that prevents seeing objects with sizes smaller than half the wavelength of light. Super-resolution optical methods and near-field optics enabled overcoming this limitation. Here we report an alternative approach based on tracking the photothermal expansion that a nano-object experiences upon visible light absorption, applied successfully in the characterization of samples with a spatial/lateral resolution down to 4 nm. Our device consists of an atomic force microscope coupled with a solid-state laser and a mechanical chopper synchronized with the natural oscillation mode of an in-house-made gold tip cantilever system. This configuration enhances the detection of nanostructures due to the intermittent light excitation and the consequent intermittent thermal expansion of the sample under investigation. The sensitivity and spatial resolution are further improved by the electric field enhancement due to the excitation of localized surface plasmons at the tip apex. Our concept is demonstrated by the analysis of a two-dimensional material (GaSe) on crystalline sp² carbon (graphite) and by an array of multiwalled carbon nanotubes lithographically designed in a SiO₂ matrix. The photothermal expansion originating from light absorption leads to an unprecedented spatial resolution for an optical absorption event imaged below 10 nm

THE EARLIEST RESULTS OF COMPREHENSIVE TREATMENT OF PATIENTS WITH CHRONIC GENERALIZED PARODONTITIS WITH THE PREDOMINANCE OF THE PARASYMPATHETIC NERVOUS SYSTEM

Introduction. In clinical Ukrainian and foreign research papers there are many publications dealing with the treatment of patients suffering from generalized periodontitis. However, there remain a number of issues which have not been covered, including the influence of the autonomic nervous system on the development, course and treatment of periodontal diseases. The aim of the study. Increase the effectiveness of treatment for patients with chronic generalized periodontitis with the predominance of the parasympathetic nervous system. Materials and methods. A comprehensive examination of the periodontal tissue condition involved 60 patients. The proposed scheme of medical therapy was applied to the patients in the main group for the comprehensive treatment. The patients from the comparison group were treated similarly to the patients in the main treatment group, but without premedication drugs. Results. It was found that the application of the proposed premedication in the comprehensive therapy of patients with generalized periodontitis can effectively suppress the degenerative-inflammatory process in periodontal tissues. It is confirmed by the PMA index decreasing, increasing the time of the hematoma formation during the vacuum test by Kulazhenko, and by improving the level of the oral hygiene. Conclusions.The proposed treatment technique allows eliminating the manifestations of inflammation and achieving stabilization of the dystrophic-inflammatory process in the periodontium in shorter periods. In the nearest terms of observation, earlier and expressed normalization of clinical and laboratory parameters, that characterize the dystrophic-inflammatory process in periodontal disease, is noted

IMMEDIATE RESULTS OF COMPLEX TREATMENT OF PATIENTS WITH GENERALIZED PERIODONTITIS OF EXTRAORDINARY DEVELOPMENT WITH A PREDOMINANCE OF THE PARASYMPATHETIC NERVOUS SYSTEM

Topicality. The clinic of generalized periodontitis is caused by a variety of manifestations of the disease in the complex anatomical and physiological complex of periodontal tissues and the general condition of the organism. Therefore, in the treatment of generalized periodontitis, it is necessary to take into account the individual features of the general and periodontal status of the patient. Aim of the study. Improving the effectiveness of treatment of patients with generalized periodontitis of acute course with a predominance of the parasympathetic nervous system. Materials and methods. A comprehensive examination of the condition of periodontal tissues of 60 patients and treatment using the proposed scheme of drug therapy. The comparison group performed similarly to the patients in the main treatment group, but without drug premedication. Results. It was found that the inclusion of the proposed premedication in the complex therapy of patients with generalized periodontitis exacerbated course could effectively affect the inflammatory process in the tissues of the periodontium. This confirms a decrease in PMA index, an increase in the time of hematoma formation during a vacuum test by Kulazhenko, and an improvement in the level of oral hygiene. Conclusions. The proposed method of treatment allows to eliminate the manifestations of inflammation and to achieve stabilization of the dystrophic-inflammatory process in the periodontium in a shorter period of treatment. In the near future, an earlier and pronounced normalization of clinical and laboratory parameters characterizing the dystrophic-inflammatory process in the periodontium is noted