[MENTAL AND SPEECH DEVELOPMENT IN CHILDREN LIVING IN ECOLOGICALLY UNFAVOURABLE REGIONS OF GEORGIA].

The ecological condition of different cities and regions in Georgia is variable. The level of anthropogenic contamination with xenobiotics in most of them significantly exceed the normal level. In almost 25% of children residing in Tbilisi, Batumi and Kutaisi the level of xenobiotics varies 5.0-10.0 mkg/dL, 16% of children have higher than 10.0 mkg/dL. We have studied the profile of mental and speech development in children living in abovementioned cities according to the level of Pb in blood. On the basis of representative selection we have studied the level of Pb in the range of 5.0 mkg/dL and 10.0 mkg/dL for two groups of children with normal development: 65.5 months- (I study group) and 89.5 months (II-study group). Control group has no Pb in blood. The situation in family was also considered. Intellectual development was assessed by Wexler verbal and nonverbal subtests, neuropsychological methods by Luria-Kristensen and visual-motor and visual-spatial evidence by WBAVMA. According to results of children from group I living in ecologically unfavourable regions average evidence for mental and speech verbal awareness were within normal range and similar to controls. As for group II the difference from normal age range was not found. The development of awareness of false belief of second order for group-I was significantly delayed which could occur due to pitfalls in cognitive field. The redevelopment of structure of motivated behaviour in children from group-I was significantly restricted compared with group-II and controls.

[NEUROLOGICAL DISORDERS OF CHILDREN LIVING IN ECOLOGICALLY AFFECTED REGION OF GEORGIA].

Article discussed the clinical evidence of children with attention deficit hyperactivity disorder (ADHD) living in different regions with polluted air. We have revealed the correlation between severity of neurological impairment and level of Hg, Pb, Zn and Cu in blood of children of three different age group (2-5y, 6-9 y and 10-13y). According to our results we found correlation between living area and level of xenobiotics and essential microelements. Thus we have concluded that beyond the level of xenobiotics and essential microelements in child's blood their primary and secondary role in the development of neurological disorders in regions of various anthropogenic impact has to be considered.

[MODERN ISSUES OF KALCIPHEROL INFLUENCE ON CHILDREN AND ADULTS' HEALTH (REVIEW)].

The purpose of this review is study of literature for the development of biological effect of Kalcipherol (D vitamin group) on children population. Different factors seem, that D- vitamin deficiency disbalance elevated, children specifically negative effect, which have a major impact on health, growth and development of infants, children and adolescents. Vitamin D and calcium deficiencies are preventable global public health problems in pediatric medicine. The laboratory assessment of vitamin D (calcidiol-25(OH)D), epidemiological studies assessing the prevalence of vitamin D deficiency, are performed to analyze the relationships between neuropsychological function and mechanisms of toxic effects in the setting of vitamin D.

COVID-19 AND CHILDREN: COMPLICATIONS AND LATE OUTCOMES.

Since December 2019, Covid-19 has become a challenge for doctors around the world, including pediatricians. In most infected children, the disease manifests itself in a mild or is char- acterized by a subclinical course. At the same time, in some cases, a severe clinical picture of the so-called late Covid disease may develop, in the form of a multisystem syndrome and other complications. In 2020-2021 at the Academic Pediatric Clinic named after G. Zhvania of Tbilisi State Medical University, we observed 60 children with post-Covid complications and late Covid syn- drome. More than half (32 children - 53.3%) were under 5 years of age, with a predominance of boys (33 children - 55%) who had a Covid-19 infection 1.5-2 months before contacting us with a positive antibody reaction. Most of them (51 children - 85%) were healthy before the disease. Vasculopathy, immune thrombocytopenia, thalassemia minor, primary diabetes, iron deficiency anemia, coagulopathy, pneumonia-atelectasis, exacerbation of the underlying disease - arthralgia, arthritis and abnormal manifestations of sleep disturbance, general weakness and dizziness were noted. Separately, it is necessary to highlight the multisystem inflammatory syndrome in chirdren - MIS-C (8 children - 13%) proceeding with clinical signs of Kawasaki disease (mucocutaneous-lymphatic syndrome) with hectic temperature, polyserositis, hepatosplenomegaly, high rates of inflammation markers, a tendency to hypercoagulability. One patient had a coronary artery aneurysm. In 3 cases, the ANA and ANF titer was increased (up to 1:640) and also with nucleic, cytoplasmic and linear fibrils fluorescence, which indicates immune reactions in Covid infection, which can explain the positive effect of corticosteroid therapy in the treatment of these patients. Only 22 (36%) patients were hospitalized, the rest were observed on an outpatient basis. Based on the aforementioned, it can be concluded that even with the asymptomatic course of Covidinfection in children, complications can be observed and the syndrome of the so-called late Covid, which dictates the need for a thorough examination of these patients and observation in dynamics.

[THE CALCIUM-PHOSPHORIC METABOLISM AND DEVELOPMENT OF BONE ORGANIC MATRIX AT CHILDREN AND ADOLESCENTS ON D-AVITAMIN BACKGROUND (REVIEW)].

The purpose of the review is to study the literature data on the manifestation of D-deficient rickets in children of various age groups. It is shown that the rapid growth of the musculoskeletal system requires timely intake of both macronutrients and vitamin D, its biologically active metabolites. The role of the relationship between the intestines, liver, kidneys and bone tissue in regulating the necessary level of phosphorus-calcium salts in bone tissue, the synthesis of its organic matrix is shown. Modern data on the content of phosphorus, calcium and d vitamin in women's milk during various periods of lactation are presented. It is shown that the prevention of their deficiency should begin already in the antenatal period of the child's development. The article presents prevalence of vitamin D deficiency in children of puberty and pre-puberty age, The hypo Vitamin D status in children with complicated forms orthopedic pathology is descid. The level of vitamin D and calcium-phospharic metabolism are presented summarizing the literature data. Vitamin D availability and vitamin D insufficiency in pediatric clinical practice is analysed, showing high prevalence of vitamin D difficiency in children in the first part of life. Analyses of results demonstrated differences of vitamin D serum concentration in length of age and food additives. Its manifestation, with confusing and wildly differing guidance being change the structure and volume of each components. Vitamin D, calcium-phosphoric deficiencies and osteomalacia are global public health problems in infants, children and adolescents.

[MODERN ISSUES OF D-VITAMIN SIGNIFICANCE IN DEVELOPMENT OF FULERUM-MOVE DEVICES OF INFANTS, CHILDREN AND ADOLESCENTS ( REVIEW)].

The purpose of this review is the study of literature for the current data on the metabolism of vitamin D and its role in development of bone tissue in children. The role of the main marker enabling assessing 25(OH)D concentration in the body the reference values has been analyzed. Summarizing the literature data, we may say that vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a mayor impact on health of infants, children and adolescents.

[MODERN ASPECTS OF THE EFFECT OF XENOBIO-TICS ON CHILDREN AND ADOLESCENTS (REVIEW)].

The literature review presents data on the effect of organic and inorganic compounds, the so-called "main" xenobiotics (lead, mercury) on children and adolescents. It is noted that the effect of each heavy metal is different. Therefore, only their total assessment (blood, urine, saliva, hair, biological tissues) makes it possible to determine the level of toxic effects on the child and confirm the clinical decision. "Carrying mercury", in the absence of clinical signs of intoxication, does not always correlate with chronic poisoning. Ranking of clinical syndromes with the level of heavy metals in the body of children, monitoring of cause-and-effect relationships, detection of the prevalence of neurological changes becomes a priority in clinical Pediatrics. At the moment, the effects of heavy metals on the health of children and adolescents are a universal medical category. It forms the strategy of clinical pediatrics and pediatric neurology and a subject of interest for ecologists, toxicologists and sociologists.

CYTOKINES PROFILE AND ITS CONNECTION WITH DISEASE SEVERITY IN COMMUNITY-ACQUIRED PEDIATRIC PNEUMONIA.

Community-acquired pneumonia is (CAP) associated with serious complications and is the leading cause of death in children. Severity of CAP is depend on an impairment of host defenses. Persistent and toxic inflammation directs to an excessively pro-inflammatory cytokine production, neutrophil hyper-responsiveness, and dysregulation of lung neutrophil apoptosis, which results in lung injury and poor patient outcomes. However, the correlation between increased cytokine levels and clinical outcome in children remains unclear. The main aim of present work was evaluation the potential association serum cytokine levels with complications and severity of pneumonia and identification marker for earlier diagnosis of pneumonia complications. For this purposes, 62 children admitted to Iashvili Central Children Hospital during 2013-2014, Tbilisi, Georgia, were investigated. The study was approved by the Ethics Committee of the Tbilisi State Medical University and written informed consent was obtained from the parents/legal guardians of all study participants. Control group consisted of 10 healthy age matched individuals. All samples (serum, urine, sputum, nasopharyngeal swabs) were analyzed for the presence of respiratory viruses and/or bacterial pathogens. The serum cytokines (IFN-gamma, TNF-alfa, IL-8, IL-10) levels were determined by enzyme-linked immunosorbent assay (ELISA) on the first and fifth day of hospitalization. The patients with community-acquired pneumonia on the first and fifth day of the treatment had significantly higher cytokine concentrations (IFN-g, TNF-a, IL-8, IL-10) than age matched individuals (p<0.01). Moreover, IL-10 and TNF-a (p<0.05) levels were statistical differ between groups with high and low saturation, However, patients with pleural effusion have significantly lower circulating IL- 8, than without effusion. Based on our results, circulatory cytokines (IL-10, TNF, IL-8) were elevated in CAP patient and can be used as markers of pneumonia severity signs (saturation, pleural effusion etc). However more studies are needed for before using cytokines as indicator of disease prognosis.

CYTOKINES AS THE PREDICTORS OF SEVERE MYCOPLASMA PNEUMONIAE PNEUMONIA IN CHILDREN (REVIEW).

In spite of many attempts to differentiate bacterial from viral disease and predict severity and outcome, the etiologic diagnosis of paediatric community acquired pneumonia and the estimation of potential outcomes remain unsolved problems in most cases. Mycoplasma pneumoniae is one of the major pathogens causing CAP in children. Although MP infection was traditionally thought to be a self-limited process, more and more severe cases even fatal cases of MP infections were reported in recent years. So it is essential for pediatricians to recognize severe or refractory or severe MP early, treat it promptly and prevent the progress of the disease. In recent years, several new biomarkers have been tested in children with CAP. Some of the biomarkers used for etiologic diagnosis in children with CAP and they also have been used the MP infection severity. Among traditional biomarkers, several cytokines appears to be effective both in selection of bacterial cases and in evaluation of severity. However, a precise cut-off level able to separate bacterial from viral cases and mild from severe cases has not been defined. Further studies enrolled with a large number of children with Mycoplasma pneumoniae is needed to be carried out to identify the potential utility of different cytokines as the good predictors.

IMPACT OF INTERNET GAMBLING ON MENTAL AND PSYCHOLOGICAL HEALTH OF CHILDREN OF VARIOUS AGES.

The aim of the study was to assess the impact of internet gambling on children's mental and physical health and find correlation between the age, duration of internet use and type of comorbidity associated with internet gambling. The study assessed 50 patients with internet gambling (35 boys, 15 girls) from 2013-2016 y. The age range was 3-15 years. 15 patients were from 3-7 y of age, 20 patients from 7-12 y and 15 - from 12-15 y of age. The core problem common for all patients were internet overuse by computer games, mobile device and other gadgets. The main problem occurring in these children were insomnia, language delay, stuttering, behavioral disturbances, aggressive behavior phobias. These complaints were correlated with age of patients. The group of patients from 3-7 years of age exhibited sleep disturbances and language impairment, mainly presented with stuttering. The complaints occurring in children from 7-12 y of age are: tics, insomnia, phobias, emotional disturbances, daily fatigue, and attention-deficit. The group of children aged 12-15 years mainly revealed poor academic performance, refuse to play sport games, refuse to play music, insomnia, aggressive behavior, attention deficit, conflict with parents, coprolalia. Thus internet overuse affects physical and psychological aspects of child development which has to be managed by parental and psychologist's joint effort.

[MITOCHONDRIAL DYSFUNCTION: MODERN ASPECTS OF THERAPY (REVIEW)].

Mitochondrial diseases are considered as one of the major problems of modern interdisciplinary neonatology and pediatrics. Mitochondrial pathology can be revealed as refractory myoclonic or multifocal seizures, craniofacial dysostosis, dysmetabolic manifestations and respiratory disorders. Central nervous system (CNS), muscles, heart, liver and kidneys is involved in this pathological process. An important criterion for diagnosis of mitochondrial dysfunction is increases in blood lactate and pyruvate levels; the absolute criterion - molecular genetic diagnostic studies of mitochondrial DNA. Polymorphism of clinical symptoms complicates the process of early diagnostics, the lack clear recommendations complicates therapy. Modern aspects of treatment of mitochondrial dysfunction in various neurological syndromes are based primarily in improving the efficiency of the processes of oxidative phosphorylation at the system level. Dietary carbohydrate restriction, and medication (Coenzyme Q10, Idebenonum, Cofactors, drugs which reduce lactic acidosis- Dimephosphon, Dichloroacetate, Antioxidants, Anticonvulsants and Antidiabetic agents, vitamins C, E, K, hemotransfusions) is prescribed. Such complex approach allows us to achieve a reduction in lactate-acidosis, and improve the condition of patients in 70% of cases.

[Morphological structure of suprarenal glands in experimental vibration-induced pathology].

Technical progress has caused development of vibration-induced pathology, which is determined by harmful factors or environmental effects. The harmful factors include physical factors--noise, mechanical vibrations, low temperature, high humidity of the air and incorrect lighting. The aim of our study was the investigation of morphological changes in suprarenal glands under condition of vibration-induced pathology. The experiment was conducted on 20 grown-up white male rats weighting 180-200 g. The animals were daily under an hour vibration during 2 months. The vibration frequency was modulated by means of a general vibration. After an experiment, animals were decapitated in condition of general anesthesia. The experiment revealed important changes in the morphological structure of suprarenal glands. The vibration pathology causes following changes: vessels' and sinusoid capillaries' uneven widening, develop the infiltrate cells, bleeding areas, necrosis and other changes. Based on above-stated it is supposed that technical progress and introduction of new technologies is one of the risk factors, which can cause neurohumoral disorders.

[Changes of concentration of renin-angiotensin system components during vibration and their correction in experiment].

The aim of the research was investigation of the state of rennin-angiotensin system during the vibration in rats. 40 (180-200gr) pubertal male rats were studied. One hour vibro seance was conducted every day during two months. The 60 animals were divided into 3 groups (20 rats in each group); the third was control group. On 20th , 40th and 60th days of the experiment the decapitation of the animals was done under general narcosis. the Concentrations of rennin, angiotensin II and angiotensin converted ensyme in the blood plasma was determined using the method of radio immunoassay, The significant changes in concentrations of rennin-angiotensin system components have been manifested. The research showed the destruction in regulation of rennin-angiotensin system. It is concluded, that the vibration provokes the destruction of reciprocal feed-back of rennin-angiotensin system in the rats.

State of hypophsis-adrenal gland in conditions of vibration pathology and its correction in experiment.

Vibration is one of the pathological factors, which causes various alterations in the cells and organs. The goal of the research was the investigation of the hypophysis-adrenal gland system during the vibration and possible methods of its correction. The experiment was held on 70 grown-up male rats from 180 to 200 gr in weight. An hour vibroseance was carried out daily during two months period. According to the means of treatment animals were divided into three groups. The control group was consisted of 10 animals. In the first group (experimental vibratory pathology without any therapy) concentration of AKTH began to increase and reached 154% by the 20th day; by the 40th day it was 130%; AKTH concentration decreased up to 87% by the 60th day. The corticosterone in the blood plasma increased gradually and by the 20th day reached approximately 188%, which by the 40th day gradually decreased to 156%, and by the 60th day it was 129%. The second group was composed of animals, which underwent liquid oxygen therapy after the vibroseance. The AKTH content in the blood plasma of the second group animals was less increased: by the 20th day it reached 134%, by the 40th day it was 117%, and by the 60th day it decreased to 84%. The corticosterone concentration in the second group was lower by the 20th day it was 168%; by the 40th day it reached approximately 143%, and by the 60th day decreased to 127%. The third group was composed of retabolil treated animals. The AKTH concentration in animals by the 20th day reached 206%, and then decreased gradually, and by the 40th day it was 189%, and by the 60th day decreased to 145%. The corticosterone content in the blood plasma was high. By the 20th day the concentration was 263%, then it gradually decreased and by the 40th day reached 242%, and by the 60th day it was 199%. According to the experimental data vibration leads to the activation of hypophysis-adrenal gland system. Increased AKTH initiated increase of corticosterone.

[Mexidol in treatment of children with generalized epilepsy and febrile seizures].

The aim of our study was to estimate the role of Mexidol in ceasing of epileptic fits and improving electroencephalographic (EEG) pathological patterns in children. 120 patients with generalized epilepsy (from 4 to 16 years old) were investigated. All patients were treated by Depakin chrono 30 mg/kg. Children were divided into 2 groups: 1st--study group consisted of 60 children with combined treatment with Depakin and Mexidol (5 mg/kg). In the control group (60 children) treatment was performed only by Depakin. 100 children with the first episode of febrile seizures (from 6 months to 4 years old) were investigated. 50 children composed the study group with monotheraphy by Mexidol and 50 patients--the control group, without any treatment. The EEG examination was done by computer EEG Topography "Brain Surveyor Saico". Using Depakin in combination with Mexidol in the study group of patients with generalized epilepsy, improvement of clinical picture of disease and normalization of EEG patterns in 93% of cases has been observed. In the study group of patients with febrile seizures, normalization of EEG pathological patterns was observed in 82% cases and in 18% its improvement was seen. The relapse of seizures at high temperature was observed in 3 patients. In control group EEG patterns were improved only in 20%, in 48% no positive effect was observed and in 41% the worsening of EEG findings was seen. The relapse of febrile seizures was observed in 26 cases. Mexidol titrated to the target doze of 5mg/kg may be effective in combination with Depakin for treatment of patients with generalized epilepsy and as monotherapy in patients with first episode of febrile seizures.

[Efficiency of mexidol during perinatal encephalopathy in early age children].

We have investigated 200 patients 0-4 months of age (boys 110 and girls - 90), 120 of them under 1 month of age and 80 children from 1 to 4 months. The evaluation of the neurologic status of patients was performed 40-60 minutes after feeding in a relaxed condition. From the additional methods of the investigation of the nervous system, the most informative was the neurosonoscopy. We have divided patients into two groups according to the clinical syndromes: I gr. neuro-reflexion irritation syndrome (118 patients), II gr.--depression syndrome (82 patients). According to the treatment regimen patients also have been divided into two groups: the basic group (104 patients) with treatment only by mexydol (mexydol in a dose of 5 mg/kg and 0,3 ml in the form of injections twice a day. Injections were initiated at the acute stage of the disease) and the control group (96 patients) with no treatment. Efficiency of mexidol was estimated comparison of the findings in the basic and control groups based both on a clinical status and on the neurosonoscopic findings. Positive dynamics was observed in patients of the basic group. Verification of mexydol efficiency was performed by neurosonoscopic investigations. In a small portion of patients positive dynamics was not observed. These patients were from the age group from 3 to 4 months, which confirms that earlier and optimal treatment contribute to the prevention of severe neurological outcomes. It may be concluded that: 1. Mexydol acting on the pathogenetic mechanisms of perinatal encephalopathy, reduces reflexion irritation and depression syndromes both in neonatal and early age children. 2. Mexydol induces normalization of pathological neurosonoscopic patterns. 3. Mexydol with its wide pharmacological spectrum of action is an effective medicine in treatment of perinatal encephalopathy.

[A case of familial Marfan syndrome without manifested ocular anomalies]. / Semeinyi sluchai sindroma Marfana bez manifestatsii glaznykh anomalii.

Three sibs aged 14, 13 and 10 years are described. The Marfan's syndrome was inherited from their father. Full penetration and pseudovariable expressivity of the mutant gene were characteristic of the case. With pronounced phenotypic manifestations of the mutation inherited, the lack of typical ocular anomalies was evident.