ONYCHOLYSIS AS A COMPLICATION OF TAXANE-BASED CHEMOTHERAPY WITH CONCOMITANT CRYOTHERAPY IN BREAST CANCER PATIENTS: TWO CASE REPORTS.

Nail changes are a common side effect of taxane chemotherapy, although onycholysis is quite a rare complication the correct management of which is poorly standardized. These case reports provide a description and analysis of onycholysis, a rare but noteworthy complication observed during taxane-based chemotherapy with concomitant cryotherapy in two patients with breast cancer. Despite prophylactic measures, both cases experienced nail complications during Paclitaxel treatment, underlining the complex nature of onycholysis during taxane therapy and highlighting the critical role of nail assessment and infection screening.

THE EFFECT OF HIGH INTENSITY WHITE NOISE ON THE ULTRASTRUCTURE OF AXO-DENDRITIC SYNAPSES IN COLLICULUS INFERIOR OF ADULT MALE CATS. QUANTITATIVE ELECTRON MICROSCOPIC STUDY.

Environmental noise is a serious problem for the society and medicine. Chronic loud noise is known to produce numerous adverse effects on different levels of the organism. In addition to behavioral changes, the involvement of different regions of the brain was documented. The analysis of structural modifications provoked by noise in brain give the possibility to suggest that one of the effects of noise may be the alterations in neurotransmission. Therefore, of special interest should be the elucidation of the effects of chronic noise on the fine structure of synapses of brain areas participating in the processing of auditory information. In the present study, using transmission electron microscope. We elucidate the effects of high intensity chronic white noise on the morphology of axo-dendritic synapses, and size and diameter of synaptic vesicles in auditory region, inferior colliculus of adult male cats. Experimental animals were exposed to 100 dB (5-20 kHz) white noise for one hour per day, for 10 consecutive days. On 11th day, after special procedures, the area of interest was examined under electron microscope. In ~ 15% large synaptic terminals the clustering of synaptic vesicles, as well as swelling, partial vacuolization or degeneration of presynaptic mitochondria were detected. Morphometric analysis of docked (with presynaptic membrane) and undocked synaptic vesicle size revealed that docked vesicles are smaller than undocked vesicles. It was observed in both control and experimental animals, however, in experimental animals, such difference was more significant. Such results suggest that due to continuous transmission, the majority of vesicles are unable to replenish their cargo via transporters. Evaluation of synaptic vesicles size undertaken in the current electron microscopic study has advanced the understanding of the pathophysiology of white noise exposure on auditory brain processing regions, in addition to our understanding of fractional neurotransmitter release at the nerve terminal and on overall brain function.

FINE ARCHITECTURE OF THE HIPPOCAMPUS IN ADOLESCENT, ADULT AND AGED RATS. ELECTRON MICROSCOPIC STUDY.

The study included adolescents (P30-36), adult (P125-130) and aged (P330-340) male Wistar rats - 4 animals in each age group. The rats were housed individually, in wire-top polypropylene cages (30-cm width x 30 cm length x 25 cm height) and maintained on a 12-h light/dark cycle. Standard food pellets and tap water were ad libitum. The animal maintenance and electron microscopic procedures were conducted in accordance with European Union Directive on the protection of animals used for scientific research. The Ultrastructure of adult and adolescent rats are almost same. However, remarkable changes are expressed between adult and senescent rats. Precisely, in the last one there are following ultrastructural modifications - lipofuscin concentrations, small destructive cytoplasmic organelles, changes in presynaptic vesicular and mitochondrial quantity. Rare apoptotic signs in neurons. Analysis of all this means that aging in rat's hippocampus causes selective changes, also it underlines changes in neurotransmission and neuronal developmental pathways.

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.

[JUVENILE DERMATOMYOSITIS AND CALCINOSIS].

Juvenile Dermatomiositis (JD) is autoimmune disease that progresses with time; JD's main differentiated syndromes are rash on the skin, poor function of muscles, and often developing invalidism. If the health practitioners manage to diagnose the JD on an early stage and prescribe the adequate treatment the disease will not progress aggressively. This approach is tangible for practical rheumatology and pediatric. The article aims to present the reasons of the development of the JD and calcinosis. The study based on the description of the patients with JD. There are distinguished the main symptoms of the disease in children: frequent and acute developments of muscles calcinosis, occasionally with diffuse character followed with hypotrophy of the muscles, contractures and invalidism. One of the patient cases that describe the article is the thirteen-year boy with JD indicating repeated sequence of the disease, with diffusive calcinosis, cellulitis followed with secondary infection and impaired vision.

Wilson disease with thrombocytopenia (case report).

We present an adolescent patient with WD accompanied with secondary amenorrhea, and thrombocytopenia. NK, a 14 year-old girl, had amenorrhea for 5 months despite having had regular menses for 2 years. An abdominal ultrasound scan revealed ascitis and some ovarian cysts. On physical examination: slight jaundice, edema of lower extremities, skin purpuric rash, enlarged abdomen, dry skin. She had no hepatomegaly and no splenomegaly. Breast and pubic hair development was concomitant with Tanner stage 4. There was performed laboratory and instrumental investigations. The patient was diagnosed as WD owing to the low level of ceruloplasmin, with increased level of copper in 24-hour urine excretion and in dry liver tissue. The needle biopsy of liver showed severe hepatocellular necrosis, inflammatory changes and fibrosis. The platelet count was found to be low with lack of increased number of megakaryocytes in the bone marrow aspiration suggesting the thrombocytopenia was not exclusively owing to hypersplenism. The absence of antithrombocyte and other autoimmune and viral antibodies excluded respectively the diagnosis of autoimmune thrombocytopenia, other autoimmune diseases and viral infections. Thus, we support the recommendation that adolescents with amenorrhea or children with thrombocytopenia without any obvious cause should be evaluated for WD, because the early detection and treatment of WD is capable of reversing described changes and restoring a normal liver function.

Effect of chronic inhalation of toluene on behavior of rats of various age groups in multi-branched maze.

The effect of a 40-day toluene inhalation on learning of young and adult rats was examined in a multi-branched maze. Experimental rats of both age groups needed more time to pass the maze and made more errors than controls. This impairment was observed in young rats immediately after termination of toluene inhalation and in adult rats immediately and 90 days after toluene.

Effects of oxytocin on behaviour and memory in rats subjected to chronic restrained stress.

We studied whether 21 days of restraint chronic stress would affect the contextual fear conditioning, a memory task with hippocampal-dependent components and anxiety- like behavior in the open field, and to determine whether oxytocin treatment could prevent the chronic stress induced memory and emotional disturbances. Restraint-stressed rats were injected daily (21 days) with oxytocin (1 mg/kg) or saline then tested in open field (day 22) and contextual fear conditioning task (days 23-24). Our data demonstrate that chronic restraint stress induces some behavioural changes in both saline-treated and oxytocin-treated animals. Particularly, in the open field the animals both groups were characterized by hyper-locomotion. However, oxytocin-treated animals spent more time in the inner area of the open field, which indicates to decreased anxiety- related behaviour in oxytocin-treated animals versus the saline-treated ones. In additional restraint stress decreased freezing reaction to context, irrespective of whether oxytocin was given or not. Our findings indicate that during stress OT may be involved in the regulation of emotional behavior and memory via different ways. The elucidation of corresponding mechanisms is of great importance.

Effect of nadolol injected prior to CRH on stress-induced plasma corticosterone level in rat.

The proposed research is the part of our investigation of the role of catecholamines in the alterations provoked by stress. Especially, we elucidate if Nadolol injected prior to CRH ICV has some effect on plasma corticosterone level. 15 mg/kg of Nadolol (the dose sufficient to prevent CRH-induced increases in heart-rate for 2 hr), dissolved in saline was administered intraperitoneally, 30 minutes prior to CRH (The dose of interest for CRH - 1 mkg/kg - was determined earlier, as provoking the maximal increase of plasma corticosterone level after 20 minutes of its ICV injection). Whole blood was collected at 11.00 am, via indwelling jugular catheter at 0 (control) and 15 minutes after Nadolol injection, also 30 and 60 min after CRH injection. After centrifugation the plasma level of corticosterone was essayed using ELISA method. 15 minutes after Nadolol injection the level of plasma corticosterone in comparing with control wasn't changed, at subsequent time-points plasma corticosterone level was increased but significant difference was observed only after 30 minutes. Thus, according our results, 30 min after injection, the dose of Nadolol, sufficient to prevent CRH-induced increase in heart rate, doesn't preclude the CRH-induced increase of plasma corticosterone - one of key signs of the stress-axis activation. The results were discussed.

Stress-system: corticotropin-releasing hormone and catecholamines (review).

The brain's stress-handling system--the limbic-hypothalamic-pituitary-adrenal axis--is one of the most thoroughly studied circuitry of the central nervous system. As a result of stress-axis activation different behavioral and physical changes develop; these changes allow the organism to adapt. For this purpose stress-system closely "works" with other elements of central nervous system, which are involved in the regulation of emotion and structures, also with axes, responsible for reproduction, growth and immunity. Dysfunction of stress-system--it's hyper- or hypoactivity--is characteristic peculiarity of many pathological states and disorders. Various molecules (corticotropin-releasing hormone, vasopressin, glucocorticoids, mineralocorticoids, ACTH, its precursor proopiomelanocortin etc.) are engaged in the regulation of stress-axis. Among these molecules corticotropin-releasing hormone is supposed to have a key role in regulating the response to stress. Besides these molecules, the end-products of the stress-axis activation: catecholamines, different hormones and cytokines - control the activity of multiple levels of this axis. According some views catecholamines play one of the essential roles in the alterations provoked by stress-axis activation. In this review we cite some classical (Crousseau et al.) and modern data concerning corticotropin-releasing hormone and catecholamine activities during stress.

Effect of acoustic stimulation on GABAergic neurons in limbic structures of krushinskii-molodkina rats.

Quantitative study of GABAergic and main cells in the hippocampus and piriform cortex of Krushinskii-Molodkina rats was performed 1 month after the incidence of seizure activity evoked by acoustic stimulation. The number of neurons significantly decreased in both regions and, particularly, in the hippocampus and central area of the piriform cortex.

Effect of myo-inositol on convulsions induced by pentylenetetrazole and kainic acid in rats.

We studied the effect of myo-inositol on pentylenetetrazole and kainic acid-induced seizures in rats. Myo-inositol significantly reduced seizure activity.

Immunological and central nervous system changes in mice suffering from Staphyloccocus aureus and treated with Saccharomyces cerevisiae var. vini living cells.

The influence of Saccharomyces cerevisiae var. vini viable cells on the Staphylococcus aureus-suffering mice was ascertained: (1) effect of S. aureus living cells on antibacterial and antitoxic antibodies, (2) effect of S. aureus on the number of neurons and macroglial cells in different areas of mouse hippocampus, (3) effect of S. cerevisiae var. vini viable cells on the above-mentioned changes of immune and nervous system. Treatment with S. cerevisiae var. vini provokes immune stimulation and change of the total number of macroglial elements in the CA1 field of hippocampus.

[Aftereffects of congenital infections in infants].

Congenital infections are among the most pressing health care problems. Congenital infections are not reason of congenital malformation and perinatal mortality only, but also pathologies that can be revealed during first year of life. Frequency for congenital viral infection displayed from birth varies between 23% and 92%. The aim of the study was the investigation of inherent infection consequences (citomegaloviral infection, herpes infection and chlamidia) in children in different age groups. Under our observation were 81 children with congenital infections. Among them 29 were with citomegaloviral infection, 17 with herpes infection; 15 chlamidia infection and 22 infections mix (citomegalovirus + herpes, citomegalovirus + chlamidia and chlamidia + herpes). In all observed children neurological simptomatic such as neuro-reflectory hyperexcitability syndrom, hypertension-hydrocephalic syndrom, musculary dystonia syndrom, hydrocephaly, retardation of psychomotor development etc. were present. After birth the worst prevalent are pathologies of cardiovascular system: functional cardiopathy, carditis, congenital heart disease (among them multivalvular disease), affection of hepatobilliar system, organs of vision and hearing etc are present also.

[Activity of lipid peroxidation processes and the condition of antioxidative defense system in children with rheumatic fever].

Aim of study consists of establishing of some clinical-biological correlates for rheumatic fever (RF) in children, namely correlations between clinical status and lipoperoxidation products -- malonidialdehide (MDA) and antioxidative enzymes in the blood. In the neutralization process of superoxside anions ceruloplazmin (CP), catalase (CAT) and transferin (TF) are key antioxidant enzymes (AOE) of antioxidative defense system (AOD). We studied 38 patients 3-15 years of age with different variants of RF. We measured the levels of MDA, CAT, CP, TF in the plasma in patients with acute rheumatic fever (ARF) and chronic rheumatic heart disease (CRHD). In all of our cases AOE (CAT, CP, TF) were high at time of diagnosis, concomitant with increased MDA and inflammatory tests. Our study revealed intensified activity of AOD enzymes in children with RF.

[Neurological symptoms of cytomegalovirus infection in children].

Cytomegalovirus is considered as one of the most common causes of congenital infections. Clinical signs of infection are present in newborns whose mothers were infected during pregnancy. Disease is most severe if mother were infected during the first trimester. Congenital cytomegalovirus infection causes damage of CNS (central nervous system) and the liver, atrophy of optical nerve and hearing retardation up to complete loss. The most severe and frequent damage is of CNS. Under our observation were 20 children of different ages, among them 8 newborns. Verification of cytomegalovirus infection was done by ELISA. Polymerase Chain Reaction (PCR) was also used for diagnostic reasons. Examination of CNS was performed by neurosonography, electroencephalography and computed tomography. Four from eight newborns died at the age of 6-8 weeks (in these cases the generalized form of infection with severe damage of CNS was present). In the rest patients treatment with specific anticytomegalovirus immunoglobulin together with syndrome therapy yielded positive effect. Lately moderate retardation of phychomotor development became apparent in all cases. 12 patients, who come to our clinic in the period from 2 months to 1.5 years of age, psychomotor retardation, micro or hydrocephaly, hyperkinesias, absentia (epileptica), convulsive syndrome and malignant hypertension were present. On tomograms intracranial calcificats and cysts, also atrophy of cerebrum and encephalomalacia was visible. Sensory hearing loss was apparent in two patients. The study showed the presence of severe and in most cases irreversible CNS damages in the cases of congenital cytomegalovirus infection.