EFFECT OF CHRONIC ADMINISTRATION OF LOW DOSES OF POLYPEPTIDES OF CATTLE CEREBRAL CORTEX AND METHIONYL-GLUTAMYL-HISTIDYL-PHENYLALANYL-PROLYL-GLYCYL-PROLINE ON BEHAVIORAL RESPONSES OF RAT OFFSPRING.

In the modern world, anyone is susceptible to the effects of stress, regardless of age, gender, culture, and social status. Stress at an early age accelerates long-term changes in the functional properties underlying emotional perception and therefore may alter the stress response later in life. Unfortunately, the interdisciplinary approach in stress research emphasised the study of stress phenomenon in the development of this or that pathology or manifestation of appropriate reactions under the influence of this or that factor, i.e. the study of a particular case, which did not significantly affect the conceptual level of interpretation of the stress phenomenon as such. Moreover, we did not come across any publications interpreting the pathogenesis of the development of the classical triad of stress, confirming, or refuting its validity. In this study, we evaluated the effect of nootropic drugs - polypeptides of cattle cerebral cortex and methionyl-glutamyl-histidyl-phenylalanyl-prolyl-glycyl-proline on the behaviour of rat offspring under conditions of maternal deprivation. The drug affects processes related to memory formation and learning, enhances attention during learning and analysis of information, improves adaptation of the organism to hypoxia, cerebral ischaemia, anaesthesia and other damaging effects. As a result of the conducted study against the background of early postnatal maternal deprivation and the use of such drugs as methionyl-glutamyl-histidyl-phenylalanyl-prolyl-glycyl-proline and polypeptides of cattle cerebral it was noted that the latter drug showed the greatest effectiveness as a means of compensating the reaction to chronic stress under conditions of maternal deprivation.

[Laparoscopic nephrectomies and kidney resections in children]. / Nachal'nyi opyt laparoskopicheskikh nefrektomii i rezektsii pochek u detei.

OBJECTIVE: To present the experience of laparoscopic nephrectomies and kidney resections in children. MATERIAL AND METHODS: There were 28 minimally invasive surgeries for renal tumors between July 2015 and March 2023 (92 months). There were 16 (57%) boys and 12 (43%) girls who underwent 22 nephrectomies and 6 kidney resections. The median age of patients was 54 (38; 76.5) months. RESULTS: In the laparoscopic nephrectomy group, the median surgery time was 135 (108-188) min, blood loss - 10 (3.75-15) ml. Total resection was confirmed in all patients. In the group of minimally invasive kidney resections, these values were 182.5 (157.5; 265) min and 50 (42.5; 117.5) ml, respectively. Histological examination confirmed total resection in all patients. In both groups, none patient developed postoperative complications. Event-free survival was 86.72% with a median follow-up of 82 months, and local recurrence-free survival was 95.8% with a median follow-up of 89.8 months. CONCLUSION: Minimally invasive nephrectomies and resections are safe in children in case of careful patient selection.

SPECIFICS OF PRESCRIBING ANTIRETROVIRAL DRUGS IN THE TREATMENT OF HIV INFECTION.

HIV infection is one of the most acute problems of our time, characterized by slow development, prolonged course, and numerous clinical manifestations. Currently, there is a large number of drugs acting on different processes of human immunodeficiency virus replication, which constitute the group of highly active antiretroviral therapy (HAART). This article shows a theoretical review of modern HAART and analyzes the prescribed treatment regimens for patients with HIV infection. The study revealed two most common combinations: nucleoside reverse transcriptase inhibitors + protease inhibitors; nucleoside + non-nucleoside reverse transcriptase inhibitors.

[Autologous kidney transplantation in a high-risk patient with locally advanced retroperitoneal neuroblastoma]. / Autologicheskaya transplantatsiya pochki u patsienta s mestnorasprostranennoi neiroblastomoi zabryushinnogo prostranstva gruppy vysokogo riska. Klinicheskoe nablyudenie.

Surgery of locally advanced neuroblastoma with risk factors is one of the most difficult in pediatric surgery. Incidence of nephrectomy during subtotal or complete tumor resection is higher due to common involvement of renal vessels. We present a patient with locally advanced retroperitoneal neuroblastoma who underwent heterotopic kidney autotransplantation.

EFFECT OF SOME IMMUNOMODULATORY DRUGS ON EMBRYONIC DEVELOPMENT OF DANIO RERIO FISH.

At the current stage of healthcare development, the inclusion of immunomodulators in the complex pharmacotherapy of various immunoinflammatory and viral diseases is widely discussed, but due to the lack of sufficient research and a broad evidence base, not all drugs with similar properties are used in medicine. According to the information obtained from the instructions for the use of immunomodulators, it was obtained that the main contraindications to their use include the prescription of children, pregnant women, and women during breastfeeding. In this study, we evaluated the effects of immunomodulatory drugs: aminodihydrophthalazindione sodium and meglumine acridonacetate, on the early developmental stages of Danio rerio (Zebrafish) embryos.

INFLUENCE OF PROFICIENCY OF SYNTHETIC FOLIC ACID ON THE NEUROLOGICAL SYMPTOMS OF RATS.

It has long been known about the need for folic acid for the vital activity of both macro-and micro-organisms. It is necessary for the processes of methylation, nucleotide synthesis and also the formation of methionine and reducing the toxic effect of homocysteine. The addition of synthetic folic acid to the diet of pregnant women, as well as at the stage of pre-pregnancy preparation, significantly reduces the risks of fetal neural tube defects, heart defects, and possibly other organs and systems of the body. In addition, folic acid can help improve fertility potential. However, there is evidence of adverse effects of folic acid proficite on the health of older adults (hiding B12-deficient status) and the offspring of mothers taking high doses prescribed by medical specialists like a risk of infectious-inflammatory and allergic diseases of the upper respiratory tract in children, eczema, also disorders of psychomotor development and insulin resistance. In 1980, the direct excitatory effect of folic acid on synaptic transmission in the central nervous system was proven. This is due to the molecular structure, it contains L-glutamate. Therefore, the aim of the work was trying to prove the existing correlation data on probable neuropathologies, including a reduced threshold of seizures, a high risk of epilepsy in a model of offspring of Wistar rats with an increased dosage of folate throughout gestation and including at the stage of pre-gravidar preparation. In the control group, the average clonus time was 1779.6 seconds, in the experimental group with a 1 mg/kg/diet dosage of 797.3 seconds, and in the second group with a 5 mg/kg/diet 439.7 seconds (p<0,01). The results obtained of the difference in the convulsive threshold may be due to changes in synaptic density as a result of an excess of synthetic folic acid during the formation of NT and subsequently during the differentiation of nervous tissue in the central nervous system (in particular, in the 3rd trimester with a massive appearance of glutamatergic receptors), which can affect the processes of neurogenesis and the formation of neural networks.

NEURODEGENERATION AND NMDA.

The N-methyl D-aspartate receptor is one of the key receptors in the human brain. As a result of radioligand analysis, it was found that the highest density of this receptor is located in the hippocampus, striatum, cortex, and amygdala. Associative memory, learning, and synaptic density are all directly related to the effective functioning of the NMDA receptor. Recent studies have shown that the number of NMDA receptors and their morphological structure decreases with age, in particular, some subunits change their shape, as well as the use of antidepressants, such as selective serotonin reuptake inhibitors, cause a delayed side effect, which manifests itself in the form of a quantitative decrease in NMDA in the brain. The antagonist of this receptor - memantine, inhibiting it can reduce the clinical picture of Alzheimer's disease, reducing tremor and papillary reflex. Another NMDA antagonist, ketamine, was used for anesthesia, but due to strong hallucinations during the period of recovery from anesthesia, it became less and less used. These substances also contribute to the work of the NMDA receptor in the future, and also affect synaptic density. Therefore, it is important to know the composition of the receptor, its downstream signaling pathways, and age-related changes in order to effectively prevent neurodegenerative diseases of the brain.

A COMPARATIVE REVIEW OF THE USE OF DANIO RERIO (ZEBRAFISH) AS A MODEL OBJECT IN PRECLINICAL STUDIES.

Danio rerio (Zebrafish) as a model object in preclinical studies have been widely used in recent years. This is facilitated by their morphological, physiological, biochemical, genetic, and embryological characteristics, as well as economic benefits and small-time costs of their breeding. The aim is to summarize the available data on the use of Danio rerio (Zebrafish) in preclinical studies. In this work a review of domestic and foreign articles on the use of Danio rerio in toxicological, pharmacological, embryological, and other research areas was carried out. Danio rerio (Zebrafish) can be used in many areas of preclinical studies of drugs. Their application in modeling novelty stress and experimental depression is especially interesting. Danio rerio are a versatile model object that allows cost-effective studies of various pharmacological drugs before they are tested on other models, particularly mammals.

COMPARATIVE ANALYSIS OF THE EFFECTS OF SOME HEPATOPROTECTORS IN EXPERIMENTALLY INDUCED MAFLD IN ADULT WISTAR RATS.

Metabolic associated fatty liver disease (MAFLD) is one of the most common chronic diseases characterized by increased fat accumulation in the liver and metabolic dysfunction. MAFLD is now taking on the character of a pandemic. In addition to dietary therapy and physical activity, hepatoprotectors are included in the pharmacotherapy of MAFLD. This study was to perform a comparative analysis of the efficacy of some hepatoprotectors in experimentally induced MAFLD in adult Wistar rats.

[Analysis of future liver remnant parameters in children after extended liver resection]. / Analiz parametrov budushchego ostatka pecheni u detei, perenesshikh ee obshirnye rezektsii.

OBJECTIVE: To analyze the initial data on future liver remnant volume and its function evaluated by 99mTc-Bromesida hepatobiliary scintigraphy in children with liver tumors. MATERIAL AND METHODS: Extended liver resections were performed in 58 patients aged 2 months - 208 months (median 26 months) for various neoplasms. Before hepatectomy, all children underwent contrast-enhanced CT with volumetry and hepatobiliary scintigraphy with 99mTc-Bromezida and subsequent quantitative assessment of its accumulation in the future liver remnant. All consecutive patients eligible for extended liver resection were retrospectively analyzed. RESULTS: The analysis included patients who underwent extended liver resection between June 2017 and March 2021. Among 91 liver resections, 58 (64%) procedures were extended hepatectomies including 2 ALPPS procedures. Median volume of future liver remnant was 44.5% (16.5-91.4), median future liver remnant function - 10.14%/min/m2 (1.8-30). Four patients with adequate liver function had insufficient volume of future liver remnant. Insufficient future liver remnant volume and its appropriate function were observed in 2 patients. Not life-threatening post-resection liver failure developed in 2 patients. CONCLUSION: Evaluation of future liver remnant function is the most sensitive method to predict post-hepatectomy liver failure in children. The cut off value of future liver remnant volume in children is below 25% and probably below 16.5%. Further data collection and research are warranted to determine significant values. These data will contribute to define the new indications for two-staged hepatectomies in children.

THYROID STATUS: IS IT POSSIBLE TO RESTORE MYELIN?

The number of demyelinating diseases of central nervous system are prone to grow nowadays. The most socially significant and well studied one is multiple sclerosis. The search of susbstances that would stop demyelinisation or reinforce the process of remyelination is in great request. Thyreoid gland hormones play a sufficient role in nervous system functioning and developing. Some studies show, that triiodothyronine regulates myelin synthesis through thyroid-sensitive nuclear receptors. In our study process of demyelination were modelled via сuprizone model, which appears to be an optimal method, since it allows to witness the process of demyelination without an autoimmune component. Results of the study show effectiveness of thyroid hormones for myelin and axon protection. In rats, under the influence of cuprizone, behavioral reactions are inhibited and changes in the structures of neurons in the cerebral cortex and lumbar spinal cord are noted. The severity of these disorders also depends on the thyroid status of the rat organism. In the normal hormonal balance, less significant changes are noted, when in a state of hypofunction these disorders are more pronounced. The cuprizone model of demyelination is an adequate experimental model of neurodegeneration and behavior disorders, and thyroid hormones can be considered as one of the components of new drugs aimed at treating multiple sclerosis.

[Liver transplantation for hepatoblastoma in children]. / Transplantatsiya pecheni pri gepatoblastome u detei.

OBJECTIVE: To improve the outcomes in children with hepatoblastoma. MATERIAL AND METHODS: There were 160 children with focal liver lesions who underwent surgery at the department of liver transplantation in 2008-2019. Patients with malignant tumors made up 77% (n=123). Hepatoblastoma (HB) prevailed (86%, n=106). Liver transplantation was performed in 19 (18%) patients with HB. Median follow-up after transplantation was 24.3 months by December 2019. Follow-up period did not exceed 4 years in more than 2/3 of patients. RESULTS: Overall and disease-free 10-year survival was 87.1% and 82.7%, respectively. Similar values were observed after resections (91.1% and 86.6%). At the same time, actuarial 4-year survival after liver transplantation for HB was 68%. CONCLUSION: Improvement of treatment outcomes may be achieved through multidisciplinary interaction ensuring timely drug therapy and liver transplantation.

[The analysis of the association of the polymorphic variants of the TPMT, COMT, and ABCC3 genes with the development of hearing disorders induced by the cisplatin treatment]. / Analiz assotsiatsii polimorfnykh variantov genov TPMT, COMT i ABCC3 c razvitiem narusheniia slukha, indutsirovannogo priemom tsisplatina.

Cisplatin and its derivatives are widely used chemotherapeutic agents for the treatment of many cancers, including hepatoblastoma, brain tumors, and germ-cell tumors. This therapy contributed to the dramatic increase in the survival rate. However, its use is restricted by the high incidence of irreversible ototoxicity associated with cisplatin application (in more than 60% of the children receiving it). Some studies have reported that genetic variants of TPMT (rs 12201199), COMT (rs4646316), and ABCC3 (rs 1051640) are conferring increased risk of developing cisplatin-induced hearing loss. However, in other studies the results were not replicated. In the present study, we replicated the previous studies based on an independent cohort of Russian patients. SNP genotypes for rs 12201199, rs4646316 and rs 1051640 were determined in DNA samples obtained from 16 patients who developed hearing loss and a group of 34 patients whose hearing was retained. The association between TPMT (rs 12201199), COMT (rs4646316), and ABCC3 (rs 1051640) variants and the hearing loss was not observed in our cohort.

[Neurosurgical aspects of the treatment of neuroblastoma patients]. / Neirokhirurgicheskie aspekty lecheniya bol'nykh s neiroblastomoi.

Neuroblastoma (NB) is the most common extracranial solid tumor in children. The neoplasm grows from progenitor cells of the sympathetic nervous system and can be detected anywhere along the sympathetic neurological circuit: retroperitoneally, mediastinally, cervically, and pelvically. Examination of children with suspected neuroblastoma is comprehensive and performed in strict compliance with a therapeutic protocol. A decision on the treatment regimen is made based on the tumor staging and the risk group of the patient. The diagnosis and treatment of NB patients are comprehensive and can be fully carried out only at the pediatric oncology department. In 10-15% of cases, an hourglass tumor spreads to the intervertebral foramina or spinal canal at one or more levels. A tumor node is always located extradurally with respect to the spinal cord. Symptoms of spinal cord compression of various severity are observed in 5-7% of patients. We present several cases of patients with neuroblastoma with intraspinal extension. Despite apparent benefits of primary surgical decompression of the spinal cord, modern experience of treatment of children with intraspinal tumor extension does not reveal advantages of surgery over chemotherapy. Neurological disorders of various nature and severity persist in the majority of patients in the long-term period, regardless of primary treatment. A higher level of spinal deformities after surgical tumor resection is observed. The issue of spinal cord decompression should be discussed by the neurosurgeon and pediatric oncologist, and the most common method of choice may be chemotherapy. The article discusses the indications and contraindications for neurosurgical interventions in NB patients and addresses the issues of NB metastasis to the brain and cranial bones as well as the opsoclonus-myoclonus syndrome.

[Classical osteosarcoma in children and adolescent].

Classical osteosarcoma is one of the most common primary malignant bone tumors in children and adolescents. It more frequently occurs in the areas of the highest growth plate proliferation: limb long bones particularly in the distal femur (30%), proximal tibia (15%), and proximal humerus (15%). In the long bones, the tumor is located usually in the metaphysis (90%), less frequently in the diaphysis (9%), and very rarely in the epiphysis. This paper considers the clinical, radiological, and histological diagnosis, and prognosis in this pathology.

[Turcot syndrome. Rare observation and literature review].

The Turcot syndrome is a rare disease which is characterized by a combination of a brain tumor with a y at which the neoplasm of the colon. About 150 of such observations are described in world literature. Our own observation and a literature review are presented in this article.

Incidence and survival of pediatric soft tissue sarcomas in moscow region, Russian Federation, 2000-2009.

The aim of the study was to assess the incidence and survival rates of soft tissue sarcomas (STSs) in children 0-14 years of age in Moscow Region, Russian Federation. The database of childhood population-based cancer registry of Moscow Region was used as a data source. Tumors were stratified according to International Classification of Childhood Cancer, 3d ed. Sixty-eight cases of STS were registered from 2000 to 2009. Crude incidence rate was 0,78, and age-standardized incidence rate using World Standard Population was 0,81 per 100.000 children/year. The highest age-specific incidence was observed in infants: 1,76 per 100.000 children/year. Rhabdomyosarcoma (RMS) was the most common histological type comprising 54,4% of all STS. 5-year observed survival (OS) of all patients with STS was 64,1 (95% CI 55,0-73,2). There was no statistically significant difference in OS between RMS-59,2 (95% CI 47,0-71,4) and nonrhabdomyosarcoma STS-69,3 (95% CI 55,8-82,8) (P = 0.63). Incidence and survival rates of STS observed in the study were comparable to the other Eastern European countries.