Geographical Distribution, Incidence, Malignancies, and Outcome of 136 Eastern Slavic Patients With Nijmegen Breakage Syndrome and NBN Founder Variant c.657_661del5.

Nijmegen breakage syndrome (NBS) is a DNA repair disorder characterized by combined immunodeficiency and a high predisposition to lymphoid malignancies. The majority of NBS patients are identified with a homozygous five base pair deletion in the Nibrin (NBN) gene (c.657_661del5, p.K219fsX19) with a founder effect observed in Caucasian European populations, especially of Slavic origin. We present here an analysis of a cohort of 136 NBS patients of Eastern Slav origin across Belarus, Ukraine, Russia, and Latvia with a focus on understanding the geographic distribution, incidence of malignancy, and treatment outcomes of this cohort. Our analysis shows that Belarus had the highest prevalence of NBS (2.3 per 1,000,000), followed by Ukraine (1.3 per 1,000,000), and Russia (0.7 per 1,000,000). Of note, the highest concentration of NBS cases was observed in the western regions of Belarus and Ukraine, where NBS prevalence exceeds 20 cases per 1,000,000 people, suggesting the presence of an "Eastern Slavic NBS hot spot." The median age at diagnosis of this cohort ranged from 4 to 5 years, and delay in diagnosis was more pervasive in smaller cities and rural regions. A total of 62 (45%) patients developed malignancies, more commonly in males than females (55.2 vs. 34.2%; p=0.017). In 27 patients, NBS was diagnosed following the onset of malignancies (mean age: 8 years). Malignancies were mostly of lymphoid origin and predominantly non-Hodgkin lymphoma (NHL) (n=42, 68%); 38% of patients had diffuse large B-cell lymphoma. The 20-year overall survival rate of patients with malignancy was 24%. However, females with cancer experienced poorer event-free survival rates than males (16.6% vs. 46.8%, p=0.036). Of 136 NBS patients, 13 underwent hematopoietic stem cell transplantation (HSCT) with an overall survival of 3.5 years following treatment (range: 1 to 14 years). Indications for HSCT included malignancy (n=7) and immunodeficiency (n=6). Overall, 9% of patients in this cohort reached adulthood. Adult survivors reported diminished quality of life with significant physical and cognitive impairments. Our study highlights the need to improve timely diagnosis and clinical management of NBS among Eastern Slavs. Genetic counseling and screening should be offered to individuals with a family history of NBS, especially in hot spot regions.

The exchange of monoamines during the experimental neurosis on the background of using of amide "2-hydroxy-n-naphthalen-1-yl-2-(2-oxo-,2-dihydroindol-3-ylidene)".

INTRODUCTION: Incessant increase in the frequency and distribution of anxiety disorders stipulates searching, research and study of the mechanism of action of new substances for their correction, including the group of 2-oxoindolin-3-glyoxylic acid derivatives. THE AIM: To research the effect of N-(1-naphthyl) amide-2-oxoindolin-3-glyoxylic acid on monoaminergic system of subjected to experimental neurosis of rats. MATERIALS AND METHODS: The experiments were performed on male Wistar rats, who have weight 180-220g and were researching the effect of 2-hydro-N-naphthalen-1-yl-2-(2-oxy-1,2-dihydroindol-3-ylidene)-acetamide (compound 18) at a dose (12 mg/kg), by intragastric drug injection of subjected to experimental neurosis rats, during 30 days (1 time in three days), for monoamines content (epinephrine, norepinephrine, dopamine and serotonin) in the blood, their decay products (homovanillic acid, vanillylmandelic acid and 5-oxyindolacetic acid) in the urine and the ratio of end products of the reaction to their predecessors. RESEARCH: It was established that during the preventive-therapeutic application of N-(1-naphthyl)amide-2-oxoindolin-3-glyoxylic acid, it effectively adjusts the level of monoamines, reducing the content of adrenaline and increasing the content of noradrenaline, dopamine and 5-HT in the blood. The compound also reduces the content of products exchange of mediators (HVA,VMA and 5-OIAA) in the urine. The 2-oxoindolin derivatives reduces the ratio between HVA/dopamine, VMA/(noradrenaline + adrenaline) and 5-OIAA/5-HT, it testifies about the normalizing of enzymes activity, which are involved in the process of exchange and maintaining the constancy of monoamines. The results show that in the mechanisms of anxiolytic action of compound 18, a significant role plays the normalization of content and exchange of neurotransmitters in the organism, which caused an experimental neurosis. CONCLUSION: Compound 2-hydro-N-naphthalen-1-yl-2-(2-oxo-1,2-dihydroindol-3-ylidene)-acetamide by the experimental 30-day neurosis, was reducing the expression of neurotransmitter imbalance in the blood, apparently due to correction of enzymatic synthesis links and biotransformation of monoamines.

Research of the protection actions of derived 2-oxoindole in acute stress.

INTRODUCTION: Correction of pathological anxiety and stress level of frustration leads to the development of new anxiolytics, notably including derivatives of 2-oksoyndolyn- 3-hlyoksylic acid. The aim of work - to study the effect of 2-oksyindolin-3-hlyoksylic acid on emotional and behavioral reactions of rats subjected to behavioral stress tests of different averiability. MATERIALS AND METHODS: In experiments on 150 white mature male rats Wistar investigated the effects of 2-oksoindolin (2-hydroxy-N-naphthalene-1-yl-2-(2-hydroxy-1,2- dihydro-indole-3-ylidene)-acetamide) with laboratory codes 18 when intraperitoneally administered to acute immobilization stress on Sel'ye on emotional and behavioral responses of animals to test «open field¼, «a raised cross maze¼ and test «conflict behavior¼ (option Vogel). RESULTS: Established that the prophylactic use of the compound 18 in a test of "open field" warned the stress changes in the latent period of the first movement, likely increased the number of exits to the center installation, warned breach vertical and horizontal motor activity and significantly increased the number of acts of grooming and reduced the number of boluses compared with stress without correction. Revealed changes suggest that the substance 18 prevents anxiety disorders conduct stress genesis. In the test «a raised cross maze¼ of 2-oksoindolin significantly increased the number of outputs rats in open arms maze and reduced the number of fecal balls compared with those in the control disorders. In the study antyconflict action found that the compound increased the number of approaches to the drinkers, but the activity in this test yielded diazepam. CONCLUSION: Installed conservation action anksyolityc 2-hydroxy-N-naphthalene-1-yl-2-(2-hydroxy-1,2-dihydro-indole-3-ylidene)-atsetamidu acute stress may be associated with indirect stimulation of GABA - benzdiazepin receptor complex, by strengthening endogenous GABA affinity to the receptors and/or indirect stimulation of GABA receptors by other neurotransmitter systems, including serotonergic, which makes compounds for further study the possibility of post stress with anxiety disorders.