INFLUENCE OF CHRONIC NEUROGENIC PAIN ON BRAIN NEUROTRANSMITTER SYSTEMS OF MALE MICE IN DYNAMICS OF MELANOMA GROWTH

2019 ◽  
Vol 65 (6) ◽  
pp. 920-924
Author(s):  
Oleg Kit ◽  
Yelena Frantsiyants ◽  
Valeriya Bandovkina ◽  
Irina Kaplieva ◽  
Inga Kotieva ◽  
...  

Biogenic amines (BA) are known to be involved in the malignant growth, and their levels change in the CNS when exposed to pain; however, the combined effect of chronic pain and cancer on the BA dynamics in the brain has not been studied. The aim of the study was to evaluate characteristics of BA balance in the brain cortex during melanoma growth with chronic neurogenic pain (CNP). Material and methods. The study included 64 male C57Bl/6 mice weighing 22-24 g. В16/F10 melanoma was transplanted under the skin of the back to animals of the main group 2 weeks after the sciatic nerve ligation. Mice with melanoma without pain were the comparison group. Levels of BA: adrenaline, noradrenaline, dopamine (DA), serotonin (5-HT), histamine, and 5-HIAA were determined by ELISA. Results. Changes in adrenaline levels were registered in the brain of mice with CNP. The growth of melanoma in males was accompanied by elevated brain levels of adrenaline and noradrenaline and decreased dopamine and serotonin. Similarities in the direction of shifts in the neurotransmitter profile were observed in melanoma development with and without CNP. Conclusions. The influence of CNP on the neurotransmitter balance in the CNS was probably one of the factors that influenced the course of transplanted B16/F10 melanoma in males of the main group.

Author(s):  
О.И. Кит ◽  
И.М. Котиева ◽  
Е.М. Франциянц ◽  
И.В. Каплиева ◽  
Л.К. Трепитаки ◽  
...  

Известно, что биогенные амины (БА) участвуют в злокачественном росте, их уровень изменяется в ЦНС при болевом воздействии, однако исследований о сочетанном влиянии хронической боли (ХБ) и онкопатологии на динамику БА в головном мозге не проводилось. Цель: изучить особенности баланса БА в коре головного мозга в динамике роста меланомы, воспроизведенной на фоне ХБ. Материалы и методы. Работа выполнена на 64 мышах-самках, весом 21-22 г. Животным основной группы меланому В16/F10 перевивали под кожу спины через 2 недели после перевязки седалищных нервов. Группой сравнения служили мыши с меланомой без боли. Уровни БА: адреналина, норадреналина, дофамина (ДА), серотонина (5-НТ), гистамина, а также 5-ОИУК определяли методом иммуноферментного анализа. Результаты. У мышей с ХБ уменьшается содержание большинства БА, однако уровень ДА не изменяется. Метаболизм 5-НТ происходит с участием МАО. Развитие меланомы сопровождается увеличением содержания ДА и 5-НТ, тогда как МАО - ингибируется. Направленность сдвигов БА при развитии меланомы на фоне ХБ оказалась практически такой же, как и без неё. В то же время ХБ ограничивает накопление 5-НТ в коре мозга при меланоме, что сопровождается более агрессивным её течением. Выводы. ХБ ограничивает включение стресс-лимитирующих механизмов в головном мозге при развитии меланомы у мышей, что приводит к более агрессивному течению злокачественного процесса. Biogenic amines (BA) are known to be involved in malignant growth, and their CNS levels change in pain; however, there are no studies of combined effects of chronic pain (CP) and cancer on BA dynamics in the brain. Aim: To study features of BA balance in the cerebral cortex during melanoma growth associated with CP. Material and methods. The study included 64 female mice weighing 21-22 g. In the main groups, B16/F10 melanoma was transplanted under the skin of the back two weeks following sciatic nerve ligation. Mice with melanoma without pain were used as the control. Concentrations of BA: adrenaline, noradrenaline, dopamine (DA), serotonin (5-HT), histamine and 5-HIAA were measured with ELISA. Results. Concentrations of BAs decreased in mice with CP although DA levels did not change. 5-HT metabolism involved MAO. The development of melanoma was accompanied by increases in DA and 5-HT whereas MAO was inhibited. The direction of BA changes during the development of melanoma was the same with and without CP. At the same time, CP with melanoma limited accumulation of 5-HT in the cerebral cortex, which resulted in even more aggressive course of cancer. Conclusion. CP restricted the activation of cerebral stress-limiting mechanisms during the development of melanoma in mice, which resulted in a more aggressive course of disease.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23516-e23516
Author(s):  
Yulia A. Pogorelova ◽  
Ekaterina I. Surikova ◽  
Elena M. Frantsiyants ◽  
Valeria A. Bandovkina ◽  
Irina V. Kaplieva ◽  
...  

e23516 Background: Sex steroids in the brain regulate neurogenesis and the body's response to stress. Chronic neurogenic pain (CNP) and the tumor growth are stress factors that often accompany each other. The purpose of the study was to analyze levels of sex steroid hormones in white matter of the brain of rats with tumor development in presence of CNP. Methods: The study included white outbred male rats (n = 74). In the main groups, a CNP model was created by bilateral sciatic nerve ligation, and after 45 days, M1 sarcoma was transplanted subcutaneously (n = 11) or into the subclavian vein (n = 11). Two comparison groups (each n = 13) included sham operated animals with M1 sarcoma transplanted subcutaneously or into the subclavian vein. Control groups (each n = 13) included animals with CNP or sham operated rats. Levels of testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) were measured by ELISA (Cusabio, China) in the brain tissues obtained on day 21 of the tumor growth. Results: Tumors transplanted subcutaneously with and without CNP grew in 100% of animals. Tumor volumes were 1.5 times (p<0.05) greater in animals with CNP, compared with rats without CNP, while the survival in the groups was similar. Levels of all studied hormones, except for E1, in the brain tissue in subcutaneous sarcoma growth were lower in presence of CNP than without it: T and E3–on average by 1.4 times (p<0.05), E2 and P4–by 3.5 times (p<0.05). In rats with intravenous transplantation of M1, tumor nodes in the lungs were registered only in rats with CNP, and the survival of animals was 36 days shorter (p<0.05) than in rats of the corresponding control group. Such specificity of selective neoplastic growth in the pulmonary tissue was combined with lower cerebral T and E3 levels than in the corresponding control–on average by 1.4 times (p<0.05), E2–by 7.2 times, and higher levels of E1–by 1.3 (p<0.05) and P4–by 2.0 times, compared to animals which did not develop the neoplastic process in the lungs without pain. Conclusions: The presence of CNP stimulates the growth of M1 sarcoma in standard subcutaneous inoculation and allows the development of tumors in the lung in intravenous inoculation. The specificity of malignant growth in presence of CNP is accompanied by changes in the brain levels of neurosteroids in rats.


Author(s):  
O. V. Shvets ◽  
Tatiana V. Gaivoronskaya ◽  
E. E. Esaulenko ◽  
N. I. Bykova

Aim. This study aims to increase the efficiency of the wound process in patients with odontogenic phlegmons of the maxillofacial region by using energotropic and antioxidant agents. Material and methods. The clinical study included 42 patients with odontogenic phlegmons of the maxillofacial region. The patients were divided into two groups: comparison group (patients received traditional treatment) and main group (patients received treatment with Cytoflavin in the treatment regimen). Results. In the main group, the appearance of the first granulations occurred 2.1 times faster (on average on the 3rd day) in comparison with the granulation tissue in patients of the comparison group. Signs of edge epithelialization of wounds appeared almost 3 days earlier (on average on the 6th day) in the main group than in the comparison group; on the 7th day, secondary sutures were already applied, which was 1.6 times faster than the same parameter group 2, clearly suggesting the acceleration of reparative processes. Conclusion. The dynamics of clinical manifestations indicates the comparative effectiveness of using Cytoflavin as part of complex therapy. This finding is confirmed by the accelerated terms of wound healing, the appearance of granulations, epithelialization of the wound edges, and the imposition of secondary sutures.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21582-e21582
Author(s):  
Yulia A. Pogorelova ◽  
Irina V. Kaplieva ◽  
Elena M. Frantsiyants ◽  
Ekaterina I. Surikova ◽  
Valeria A. Bandovkina ◽  
...  

e21582 Background: The fibrinolytic system of the brain is important for its normal functioning and participation in processes that are significant in various stressful influences, including tumor growth and chronic neurogenic pain (CNP). These pathological conditions change the activity of the brain neurotransmitter system. On the other hand, urokinase deficiency is associated with significant inhibition of tumor growth, while CNP – with its stimulation. The purpose of the study was to analyze the effect of CNP on the levels of biogenic amines in the brain of mice with urokinase deficiency (uPA-/-) with transplanted B16/F10 melanoma. Methods: The study included male and female mice: С57ВL/6 (uPA+/+, n = 48) and C57BL/6-Plautm1.1Bug-ThisPlauGFDhu/GFDhu (urokinase gene-knockout - uPA-/-, n = 48). Mouse strains were divided into subgroups (each n = 6): intact; with CNP (bilateral sciatic nerve ligation); 21 days after subcutaneous transplantation of B16/F10 melanoma; 21 days of B16/F10 melanoma growth in presence of CNP (B16/F10+CNP), with tumor transplantation 2 weeks after the sciatic nerve ligation. Levels of adrenaline (A), noradrenaline (NA), dopamine (DA), histamine, serotonin (5HT), and 5-hydroxyindoleacetic acid (5OHIA) were determined in the brain by ELISA (Cusabio, China). Statistical processing - Statistica 10.0. Results: Levels of NA, DA and 5HT in the brain of intact uPA-/- mice were 3.5, 2.1 and 1.9 times higher (p < 0.05), respectively, than in intact uPA+/+ animals, while histamine and 5OHIA were on average 2.0 times lower. The dynamics of cerebral levels of biogenic amines in uPA-/- mice with pathological factors, alone or combined, had practically no gender specificity, with rare exceptions. So, 5HT levels increased up to 4.5 times in uPA-/- mice of both sexes in response to CNP or B16/F10 growth. Melanoma growth in presence of CNP, on the contrary, decreased 5HT by 3-10 times and DA by 1.6 times (p < 0.05) both in males and females, and decreased NA by 1.6 times (p < 0.05) in females. Conclusions: CNP together with melanoma inhibits the initial activation of the HA-, DA- and 5HT-ergic systems in the brain of uPA-/- mice, which may be an important pathogenetic mechanism of the cancellation of genetically determined inhibition of subcutaneous B16/F10 melanoma growth in urokinase deficiency.


2021 ◽  
pp. 14-19
Author(s):  
Tamara Mikhailovna Medoeva ◽  
Madina Zaudinovna Dugieva ◽  
Vadim Viktorovich Portnov

Chronic salpingo-oophoritis (CSO) is one of the most common diseases among the entire gynecological pathology, the frequency of which reaches 65-68%. Despite the progress made in the treatment of CSO, there is a serious problem due to the steady growth and complications leading to infertility, ectopic pregnancy and the development of chronic pelvic pain syndrome, which significantly reduces the quality of life of patients. In this regard, the development of promising pharmaco-physiotherapeutic methods with pronounced analgesic, anti-inflammatory, immunomodulatory and bacteriological effects to increase the therapeutic effectiveness and improve the quality of life of patients with salpingo-oophoritis is an important task of modern gynecology and physiotherapy. Objective: To study in a comparative aspect the effect of the combined use of transvaginal electrophoresis of the collagenase complex and pulsed magnetic therapy and their mono-effects on the quality of life of patients with chronic salpingo-oophoritis. Materials and research methods. The study included 77 patients aged 18 to 42 years (median age was 26,7±2,8 years) with a diagnosis of chronic salpingo-oophoritis of non-specific etiology. More than half of the patients (59,7%) were women under 25 years of age. All patients were divided into three groups that were comparable according to the main clinical and anamnestic data, somatic and obstetric-gynecological status: group 1 — the main group — included 28 patients who received a course of combined application of transvaginal electrophoresis of the collagenase complex and pulsed magnetic therapy; group 2 — comparison group 1 — included 25 patients who received acourse of transvaginal electrophoresis of the collagenase complex; group 3 — comparison group 2 — included 24 patients who received a course of pulsed magnetic therapy. The quality of life was assessed by the indicators of the Quality of Life Index (QOL), which takes into account the three most important and informative aspects of patients’ lives: physical condition and its dynamics, mental (psychological) health and daily functioning. The results of the study. Based on the obtained results, it was proved that the most pronounced results were achieved in patients of the main group who received a course of transvaginal electrophoresis of the collagenase complex in combination with pulsed magnetic therapy, where the quality of life improved by 89,3% according to the QOL index, compared to the monotherapy with transvaginal electrophoresis and pulsed magnetic therapy — 75,7% and 73,1%, respectively.


2021 ◽  
Vol 8 (1) ◽  
pp. 20-29
Author(s):  
O. I. Kit ◽  
E. M. Frantsiyants ◽  
I. V. Neskubina ◽  
E. I. Surikova ◽  
I. V. Kaplieva ◽  
...  

Purpose of the study. To analyze the calcium levels in mitochondria of cells in different organs in standard and stimulated growth of experimental В16/F10 melanoma. Materials and Methods. The study included female С57ВL/6 mice (n=168). Experimental groups: intact group (n=21), group with a model of chronic neurogenic pain (CNP) (n=21), group M – B16/F10 melanoma (n=63), group M+CNP – mice (n=63) with transplantation of B16/F10 melanoma 3 weeks after CNP model creation. The concentration of calcium in mitochondrial samples was determined by a biochemical method (Abris+, Russia). Results were statistically analyzed using the Statistica 10.0 program. Results. CNP decreased calcium levels in mitochondria of cells in the brain by 1.4 (р=0.00153) times, liver by 2.6 times and heart by 3.2 times and increased the levels in the skin by 97.1 times. In standard growth of experimental melanoma, levels of calcium in cell mitochondria in most of the studied organs increased at the initial stage of the melanoma growth, and decreased to intact values and lower by the terminal stage. In the mitochondria of tumor cells, calcium levels were stably high at all stages of standard tumor growth. At the initial stage of CNP‑stimulated tumor growth, a decrease in calcium in the mitochondria of the skin by 5.7 times and its accumulation in the mitochondria of the brain by 6.6 times, heart, and kidneys were recorded by 1.5 times. At the terminal stage of stimulated melanoma growth, extremely low calcium values were recorded in the mitochondria of all organs. A stably low level of calcium was registered in the mitochondria of tumor cells at all stages of stimulated melanoma growth. Conclusions. The growth of experimental B16/F10 melanoma in female mice is accompanied by mitochondrial dysfunction affecting most organs. Stimulation of the growth of experimental melanoma with chronic neurogenic pain, unlike the standard growth variant, changes accumulation of calcium in the mitochondria of cells both in organs and in the tumor itself. The chronic pain syndrome accompanying a malignant process can influence its course with the involvement of mitochondria and the modification of their functions.


2020 ◽  
Vol 66 (2) ◽  
pp. 151-155
Author(s):  
E.M. Frantsiyants ◽  
V.A. Bandovkina ◽  
I.V. Kaplieva ◽  
N.D. Cheryarina ◽  
E.I. Surikova ◽  
...  

The aim of the study was to determine the level of sex steroid hormones in white matter of the brain of rats with tumors combined with chronic neurogenic pain (CNP), which was modeled by bilateral sciatic nerve ligation. The study included albino male rats (n=74). In the main group, M1 sarcoma was transplanted subcutaneously (n=11) or into the subclavian vein (n=11) 45 days after CNP modeling. Two comparison groups (n=13 each) included sham operated animals (without CNP) with M1 sarcoma transplanted subcutaneously and intravenously. Control groups included animals with CNP and sham operated animals. Rats were euthanized on day 21 of the carcinogenesis. Levels of total and free testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) in the brain white matter were measured using ELISA kits (“Cusabio”, China). CNP caused a decrease in the total and free T by 1.5 times (p


2019 ◽  
Vol 20 (3) ◽  
pp. 207-214
Author(s):  
Aksinia Lipatova ◽  
Azamat Kade ◽  
Artem Trofimenko ◽  
Viktor Ovsiannikov ◽  
Oleg Tcymbalov ◽  
...  

Abstract The aim of study is to analyze the tDCS influence on stress-induced disorders in rats with low stress sustainability and endurance. The animals with a low stress sustainability and endurance were divided into 3 groups: the comparison 1, the comparison 2 and the main. The control group consisted of intact rats. The rats of the comparison group 1 were subjected to orthostatic stress 24 hours after the 1st forced swimming test. The rats of the comparison group 2 and the main one were conducted the 2nd forced swimming test on the 7th day of the experiment, and 24 hours later they were subjected to the orthostatic stress. Rats of the main group got tDCS sessions after the 1st forced swimming test. The development of the orthostatic stress is accompanied by an increase in plasma content the following components: adrenaline by 88.9%, ACTH in 10.5 times, corticosterone by 70.1%, IL-1β by 178.2%, IL-6 in 6.7 times, IL-10 by 37.1% in comparison with intact animals. The usage of tDCS in rats with low stress sustainability and endurance increased the swimming duration by 47.7%. During the OS it was also accompanied by a decrease in plasma content: adrenaline in 1.4 times, ACTH in 8.2 times, corticosterone in 1.4 times, IL-1β in 1.5 times, IL-6 in 2.2 times, IL-10 in 1.2 times, relative to the comparison group 2. The obtained data showed the essential effect of tDCS on stress-related changes in the content of cytokines and hormones of blood.


Author(s):  
Lyubov A. Cherevaschenko ◽  
L. YU. Dadova ◽  
Nikolay N. Kulikov ◽  
Anatolii T. Tereshin ◽  
Igor A. Cherevashchenko

Background. Treatment of chronic cerebral ischemia should be aimed both to the main etiological factor and to the pathogenetic mechanisms of cerebral ischemia and hypoxia. The action of ozone therapy is characterized with a multilateral positive effect on the main aspects of chronic cerebral ischemia pathogenesis, such as chronic cerebral hypoxia, impaired microcirculation, rheological disorders, and activation of lipid peroxidation. The use of iodine-bromine baths in chronic cerebral ischemia has been proved to be accompanied by an improvement in cerebral circulation, normalization of the brain bioelectric processes, an initially impaired condition of the autonomic nervous system, and an increase in the level of adaptive capabilities of the body. Aim: to develop effective pathogenetically substantiated methods for the combined use of iodine-bromine baths and ozone therapy in patients with chronic cerebral ischemia to increase the effectiveness of health resort treatment. Methods. In accordance with the tasks set in the work, 90 patients with chronic cerebral ischemia of the degree 1, who were randomized into three treatment groups, were examined and treated. Patients of the control group (n = 30) received iodine-bromine baths, patients of the comparison group (n = 30) received ozone therapy, patients of the main group (n = 30) received iodine-bromine baths and ozone therapy. Examination of patients included Doppler ultrasound, electroencephalography, rheoencephalography, сardiointervalography, lipid metabolism studies, fibrinogen content studies. Results. As a result of treatment, the improvement of clinical symptoms and the normalization of biochemical and neurophysiological parameters were noted in patients of all treatment groups. Overall efficiency (improvement and significant improvement) was 53.3% in the control group, in the comparison group it was 63.3%, and 73.3% in the main group. Conclusion. The authors proved the practicability of rehabilitative treatment of early forms of vascular diseases of the brain at the stage of sanatorium and resort rehabilitation, which is due to significant compensatory reserves and high plasticity of the structural and functional formations of the brain with preserved ability to develop nonspecific elements of the nervous tissue and restore reversibly damaged structures.


2018 ◽  
pp. 23-29
Author(s):  
Yu.Yu. Mazur ◽  
◽  
V.I. Pyrohova ◽  

Dysbiotic processes in the vagina, in particular aerobic vaginitis, are closely related to the local immune status violations, interfere the cervical epithelium physiological metaplasia, and also create favorable conditions for sexually transmitted infections accession, in particular the human papillomavirus. This complex of disorders is one of the determining factors for both the prolonged complicated course of cervical ectopy and its recurrence. The objective: was to optimize the treatment tactics in patients with cervical ectopy complicated by aerobic vaginitis. Materials and methods. It was carried out a comprehensive examination and treatment of 70 women of reproductive age (18–49 years) with cervical ectopy complicated by the aerobic vaginitis presence. All patients were questioned with a study of the reproductive anamnesis, bacterioscopic, cytological examination, simple and advanced colposcopy, pH-metry of vaginal environment, vaginal microbiota investigation. Depending on the treatment regimen, the patients were randomly divided into 2 groups. Group 1 (main group, n=35) – included patients treated according to the proposed scheme: on the first stage patients were prescribed vaginal suppositories containing dexpanthenol and chlorhexidine bigluconate – 1 suppository intravaginally twice a day and a complex multi-strain probiotic – 1 capsule twice a day for 2 weeks. On the second stage the patients were prescribed pessaries containing Triticum vulgare according to the scheme – 1 pessary intravaginally at night for 10 days a month (with the start of the use immediately after the next menstruation end) for 3 months. Group 2 (comparison group, n=35) – women who received treatment according to the current recommendations of the Ministry of Health of Ukraine. Group 3 (control group, n=30) included conditionally healthy women who have applied for routine preventive gynecological examination. Results. Clinical evaluation of the treatment first stage effectiveness showed a reduction in the complaints in patients of both study groups in 100% of cases. Both after the first and after the second stage of the proposed treatment scheme effective vaginal mucous membranes decontamination was revealed, conditionally pathogenic bacteria were not found in diagnostically significant titers, the number of leukocytes and the vaginal secret pH were normalized, and the average score on the Donders G. et al. scale showed no signs of aerobic vaginitis in the patients of the main group. The cytological norm of Pap-smear was reached by 91.43±7.43% of main group and 71.43±7.64% of the comparison group women (p<0.05); and in case of evaluation using the Bethesda system (2001) – 97.14±2.82% of group 1 and 80.00±6.76% of group 2 patients (p<0.05). After the second stage of treatment the average size of cervical ectopy significantly (p<0.05) decreased in the patients of the main group compared to group 2 (by 32.68% compared to the average area before treatment). In 5 (14.29%) patients of the main group and 2 (5.71%) patients of the comparison group after the treatment cervical ectopy was not found during the control colposcopy. Сonclusion. In the part of women physiological cervical ectopy with the onset of sexual activity is complicated by the development of the vaginal dysbiotic processes and vaginitis, which create unfavorable conditions for the cervix epithelization and simultaneously increase the risk of sexually transmitted infections, in particular the human papillomavirus infection. Therapeutic measures aimed at normalizing the vaginal microbiota, recolonization of its lactoflora and the creation of favorable conditions for the physiological cervix epithelization are pathogenetically substantiated in this case. The proposed treatment scheme (complex application of vaginal antiseptic in combination with probiotic and on the next stage – of the reparative action drug) made it possible to reduce the complaints, eliminate the signs of aerobic vaginitis, normalize the vaginal microbiota state, reduce the cervical ectopy area, and in 14.29% cases – to achieve complete cervical epithelization. Key words: cervical ectopy, aerobic vaginitis, vaginal microbiota, vaginal suppositories, probiotic.


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