Antibodies to neurotransmitters - neuroimmune markers in individual prefention of addiction

Author(s):  
Л.А. Ветрилэ ◽  
Т.И. Невидимова ◽  
Е.И. Мастерова ◽  
Н.А. Бохан ◽  
И.А. Захарова ◽  
...  

Цель исследования - изучение содержания аутоантител к нейромедиаторам дофамину, норадреналину, серотонину, глутамату и ГАМК на разных стадиях развития зависимости от ПАВ, а также влияние различных видов наркотиков на их уровень в сыворотках крови. Методика. Исследование выполнено на базе отделения аддиктивных состояний и лаборатории клинической психонейроиммунологии и нейробиологии НИИ психического здоровья Томского НИМЦ РАН. Группу здоровых людей составили 148 студентов средних специальных и высших учебных заведений. Группа наркологических пациентов состояла из 203 лиц. Кровь для исследования у наркологических пациентов брали однократно при поступлении в стационар или на диспансерном приеме. У добровольцев кровь брали однократно при обследовании. Антитела к нейромедиаторам дофамину (ДА), норадреналину (НА), серотонину (5-ОТ), глутамату (ГЛУ) и ГАМК определяли методом твердофазного ИФА (ELISA) на полистироловых 96-луночных планшетах, сенсибилизированных тест-антигеном. В качестве тест-антигенов использовали конъюгаты нейромедиатора с бычьим сывороточным альбумином (БСА). Конъюгированные антигены ДА-БСА и 5-ОТ-БСА синтезировали с использованием диазотированного белка. Конъюгаты НА-БСА, ГЛУ_БСА и ГАМК-БСА синтезировали с помощью глутарового альдегида. Полученные данные статистически обрабатывали с использованием непараметрического критерия Манна-Уитни и точного метода Фишера. Результаты. Установлено, что уровень антител к нейромедиаторам (ДА, НА, 5-ОТ, ГЛУ, ГАМК) может отражать изменения в нейротрансмиттерных системах головного мозга, происходящие при развитии зависимости от ПАВ и выявлять особенности действия различных наркотических веществ. Наиболее существенное усиление продукции аутоантител к нейромедиаторам наблюдалось у пациентов с опийной наркоманией. Пациенты, злоупотреблявшие психоактивными веществами без развития зависимости, но с вредными последствиями для здоровья, характеризовались низким уровнем аутоантител к нейромедиаторам. При этом следует особо отметить более выраженное снижение уровня аутоантител к глутамату в этой группе пациентов. Заключение. Полученные данные свидетельствуют, что аутоантитела к нейромедиаторам особенно к дофамину, норадреналину, глутамату могут рассматриваться в качестве нейроиммунных маркеров стадийного развития аддиктивных состояний. The purpose. The aim of this work was to study the level of autoantibodies to neurotransmitters dopamine, noradrenaline, serotonin, glutamate and GABA at different stages of development of the psychoactive substances dependence, as well as the effect of various types of narcotics on their serum levels. Methods. The study was performed on the basis of the department of addictive states and the laboratory of clinical psychoneuroimmunology and neurobiology of the Mental Health Research Institute Tomsk NRMC RAS. The group of healthy people was 148 students of secondary special and higher educational institutions. The group of narcological patients consisted of 203 persons. Blood for study in narcological patients was taken only once on admission to hospital or on a dispensary. The volunteers received blood once during the examination. Antibodies to neurotransmitters dopamine (DA), norepinephrine (NA), serotonin (5-OT), glutamate (GLU) and GABA were determined by solid-state ELISA (ELISA) on polystyrene 96-well plates sensitized with test antigen. As test antigens were used. neuromediators conjugate with bovine serum albumin (BSA). Conjugated DA-BSA and 5-OT-BSA antigens were synthesized using a diazotized protein. Conjugates of NA-BSA, GLU-BSA and GABA-BSA were synthesized with glutaraldehyde. The data obtained were statistically processed using the nonparametric Mann-Whitney test and Fisher’s exact method. Results. As a result of the study, it was established that the level of antibodies to neurotransmitters (DA, NA, 5-OT, GLU, GABA) may reflect changes in neurotransmitter systems of the brain that occur when development of the psychoactive substances dependence and may to reveal the specific features of the action of various narcotic substances. The most significant increase in the production of autoantibodies to neurotransmitters was observed in patients with opiate addiction. Patients who abused psychoactive substances without dependence development, but with harmful health effects, were characterized by a low level of autoantibodies to neurotransmitters. In this case, we should especially note a more pronounced decrease in the level of autoantibodies to glutamate in this group of patients. Conclusions. The data obtained indicate that autoantibodies to neurotransmitters, especially dopamine, norepinephrine, glutamate can be considered as neuroimmune markers of the stage development of addictive states.

1979 ◽  
Vol 90 (3) ◽  
pp. 385-393 ◽  
Author(s):  
José Borrell ◽  
Flavio Piva ◽  
Luciano Martini

ABSTRACT Drugs able to mimic or to antagonize the action of catecholamines have been implanted bilaterally into the basomedial region of the amygdala of adult castrated female rats. The animals were killed at different intervals after the implantation of the different drugs, and serum levels of LH and FSH were measured by radioimmunoassay. The results have shown that the intra-amygdalar implantation of the alpha-adrenergic blocker phenoxybenzamine induces a significant increase of the release both of LH and FSH. The implantation of the beta-adrenergic blocker propranolol brings about a rise of LH only. The dopamine receptor blocker pimozide stimulates the release of LH and exerts a biphasic effect (stimulation followed by inhibition) of FSH secretion. The alpha-receptor stimulant clonidine and the dopaminergic drug 2-Br-alpha-ergocryptine were without significant effects. From these observations it is suggested that the adrenergic signals reaching the basomedial area of the amygdala (possibly from the brain stem) may be involved in the modulation of gonadotrophin secretion.


Author(s):  
Т.П. Ветлугина ◽  
Е.В. Матафонова ◽  
Н.А. Бохан ◽  
В.Б. Никитина ◽  
А.И. Мандель ◽  
...  

Цель исследования: изучение динамики показателей иммунитета и уровня кортизола у больных опийной наркоманией в процессе терапии синдрома отмены. Методика. В исследование включено 136 больных опийной наркоманией (инъекции экстракта опия) с сформировавшейся физической зависимостью. Пациенты получали в стационаре стандартную терапию с полной отменой наркотика. Исследование проводилось на следующих этапах: при поступлении в стационар (опийный абстинентный синдром - ОАС); на 5-7-е сут. терапии (переход в постабстинентное состояние - ПАС); на 25-28-е сут. лечения (становление терапевтической ремиссии - СТР). Лабораторные методы включали определение количества лимфоцитов с рецепторами CD3, CD4, CD8, СD16, с рецепторами к дофамину (D-RFC); содержание иммуноглобулинов М, G, А, уровня кортизола и циркулирующих иммунных комплексов (ЦИК) в сыворотке крови. Результаты. Основной иммуноэндокринный паттерн на всех этапах терапии синдрома отмены характеризуется дефицитом субпопуляций Т-лимфоцитов CD3, CD4, СD8; увеличением числа лимфоцитов с рецепторами к дофамину (D-RFC); активацией гуморальных факторов иммунитета (IgM, IgG, ЦИК); высокой концентрацией кортизола. На этапе ОАС и ПАС эти изменения были наиболее выражены; на 25-28-е сут. лечения отмечена позитивная динамика Т-лимфоцитов СD3 и цитотоксических Т-лимфоцитов (СD8); хелперы/индукторы CD4 оставались устойчиво сниженными; D-RFC лимфоциты, параметры гуморального иммунитета и концентрация кортизола - повышенными. Длительный срок наркотизации при употреблении высоких доз наркотика связан с большей выраженностью нарушений. Заключение. Установленная дизрегуляция параметров иммуноэндокринной системы у больных опийной наркоманией на всех этапах терапии синдрома отмены в наблюдаемые сроки (25-28 сут.) свидетельствует о неустойчивости достигнутой терапевтической ремиссии и необходимости проведения дальнейших реабилитационных мероприятий. The purpose: investigate changes in immunity parameters and cortisol level in subjects with opiate addiction during the treatment of opiate withdrawal syndrome. Methods. The study enrolled 136 subjects with opiate addiction with physical dependence receiving injections of opium extract. Patients received conventional therapy with complete opiate withdrawal. The study was performed at the following stages: at admission to the hospital (acute withdrawal syndrome (AWS); on days 5-7 of therapy (transition into post-withdrawal state - PWS); on days 25-28 of therapy (formation of therapeutic remission - FTR). Laboratory methods included determination count of lymphocytes with receptors CD3, CD4, CD8, СD16, with receptors to dopamine (D-RFC); the serum levels of IgМ, IgG, IgА, cortisol, circulating immune complexes (CIC). Results. The principal immunoendocrine pattern for all stages of withdrawal syndrome therapy is characterized in comparison to the reference normal values quantitative deficit of CD3, CD4, СD8 Т-lymphocyte subpopulations, increased count of lymphocytes with receptors to dopamine, activation of humoral immunity factors (IgM, IgG, CIC), high cortisol level. At AWS and PAS stages such changes are most pronounced; on days 25-28 of therapy positive changes in cytotoxic Т-lymphocytes (СD8) and Т-lymphocytes СD3 was revealed. CD4 count remained steadily reduced, count of lymphocytes with receptors to dopamine and cortisol level were elevated. Clinical and immunological analysis demonstrated that consumption of high opiate doses, long-term narcotization are associated with higher intensity of disorders detected. Conclusion. Dysregulation of immunoendocrine parameters was revealed in subjects with opiate addiction at all stages of withdrawal syndrome therapy within the term observed evidencing instability of therapeutic remission achieved and necessity in further rehabilitation events.


1979 ◽  
Vol 83 (1) ◽  
pp. 113-118 ◽  
Author(s):  
E. L. BITTMAN ◽  
B. D. GOLDMAN

SUMMARY Female hamsters rendered acyclic by exposure to short photoperiods (10 h light: 14 h darkness) showed diurnal surges of both LH and FSH which persisted after removal of the ovaries and adrenal glands. The reduced increase in gonadotrophin secretion after ovariectomy, typical of hamsters exposed to short days, was also not contingent upon the presence of the adrenal glands. The results demonstrate that 'supersensitivity' of the neuroendocrine axis to feedback of ovarian or adrenal steroids cannot fully account for either the daily surges of gonadotrophins or the diminished response of LH and FSH to ovariectomy in hamsters maintained on short days. It is suggested that these changes result instead from other pineal-mediated actions of short photoperiods upon the brain.


2019 ◽  
Vol 27 (1) ◽  
pp. 35-67
Author(s):  
Neven Ricijaš ◽  
Valentina Kranželić ◽  
Lorena Leskovar

Studies confirm that adolescents experiment with the use of psychoactive substances during their growth. The main motivational processes are related to their desire to behave in accordance with social norms, an identity of individuality, to escape from discomfort and self-regulation. Attitudes, beliefs, and knowledge about psychoactive substances have been linked with substance use behaviour, but showed weak to moderate correlation. The main goal of this study was to gain insight into the frequency of psychoactive substances consumption of young men with behavioural problems placed in educational institutions, while the specific objectives were to explore the differences in the frequency of substance use with regard to the type of institution as well as the level of knowledge about psychoactive substances A total of N=74 young men placed in the justice system institutions (39.2%) and social welfare institutions (60.8%) participated in the study. The age of the participants ranges from 14 to 21 years of age (Mage=16.90, SDage=1,627). In addition to general socio-demographic data, the instrument measured knowledge about psychoactive substances, as well as the lifetime and past-year prevalence and the frequency of consumption. The results show a somewhat more frequent psychoactive substances use among young men institutionalized within the justice system, but also among participants with a higher level of knowledge of psychoactive substances. It is important to emphasize that the effects of differences are low to moderate. The results are interpreted in the context of other domestic and foreign prevalence studies and within the perspective of the importance of knowledge in creating interventions for young people in the area of the prevention of psychoactive substances use.


2017 ◽  
Vol 313 (5) ◽  
pp. G410-G418 ◽  
Author(s):  
Matthew McMillin ◽  
Sharon DeMorrow ◽  
Shannon Glaser ◽  
Julie Venter ◽  
Konstantina Kyritsi ◽  
...  

Melatonin is a hormone produced by the pineal gland with increased circulating levels shown to inhibit biliary hyperplasia and fibrosis during cholestatic liver injury. Melatonin also has the capability to suppress the release of hypothalamic gonadotropin-releasing hormone (GnRH), a hormone that promotes cholangiocyte proliferation when serum levels are elevated. However, the interplay and contribution of neural melatonin and GnRH to cholangiocyte proliferation and fibrosis in bile duct-ligated (BDL) rats have not been investigated. To test this, cranial levels of melatonin were increased by implanting osmotic minipumps that performed an intracerebroventricular (ICV) infusion of melatonin or saline for 7 days starting at the time of BDL. Hypothalamic GnRH mRNA and cholangiocyte secretion of GnRH and melatonin were assessed. Cholangiocyte proliferation and fibrosis were measured. Primary human hepatic stellate cells (HSCs) were treated with cholangiocyte supernatants, GnRH, or the GnRH receptor antagonist cetrorelix acetate, and cell proliferation and fibrosis gene expression were assessed. Melatonin infusion reduced hypothalamic GnRH mRNA expression and led to decreased GnRH and increased melatonin secretion from cholangiocytes. Infusion of melatonin was found to reduce hepatic injury, cholangiocyte proliferation, and fibrosis during BDL-induced liver injury. HSCs supplemented with BDL cholangiocyte supernatant had increased proliferation, and this increase was reversed when HSCs were supplemented with supernatants from melatonin-infused rats. GnRH stimulated fibrosis gene expression in HSCs, and this was reversed by cetrorelix acetate cotreatment. Increasing bioavailability of melatonin in the brain may improve outcomes during cholestatic liver disease. NEW & NOTEWORTHY We have previously demonstrated that GnRH is expressed in cholangiocytes and promotes their proliferation during cholestasis. In addition, dark therapy, which increases melatonin, reduced cholangiocyte proliferation and fibrosis during cholestasis. This study expands these findings by investigating neural GnRH regulation by melatonin during BDL-induced cholestasis by infusing melatonin into the brain. Melatonin infusion reduced cholangiocyte proliferation and fibrosis, and these effects are due to GNRH receptor 1-dependent paracrine signaling between cholangiocytes and hepatic stellate cells.


Author(s):  
Charles Rodrigues

Abstract.Previous literature considers the existence of intellectual differences in children with ADHD when the parents are addicts to psychoactive substances. The aim of this work was to verify this intellectual difference between children with ADHD, with influence or not, of cocaine use by the father, during ovulation and fertilization of the mother. The sample was composed by 45 children, all male, with clinical diagnosis ADHD, accompanied on 12 educational institutions, 9 publics and 3 private, of the District of Lisbon. The sample was divided into two groups and subjected to quantitative assessment by applying the WISC III. The results present statistically significant differences, whereby we may conclude that there more intellectual’s difficulties in children with ADHD, when the father had cocaine use during ovulation periods and fertilization of the mother.Keywords: ADHD, cocaine, intelligence, ovulation, fertilization.Resumo.Literatura prévia considera a existência de diferenças intelectuais em crianças com PHDA quando o progenitor ou progenitores são adictos a substâncias psicoativas. O objectivo deste trabalho foi verificar esta diferença intelectual entre crianças com PHDA, com influência ou não, do consumo de cocaína por parte do progenitor, nos períodos de ovulação e fecundação da progenitora. A amostra foi composta por 45 crianças, todas do sexo masculino, com diagnóstico clínico PHDA, acompanhadas em 12 instituições escolares, 9 públicas e 3 privadas do Distrito de Lisboa. A amostra foi dividida em dois grupos e submetida a uma avaliação quantitativa efectuada através da aplicação da WISC III. Os resultados apresentam diferenças estatisticamente significativas, das quais se pode concluir que existem maiores dificuldades intelectuais em crianças com PHDA, quando o progenitor tenha efectuado consumo de cocaína nos períodos de ovulação e fecundação da progenitora.Palavras-chave: PHDA, cocaína, inteligência, ovulação, fecundação


2020 ◽  
Vol 5 (1) ◽  
pp. 1
Author(s):  
YOSEP SETIAWAN

Educational institution is an institution of the brain industry. Therefore, education is a vehicle for mental exercise. With education will be able to sharpen the brain to form human beings quality. Qualified people are intelligent human beings comprehensive and competitive savvy are reflected in personal moral, creative, and productive and full responsibility in living our daily lives. But the spotlight and complaints against educational institutions still occur, various perceived problems among students learn the lower interest. Students tend to subjects who tested nationally (National Examination), the methods used by teachers in teaching the more commonly used methods of lecture and question and answer, sometimes the discussion so that the lessons seem monotonous and less innovative, subjects received more students cederung nature doctrine in the form of memorization alone and rarely developed in the context of everyday life so that lessons just more leads to mastery of concepts and tend to train cognitive abilities-intellectual, not a lot of touching the realm of other intelligence in accordance with the potential of the students. The other problem is the tendency of the still rampant behavior is not commendable at this time in various forms, for example, students commit suicide because they do not pass the exam, involved in drugs, fighting between students, the behavior of cheating, careless, style punky, smoking, going out, and so become a reason for choosing this topic as study materials. The problem is what strengthens the belief writers to examine and assess the importance of the development of multiple intelligence through integrative learning-based game in an attempt to develop students' potential intelligence to realize a comprehensive and intelligent smart students competitive. This paper formulated into some discussion that begins with an introduction that lists reasons for the importance of this issue is discussed, and then forwarded to the review of the concept of multiple intelligence. Followed by a study on the definition, purpose and benefits of the games, the development of multiple intelligence through integrative learning-based games and ending with examples of games in integrative learning process.


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