Circuits Regulating Pleasure and Happiness in Schizophrenia: The Neurobiological Mechanism of Delusions

A recently developed model describes how evolutionary old neuronal systems allow free-moving animals, including humans, to escape from threats and discomfort and to acquire sufficient necessities to maintain life and to continue as a species. The amygdala has an essential role in regulating these fundamental reward-seeking and misery-fleeing behaviours. This is probably related to the ancient character of the corticoid and ganglionic parts of the amygdaloid complex. During evolution almost the entire ventral and lateral pallium (cortex) of the first vertebrates went up into the superficial and deep amygdalar nuclei, and their entire striatum and pallidum went up into the extended amygdala. An important role of the amygdala is selecting the sensory cues which are relevant for reward-seeking and misery-fleeing behaviour and should be paid attention to in order to increase the animal’s chances. This corresponds to attentive salience. Disturbances of this process in humans may lead to delusions. It has been suggested that in patients with schizophrenia this aberrant salience results from dopaminergic hyperactivity. The authors of this chapter believe that aberrant salience can result from dysfunctions everywhere within the chain: neocortex, corticoid amygdala, hippocampal complex, medial septum, medial habenula, midbrain nuclei and ventral tegmental area

Technology of Creation Periodic Structure on Surface Crystal of Paratellurite

In this paper presents the artificial periodic structures, first obtained by method of anisotropic etching the surface of single-crystal of paratellurite. The technology of this method is in detail presented in relation to paratellurite. The geometry of the structures was analyzed with an optical interferometric profiler NanoMap 1000 WLI

Technology of Creation Periodic Structure on Surface Crystal of Paratellurite

In this paper presents the artificial periodic structures, first obtained by method of anisotropic etching the surface of single-crystal of paratellurite. The technology of this method is in detail presented in relation to paratellurite. The geometry of the structures was analyzed with an optical interferometric profiler NanoMap 1000 WLI

Complementary addressed modification of oligonucleotide d(pGpGpCpGpGpA) with platinum derivative of oligonucleotide d(pTpCpCpGpCpCpTpTpT)

AbstractNew heterobifunctional reagent [BrPt(dien)—(CH2)6—(dien)Pt(H2O)]3+ (I) (− dien = diethylenetriamine residue) is proposed for preparation of complementary addressed reagents, reactive derivatives of oligonucleotides and polynucleotides. Two reactive groupings of (I) bind to oligonucleotides at different rates due to the higher reactivity of −[(dien)Pt(H2O)]2+ as compared to −[(dien)Pt Br]+. Using (I), bromodiethylenetriaminoplatinum group was attached to the oligonucleotide d(pTpCpCpGpCpCpTpTpT) (II) by rapid reaction of aquatriaminoplatinum group of (I) with guanosine residue of (II). The reactive oligonucleotide derivative III thus obtained was shown to modify predominantly 5′-terminal guanosine residue in the complementary oligonucleotide d(pGpGpCpGpGpA) (IV)

Конвергенция частного и публичного права в современном законодательстве Российской Федерации

Division of the right into branches is an exclusive gain of the Soviet doctrine. Any modern legal system didn't provide and doesn't provide such division. The private law in a general view is set of the legislatively-legal complexes regulating a civil turn. In this case it is a question of files of the legislation and the legal phenomena coordinated by it which basis we see in certificates.Разделение права на отрасли есть исключительное завоевание советской доктрины. Ни одна современная правовая система не предусматривала и не предусматривает такого деления. Частное право в общем виде является совокупностью законодательно-правовых комплексов, регулирующих гражданский оборот. В данном случае речь идет о массивах законодательства и соподчиненных им правовых явлениях, основу которых мы усматриваем в кодифицированных актах

Ассоциация полиморфных вариантов гена мозгового нейротрофического фактора (BDNF rs6265) и гена переносчика глутамата второго типа (SLC1A2 rs4354668) с течением рассеянного склероза у пациентов, проживающих в Томской области

Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that affects people of working age and ultimately leads to disability. This disease is of polygenic origin. The role of factors related to the pathogenesis of the disease and affecting both neuroinflammation and remyelination is studied. Aims: Our goal was to investigate the association of single nucleotide polymorphisms BDNF rs6265 and SLC1A2 rs4354668 with the risk of occurrence, clinical manifestations and the course of MS.Materials and methods: The study included 302 patients with MS, 268 healthy volunteers were enrolled in a control group. The obtained blood was used for DNA extraction by standard phenol-chloroform method. The identification of allelic variants of genes SLC1A2 (rs4354668) and BDNF (rs6265) was performed by polymerase chain reaction.Results: When comparing the frequencies of genotypes and alleles of polymorphic variants of BDNF and SLC1A2 genes between the groups of MS patients and the control group, no statistically significant differences were revealed. Comparison of genotype and allele frequencies of patients depending on sex, age of onset of the disease also did not reveal statistically significant differences. The study of the association of polymorphic variant of the gene BDNF (rs6265) with clinical manifestations of the disease revealed the association of genotype CC with oculomotor and trigeminal disorders at the onset of the disease (F=7, p=0.017). The study of the polymorphic variant rs4354668 of the glutamate transporter gene SLC1A2 revealed the association of allele G with an earlier (within 5 years from the moment of debut) transition of the disease to the stage of secondary progression, despite the therapy with DMT (χ2=5.940; p=0.010; OR 1.58; 95% CI 1.09−2.29). Homozygous genotype of TT (χ2=6.393; p=0.041; OR 0.50; 95% CI 0.28−0.88) and allele T (χ2=5.940; p=0.010; OR 0.63; 95% CI 0.44−0.92) of the polymorphism rs4354668 of the glutamate transporter gene SLC1A2 are significantly more common in the group of patients with late transition (15 years or more from the moment of debut) to the secondary progressive course.Conclusions: In our study we revealed the relationship of the studied polymorphic variants of genes with clinical signs at the onset of the disease and with the clinical manifestations of MS in patients living in the Tomsk region.Обоснование. Рассеянный склероз ― аутоиммунное заболевание нервной системы, поражающее людей трудоспособного возраста и приводящее в конечном итоге к инвалидизации. В последние годы наблюдается рост числа больных, связанный как с истинным увеличением заболеваемости, так и с качеством диагностики.Цель исследования ― оценка ассоциации однонуклеотидных полиморфных вариантов генов BDNF rs6265 и SLC1A2 rs4354668 с риском возникновения, клиническими проявлениями и течением рассеянного склероза.Методы. В исследование было включено 302 пациента с рассеянным склерозом, 268 здоровых добровольцев составили группу контроля. Пациенты находились на лечении в неврологической клинике Сибирского государственного медицинского университета. Определение аллельных вариантов генов SLC1A2 (rs4354668) и BDNF (rs6265) проводили методом полимеразной цепной реакции. Амплификацию и анализ результатов осуществляли с помощью приборов StepOnePlus и Quant Studio 5 (Applied Biosystems, США).Результаты. При сравнении частоты генотипов и аллелей полиморфных вариантов генов BDNF и SLC1A2 между группами пациентов с рассеянным склерозом и группой контроля статистически значимых различий не выявлено. Сравнение частоты генотипов и аллелей пациентов в зависимости от пола, возраста начала заболевания также статистически значимых различий не выявило. При исследовании связи полиморфного варианта гена BDNF (rs6265) с клиническими проявлениями болезни найдена ассоциация генотипа СС с глазодвигательными и тригеминальными расстройствами в дебюте заболевания (F=7; p=0,017). При исследовании полиморфного варианта rs4354668 гена глутаматного транспортера SLC1A2 выявлена ассоциация аллеля G с более ранним (в течение 5 лет от момента дебюта) переходом заболевания в стадию вторичного прогрессирования, несмотря на терапию препаратами, изменяющими течение рассеянного склероза (χ2=5,940; р=0,010; OR 1,58; 95% CI 1,09−2,29). Гомозиготный генотип ТТ (χ2=6,393; р=0,041; OR 0,50; 95% CI 0,28−0,88) и аллель Т (χ2=5,940; р=0,010; OR 0,63; 95% CI 0,44−0,92) полиморфизма rs4354668 гена глутаматного транспортера SLC1A2 статистически значимо чаще встречаются в группе пациентов с поздним переходом (через 15 и более лет от момента дебюта) во вторично-прогрессирующее течение.Заключение. В нашем исследовании выявлена связь изучаемых полиморфных вариантов генов с клиническими признаками в дебюте заболевания и с особенностью течения заболевания у пациентов, проживающих на территории Томской области

COMT gene polymorphism and antipsychotic-induced hyperprolactinemia in schizophrenia patients

Hyperprolactinemia (HPRL) is considered to be a frequent and typical adverse drug reaction caused by antipsychotic medications first and foremost due to excessive dopamine D2 receptors blockade. The aim is to study the set of polymorphisms of genes encoding neurotransmitter synthesis and metabolism enzymes COMT, TPH1 and TPH2 in schizophrenia inpatients. A comprehensive examination of 446 schizophrenia inpatients, aged 18-75 years, was conducted. Genotyping of DNA samples in patients with or without HPRL was carried out for 14 polymorphisms of COMT, TPH1, and TPH2 genes. We revealed an association between carriership of the COMT rs165774* G allele and HPRL. As a result of the study, a regression model was designed to predict the risk of developing HPRL in schizophrenia inpatients, taking into account age, gender, and treatment duration, the dosage of drugs in chlorpromazine equivalents as independent covariates and genotypes of the studied polymorphisms

Glutamate Concentration in the Serum of Patients with Schizophrenia

Glutamate is the major neurotransmitter with multiple functions in the central nervous system. Glutamate-mediated excitotoxicity is involved in the pathophysiological processes in schizophrenia. The purpose of this study was to determine the concentration of glutamate in the serum of patients with paranoid schizophrenia compared with healthy individuals, and depending on the duration of the schizophrenic process and leading clinical symptoms. We investigated the level of glutamate in the serum of 158 patients with paranoid schizophrenia and 94 healthy persons. Higher concentrations of glutamate in schizophrenic patients compared with healthy persons have been found. The maximum concentrations of glutamate were detected in patients with disease duration of more than ten years. Glutamate level in the serum does not depend on the prevailing negative or positive clinical symptoms. The increased concentration of glutamate can hypothetically contribute to dopaminergic and glutamatergic imbalance, leading to the development of psychotic symptoms and cognitive dysfunction