Effect of Glutamate Antibody F(ab)2 Fragments on Memory Changes in Aged C57BL/6 Mice.

Intranasal administration of F(ab)2 fragments of anti-glutamate antibodies to 12-month-old C57BL/6 mice improves passive avoidance conditioning and have no effect on horizontal and vertical locomotor activity in the open-field test. In contrast to full-length antibodies to glutamate, their F(ab)2 fragments significantly increase the number of animals developed a conditioned passive avoidance reflex.

Cerebral Expression of the Neuregulin-1 Gene NRG1 during Induced Spatial Memory Impairment and Its Reversal in Aging Mice.

We studied the effects of chronic intranasal administration of amyloidogenic fibrils of the proinflammatory protein S100A9 alone or in combination with glutamate antibodies on the expression of the neuregulin-1 gene (NRG1), a regulator of various physiological processes, in particular, regulation of neurogenesis and apoptosis, in the hippocampus, prefrontal cortex, and cerebellum of aging C57BL/6 mice under conditions of long-term memory disturbances. Under conditions of amnesia induced by S100A9 fibrils, pronounced (>90%) blockade of the expression of the NRG1 gene was found in all cerebral structures. Glutamate antibodies prevented/corrected disturbances in the cerebral expression of the NRG1 gene, thereby maintaining the activity of the NRG1/ErbB molecular signaling system, probably associated with the formation of spatial memory.

Assessment of iron metabolism disorders and adequate treatment of anemic syndrome in patients with breast cancer on the background of adjuvant chemotherapy.

Early and adequate correction of the anemic syndrome (AS) of cancer patients can prevent deterioration in the quality of life and be considered as a reserve for increasing the effectiveness of treatment for breast cancer (BC). The aim of the study was to assess the status of iron using modern methods of ferrokinetics in breast cancer patients on the background of adjuvant chemotherapy for early diagnosis and adequate treatment of AS. The object of the study included 21 breast cancer patients with a relatively favorable prognosis, with luminal types A and B (Her 2 / neu positive or negative), three times negative type. The examination was carried out in the postoperative period, against the background of adjuvant chemotherapy. The main metabolites of ferrokinetics were studied: hepcidin 25 (GP25); ferritin (FR); soluble transferrin receptors (rRTP); transferin (TRF); iron (Fe); erythropoietin (EPO); CRP and IL-6 indicators. AC correction was performed (ferinject, epotin-alpha, B12). 10 (47.6%) patients with breast cancer had AS. Most of them were diagnosed with IDA with microcytic, hypochromic characteristics of erythrocytes, low concentration of FR, Fe, GP25, IL-6, CRP, and high levels of TRP and rRTP. Functional iron deficiency (FDF) was established in some patients. In contrast to patients with IDA, they had a high concentration of FR, CRP and significant production of GP25, IL-6. The EPO level was not optimal for the majority of patients with AS. In isolated cases, during treatment with recombinant erythropoietins, a deficiency of vitamin B12 (cyanocobalamin) was revealed. The rational use of iron preparations, vitamins, and recombinant forms of EPO made it possible to restore Fe metabolism, stabilize the hemoglobin level, and also improve the condition of most breast cancer patients. The obtained data on IL-6, GP25, CRP indicate a certain relationship between them in the development of anemia with VDF in breast cancer patients and the need for further study of the characteristics of iron metabolism in cancer patients.

Effects of Antibodies to Glutamate on Cerebral Expression of the Tnfrsf1A Gene under Conditions of Spatial Amnesia Induced by Proinflammatory Protein S100A9 Fibrils in Aging Mice.

Proinflammatory S100A9 protein is a promoter of inflammation-linked neurodegeneration and the Tnfrsf1A gene encodes the TNF receptor 1A that binds TNFα to function as a regulator of inflammation. We studied the effects of chronic intranasal administration of in vitro prepared S100A9 fibrils alone or in combination with anti-glutamate antibodies on the expression of the Tnfrsf1A gene in the hippocampus, prefrontal cortex, and cerebellum of aging C57BL/6 mice under conditions of impaired spatial memory. A differential cerebral pattern of Tnfrsf1A gene activity and its modification by S100A9 fibrillar structures were observed: inhibition of Tnfrsf1A gene expression in the hippocampus and cerebellum and its activation in the prefrontal cortex. Anti-glutamate antibodies normalized the expression of the Tnfrsf1A gene in the prefrontal cortex by affecting the TNF signaling pathway and preventing the development of inflammation.

Correlation of Antibodies to Neurotransmitters in the Sera of Women with Alcohol Dependence and Depressive Disorders.

Comparative analysis of blood sera from women with alcohol dependence and depressive disorders or from conditionally healthy women revealed reduced level of antibodies to dopamine, norepinephrine, serotonin, glutamate, and GABA in blood serum in women with dysthymic disorder and a depressive episode and their increased content in women with alcohol dependence in combination with depressive disorders.

Delayed Behavioral and Neurochemical Effects of Anti-Glutamate Antibodies in Aging C57BL/6 Mice.

We analyzed delayed effect of intranasal administration of anti-glutamate antibodies on mnestic function and tissue concentrations of neurotransmitters in the hippocampus and prefrontal cortex in aging C57BL/6 mice. It was found that after 14-day administration of anti-glutamate antibodies, improvement of the passive avoidance conditioning persisted for 7 days after the treatment was discontinued. In 7 days after discontinuation of treatment, increased content of dopamine and its metabolites as well as aspartic acid and taurine was observed in the hippocampus of mice treated with anti-glutamate antibodies. In the prefrontal cortex, administration of anti-glutamate antibodies had no effect on the levels of neurotransmitters, but increased the concentration of glutamate.

The role of interleukin-6 and hepcidin 25 in the pathogenesis of anemic syndrome associated with malignant neoplasms with breast cancer patients before neoadjuvant chemotherapy.

A study of interleukin-6 (IL-6), hepcidin-25 (GP-25) was conducted in 22 patients with breast cancer before neoadjuvant chemotherapy and in 27 healthy women in the control group. Significant expression of the GP-25 protein was revealed in breast cancer patients, compared to control. The rates were high both in patients with anemic sindrome (AS) and without it (p <0.01). Latent iron deficiency, AS, IDA and functional iron deficiency (FJ) were more often detected in patients with stage III disease. A significant difference in the parameters of GP-25 and IL-6 was noted, the indicators were higher in patients with stage III (p <0.01). No close correlation was found between IL-6, GP-25 and other acute-phase proteins (FR, CRP) at the initial stages of AS formation. On the contrary, a positive correlation was observed in patients with IDA and FJ between IL-6 and all acute-phase proteins (GP-25, FR, CRP). However, a small number of observations do not allow an unambiguous conclusion about the role of IL-6 and GP-25 expression in the development of AS in cancer patients with breast cancer and requires further study.

Antibodies to Glutamate Facilitate Spatial Memory Formation in the Morris Water Maze in Aging C57BL/6 mice.

Intranasal administration of antibodies to glutamate in a dose of 250 µg/kg for two weeks facilitated spatial learning and memory formation in the Morris water maze in aging C57BL/6 mice. In animals treated with glutamate antibodies, the content of serotonin and dopamine metabolites 3-MT and HVA in the hippocampus decreased, but no changes in the metabolism of neurotransmitter acids were revealed. In the prefrontal cortex, dopamine level decreased and the content of its metabolite DOPAC increased; in parallel, an increase in excitatory and inhibitory amino acids (aspartic acid, glutamate, glycine, taurine, and GABA) was observed.

[Characterization of anemic syndrome in cancer patients with sepsis in the early postoperative period.]

A study of the main indicators of red blood (RBC, HGB, HCT, MCV, MCH) and the concentration of EPO, sTfR in 9 cancer patients with anemic syndrome (AS) against sepsis was carried out. Among them, patients with chronic disease anemia (ACh), with normocytic, normochromic characteristics of red blood cells and low hematocrit predominated. In 2 patients, microcytosis and erythrocyte hypochromia were noted, the concentration of sTfR was significantly higher than normal (0.9 ± 0.07 µg / ml), amounted to 2.7 µg / ml in one of them and 1.9 µg / ml in the other, which testified to t iron deficiency erythropoiesis (IDE) on the background of the ACh,. In 7 patients with ACh without IDE, sTfR values were within the normal range (0.1-1.2) µg / ml, the median was 0.5 µg/ml. In all patients with sepsis, the production of EPO was inadequate for the severity of the AS, to a lesser extent in patients with IDE. The average EPO production in the group was 19.4 ± 5.1 (7.7-52.8) mU / ml, median = 12.1 mE / ml. Further studies of EPO, sTfR are planned in order to determine their role in therapeutic tactics in the correction of AS in cancer patients with sepsis.

[Modern ferrokinetics metabolites in the diagnostics of anemic in patients with disseminated stages of Hodgkin's lymphoma when conducting intensive chemotherapy.]

Evaluation of anemic syndrome (AS) was performed in 79 patients with advanced stages of Hodgkin's lymphoma (LH) at various stages of chemotherapy (CT) according to the EACOPP-14 scheme. Against the background of the treatment, the number of erythrocytes and, accordingly, the HCT indices decreased with each subsequent cycle of chemotherapy (CTC) and reached the maximum reduction to 5, 6 th CCT. Absolute iron deficiency (IDA), which was combined with a low level of EPO and an inadequate degree of anemia, was found in a few LH patients (5 people, 6.3%). Functional iron deficiency (FDZH) was diagnosed in 9 patients (11.4%), had the same morphological signs as IDA. Namely, microcytosis, erythrocyte hypochromia and low hemoglobin content in reticulocytes (RET-HE). In contrast to IDA, patients with FDZh concentration of FR, GP-25 and IL-6 were high. Despite the fairly large reserves of iron, the level of rRTF testified to the "iron hunger" of the erythrocariocytes of the bone marrow, its index exceeded the upper limit of the norm, while RET-HE was low. In 34 (43%) patients, LH revealed a deficiency of endogenous erythropoietin (EPO), which was observed not only in patients with AHZ, but also in patients with IDA. Lower levels of EPO were detected in patients with leukopenia and very low erythropoietic activity of the bone marrow.

[Development of strategic approaches to modern diagnosis of anemic syndrome in patients with breast cancer.]

A study of the clinical analysis of blood and major metabolites of ferrokinetics in 107 breast cancer patients before treatment was conducted. In 31 (28.9%) patients revealed anemic syndrome (AS). A feature of the AS is pronounced microcytosis, erythrocyte hypochromia and low hemoglobin content in reticulocytes. Most often (n = 22; 71%) there was iron deficiency (IDA), which was characterized by a low concentration of iron (F), ferritin (FR), hepcidin 25 (GP25), interleukin-6 (IL-6) and high - soluble transferrin receptors (rTFR), transferrin (TRF). In 9 (29%) patients with AS, on the basis of a high concentration of FR, GP25, IL-6, the anemia of chronic disease (AHZ) with functional iron deficiency (FDI) was established. In 23 (74.2%) patients with AS, the was a deficiency of erythropoietin (EPO), the lowest rates were found in the group of patients with a common tumor process and FDI, with less in patients with IDA.

Effect of Antibodies to Glutamate on Age-Related Memory Changes in C57Bl/6 Mice.

Chronic intranasal administration of antibodies to glutamate to aging C57Bl/6 mice improved passive avoidance conditioning, had no effect on horizontal and vertical locomotor activity, but slowed locomotion in the open-field test. Administration of antibodies to glutamate increased the content of dopamine and its metabolites in mouse hippocampus, but had no effect on the metabolism of neurotransmitter amino acids. In the frontal cortex, antibodies to glutamate did not affect neurotransmitter metabolism, but increased the level of both excitatory and inhibitory amino acids without changing their ratio.

Antibodies to Glutamate Reversed the Amnesic Effects of Proinflammatory S100A9 Protein Fibrils in Aged C57Bl/6 Mice.

Chronic intranasal administration of fibrillar structures of proinflammatory S100A9 protein impaired passive avoidance learning in old C57Bl/6 mice. Combined treatment with S100A9 fibrils and antibodies to glutamate was followed by an increase in horizontal locomotor activity of animals in the open-field test and did not disturb spatial memory.

[Results of December joint plenum of Russian Scientific Society of pathophysiology and Scientific Council on general pathology and Pathophysiology. New areas of research in the pathophysiology].

Contains information on the joint plenum of Russian scientific society of pathophysiology and Scientific Council on General Pathology and Pathophysiology, held 17-18 December 2014 in Moscow at the FSBSI "Institute of General Pathology and Pathophysiology".

[Autoantibodies to glutamate and GABA in opiate addiction].

Blood serum from 129 patients with opium addiction at different stages of the disease and 63 donors (control group) was examined for the presence of autoantibodies to the exciting and inhibitory amino acids glutamate and GABA. It was shown enhanced production of autoantibodies to glutamate and GABA. Dependence of the level and frequency of detec- tion of autoantibodies to glutamate and GABA on the stage of the disease was revealed.

Ratio of antibodies to neurotransmitters in the serum of students, occasional drug users.

The survey included volunteer students of secondary and higher educational institutions. Two groups have been formed based on the results of clinical and laboratory studies. Group 1 comprised students occasionally using cannabinoids and amphetamines (risk group for psychoactive substances addiction) and group 2 included students who do not use drugs. The serum level of autoantibodies to norepinephrine, dopamine, and serotonin was reduced in the risk group.

[The influence of glutamate antibodies on the level of neurotransmitter monoamines in brain structures of rats with ischemic damage of prefrontal cortex].

Experiments on the model of bilateral photothrombosis in prefrontal cortex showed that antibodies to glutamate one-time administered intranasally 1h after ischemic damage to the brain cortex lead to decrease of neurodegenerative influence of excitatory neurotransmitter after photothrombosis. It was showed the change of the level of dopamine, serotonin and their metabolites in hippocampus and prefrontal cortex.

[Protective action of glutamate antibodies on increased expression of genes of programmed death of rat brain cells induced by injection of a ß-amyloid fragment (25-35)].

Glutamate antibodies intranasally administered to Wistar rats at a dose of 300 µg/kg reduced the elevated levels of expression of Aifml, Casp3, and Parp 1 genes in the prefrontal cortex and Aifml and Casp3 genes in the hippocampus on the third day after administration of the ß-amyloid fragment Aß25-35 into the Meynert nuclei of the brain. Changes in Aifm1, Bax, Casp3, and Parp 1 gene expression were not found in the hypothalamus, and changes in Bax gene expression were not found in the brain structures studied. The discovered features of gene expression in the prefrontal cortex and hippocampus are considered in terms of development of various cell-death programs, which are modulated by glutamate antibodies.

[The saving role of glutamate antibodies with the acute ischemic damage of the rat brain prefrontal cortex].

On the model of acute ischemic damage of prefrontal areas of the rats brain cortex was shown, that intranasal injection of glutamate antibodies over one hour after ischemic damage of brain prefrontal areas leads to diminishing of glutamate content in hippocampus and prefrontal cortex.

[Antibodies to neurotransmitters as possible neuroimmune risk markers of formation dependence to psychoactive substances].

In the sera of patients with opioid addiction has been found elevated levels of autoantibodies to the neurotransmitters dopamine, norepinephrine and serotonin in comparison with a control group of healthy people of the same age. In the group of patients with acute withdrawal was showed a reduction of antibody to dopamine, noradrenaline and serotonin in the blood serum when compared with patients in the period of postabstinent disorders. In the group of patients with risk for the formation of substance dependence in serum was observed decrease in autoantibodies to dopamine and norepinephrine compared with the control group.