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Intranasal administration of antibodies to glutamate for 14 days improved passive avoidance conditioning and reduces the content of IL-6 within 7 days after their withdrawal in the prefrontal cortex and hippocampus of aging C57BL/6 mice., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: The authors declare no conflict of interest.

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., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: The authors declare no conflict of interest.

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.

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., Competing Interests: The authors declare no conflict of interest.

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.

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., Competing Interests: The authors declare no conflict of interest.

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., Competing Interests: The authors declare no conflict of interest.

Amyloid formation and neuroinflammation are major features of Alzheimer's disease pathology. Proinflammatory mediator S100A9 was shown to act as a link between the amyloid and neuroinflammatory cascades in Alzheimer's disease, leading together with Aβ to plaque formation, neuronal loss and memory impairment. In order to examine if S100A9 alone in its native and amyloid states can induce neuronal stress and memory impairment, we have administered S100A9 species intranasally to aged mice. Single and sequential immunohistochemistry and passive avoidance behavioral test were conducted to evaluate the consequences. Administered S100A9 species induced widespread cellular stress responses in cerebral structures, including frontal lobe, hippocampus and cerebellum. These were manifested by increased levels of S100A9, Bax, and to a lesser extent activated caspase-3 immunopositive cells. Upon administration of S100A9 fibrils, the amyloid oligomerization was observed in the brain tissues, which can further exacerbate cellular stress. The cellular stress responses correlated with significantly increased training and decreased retention latencies measured in the passive avoidance test for the S100A9 treated animal groups. Remarkably, the effect size in the behavioral tests was moderate already in the group treated with native S100A9, while the effect sizes were large in the groups administered S100A9 amyloid oligomers or fibrils. The findings demonstrate the brain susceptibility to neurotoxic damage of S100A9 species leading to behavioral and memory impairments. Intranasal administration of S100A9 species proved to be an effective method to study amyloid induced brain dysfunctions, and S100A9 itself may be postulated as a target to allay early stage neurodegenerative and neuroinflammatory processes.

Alzheimer's disease (AD) involves dementia conceivably arising from integrated inflammatory processes, amyloidogenesis, and neuronal apoptosis. Glutamate can also cause neuronal death via excitotoxicity, and this is similarly implicated in some neurological diseases. The aim was to examine treatment with in vitro generated proinflammatory protein S100A9 aggregate species alone or with glutamate antibodies (Glu-Abs) on Morris water maze (MWM) spatial learning and memory performance in 12 month old mice. Amino acid and monoamine cerebral neurotransmitter metabolic changes were concurrently monitored. Initially, S100A9 fibrils were morphologically verified by atomic force microscopy and Thioflavin T assay. They were then administered intranasally alone or with Glu-Abs for 14 days followed by a 5 day MWM protocol before hippocampal and prefrontal cortical neurochemical analysis. S100A9 aggregates evoked spatial amnesia which correlated with disrupted glutamate and dopaminergic neurochemistry. Hippocampal glutamate release, elevation of DOPAC and HVA, as well as DOPAC/DA and HVA/DA ratios were subsequently reduced by Glu-Abs which simultaneously prevented the spatial memory deficit. The present outcomes emphasized the pathogenic nature of S100A9 fibrillar aggregates in causing spatial memory amnesia associated with enhanced hippocampal glutamate release and DA-ergic disruption in the aging brain. This finding might be exploited during dementia management through a neuroprotective strategy.

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.

Memory deficits may develop from a variety of neuropathologies including Alzheimer's disease dementia. During neurodegenerative conditions there are contributory factors such as neuroinflammation and amyloidogenesis involved in memory impairment. In the present study, dual properties of S100A9 protein as a pro-inflammatory and amyloidogenic agent were explored in the passive avoidance memory task along with neurochemical assays in the prefrontal cortex and hippocampus of aged mice. S100A9 oligomers and fibrils were generated in vitro and verified by AFM, Thioflavin T and A11 antibody binding. Native S100A9 as well as S100A9 oligomers and fibrils or their combination were administered intranasally over 14 days followed by behavioral and neurochemical analysis. Both oligomers and fibrils evoked amnestic activity which correlated with disrupted prefrontal cortical and hippocampal dopaminergic neurochemistry. The oligomer-fibril combination produced similar but weaker neurochemistry to the fibrils administered alone but without passive avoidance amnesia. Native S100A9 did not modify memory task performance even though it generated a general and consistent decrease in monoamine levels (DA, 5-HT and NA) and increased metabolic marker ratios of DA and 5-HT turnover (DOPAC/DA, HVA/DA and 5-HIAA) in the prefrontal cortex. These results provide insight into a novel pathogenetic mechanism underlying amnesia in a fear-aggravated memory task based on amyloidogenesis of a pro-inflammatory factor leading to disrupted brain neurochemistry in the aged brain. The data further suggests that amyloid species of S100A9 create deleterious effects principally on the dopaminergic system and this novel finding might be potentially exploited during dementia management through a neuroprotective strategy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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.

Alpha-synuclein (α-syn) toxic aggregates delivered by the nasal vector have been shown to modify the neurochemistry of dopamine (DA) which is associated with parkinsonian-like motor symptoms. The aim was therefore to study the intranasal effects of α-syn oligomers, fibrils or their combination on the motor behavior of aged mice in relation to possible noradrenergic and serotonergic correlates. In vitro generated α-syn oligomers and fibrils were verified using atomic force microscopy and the thioflavin T binding assay. Levels of noradrenaline (NA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were detected using HPLC with electrochemical detection in the substantia nigra (SN) and striatum. The oligomers or fibrils administered alone or in a 50:50 combination (total dose of 0.48 mg/kg) were given intranasally for 14 days and "open-field" behaviour was tested on days 0, 15 and 28 of the protocol, at which time brain structures were sampled. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e. 14 days after treatment completion) induced hypokinesia and immobility whilst the aggregate combination additionally produced rigidity. The α-Syn oligomer/fibril mixture also instigated PD-like motor symptoms which correlated heterochronically with elevated NA levels in the striatum but then later in the SN while intranasal fibrils alone augmented 5-HT and 5-HIAA nigral concentrations throughout the protocol. In contrast, α-syn oligomers displayed a delayed serotonin upsurge in the SN. Neurodegenerative and/or actions on neurotransmitter transporters (such as NET, SERT and VMAT2) are discussed as being implicated in these α-syn amyloid induced neurochemical and motoric disturbances., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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".

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.

Parkinson's disease (PD) is a neurodegenerative disorder in which both alpha-synuclein (α-syn) and dopamine (DA) have a critical role. Our previous studies instigated a novel PD model based on nasal inoculation with α-syn aggregates which expressed parkinsonian-like behavioral and immunological features. The current study in mice substantiated the robustness of the amyloid nasal vector model by examining behavioral consequences with respect to DA-ergic neurochemical corollaries. In vitro generated α-syn oligomers and fibrils were characterized using atomic force microscopy and the thioflavin T binding assay. These toxic oligomers or fibrils administered alone (0.48 mg/kg) or their 50:50 combination (total dose of 0.48 mg/kg) were given intranasally for 14 days and "open-field" behavior was tested on days 0, 15 and 28 of the protocol. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e., 14 days after treatment completion) induced rigidity, hypokinesia and immobility. This was accompanied by elevated nigral but not striatal DA, DOPAC and HVA concentrations in response to dual administration of α-syn oligomers plus fibrils but not the oligomers by themselves. α-Syn fibrils intensified not only the hypokinesia and immobility 14 days post treatment, but also reduced vertical rearing and enhanced DA levels in the substantia nigra. Only nigral DA turnover (DOPAC/DA but not HVA/DA ratio) was augmented in response to fibril treatment but there were no changes in the striatum. Compilation of these novel behavioral and neurochemical findings substantiate the validity of the α-syn nasal vector model for investigating parkinsonian-like symptoms., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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 β-amyloid fragment Aβ25-35 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.

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.

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.

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.

Experiments on rats have showed that neurodegenerative damage to the brain induced by injection of a neurotoxic β-amyloid protein fragment β25-35into the basal giant cell nuclei of Meynert activated caspase-3 in the prefrontal cortex and hippocampus on day 3 after injury. Intranasal administration of antibodies to glutamate in a dose of 300 μ g/kg 1 h after damage reduced enzyme activity in these structures in a rat model of Alzheimer's disease.

In experiments on rats showed that intranasal administration of glutamate antibodies in a dose of 300 microg/kg after 1 h after bilateral injection of neurotoxic fragment of beta-amyloid protein (25-35)--Abeta(25-35)--into the Meynert nuclei restores learning ability in the test of passive avoidance on 3 and 14 days of the experiment. Antibodies to glutamate decrease significantly increasing caspase 3 activity, detected on Day 3 after injection of Abeta(25-35), in samples of the prefrontal cortex and hippocampus but not hypothalamus. Intranasal administration of gamma-globulin had no effect on the performance of violations of mnestic functions and caspase 3 activity.

The intranasal administration of glutamate antibodies in the dose of 300 microg/kg one hour after damage on the level of mRNA expression of Dffb gene which codes caspase-activated DNase which participates in intranucleosome fragmentation of genome DNA in apoptosis was investigated in experimental Alzheimer's disease induced by injection of neurotoxic fragment of beta-amyloid protein Abeta25-35 in Meynert basal magnocellular nuclei on rats. On the Day 3 after Abeta25-35 injection is observed significant decrease of the level of mRNA expression of Dffb gene in prefrontal cortex in 37%, and in hippocampus in 62% in the experiment group versus the control group. These differences were not found in the hypothalamus when comparing the experimental and control animals. It was suggested that repressive effect of glutamate antibodies on the level of mRNA expression of Dffb gene reflects stabilization of processes taking place in brain cells in experimental Alzheimer's disease, and in its turn the intensiveness of nerve and glial cells apoptotic death is decreased.

It was stated, that with bilateral photochemically induced thrombosis of the prefrontal cortex peptide semax and the AB-Glu by intranasal injection provoke pronounced neuroprotective and antiamnestic action. Intranasal injection semax (250 mkg/kg/daily during six postoperative days) and AB-Glu (250 mkg/kg in 1 hour after phototrombosis) demonstrate diminishing of cortex damage volume and relieve preservation and reproduction rat passive avoidance reflex, acquired before bilateral photochemically induced thrombosis of prefrontal cortex.

Experiments on the model of bilateral photothrombosis in the prefrontal cortex showed that antibodies to glutamate administered intranasally 1 h after ischemic damage to the brain cortex led to a decrease in glutamate content in the hippocampus and prefrontal cortex and had no effect on aspartate concentration in these structures of the brain.

This paper describes the strategy for pregnancy and labour management in women with the history of myocardial infarction after multiple stenting of coronary arteries using stents with cytostatic coating. The authors discuss a broad range of diseases underlying coronary lesions in young pregnant women receiving antiaggregation therapy. Neither multiple stenting nor intake of aspirin and ticlopid provoked teratogenic effect.

Complex evaluation neurotrophic protein S100b, differentiation factor HLDF, idio-and antiidiotypic antibodies against these proteins in patient sera with hypertension-induced cerebrovascular disorders was performed by ELISA. In patients with essential hypertension, cerebral hypertensive crisis and ischemic stroke S100b and anti-S100b concentration was found to be higher, whereas HLDF and anti-HLDF ones were lower compared with control. Different dynamics of S100b, HLDF content and antibody level was shown within 21 days of observation. These findings may be useful in further diagnostic and prognostic studies of hypertension-induced cerebrovascular disorders.