Immunohistochemical Analysis of Mitochondrial Dynamics in Different Zones of the Hippocampus during Experimental Modeling of Alzheimer's Disease.

We performed a comparative assessment of the immunohistochemical distribution of markers of mitochondrial fission (Drp-1), mitochondrial fusion (Mfn-2), and mitochondrial biogenesis (PGC-1α) in pyramidal neurons of different zones of the hippocampus in mice with intrahippocampal administration of ß-amyloid peptide 25-35. The most pronounced changes in the dynamics associated with a decrease in the amount of the fission marker and an increase in the amount of the fusion marker were observed in the CA3 field on day 38 after peptide administration. In the CA1 field, a significant decrease in the marker of mitochondrial biogenesis PGC-1α was found on day 38, which can indicate a decrease in the intensity of mitochondrial biogenesis. Early mitochondrial changes can play an important role in the pathogenesis of all types of memory impairment in Alzheimer's disease.

[Morphological characteristics of the brain nervous tissue during aging]. / Morfologicheskaya kharakteristika nervnoi tkani golovnogo mozga pri starenii.

OBJECTIVE: Identification of morphological manifestations and evaluation of morphometric parameters of the nervous tissue in various structures of the human brain during aging. MATERIAL AND METHODS: Autopsy material was obtained from patients whose causes of death were not associated with neurological diseases. Three age groups were studied: young (35-45 years old) (n=10); eldery (75-89 years old) (n=20); centenarians (over 90 years old) (n=10). Quantitative analysis of large neurons in the compact part of the substantia nigra, basal ganglia, layer V of the cortex, and the pyramidal layer of the hippocampus was carried out. In addition, the brain mass, the thickness of the cortex of the precentral gyrus were measured, the glial index was calculated, and the morphological signs of age-related involution of the brain tissue and intracerebral vessels were assessed. RESULTS: In senile and centenarians, compared with young people, there was a progressive reduction in large neurons of layer V of the cortex, basal ganglia, the pyramidal layer of the hippocampus and substantia nigra, a decrease in brain mass and thickness of the cortex of the precentral gyrus, as well as an increase in the glial index. Changes in blood vessels characteristic of aging are described. Also, during aging, signs characteristic of neurodegeneration were found. CONCLUSION: The results of the study confirm that such brain structures as the cortex of the precentral gyrus, the hippocampus, the basal ganglia, and the substantia nigra lose large neurons with age, followed by the development of gliosis. The identified morphological changes characteristic of aging are phenomenologically similar to a certain set of morphological changes in neurodegenerative diseases of late age.

[Molecular Mechanisms of Interactions between Mitochondria and the Endoplasmic Reticulum: A New Look at How Important Cell Functions are Supported].

Interactions between the endoplasmic reticulum (ER) and mitochondria have received insufficient attention until recently. However, distorted contacts between the ER and mitochondria were identified as an important factor in the etiopathogenesis of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In view of these new data, the mechanisms of ER-mitochondrial interactions are necessary to study in detail in order to develop new diagnostic and therapeutic approaches to neurodegenerative diseases and to extend basic knowledge of the physiology of the eukaryotic cell. The review focuses on the functions of mitochondria-associated ER membranes (MAMs). Structural elements of the MAM system, their contributions to the vital cell functions (calcium and lipid homeostasis, autophagy, fusion and division of mitochondria, and the regulation of their number), and the role of MAM dysfunctions in the pathogenesis of various neurodegenerative diseases are considered.

[THE DIAGNOSTICS OF HEREDITARY DISORDERS OF METABOLISM OF PURINES AND PYRIMIDINES IN CHILDREN USING HIGH PERFORMANCE LIQUID CHROMATOGRAPHY OF ELECTRO-SPRAY TANDEM MASS-SPECTROMETRY].

The article presents data concerning new technique of diagnostic of diseases of metabolism of purines and pyrimidines using high performance liquid chromatography combined with electro-spray mass-spectrometry. The procedure of analysis is described in detail: from pre-analytical stage to interpretation of data of liquid chromatography mass-spectrometry, control of quality of data analysis, mass-spectrometry parameters and chromatographic conditions of analysis of purines, pyrimidines and their metabolites. The reference values are presented for purine and pyrimidine nucleosides and bases in urine of healthy individuals. The chemical structure of purines, pyrimidines and their metabolites and examples of chromato-mass-spectrograms under various hereditary disorders of metabolism of purines and pyrimidines are presented as well. The article is targeted to pediatricians of all profiles, medical geneticists and physicians of laboratory diagnostic.

[The hypoxic syndrome in children with cardiomyopathy].

The children with inherited cardiopathy including hypersensitive (n = 85) and dilatation (n=10) cardiopathy as well as cardiopathy under Ehlers-Danlos Syndrome (n = 70) combined with different inherited heart disease were examined to establish signs of hematic and tissue hypoxia. The most typical signs turned out periodic decrease of blood pCO2 with increasing of content of lactate and pyruvate in blood and saliva, multiple caries of teeth and high rate of systemic hypoplasia of enamel of both temporary and permanent teeth. The study established decrease in blood of level of macro-ergic compounds (ATP, ADF AMP) with increasing of excretion calcium and phosphates with urine. The increase of rate of mutations of hypoxanthine guanine phosphoribosyltransferase in lymphocytes with increasing of content of uric acid in blood and/or in urine was detected. The study revealed increasing of processes of peroxide oxidation, alterations of morphology of cells of skeletal muscles (RRF) and accumulation ofcalcium, lipids and alteration of structure of mitochondria.

[The endogenous intoxication in pathogenesis of nephropathies].

The endogenous intoxication of organism can be a primary cause of changing in content of protein molecules with enhancement of their capacity to adsorb microelements fastening conformation of proteins. Such an alteration add them antigen characteristics conditioning autoimmune damage of tissues, kidneys included. The most frequent syndromes (cases?) ofendogenous intoxication effecting kidneys pathology are presented.

[D.P.Zuikhin and his contribution to the establishment and development of the system of medical maintenance of nuclear submarines personnel].

A highly qualified physician, an outstanding leader, a scientist Dmitry Zuikhin (1924-1988) was directly involved into establishment of a system of medical support for submariners in the sea and on shore, he proved the necessity of forces and means for the medical service fleet. He was a pioneer in this challenging and new field of naval medicine. His energy, perseverance and determination helped to establish in the early 1960 a system of medical support for nuclear submarines personnel, which was subsequently implemented in all associations and connections of nuclear submarines of the Northern and Pacific fleets.

[The evaluation of eosinophilogram of peripheral blood in children with eosinophilia].

The need in study and interpretation of eosinophilograms in children with allergic diseases is conditioned by higher rate of eosinophilia, large specter of morphologic and functional signs of eosinophils, dependence of indicators from character of clinical course of disease, presence of complications and schemes of treatment. The level of laboratory techniques applied in routine clinical practice to evaluate morphological and functional characteristics of eosinophils is not developed enough. The implementation of such modern high-tech techniques as computer morphometry, highly sensitive and highly specific modifications ELISA, which are applied to detect associated with eosinophilia cytokines, chemokines and growth factors make it possible to approach to this issue at the new qualitative level.

Biochemical indicators of atherogenic and protective activity of xydiphone in experimental animals.

Atherosclerotic plaque formation and vascular calcinosis were modeled in a subchronic experiment. Reduced HDL and elevated LDL concentrations, increased atherogenic index and albumin toxicity index, and high blood levels of triglycerides and uric acid were early markers of pathology. Xydiphone in combination with vitamin D effectively reduced these changes and the degree of vascular calcinosis.

[The diagnostic of peroxisomic diseases in children].

The article presents the results of analysis of long-chained fat acids, fitanic acid and pristanic acid using gas chromatography method. The information is provided concerning the biochemical characteristics of mentioned compounds and their biologic role. The procedure of their analysis is described. The reference values of levels of main long-chained fat acids in blood plasma are presented. The dynamics of modifications of these values under various pathologies is analyzed, including the inherited peroxis diseases in children.

[The characteristics of lipid metabolism in children with congenital hypothyroidism against the background of substitutive therapy with L-thyroxin].

The article presents the results of study of lipid metabolism. The sample consisted of 40 children with congenital thyroid deficiency at different stage of disease compensation and receiving substitutive therapy. Such disorders of lipid metabolism as hypertriglyceridemia and decrease of concentration of high density lipoproteins are established. The results testify the increased risk of atherogenic tendency. The hyper- and dyslipidemia are more often registered in patients at the stage of sub-compensated thyroid deficiency. The correlation of dosage of thyroxin with application of L-carnitine contributes to normalization of indicators of lipid metabolism.

[Diagnostics of mycotic sensitization in children with allergic respiratory diseases by the ImmunoCAP technique].

The need to verify sensitization to mycotic allergens in children with allergic bronchopulmonary diseases is due to the severity of their clinical course, the high frequency of complications, and the inadequate efficiency of conventional treatment regimens. The sensitivity of most techniques used in clinical practice to estimate the level of specific artibodies to mycotic antigens is inadequately high. Recently clinically introduced high-technology diagnostic methods allow one to attack the problem at a qualitatively new level. The application of one of these methods, namely the highly sensitive semiautomatic diagnostic technology ImmunoCAP, permits the determination of the rates of IgE- and IgG-associated specific immune reactions in children with allergic respiratory diseases.

[Activation of reconstructive processes in rat tissues under the action of radiofrequency current with a periodic impulse mode of modulation].

The action of a current in the radio frequency range with a periodic impulse mode of modulation on the activation of recovery processes in the skin and skeletal muscles has been studied. The action of a radio frequency current with a power of 1 W, as opposed to that of the weaker action (0.1 W) and stronger (4 W) action, leads to the activation of recovery processes in the skin and skeletal muscles. Recovery processes are manifested in the increase in proliferation and activation of angiogenesis in the skin, and also in formation of new muscle fibers. Recovery processes in muscles are accompanied by activation and migration of satellite cells of muscle tissue in the zone of action of the radio frequency current.

[Allergic inflammation as one of the factors of pathogenesis of overactive urinary bladder].

Overactive bladder (OAB) is still a serious problem because of its high prevalence in men and women. Endoscopic or open detrusor biopsies were obtained from 28 (24 male and 4 female) patients of 52 to 75 years of age with obstructive or idiopathic OAB of 1 to 10 year duration. The control group included 6 males and 2 females without OAB symptoms. Allergic inflammation with involvement of mast cells, parasympathetic element hyperplasia, ultrastructural changes of myocytes with structural damage to mitochondria were detected in the detrusor of patients with both obstructive and idiopathic OAB. Succinate dehydrogenase activity was low but lactate dehydrogenase activity was enhanced in lymphocytes of peripheral blood. Severity of these changes correlated with morphological features of decreased tissue respiration in the detrusor muscles. In view of the detected inflammatory pathogenetic aspects it is recommended to add antiallergic drugs improving detrusor bioenergetics to combined treatment of OAB.

[Mast cells and innervation of the wall of the hyperactive urinary bladder].

Anterior urinary bladder wall biopsy specimens were examined in 24 males and 4 females, aged 52 to 76 years, who had been suffering from the hyperactive urinary bladder for 1-10 years. Increases in the number and activity of interstitial mast cells and their degranulation and the symptoms of chronic immune inflammation were revealed. Neuromuscular spastic dysfunction of the detrusor is considered to result from the activation of mast cells.

[The use of noben for correction of mitochondrial disorders in Friedrich's disease].

The results of treatment with noben (idebenon), an improved structural analogue of coenzyme Q10, of 34 patients with Friedrich's disease are presented. In all cases, the clinical diagnosis was confirmed by the presence of a typical mutation, an expansion of trinucleotide GAA-repeats, in the FRDA gene. All patients received noben as a main drug in dosage 5 mg/kg daily during 3 months. An examination of the patients included modern laboratory and instrumental methods, analysis of levels of lactic and pyruvic acids and their ratio in the peripheral blood. Also parameters of lipid peroxidation and mitochondrial dehydrogenase activity in peripheral lymphocytes were studied. Positive changes were found in the majority of patients for muscle strength in extremities, tolerability to physical loadings, general fatigue, movement activity, speech and coordination functions, along with significant improvement of biochemical and cytochemical status. The results obtained suggest a positive effect of noben on cell energy metabolism in this severe disorder from the group of mitochondrial cytopathies.