[CLINICAL AND PATHOGENETIC PECULIARITIES OF DEVELOPMENT OF ENDOTHELIAL DYSFUNCTION].

The purpose of the study was to examine the relationship between functional parameters, arterial rigidity, lipid profile, markers of systemic inflammation and endothelial dysfunction in patients with COPD and COPD + coronary heart disease. We examined 110 subjects divided into 3 groups. G group 1 included 40 patients with severe and very severe COPD, group 2 consisted of 40 patients with severe and very severe COPD + coronary artery disease, the control group was comprised of 30 healthy volunteers. We studied parameters of respiratory function, the level of blood oxygenation, the main characteristics of arterial rigidity plasma lipid, TNF-α, CRP, fibrinogen, sPECAM-1 levels and the expression of CD38/ADP-ribosylcyclase in peripheral blood lymphocytes. The study revealed increased rigidity of the central arteries in the patients of groups 1and 2 regardless of the duration of observation and the presence of coronary artery disease, as evidenced by the increase of the pulse wave velocity in the aorta. Patients of both groups had elevated levels of TNF-α, CRP and fibrinogen indicating systemic inflammatory response. Taken together, the enhanced expression of CD38 in peripheral blood lymphocytes, elevated concentration of soluble CD31 (sPECAM-1) in both groups related to bronchial obstruction and neutrophil elastase activity as well as increased rigidity of the vascular bed gives evidence that the CD38 and sCD31 relationship plays a role in the formation of endothelial dysfunction, and dysregulation of vascular tone in COPD patients. Disorders of lipid metabolism combined with increased rigidity of the vascular wall, elevated levels of markers of systemic inflammation and endothelia dysfunction, suggest that patients with COPD are at risk of cardiovascular events.

[THE RELATIONSHIP BETWEEN DISORDERS-OF EXTERNAL RESPIRATION AND RIGHT HEART REMODELING IN PATIENTS WITH ATOPIC BRONCHIAL ASTHMA].

This study aimed at the evaluation of the state of the respiratory system and its possible influence on the structural and functional characteristics of the right heart in patients with atopic bronchial asthma (BA) with a view to optimizing diagnostics and prevention of cardiovascular complications. The study included 189 subjects of whom 148 with BA were divided into 3 groups depending on the severity of the disease. Forty practically healthy volunteers comprised the control group. The external respiration function and right ventricle functional parameters were the main variables measured in all the participants of the study. It was shown that disorders of external respiration and pulmonary hyperinflation progressed with severity of BA and thereby promoted right ventricular myocardium remodeling and dysfunction that in turn led to chronic cardiac insufficiency. It is concluded that functional changes in the right heart in of patients with BA of different severity are associated with remodeling of the respiratory tract.

[Relationship between endothelial dysfunction and mechanisms of systemic inflammation in left heart remodeling in patients with bronchial asthma].

The aim of the work was to study clinical and pathophysiological features of endothelial dysfunction, structural and functional state of the left heart in patients with bronchial asthma (BA). The study included 290 patients. 250 of them presented with moderate or severe BA during exacerbation and within 12 months after the onset of observation, 40 healthy volunteers served as controls. The endothelial function was disturbed in 63 and 74% of the patients with moderate and severe BA respectively. They showed reduced endothelium-dependent vasodilation in combination with a significant increase of the plasma sDC31/ sPECAM-1 level. It is concluded that patients with BA develop structural and functional changes in the left ventricular myocardium proportional to the severity of BA which leads to diastolic dysfunction.

[Early reactive changes of myelin sheath in the area of myelin sheath gaps (nodes of Ranvier) in nerve fibers (a supravital study)].

Using the inverted phase contrast microscope, the supravital study of structural dynamics of single myelin sheath gaps (nodes of Ranvier) of isolated frog myelin nerve fibers was performed after mechanical injury and in the medium with the decreased ion force under the conditions which induce, in electrophysiological experiments, the expression of the axolemmal K+-channels in the paranodal area. Videorecording has shown that within this area the myelin sheath stratification appeared that was associated with the swelling of Schwann cell cytoplasm enclosed in the terminal membranous loops of myelin. An increase of the degree of stratification of the lamellar myelin complexes make them invisible in the light microscope; therefore, it is not the translocation of the myelin sheath from the node cleft that is recorded, as many authors believed, but a shift of only the visible border of the compact, yet unstratified myelin sheath. Hence, the removal of myelin (demyelination) was absent, and the electrophysiological effect can be accounted for by a significant fall of electrical resistance in paranodal area as a result of swelling of terminal loops and stratification of the myelin sheath. Preparations examination also revealed a decrease of the axonal diameter in, which is proportional to swelling of the myelin sheath terminal parts. Since the outer fiber diameter did not change, it can be concluded that the process observed is the result of swelling of the Schwann cell cytoplasm due to the axoplasm water fraction which may be a peculiar process of axo-glial interactions.

[Syncytial perforations of human neuronal embryo membranes].

An electron microscopy study of the anlage of cerebral cortex of human embryo has been carried with the aim of determining the presence of syncytial interneuronal connections in embryogenesis. It has been determined that, in part of the neurons, the glial embryo is absent and their external cell membranes are directly attached to each other by forming elongated or dotted tight junctions. Sometimes these junctions are perforated and, on their basis, the true syncytial interneuronal connections are formed. Natural structural properties of these connections are the following: formation of the base of tight membrane contacts, obligatory rounding of perforation edges, and the presence of residual particles in the form of spherical vesicles in the lumen of perforations. Results obtained allowed us to conclude that, in the anlage of cerebral cortex of embryos obtained during surgical abortion of pregnancy, apart from the formation of synaptic contacts, or until their formation, there is the possibility of syncytial interneuronal connections appearing. This should be considered during the transplantation of the developing brain.

Syncytial cytoplasmic anastomoses between neurites in caudal mesenteric ganglion cells in adult cats.

The fact that most published data on syncytial cytoplasmic anastomoses are based on the autonomic nervous system in the early postnatal period of development, when many nerve fibers are poorly ensheathed by glia or have no glial sheaths at all, has led to the assumption that these anastomoses do not exist in adults because of the significant development of the glia and glial insulation of individual neurites from each other. We tested this assumption using electron microscopic studies of the caudal mesenteric ganglion in adult cats. A high level of glial ensheathing of neurites was observed. However, syncytial pores were seen between contacting neurites lacking glial sheaths in almost every specimen. This is the first report describing axodendritic synapses with perforations in the presynaptic zone outside the synaptic specializations in the autonomic nervous system. It is suggested that although syncytial cytoplasmic connections are seen in adult animals, they do not contradict the neuron theory.

[Experimental modeling and the discussion on the syncytial connections in the nervous system].

To solve the problem of the possibility of syncytial connection in the nervous system, this paper for the first time presents the evidence of experimental syncytial fusion of neurons. Neurons, isolated from the ganglia of the mollusc Lymnaea stagnalis and freed from the surrounding glia by pronase treatment, were drawn together by centrifugation and were kept in the culture medium for two days in the aggregated state. The neurons preserved the ability to generate normal processes. At the borders of adjacent cells, contacting mutual protrusions (feet) were formed that were separated from each other by vacuole-like enlargements of the intercellular clefts. Using the electron microscope, it was shown that at the borders of contacting feet the external cell membranes were destroyed. Only residual fragments of the destroyed membranes were detected. The cytoplasm of one adjacent cell was continuous with the cytoplasm of the other. Thus, the experiments confirm once more the correctness of the cell theory concerning the common main properties of all the cells and expand the concepts of the neuronal theory by the statement that in the nervous system, along with chemical synapses and electrical membrane contacts, the syncytial interneuronal connections are also possible.

[Syncytial cytoplasmic anastomoses between the neurites of caudal mesenteric ganglion cells in adult cats].

Since the majority of the published data on syncytial cytoplasmic anastomoses relate to the autonomic nervous system in the early postnatal period of development, when many nerve fibers are still poorly covered by glia or have no glial sheaths at all, it was suggested that such anastomoses were not present in adults due to the significant development of glia separating individual neurites from each other. To check this assumption, we have performed an electron microscopic study of the adult cat dorsal caudal mesenteric ganglion. The cell neurites were found to be frequently covered by glial sheaths. However, almost in every sample, the syncytial pores were detected between the contacting neurites lacking glial covering layers. Sometimes serial syncytially connected neurites were seen. Axo-dendritic synapses with presynaptic perforations outside the synaptic specializations were described in the autonomic nervous system for the first time. These observations therefore provide evidence of syncytial cytoplasm connections in normal adult animals, however this does not reject the neuronal doctrine.

[Cytoplasmic syncytial interneuronal connection in molluscs].

The absolute criteria developed by the authors have been presented; they allow revealing cytoplasmic syncytial connections between processes of nerve cells in vivo and in vitro at the light microscopy level by using classical methods and time lapse videoshooting in the phase contrast. With aid of electron microscopy, metastable membrane contacts and their perforations, cytoplasmic syncytial interneuronal pores, and fusion of nerve processes are demonstrated. In the culture of isolated molluscan neurons, the process of formation of syncytial connection between processes of the same neuron or of different neurons is reproduced. Processes of one neuron, which have syncytial connection with another neuron, are shown to remain viable after death of its neuronal soma. The cytoplasmic varicosities formed on processes of one neuron are able to overcome the place of syncytial contact with processes of another neuron and to move to the body of the latter. A hypothesis is put forward that the cytoplasmic syncytial connection between nerve processes is formed under the condition of the absence of their glial sheaths.

[Neuronal division or enucleation].

In this work,using the classical neurohistological Bielschowsky-Gros method, all the morphological phenomena were reproduced that were earlier interpreted by many authors as the signs of neuron division, budding and fission. It is suggested that these phenomena are associated with the effect of enucleation demonstrated in many cells of other tissue types exposed to different physical and chemical factors. The experiments were conducted in tissue culture, using the isolated neurons of the mollusk Lymnnaea stagnalis, in which the neural cells were treated with actin microfilament inhibitor cytochalasin B. Phase-contrast time-lapse video recording during 4-8 hours demonstrated the effects of nucleus displacement, ectopy and bulging up to almost complete fission of neuronal body. These effects reproduce the images obtained in static fixed preparations under "normal" and various experimental conditions. Sometimes, at the early experimental stages, the bulging of cytoplasm was also detected. Control experiments in which the neurons were treated with the culture medium containing cytochalasin B solvent dimethyl sulfoxide, showed no changes in neurons during 8-hour period. It is suggested that the images, interpreted earlier as neuron division or fission, could be explained by inhibition of actin microfilaments, which sometimes may develop spontaneously in cells experiencing individual metabolic changes compromising the cytoskeleton stability maintenance.

The question of the fusion of neuron processes.

The authors, whilst accepting the neuron theory, present data indicating the possibility that neuronal syncytia exist when myelin-coated ring-like structures form in the dendritic field, in nerve arcades close to neuron bodies, and on formation of thick, straight anastomoses between neuron bodies. Studies using computerized time-lapse videomicroscopy in cultures of isolated neurons demonstrated the mechanism by which these structures form. This report provides the first evidence of the time parameters of the fusion of the processes of a single live neuron; the fusion of fragments of an isolated glial-free fiber was demonstrated.

[The problem of the fusion of the neuron pseudopodia].

This article discusses the old problem of contact or syncytial connections of neurons in the nervous system. The authors confirm the correctness of neuron theory, but still present some data on a possibility of neuronal syncytium in such cases as formation of myelin-covered ring-shaped structures in the zone of dendrites, nervous arcades in the area of neuronal soma or in thick straight anastomoses between neuron bodies. Authors were able to demonstrate the formation of such structures in the isolated neuron culture with the help of computer time-lapse phase contrast microscopy. The proof and time parameters of fusion of the processes of the same living neuron are given for the first time. The fusion of fragments of isolated non-glial nerve fibre was demonstrated. The data of electron microscopy were presented in a preceding accompanying article.

[Accidental involution of the thymus after splenectomy (an experimental study)]. / Aktsidental'naia involiutsiia timusa posle splenéktomii (immunogistologicheskoe issledovanie).

Using immunological, general clinical and luminescent histochemical methods experimental study of immunological status and bioamine-containing thymus structures was performed on third, seventh and fifteenth postsplenectomy days in 90 outbred albino male rats. Splenectomy leads to significant changes in blood immunological parameters and morphofunctional state of thymus bioamine-containing structures. Significant increase of biogenic amines content in all thymus structures, leukocyte number, complement activity neutrophilic granulocytes phagocytic activity, were registered in 3 days. Further growth of bioamine content, decrease of cortical and medullary substances diameter, significant number growth of juvenile forms of mast cells were observed in 7 days. Essential decline in erythrocyte number, hemoglobin and IgG and IgA content, leukocytosis with leukemoid reaction development were defined in blood formula. On 15th postsplenectomy day maximal biogenic amine concentration, especially histamine was reached and further reduction in cortex and medulla as well as decline of all the immunoglobulins and decrease of neutrophilic granulocytes phagocytosis were determined. Thus, splenectomy and subsequent development of accidental involution leads to secondary immunodeficiency and severe anemia.

[A chemiluminescence study of isolated polymorphonuclear leukocytes and whole blood from patients with acute pneumonias]. / Issledovanie khemiliuminestsentsii izolirovannykh polimorfnoiadernykh leikotsitov i tsel'noi krovi u bol'nykh ostrymi pnevmoniiami.

A study was made of the production of active forms of oxygen (AFO) by liminol-dependent spontaneous chemiluminescence (LSC) of isolated polymorphonuclear leukocytes (PNL) and whole blood in 39 patients with acute pneumonias in different disease periods. The majority of the patients manifested activation of oxygen metabolism of PNL, with the intensity of LSC of whole blood appreciably exceeding LSC of neutrophils isolated from the given blood sample. If the production of AFO is insufficient, the acute period of pneumonia is characterized in most cases by the complicated disease course. Studies into LSC of whole blood is more informative for predicting complications within these times. The lack of the increment of the whole blood LSC intensity on the second week of the disease as compared to the first week as well as a rapid decrease of the initially high level of LSC to the level not differing from the donor's parameters is prognostically unfavourable as regards complete recovery. Inadequately high and long (during 3 weeks) generation of AFO detectable by both methods was associated with the lingering course of pneumonia. The monitoring of LSC of PNL and whole blood allows predicting complications of acute pneumonia together with administering corrective therapy with the aid of immunomodulators and antioxidants.

[Study of luminol-dependent chemiluminescence of peripheral blood in acute pneumonia]. / Issledovanie liuminolzavisimoi khemiliuminestsentsii periferi- cheskoi krovi pri ostroi pnevmonii.

Active oxygen forms (AOF) were measured in whole peripheral blood of 40 acute pneumonia patients using luminol-dependent spontaneous chemiluminescence (LDSC) and luminol-dependent zymosan-stimulated chemiluminescence (LDZSC) in the time course of the disease. Within week 1 of the disease both LDSC and LDZSC were increased in the majority of patients whereas low levels of AOF production served a predictor of poor prognosis in relation to acute pneumonia complications. If high intensity of LDSC and LDZSC persisted for 2 weeks pneumonia was likely to resolve completely though complications were possible. Protracted disease was associated with 3-week high AOF production. The data give evidence for possible application of LDSC and LDZSC of whole peripheral blood to predict complications and incomplete resolution of acute pneumonia.

[Functional status of neurons of the myenteric plexus of the stomach free of central control]. / Funktsional'noe sostoianie neironov mezhmyshechnogo spleteniia zheludka, lishennykh tsentral'nogo kontrolia.

Spike activity of the stomach wall smooth muscles, changes of the intramural neurons size and the nucleic acids amount in the neuron cytoplasm and gliocyte nuclei within the intramural ganglia of the dog stomach, were studied within 2 weeks, 4 and 6.5 months after bilateral trunk vagotomy. The intramural nervous system was shown to take up organizing of phases of the myo-electrical complex, the latter revealing a higher rate of the spike activity. The population of small neurons increases in the intramural ganglia, the amount of nucleic acids reducing both in the neuron cytoplasm and in gliocyte nuclei. The functional deficiency of the intramural neurons seem to underlie the disturbances of electrical and motor functions of the digestive tract walls in lesion of the central control.

[Bombesin and monoamine-containing cells of the rat stomach]. / Bombezin i monoaminsoderzhashchie kletki zheludka krysy.

Revealing of enterochromaffine and enterochromaffine-like cells of the rat stomach was undertaken under the effect of bombesin and alpha- and beta-adrenoblocking agents. Fibers containing gastrin-releasing-peptide were immunohistochemically revealed in neural plexus of the rat digestive tract. Spontaneous rhythmic release of the stomach monoamine cells' secret was shown. The effect of bombesin on the enterochromaffine-like cells of the rat stomach fundus containing histamine, was shown to be actualized through beta-adrenoreceptors. Serotonin excretion from the enterochromaffine cells of the stomach antrum depends neither on bombesin nor on the adrenergic effects.