CARDIAC IMPLANTABLE ELECTRONIC DEVICE INFECTIONS - PREVENTION, DIAGNOSIS, TREATMENT AND IMPACT ON QUALITY OF LIFE.

For several decades, highly refined cardiac implantable electronic devices (CIED) are used to prevent and manage various types of cardiac pathology, which have saved the lives of many patients. Cardiac implantable electronic devices help maintain and improve the quality of life by regulating the heart rate, terminating life-threatening arrhythmias, and improving systolic function, including pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization therapy devices. Regardless of the benefits received after its implantation, in some cases, serious complication has appeared, such as CIED infections, associated with severe morbidity, mortality, financial expenses and changes in the quality of life. Exactly, in this article will be addressed the issues of prevention, diagnosis, and treatment of this condition, which will help specialists to properly assess the problem and to find a way to effectively solve it.

BIOCHEMICAL ASPECTS OF SYMPTOMATIC TREATMENT IN PATIENTS WITH COVID-19 (REVIEW).

The new Coronavirus has challenged modern medicine. The disease caused by this virus, COVID-19, is characterized by a high rate of lethality, especially in the older age group. There is still no vaccine and no specific treatment, therefore prevention remains the main way to fight the virus. SARS-COV-2 is characterized by high virulence and contagiousness, that's why the main preventive recommendation is social distance. The article reviews the features of this virus, ways of invading the virus in the body, the possible pathogenesis of the disease and the biochemical and pharmacological aspects of symptomatic treatment. The article also discusses the views of various authors, the results of previous studies and sets new perspectives on fighting the virus. The article discusses the mechanism of action of all drugs and the possible impact on the course and outcome of the disease, which has led to differences of opinion among various groups of scientists since the spread of the virus.

Addictive potential of Tianeptine - the threatening reality.

A total of 24 patients (male volunteers), consumers of opiates in the past and suffering from Tianeptine abuse, were under clinical observation. The age range of patients was from 21 to 33 years. Tianeptine consumption history was 5 months duration on the average. The daily dose of preparation was 40 tablets (500 mg intravenous injections on the average). Patients used Tianeptine in combination with antihistamines (Promethazine, Suprastin). Research was carried out with the use of clinical, psychological and laboratory methods. Has been used Ch. Spilberger's scale of anxiety and T. Balashov's scale of depression. Comparison of withdrawal syndrome developed after cessation of Tianeptine and opiates consumption has shown that in case of Tianeptine, in the dynamic of withdrawal syndrome predominates well expressed high-level of anxiety and depression, while at opiates consumption - withdrawal syndrome is characterized by algesic events and vegetodysfunctions. Supposedly, Tianeptine, in contrast to other anti-depressants, stimulates release of neurotransmitter dopamine in nucleus Accumbens, that probably determine addictive potential of this drug. High level of anxiety, excitability and vegetodysfunctions, presumably could be explained by activation of the NMDA (glutamate receptors) receptor system in Locus coeruleus, and in vegetative ganglion. In the present article potential threat that may develop at Tianeptine consumption, especially in former opiate consumers, without medical purposes has been emphasized.

[Estrogens and pharmacological modulation of estrogen receptors].

Estrogens belong to more or less frequently prescribed preparations. Main fields of application of these preparations (as in monotherapy as well as in combination) are contraception and hormone replacement therapy during menopause. More uncommon indications of estrogens are growth inhibition and hypogonadism (in this case they are prescribed along with gonadotropic hormones). Synthesis and metabolism of estrogens, as well as their intracellular receptors are well studied these days, which allow us to understand physiology and pharmacology of these hormones. In pharmacology the main stage is detection of estrogen receptors inside of cells of targets. There are two types of estrogen receptors alpha- and beta- coded by different genes. A number of steroid and non-steroid compounds have characteristics of estrogens. Likely in the future their popularity will increase, as by the aging of population number of those women, who receive replacement therapy, will increase. Investigations to find an ideal elective modulator of estrogen receptors, that will possess anti-estrogenic activity in connection with mammal gland and develop indifference in connection with endometrium and at the same time will display ability to reduce hot flushes, bone resorption, atrophy of mucous membranes of vagina and urinary bladder, as well as it will favorably effect on metabolism of lipoproteins are carried out.

Vasostabilizing effect of Dotarizine (Ca(2+)-channel blocker) on cerebrovascular reactivity in rabbits.

Disturbances of the cerebrovascular reactivity in cases of migraine with aura are well-known. It has been suggested that the vasostabilizing effects of novel prophylactic pharmaceuticals are determined by their antiserotoninergic and/or nitric oxide releasing properties. Dotarizine, a representative of Ca2+ channel blockers from diphenilbutilpiperazines group also reveals antiserotoninergic 5-HT2A and 5-HT2C receptor-specific properties. The vasodilatatory and antivasoconstrictive properties of this compound were reported previously. In this study the efficacy of Dotarizine chronic oral administration on cerebrovascular reactivity during hyperventilation was examined with respect to its duration of action. Experiments were carried out on 13 rabbits. There was an interval of two days between a five days compound administration and performed hyperventilation. Blood flow velocities (BFV) in the middle cerebral artery (MCA) and basilar artery (BA) were measured in control conditions, after 10 min hyperventilation and in the tenth minute of recovery of normoventilation. Our data reveal a decrease of antivasoconstrictive properties of Dotarizine between its administration and vasoconstrictive test. Subsequent normoventilation showed a distinct vasostabilising effect of this compound with evident regional differences in its influence on cerebral vessels. Thus Dotarizine might be useful as prophylactic medication in migraine therapy, due to its Ca2+ channel blocking and antiserotoninergic properties, but the time-frame of its efficacy has to be defined.

Regional differences of cerebrovascular reactivity effected by calcium channel blocker - dotarizine.

Dotarizine, a novel antimigraine prophylactic drug, is chemically related to Diphenylbutylpiperazines, which are known to have Ca(2+)-antagonistic, alpha-adrenolytic and antihistaminic properties. Additionally, Dotarizine exhibits strong 5-HT2 receptor-specific antiserotoninergic properties. The vasostabilizing effect of Dotarizine on cerebrovascular reactivity during different ventilation conditions was demonstrated in various in vitro and in vivo studies. In the presented study, the effect of chronic oral administration of the drug on vascular reactions of different areas of cerebral vessels following hyperventilation was investigated. The experiments were carried out on two groups of experimental animals (rabbits). In the first group (6) 25 mg/kg of Dotarizine dissolved in 0.25% agar was administered orally for 5 days twice daily. The control group of animals (6) was fed with agar of the same concentration according to the same time schedule. During the experiment, 15 min hyperventilation was performed and blood flow velocity (BFV) in the middle cerebral artery (MCA) and the basilar artery (BA) was recorded using Transcranial Doppler apparatus (TCD) before and after hyperventilation state. The obtained results revealed a strong antivasoconstrictive effect of Dotarizine on cerebral vessels reactivity during hyperventilation. In the control experimental group, the 15 min hyperventilation caused a decrease in the mean BFV in MCA and BA by 36 and 14%, respectively, and in the drug-treated group under the same ventilation conditions the decrease of the mean BFV in BA was only 6% and even a slight increase (8% as compared with control values) of BFV in MCA was observed. Comparison of the pulsatility index (PI) values demonstrated a significant decrease of vascular resistance in MCA in the Dotarizine-treated group of animals (P<0.1). From the obtained results it can be concluded that chronic oral administration of a novel compound (Dotarizine) diminishes the vasoconstrictive effect of hyperventilation on cerebral vessels in rabbits. The influence of this drug demonstrates regional differences in the cerebrovascular reactivity and it appears to change the vascular resistance in the small arteries of the cerebrovascular system. Thus, it can be recommended as a good prophylactic antimigraine compound due its vasostabilizing properties.

The effect of Dotarizine--(Ca2+ channel blocker)--on vascular reactivity and ultrastructure of cerebral capillaries in animals subjected to anoxia.

Dotarizine--the novel piperazine derivative--belongs to wide spectrum Ca2+ channel antagonists. It was reported to have strong vasodilatatory and antiserotoninergic activities. Comparing with other Ca2+ channel blockers Dotarizine was found to have lower oral toxicity. In the present study the influence of the oral administration of the novel compound on the blood flow velocity changes in different cerebral arteries--in basilar artery (BA) and middle cerebral artery (MCA)--was investigated under hypoxic conditions. The ultrastructural morphological changes of intracerebral vessels endothelium in treated and untreated anoxic animal groups were also demonstrated. The experiments were carried out on rabbits. In the experimental group 25 mg/kg of Dotarizine dissolved in 0.25% agar was administered orally three times at the 10 hours' intervals. The sham group of animals was fed with agar of the same concentration. During anoxic conditions strong vasodilatory effects were observed in both investigated vessels of drug-treated animals. In the experimental group marked ultrastructural differences in parenchymal vessel endotheliumin comparison to sham group were revealed. Thus, the oral administration of Dotarizine might have effect on the various parts of the cerebrovascular system and can play significant role in improvement of various cerebrovascular disorders.

Regional differences in the cerebrovascular reserve following acute global ischemia in rabbits.

The changes of the blood flow velocity in different cerebral arteries under normal and postischemic conditions were investigated in order to evaluate cerebrovascular reserve capacity after the brain ischemia. The experiments were carried out in rabbits. Administration of acetazolamide (Diamox) of 20 mg/kg was performed in all experimental animals and the blood flow velocity in the middle cerebral artery (MCA) and the basilar artery (BA) was measured using the transcranial Doppler sonography. In the control group of animals the intravenous administration of Diamox caused significant increase of the blood flow velocity in the MCA and the BA. In the second group of animals subjected to the acute global ischemia (occlusion of two vessels + hypotension) of 10 min duration prior to the Diamox administration, no increase of the blood flow velocity in the MCA was observed parallel with an increase in the BA. In some animals there was a decrease in the blood flow velocity in MCA. This could be a consequence of stealing phenomenon, as an increase of cerebral blood flow in the posterior fossa compartment, at the cost of the supratentorial circulation. Identification of the areas damaged after the brain ischemia was performed by the 2,3,5-triphenyltetrazoliumchloride (TTC) staining technique. This revealed more pronounced ischemic lesions in the cerebral cortex in comparison to the region of the basal ganglia.

The effect of Dotarizine (Ca2+ channel blocker) on cerebral vessel reactivity in animals subjected to hyperventilation and anoxia.

Dotarizine--a novel piperazine derivative--belongs to wide spectrum Ca+ channel antagonists. It was reported to have strong vasodilatory and antiserotoninergic activities. Unlike other Ca+ channel blockers Dotarizine was found to have lower oral toxicity. In the presented study the influence of the oral administration of the novel compound on the blood flow velocity changes in different cerebral arteries--in basilar artery (BA) and middle cerebral artery (MCA)--was investigated under hyperventilation and hypoxic conditions of rabbits. In the first experimental group 25 mg/kg of Dotarizine dissolved in 0.25% agar was administered orally three times at the 10 hours' intervals. The sham group of animals was fed with agar of the same concentration. The results revealed that oral administration of Dotarizine diminished the vasoconstrictive effect of hyperventilation and this was more pronounced in MCA than in BA. During anoxic conditions stronger vasodilatory effects were observed in both groups of vessels and the low value of pulsatility index (PI) reflected pronounced decrease of the peripheral resistance, in comparison to the control group. Thus, the oral administration of Dotarizine decreases the peripheral resistance of cerebral vessels and therefore seems to have influence on the minute arteries of cerebrovascular system of the brain.

[Axial shift of erythrocytes in arteries supplying blood to the cerebral cortex]. / Osevoi sdvig éritrotsitov v arteriiakh, snabzhaiushchikh krov'iu koru golovnogo mozga.

In experiments with rabbits the widths of the axial flows of erythrocytes and of the parietal plasma layers were assessed in pial arterial ramifications supplying the cerebral cortex after their in vivo and in situ fixation under conditions of control and vasodilatation. A strict proportional relationship was revealed between the width of red cell flows and the diameter of pial arteries of 15-200 microns wide. However, the relative plasma volume in the microvessels below 50 microns in diameter was comparatively greater than in the larger vessels. The obtained results prove the feasibility of assessing the microvessels' diameters in tissues where one can see the red cell flow but the vascular walls are invisible. One of the reasons for the lower hematocrit in smaller blood vessels as compared to the larger ones was also elucidated.

[Features of physiologic mechanisms regulating microcirculation in the cerebral cortex of birds and mammals]. / Osobennosti fiziologicheskogo mekhanizma regulirovaniia mikrotsirkuliatsii v kore golovnogo mozga ptits i mlekopitaiushchikh.

The responses of pial arteries to increased activity of the cerebral cortex as well as their innervation at various stages of phylogenic development, were studied with the aid of serial photomicrography with subsequent frame-to-frame analysis in adult rabbits and hens. Following the application of 0.5% isotonic strychnine solution to brain surface, the dilatation of all the segments of the pial artery ramifications was considerably more obvious in rabbits than in hens. The latencies of the vascular responses differed in a similar way. Histochemical studies revealed a considerably richer adren- and cholinergic innervation in rabbit pial arteries as compared with those of hens. The vascular responses and the neurogenic control of the pial arterial bed seem to become steadily refined, together with its anatomy, in the course of evolutionary development.

[Structural and functional units in the pial microvascular system]. / Strukturno-funktsional'nye edinitsy v pial'noi mikrovaskuliarnoi sisteme.

A study was made of the pial arterial microcircles formed upon successive branching and anastomosing of the terminal pial vessels on the brain cortex surface at different levels of the phylogenetic development of the vertebrata. It was discovered that the pial arterial microcircles progressively become more complicated in the following order: chicken, rabbit, cat, dog, monkey. The morphological signs of the microcircles undergo progressive development: 1) they are formed primarily from small pial arterial branches possessing high vasomotor activity; 2) the area of each circle becomes less and less and their amount per unit of the brain surface increases respectively; 3) the quantity of the feeding arterial branches rises despite the reduction of the circle size; 4) the number of outgoing precortical and radial arteries entering the brain cortex increases; 5) the areas of the brain cortex supplied by individual radial arteries become less and less. This ensures increasingly delicate regulation of adequate blood supply of the smallest areas of the brain cortex.

The modular organization of the pial arterial system in phylogeny.

We have investigated the pial arterial microcircles formed by the consecutive ramifications and anastomoses of minute pial vessels on the surface of the cerebral neocortex in various vertebrate species, representatives of various levels of phylogenic development. We found that the pial arterial microcircles became gradually more complex in the following order: hen less than rabbit less than cat less than dog less than monkey. The gradual development of microcircles involves various features in these species: They become formed predominantly of smaller pial arterial branches whose vasomotor activity is much higher as compared with that of the larger ones; each circle occupies a smaller area, and hence the number of circles per surface of neocortex increases; the density of arterial branches feeding the circles increases despite the smaller size of the latter; the number of off-shooting precortical and radial arteries penetrating the cortex increases; the areas of neocortex fed by individual radial arteries get gradually smaller. Thus, the development of the pial arterial bed contributes more and more toward precise spatial regulation of an adequate blood supply to increasingly smaller areas of neocortical tissue as we rise toward higher levels in phylogeny.