[Current conception of stress and adaptation subject to new data of tissue hypoxia genesis].

State-of-the-art conception of stress is represented as an interrelation between stress, tissue hypoxia and adaptation. Under the influence of stressors the cell metabolism changes with producing of chemical substances capable pathologically to get bound with cell receptors. These substances change in cells optimal energy transformation (biochemical stage) and disturb cell functions (pharmacological stage). Biochemical and pharmacological stages of stress in uncellulates and in human cells are homotypic. The clinical stage of stress is typical only for humans and animals. Dysfunction of plane muscles (PM) myocytes leads to local microcirculation disturbances, transitory hypoxia and partial disorder in affected organ function. Local microcirculation disturbances are accompanied by serotonin release from damaged platelets, which leads to complete functional recovery of PM myocytes, microcirculation and affected organ function, or to formation of local "mute" focuses of tissue necrosis--the adaptation is effective. Insufficient serotonin release from damaged platelets leads to extension of hypoxia focus, lesion, tissue necrosis. The stress loses its nonspecificity and turns into infarction of myocard, brain etc., with specific clinical course--the adaptation is not effective.

[Regional anesthesia and timely treatment for neuropathy in patients with pyonecrotic forms of the diabetic foot].

Regional anesthesia was studied for its impact on the functional status of a peripheral nerve in 20 patients with purulent diseases of the lower extremities in the presence of diabetes mellitus. The impact of conservative therapy on the peripheral nerve was also studied in these patients. There was no negative impact of regional methods of anesthesia on the function of the nerve, its improvement due to treatment with alpha-lipoic acid and serotonin adipinate.

[Effect of serotonin-adipinate on the ultrastructure and synthetic activity of endotheliocytes of microhemocirculatory bed of human brain (autopsy material, early autopsies)]. / Vozdeistvie serotonina adipinata na ul'trastrukturu u sinteticheskuiu aktivnost' éndoteleotsitov mikrogemotsirkuliarnogo rusla golovnogo mozga cheloveka.

Electron-microscopic and radioautographic investigation showed the ability of brain capillary endotheliocytes for retaining functional activity in total ishemia. Administration of serotonin adipinate in an early postoperative period supports intracellular processes and plays a protective role.

[A revised classification of hypoxic conditions]. / Utochnenie klassifikatsii gipoksicheskikh sostoianii.

The precised classification of circulatory hypoxia described in the paper is principally different from those published earlier by that it discriminates between hypoxia preconditioned by impaired cardiac-muscle constriction, on the one hand, and hypoxia due to malfunctions of smooth muscles (SM), on the other hand. The genesis of SM malfunctions is predetermined by impaired interactions of serotonin with SM serotonin receptors. The clinical use of serotonin adipinat reduces the local organic and total-tissue hypoxia in different pathologies and provides for better treatment results. The mentioned precised classification can be used to gain more data on the tissue-hypoxia pathogenesis and to schedule the clinical-and-experimental research on the purpose-oriented basis.

[The treatment of critical lower limb ischemia using serotonin]. / Lechenie kriticheskoi ishemii nizhnikh konechnostei s ispol'zovaniem serotonina.

This paper describes the first experience with conservative treatment of 30 men suffering from critical lower limb ischemia using serotonin as an agent which may return endogenous vasomotility to normal and eliminate tissue hypoxia. Good and satisfactory results were obtained in 76% of patients (43 and 33% respectively). Deterioration followed by amputation was marked in 7% of patients. The removal or considerable abatement of rest pains was recorded in 86% (53 and 33% respectively) of cases. Amputation was performed in 10% of patients. It is recommended that serotonin adipinate should be included into multiraodality therapy of atherosclerotic critical lower limb ischemia. The use of the treatment method suggested will allow to improve the treatment results, to reduce the number and level of amputations, and to minimize the percentage of disability.

[Prophylaxis and treatment of serotonin insufficiency in surgical patients]. / Profilaktika i lechenie serotoninovoi nedostatochnosti u khirurgicheskikh bol'nykh.

The authors demonstrate that appearance in blood of chemical substances (ligands) capable to bind with serotonin receptors of smooth muscles (SM) leads to serotonin insufficiency. Intravenous injection of serotonin adipinat corrects serotonin insufficiency (biochemical stage) which leads to restoration of disordered function of SM (pharmacological stage). Normal function of SM eliminates functional intestinal obstruction (from the first hours after surgery), vascular insufficiency, tissues hypoxia (clinical stage) in surgical patients with different diseases. Serotonin adipinat was used in more than 900 surgical patients. It is concluded that this drug is a necessary component of prophylaxis and treatment of functional intestinal obstruction, vascular insufficiency, local and regional tissues hypoxia.

[Serotonin and serotonin receptors in the genesis of stress and adaptation]. / Serotonin i ego retseptory v geneze stressa i adaptatsii.

The paper presents a current concept of the genesis of stress and adaptation with regard to new data on serotonin and its receptors. There is evidence that stress is transient hypoxia that results from dysfunction of smooth muscles (SM) in the microcirculatory bed (a pharmacological stage) with partial or complete dysfunction of the organ or system where dysfunction has occurred (a clinical stage). Impaired interaction of serotonin with GM serotonin receptors, which occurs with excess serotonin receptor ligands due to various stress factors, underlie the pharmacological and clinical manifestations of stress. The occurrence of transient hypoxia is followed by the activation of antistress (adaptive) processes in the organism with thrombocytic release of serotonin. In endogenous hyperserotoninemia, microcirculation improves, a hypoxic area ceases, and/or damaged and necrotic tissues localize. With this, endogenous serotonin-induced recovery of different organs is the essence of an adaptive process. Clinical and experimental evidence suggesting that exogenous serotonin administration just simulates an elevation in the concentration of endogenous serotonin as a material substrate of the human adaptive system.

Microcirculatory disturbances in gastric mucosa during ulcer disease and effects of serotonin on their dynamics.

Experiments on rat model of stress-induced gastric ulcers revealed marked circulatory disturbances in ulcerated gastric mucosa associated with arteriolar spasm and venous congestion and leading to perivascular edema, diapedesis of erythrocytes, and microhemorrhages. These changes were most pronounced on day 1 after ulcer modeling and progressively decreased during healing (day 14-21). On day 3, arterial hyperemia developed against the background of venous congestion, which was probably related to progressive repair. Serotonin adipinate administered after ulcer modeling accelerated the development of arterial hyperemia (day 1) and reduced venous congestion and extravascular changes. Pretreatment with serotonin was even more effective in attenuating venous congestion and extravascular changes.

[The concept of the clinical use of serotonin adipinate in treating surgical patients]. / Kontseptsiia klinicheskogo primeneniia serotonina adipinata pri lechenii khirurgicheskikh bol'nykh.

The influence of serotonin adipinate on the mechanisms of development of tissue hypoxia, disturbances of the microcirculatory bed and smooth muscles before, during and after operative interventions was studied in experiments and clinical practice. The syndrome of serotonin insufficiency is described including smooth muscle insufficiency which can be abolished by serotonin adipinate administered at the early postoperative period irrespective of the cause of surgery, age and sex of the patient. Good results were obtained in treatment of patients after operations on the liver, pancrease, heart, in patients with the diabetic foot and in other diseases. No complications or lethal outcomes resulting from using serotonin adipinate were noted.

[Origin of microcirculation disorders in tissue hypoxia, shock and disseminated intravascular blood coagulation]. / O geneze narushenii mikrotsirkuliatsii pri tkanevoi gipoksii, shoke i disseminirovannom vnutrisosudistom svertyvanii krovi.

The origin of microcirculation disorders in tissue hypoxia, shock, and disseminated intravascular coagulation is discussed with consideration for the heretofore unknown capacity of free hemoglobin and free myoglobin to cause smooth muscle convulsions and accelerate platelet destruction.

[Use of serotonin for treatment of patients with diabetic angiopathies]. / Primenenie serotonina dlia lecheniia bol'nykh s diabeticheskimi angiopatiiami.

In 26 patients (female 11, males--15) with diabetic angiopathy (necrosis of the foot or toes) local measurement of pO2 by transcutaneous mode was carried out before and during introduction of serotonine adipinate. Simultaneously with evaluation of pO2 in 14 patients electromyography (EMG) was made. Serotonine adipinate was introduced intravenously with a speed of 5.0-10.0 mg per hour. In this group mean age of the patients made up 57.4 years, mean values of initial pO2 25.6 mm Hg, and mean indices of pO2 at the moment of serotonine treatment 38.5 mm Hg. Average increase of pO2 during serotonine infusion was registered as 50.4% in comparison with mean initial data. In all 14 patients, who underwent simultaneous measurement of pO2 and registration of EMG, reinforcement of electrical activity of smooth muscles (SM) of various intensity and increase in tissue pO2 were detected. Improvement of microcirculation (increase of transcutaneous pO2, reinforcement of electrical activity of SM as a result of serotonine introduction) evidences that functional and morphological changes of serotonine receptors of SM are involead in genesis of diabetic angiopathy. The data obtained showed that in diabetes mellitus, besides insulin deficiency, insufficiency of such an endogenous factor as serotonine duclops. Thus, serotonin should be used for prophylaxis and treatment of diabetic angiopathies.

[Use of serotonin adipinate in combined therapy of hemodynamic disorders in acute poisoning by psychopharmacological preparations]. / Primenenie serotonina adipinata v kompleksnoi terapii narushenii gemodinamiki pri ostrykh otravleniiakh psikhofarmakologicheskimi preparatami.

Serotonin adipinate in a dose of 40-60 mg was injected by drip infusion to 30 patients with acute poisoning by psychotropic drugs for correcting circulatory disorders. The drug corrected hemodynamic disorders in the lesser and greater circulation by increasing the stroke volume and normalizing total peripheral vascular resistance and central blood volume.

[Use of serotonin adipinate in acute oral poisoning]. / Primenenie serotonina-adipinata pri ostrykh peroral'nykh otravleniiakh.

Ninety-five patients with acute poisonings with psychotropic agents, barbiturates, amitriptyline, leponex, cholinolytics, and organophosphorus insecticides were treated by gastro-enteroadsorption making use of activated coal. In order to enhance propulsive function of the gastrointestinal tract, serotonin adipinate was repeatedly administered in a dose of 5 to 20 mg. Evacuation of the enteroadsorbent in the rectum was enhanced fivefold in comparison with a control group of similar patients administered traditional drugs (proserine, pituitrin, cerucal). As a result of such therapy, the toxicogenic phase of poisoning was shortened and mortality in the observed group reduced twofold in patients poisoned with psychotropic agents, 5.4 times in those with barbiturate poisoning, and 3.5 times in those with organophosphorus poisoning.

[Are the serotonin receptors life receptors?]. / Iavliutsia li serotoninovye retseptory "retseptorami zhizni"?

The paper gives evidence for the fact that serotonin and serotonin receptors are responsible for the occurrence of primary contractions of smooth muscles, primary cardiac contractions and primary brain electric activity (EEG genesis). It is concluded that the function of the smooth muscle, brain and heart cannot take place without serotonin and its receptors. This suggests that the serotonin receptors are life ones.

[The ability of hemoglobin and myoglobin to evoke a spasm of the smooth musculature and to accelerate thrombocyte destruction. A description of serotonin-ferroprotein receptors]. / Sposobnost' gemoglobina i mioglobina vyzyvat' spazm gladkoi muskulatury i uskoriat' razrushenie trombotsitov. Opisanie serotonin-ferroproteinovykh retseptorov.

The previously unknown properties of ferroproteins (hemoglobin and myoglobin) to cause smooth muscle spasm and to accelerate platelet degradation are described in the paper. Ferroproteins are shown to interact with some serotonin receptors. Some serotonin receptors of smooth muscles and platelets which hemoglobin and myoglobin interact with are termed serotonin-ferroprotein receptors (S-Fe-pr-receptors). The found properties of ferroproteins provide a deep insight into the understanding of physiological and pathophysiological processes with the participation of hemoglobin, myoglobin, platelets, smooth muscles, serotonin, and serotonin receptors.