Evaluation of the Content of Aquaporin-5 and Epithelial Sodium Channel in the Lungs of Rats during the Development of Toxic Pulmonary Edema Caused by Intoxication with Acylating Pulmonotoxicants.

We studied the content of aquaporin-5 (AQP5) and epithelial sodium channel (ENaC) in rat lungs during the development of toxic pulmonary edema (TPE) caused by intoxication with phosgene and perfluoroisobutylene (1.5 LC50). The lung body weight index (LBI) was calculated and histological examination of the lung tissues was performed. Localization and expression of AQP5 and ENaC were determined by immunohistochemistry. Intoxication led to a significant (p<0.05) increase in LBI and histological changes typical of TPE 1 and 3 h after the exposure. In 1 and 3 h after phosgene intoxication, the AQP5 and ENaC content significantly (p<0.05) increased in comparison with the control. Similar changes in the AQP5 and ENaC content were observed 1 and 3 h after exposure to perfluoroisobutylene. It was hypothesized that AQP5 plays an important role in the formation of TPE caused by intoxication with acylating pulmonotoxicants. An increase in the content of ENaC can be considered as a compensatory reaction of the body aimed at clearance of the alveolar fluid.

Ultrastructural Changes in the Air-Blood Barrier of Rats in Acute Intoxication with Furoplast Pyrolysis Products.

Rats were exposed to fluoroplast-4 pyrolysis products (sample weight 2.6 g, pyrolysis temperature 440-750°C, pyrolysis duration 4 min) containing perfluoroisobutylene over 15 min. Lung tissue samples for histological and electron microscopic examination were isolated in 3 and 30 min after intoxication and processed routinely. Histological examination revealed no structural changes in the lungs. In ultrathin sections of rat lungs, some changes in the structure of type I pneumocytes were detected in 3 min after the exposure: detachment of cytoplasmic processes and the appearance of transcytosis pores. These changes attested to impaired cell-cell interactions and their adhesion to the basement membrane, where structural disorganization and edema of the collagen matrix were observed. In 30 min following exposure, the signs of damage to type I pneumocytes became more pronounced. The increase in the equivalents of transcellular and paracellular permeability in the alveolar lining profile was observed. No changes in the pulmonary capillary endotheliocytes were detected, which suggest that type I pneumocytes are the primary target of the toxic effect of perfluoroisobutylene. The vulnerability of a particular cell population, in view of specific metabolism of these cells, can be the key to deciphering of the mechanisms of the toxic effect of pyrolysis products of fluorinated polymer materials.

Mechanisms of Pulmonary Toxicity of Perfluoro-n-Alkane Pyrolysis Products with Consideration of the Structural Features of the Blood-Air Barriers.

Perfluoroisobutylene a is pulmonotoxic chemical generated during pyrolysis of perfluoro-nalkanes (polytetrafluoroethylene). The mechanisms of acute pulmonary toxicity induced by perfluoroisobutylene have not been studied yet. The analysis of tissues of brown frogs showed that the products of polytetrafluoroethylene pyrolysis induce typical inflammatory response in the lungs (fluid accumulation, erythrocyte stasis, desquamation of the epithelium, and capillary plethora in lung septa) and oropharyngeal cavity (degeneration of ciliated epithelium, hyperemia of underlying vessels with plasmatic imbibition of the connective tissue, and margination of segmented leukocytes and monocytes). The absence of surfactant is a specific feature of the blood-air barrier of the oropharyngeal cavity in frogs compared to the lungs. It can be hypothesized that toxic effects of perfluoroisobutylene are determined by its influence on epithelial (pneumocytes and cells of nonkeratinized stratified ciliated epithelium) and endothelial cells. Even though the effects of the agent on surfactant cannot be excluded, they do not determine the probability of development of inflammatory response.

Assessment of Functional Disturbances in the Central Nervous System Caused by Severe Carbon Monoxide Poisoning in Rats.

An experimental model was developed for assessment of disturbances in CNS functions of laboratory animals caused by severe carbon monoxide poisoning. Normalization of the state of experimental rats after acute poisoning was accompanied by the development of cognitive abnormalities. Disturbances in the long-term memory were observed on days 1 and 14 after CO poisoning, while abnormalities in the short-term memory developed on days 1, 7, and 14. Learning impairment were recorded on day 8, while the training course began on day 7.

[Actual issues of an improvement of the medical aid delivery system in case of acute radiopathology in the Armed Forces of the Russian Federation].

Actual issues of an improvement of the medical aid delivery system in case of acute radiopathology in the Armed Forces of the Russian Federation. The article provides information on characteristics of the stage system of medical aid delivery in case of acute radiologic traumas. The authors formulated main directions of improvement of the system under modern conditions. It is shown that as a basis of its improvement may be considered the complex of measures, including formation of standardized clinical recommendations (treatment protocols) on medical care delivery to the wounded at different stages of medical evacuation, expanding of possibilities of special medical aid delivery to patients with acute radiopathology, including formation of mobile reserves for deployment of specialized units under conditions of mass admission of patients with severe forms of radiopathology; renewal of the training system for medical specialists working in the field of acute radiopathology; implementation of information technologies; improvement of interdepartmental interaction on the problems of medical consequences after radiologic emergency situations in peacetime.

[Chemicals as fire damaging factor].

The article provides an overview of published scientific data about toxic chemical compounds formed during thermal degradation of various materials. In case of fire the complex of physical and chemical factors affect the human, along with injuries, thermal burns of the skin and respiratory tract there is a lack of oxygen in the inspired air and the impact of thermal degradation products. The greatest number of deaths in.a fire due to the inhalation by the victims smoke and toxic gases. The impact of the combination of toxic substances leads to the development of various forms of toxic process. The main causes of poisoning at the fires due to the effects of toxic substances and substances which can cause structural and functional disorders of the respiratory organ. Intoxication manifestations by some of them appear already in the fire zone, in other cases, in cases of poisoning by the compounds of the slow motion, there is the latent period of of intoxication. Knowledge of the spectrum of toxic products thermal destruction on the human during the fire, it is necessary to develop approaches to improve medical care and creation of tools of medical protection.

[Consequences learned from the use of chemical weapons during the First World War for the modern military medicine].

The article describes the way medical service dealed with problems resulted from the use of chemical weapons during the First World War (1914-1918). It was revealed that many of the abovementioned problems remain unsolved up to the present moment. It is stated the existence of the threat of use of chemical weapons in modem military conflicts, which expands the area of responsibility for medical chemical protection. The authors proved necessity and algorithm of the training system, considered as a part of medical protection in case of adverse factors of chemical nature.

[Experimental Evaluation of Radioprotective Efficacy of Synthetic Genistein on Criteria of Glutathione System and Lipid Peroxidation in Erythrocytes of Peripheral Blood in Irradiated Rats].

The study was aimed to evaluate experimentally the radioprotective effectiveness of synthetic genistein in terms of the glutathione system and lipid peroxidation in erythrocytes of irradiated rats. The animals were exposed to single acute X-ray irradiation at a dose of 6 Gy. Genistein was administered intraperitoneally at 200 mg/kg 1 hour before radiation exposure. The irradiation caused the initiation of lipid peroxidation in the background depletion of reduced glutathione. Decrease by 25% in the number of malondialdehyde in the rats treated with genistein was registered 5 min after irradiation compared with the control. It is established thatl day after irradiation the level of reduced glutathione in the rats treated with genistein was 26% higher. However, intraperitoneal administration of genistein did not cause statistically significant changes in the activity of glutathione reductase, glutathione-S-transferase, or glucose-6-phosphate dehydrogenase during the whole period of observation. The results suggest that the radioprotective effect of synthetic genistein is implemented, along with other mechanisms, by stimulating the glutathione system and reducing the severity of lipid peroxidation.

[The experimental evaluation of antiradiation effectiveness of genistein by survival rates and bone marrow hemopoiesis of mice irradiated by X-rays].

The study was aimed at evaluating the radioprotective effectiveness of genistein administered at different times before or after acute irradiation. Evaluation ofradioprotective efficiency was performed by studying the 30-day survival rate, life expectancy, bone marrow hemapoiesis using the method of endogenous and exogenous colony formation. We have established that genistein at a dose of 200 mg/kg when administered 1 hour prior to irradiation has the highest radioprotective efficiency. In this case, genistein protects mice against death due to X-ray radiation at doses LD(50-90/30), increasing their survival rate by 30-44%, and reduces expression of post radiation disorders of bone marrow hematopoiesis.

Evaluation of the neurological status in experimental acute alcohol intoxication.

Approaches to evaluation of the severity of neurological disorders in animals with experimental acute severe alcohol intoxication were developed. Using the method of statistical analysis, we selected criteria, which can be used for evaluation of the severity of inhibition of the nervous system in studies of the alcoholism pathogenesis and for improvement of methods for correction of severe intoxication at the preclinical stage of drug efficiency evaluation.

[Prophylaxis and medical care in poisoning by toxic burning products].

Poising by toxic burning products are possible as in conditions of battle, so in daily actions of troops. Sanitarian-hygienic arrangements and prohibitive measure, using of filtrating respirator with a complex of supplementary workholder or isolating respirator are necessary to prevent cases of poising. On occasion of poising, success of the treatment depends on timeliness of providing of the first aid and on speed of patient evacuation in hospital. Using of antidote of carbon oxide of specimen acizol levels up the patients' chance on surviving and contributes to success of the following medical measures (oxygenation, symptom therapy).

[The glutathione-dependent antioxidant system in rats during acute intoxication by hydrazine]. / Glutation-zavisimaia antioksidantnaia sistema u krys v usloviiakh ostrogo otravleniia proizvodnymi gidrazina.

Intensity of lipid peroxidation in the liver, kidney and brain tissues, and functioning of the glutathione system were studied in purebred rats after acute intoxication by 1.1-dimethyl hydrazine at the dose of 104.5 mg/kg of body mass (LD50) and phenyl hydrazine at the dose of 170 mg/kg of body mass (LD50). According to results of the investigation, the character and direction of changes in LPO and the antioxidant system due to intoxication by hydrazines are materially dependent on their structure and affected organs and tissues. For instance, intoxication by phenyl hydrazine markedly activates free-radical activation in all analyzed tissue with accumulation of malone dialdehyde against depletion of reduced glutathione in tissue and deactivation of enzymes involved in the antioxidant defense. Intoxication by dimethyl hydrazine was associated with moderate activation of free-radical oxidation in liver with a downward LPO trend in kidney and brain at the cost of exaggerated activity of enzymes in the glutathione system and maintenance of sufficient reserve of reduced glutathione. Hence, aryl hydrazine derivatives possess more distinct pro-oxidant properties.