Objective: to detect lung morphological changes in acute intoxications with clozapine, ethanol, and their combination 3 and 24 hours after poisoning. Materials and methods. Experiments were carried out in outbred male rats weighing 270—300 g. Clozapine was given in a dose of 250 mg per kg animal body weight under chloralose anesthesia. Following 3 and 24 hours, the animals were withdrawn from the experiment by decapitation. Lung histological sections from 6 rats that had received oral clozapine 250 mg/kg, 6 rats that had oral ethanol 8.6 ml/kg, and 6 rats that had a combination of ethanol and clozapine orally in the above doses were examined 3 hours after intoxication. Those from 18 rats that had been orally given the similar agents in the above doses and withdrawn from the experiment were also investigated 24 hours after drug administration. The sections were compared with those from 6 rats that had not received the above agents. Nonparametric methods (χ2 test) were used for statistical processing. The investigators assessed the following morphological signs: circulatory disorders (plethora, hemorrhages), interstitial and alveolar edema, damage to the bronchial and alveolar epithelium and to the endothelium, and a cell reaction. The differences were considered significant at p<0.05. Results. In the control animal group, histological examination did not reveal any circulatory disorders and damage to the bronchial and alveolar epithelium and to the endothelium. Three hours after its administration, the animals that had received clozapine were observed to have acute pulmonary circulatory disorders (plethora in the pulmonary artery system, focal plethora of the capillaries of interalveolar septa and that of veins) that increased 24 hours after its ingestion. If death occurred 3 hours after ethanol intake, there was obvious perivascular edema, plethora, and hemorrhage; some alveoli contained transudate. Moderate venous plethora was seen 24 hours following ethanol administration. The secretory activity of the bronchial mucosa decreased. Three hours after coadminis tration of clozapine and ethanol, there were acute pulmonary circulatory disorders (marked plethora, multiple hemorrhages, and alveolar edema), bronchial epithelial lesion (desquamation), and no staining of endothelial cell nuclei. Lymphocyte accumulation was observed around the veins and arteriovenous anastomoses. Perivascular edema was absent. The lesions increased 24 hours after coadministration of clozapine and ethanol. Conclusion. The changes found at lung histological examination of the animals receiving clozapine alone and its combination with ethanol in conjunction with the results of forensic chemical analysis may be used to diag nose relevant intoxications and to establish their duration.

Genetic predisposition partially accounts for the clinical variability of the course of an infectious process. A total of 750 people, including 419 (81.1%) male patients aged 42.9±0.9 years, admitted to the clinics of the V. A. Negovsky Research Institute of General Reanimatology (Moscow, Russia), were genotyped to establish the influence of genetic factors on their susceptibility to critical conditions. Materials and methods. Tetra-primer allele-specific polymerase chain reaction was used to investigate single-nucleotide polymorphisms (SNP) in the xenobiotic detoxification and oxidative stress genes (CYP1A1 (three sites), AhR, ABCB1, SOD2, GCLC and CAT) and in the vascular homeostasis genes (ACE, AGT, AGTR1, NOS3, VEGFα and MTHFR). Results. A total of 268 nosocomial pneumonia (NP) cases were registered in a patient group. Individual SNP analysis has shown that among the patients with NP the risk of acute respiratory distress syndrome (ARDS) is associated with the carriage of the following genotypes: CYP1A1 rs2606345-Т/Т (p=0.0027, OR=2.38; 95% CI: 1.35—4.17) and AhRrs2066853-G/A-A/A (p=0.0012, OR=2.94; 95% CI: 1.54—5.60). The frequency of the C allele of the AGTR1 gene (re5186) was much higher among the survivors (in the NP group). The assessment of a multiplicative genetic model of genes that had demonstrated the highest single-locus effects because of a ARDS risk, as well as in-hospital mortality, could establish the complex genotype including a combination of risky alleles of the detoxi- fication and vascular homeostasis genes (CYP1A1 rs2606345-T — AhR rs2066853-A and ACE rs4340-D — AGT rs699-C — AGTR1 rs5186-C), which was associated with the increased risk of both NP and ARDS, as well as with the likelihood of a fatal outcome. Conclusion. An understanding of the risk factors of NP and ARDS will aid in predicting the outcome of the underlying disease and in developing possible preventive measures.

The success of the treatment of a patient depends on the proper identification of the pathological process and its complications on time. The procedure of the diagnostics is carried out accord� ing to a nosological principle, which is the basic principle of medicine. The other basic principles are also to be taken into account during the procedure of the verification of a certain pathological processes. First, it is necessary to determine the origin of the pathological process and the class it belongs to in accordance with the international classification of diseases (cardiovascular diseases, respiratory diseases, cancerous dis� eases, infectious disease etc.).The most important require� ment for diagnosis is identification of the etiology of the dis� ease. For example, in case of an infectious disease this determines the accuracy of the diagnosis and subsequent ade� quate antibiotic therapy. One of the main basic principles is pathogenetic. The pathogenesis (mechanisms of develop� ment) of the disease is a kind of pathologic process. The pathologic process of inflammation is a basis of infectious dis� eases and infectious complications. A necessary requirement

Objective: to study associations of DNA polymorphism in acute community-acquired pneumonia (ACAP). Subjects and methods. The study enrolled 243 patients with ACAP; a control group included 178 healthy individuals. Genetic variability was investigated for the following candidate locuses: the ACE renin-angiotensin system gene, the CCR5 chemokine receptor gene and 4 xenobiotic detoxification genes (CYP1A1, CSTM1, GSTT1, and GSTP1). According to the earlier data on the effect of CYP1A1 alleles on predisposition to pneumonia, haplotypes were determined by 3 polymorphic sites of this gene. Results. Protective and predisposing geno- and haplotypes were described by the above loci and their combinations. Homozygotes for the deletion at the ACE locus (OR=1.8; p=0.013); GSTM1-pos-itive genotypes (OR=1.7; p=0.010) and homozygotes for 606T allele in the CYP1A1 gene (OR=1.6; p=0.020) were found to have a higher predisposition to pneumonia. A combination of the two latter genotypes (OR=1.9 at p=0.006; its frequency in the control was more than 20%) proved to be prognostically most effective. Conclusion: three polymorphic markers were identified in the CYP1A1, GSTM1, and ACE genes associated with the development and course of ACAP. Key words: gene polymorphism, xenobiotic detoxification genes, pneumonia.

Objective: to evaluate the efficiency of artificial ventilation (AV) after administration of the exogenous surfactants Curosurf and Surfactant BL in premature neonates with respiratory distress syndrome (RSD). Subjects and methods. The paper presents the results of evaluation of the efficiency of therapy with exogenous surfactants, by examining the blood gas composition and AV parameters. The study included 122 premature neonates with severe RSD. According to the type of a used surfactant, two groups of neonates were identified: Group 1 comprised 67 neonates who were given Curosurf and Group 2 consisted of 55 neonates who had Surfactant BL. Results. The study has revealed some differences between the drugs. Four hours after administration of Curosurf, the neonates with RSD showed heterodirectional changes in partial blood oxygen tension; no abnormal changes in this index were found in most neonates; however, hyperoxia or hypoxia appeared in some newborn infants. After administration of Surfactant BL, no hyperoxia was virtually detected. Hyperoxia did not depend on the baseline oxygen fraction in the inspired gas mixture in most cases. The found changes were transient. To choose ventilation parameters was based on an attempt to bring partial blood oxygen tension closer to the normal values. The main task of the treatment was achieved: this was to carry out sparing AV in premature neonates, allowing no mechanical injury to the immature lung or ventilation complications. Conclusion. pO2 variability after administration of exogenous surfactants calls for a considerate attitude to the choice of AV parameters and an individual approach to a patient. The specific features of the pharmacological action of exogenous surfactants should be taken into account when they are used. In this connection, blood gas composition should be frequently investigated – particularly within the first 24 hours after administration of the agents in order to timely modify AV parameters.

Objective: to study the effects of the surfactants Surfactant-BL and Curosurf on pulmonary oxygenizing properties in preterm neonatal infants with respiratory distress syndrome (RDS). The studies were performed in 81 preterm neonates with severe RDS. For the therapy of RDS, the exogenous surfactants Surfactant-BL and Curosurf were used in 52 and 29 children with RDS, respectively. The similarity of infants from both groups was statistically confirmed. Blood gas composition and artificial ventilation parameters were examined. Results. The administration of the exogenous surfactants Surfactant-BL and Curosurf normalized blood gas composition, enhanced alveolar ventilation, and improved pulmonary ventilation-perfusion relationships. The exogenous surfactants permit the performance of artificial ventilation when the values are close to the physiological ones. There were no significant differences in the effects on the surfactants on gas exchange parameters. Key words: respiratory distress syndrome, surfactant, artificial ventilation, mean airway pressure, blood gas composition.