[Renal distress syndrome in surgery and uronephrology: concept, pathogenesis, basics of prevention and correction]. / Renal'nyi distress-sindrom v khirurgii i uronefrologii: ponyatie, patogenez, osnovy profilaktiki i korrektsii.

OBJECTIVE: Based on objective criteria of the structural and functional state of the kidneys in various urgent surgical and uronephrological pathologies (peritonitis, pancreonecrosis, intestinal obstruction, urinary peritonitis, acute purulent secondary pyelonephritis) to identify and prove the general pattern of development of renal changes, their influence on the pathogenesis of homeostasis disorders at the organizational level and to form the evidence base of a new symptom complex - renal distress syndrome in surgery and uronephrology; to establish the effectiveness of Remaxol in its correction. MATERIAL AND METHODS: Experimentally on 60 mongrel dogs with acute peritonitis, pancreatitis, intestinal obstruction of varying severity, the state of renal function, including detoxification, was assessed based on the assessment of the inflow-outflow difference in the level of toxins and in the parenchyma of organs - the composition of lipids, the activity of peroxidation of membrane lipids and phospholipases. Clinical and laboratory studies included patients with acute peritonitis (48), acute pancreatitis (18), intestinal obstruction (21), acute purulent secondary pyelonephritis (19). Patients with peritonitis (20) underwent standardized therapy (the first subgroup) or with the inclusion of Remaxol (28) (the second subgroup). RESULTS: In the experiment and in the clinic, in acute surgical and some urological diseases with a different nature of the inflammatory process, there is a significant decrease in renal function. The recorded acute renal injury is combined with a pronounced membrane-stabilizing process in the tissue structures of the kidneys, the degree of which is associated with the severity of the disease. In order to correct and stabilize the indicated changes, Remaxol was used. The drug increased kidney tolerance to trigger pathogenetic agents, which improved the functional status of the kidneys. These data confirm the significance of the studied molecular mechanisms in kidney damage in urgent pathology. CONCLUSION: Experimental and clinical evidence has been obtained for the formation of a new concept - a symptom complex in acute surgical and uronephrological diseases of the abdominal cavity and retroperitoneal space called renal distress syndrome. Renal distress syndrome in surgery and uronephrology is a set of pathological processes of the body, the most important manifestation of which is the progression of endogenous intoxication due to a violation of the functional status of the kidneys as a result of membrane-stabilizing phenomena of organ cells due to oxidative stress and phospholipase activity.

[Hepatic distress syndrome in surgery: concept, pathogenesis, prevention and correction]. / Gepaticheskii distress-sindrom v khirurgii: ponyatie, patogenez, osnovy profilaktiki i korrektsii.

OBJECTIVE: To establish the universality and regularity of hepatic disorders, their role in pathogenesis of homeostasis impairment and determine scientific base for a new syndrome - hepatic distress syndrome in surgery. MATERIAL AND METHODS: Chronic experiments on outbred dogs were carried out. Acute peritonitis was simulated in the first group (n=15), acute destructive pancreatitis in the second group (n=15), acute obstructive intestinal obstruction in the third group (15). In the fourth group, experimental acute peritonitis (n=15) was followed by Remaxol infusions (20 ml/kg). Liver function was evaluated using the indicators of endogenous intoxication, lipid metabolism markers, as well as composition of lipids in liver tissue. Clinical studies included 44 patients with peritonitis (the first subgroup - standard therapy (n=20), Remaxol infusion in the second subgroup (n=24), severe acute pancreatitis (n=18), acute adhesive intestinal obstruction (n=20)). Patients underwent surgery. Along with routine indicators, we analyzed severity of endogenous intoxication, lipid peroxidation, phospholipase activity, serum lipids and red blood cell count. RESULTS: Experimental and clinical studies have shown significant liver damage in all diseases with various pathogenesis. Regardless of urgent disease, one of the leading component is membrane-destabilizing process. The last one is determined by excessive activity of membrane lipid peroxidation and phospholipases in liver tissue. Severe abnormalities are followed by impairment of liver detoxification ability and liver may be a source of toxins per se. Remaxol infusion in the treatment of experimental and clinical acute peritonitis increased liver tolerance to trigger pathogenetic agents. This process resulted improvement of laboratory and clinical parameters. In general, we obtained high significance of liver damage in pathogenesis of acute urgent abdominal pathology. CONCLUSION: Experimental and clinical data for determining hepatic distress syndrome as important aspect in acute abdominal surgical diseases have been obtained. Hepatic distress syndrome in surgery is a combination of abnormal processes with progression of endogenous intoxication, oxidative stress and phospholipase activity following membrane-destabilizing phenomena and secondary liver dysfunction.

Production of HD Molecules in Definite Hyperfine Substates.

Polarized atomic beam sources have been in operation for many years to produce either nuclear polarized atomic hydrogen or deuterium beams. In recent experiments, such a source was used to polarize both isotopes independently at the same time. By recombination of the atoms, hydrogen-deuterium molecules with all possible nuclear spin combinations can be created. Those spin isomers are useful for further applications, like precision spectroscopy, as polarized targets for laser-particle acceleration, polarized fuel for fusion reactors, or as an option for future measurements of electric dipole moments.

[Systemic coagulopathic distress syndrome in surgery: concept, pathogenesis, prophylaxis]. / Ponyatie sistemnogo koagulopaticheskogo distress-sindroma v khirurgii, ego patogenez i printsipy profilaktiki.

OBJECTIVE: The purpose of the study is to determine the correlation of changes in the humoral and tissue components of the hemostasis system with lipid metabolism in case of various urgent surgical diseases, on the basis of which the systemic coagulopathic distress syndrome can be used as the scientific basis for the definition of a new syndrome. MATERIAL AND METHODS: The work includes the results of experimental and clinical laboratory tests. Experiments on dogs: in the first group (n=18) destructive pancreatitis; in the second (n=18) - fecal peritonitis; in the third (n=15), acute obstructive intestinal obstruction; in the fourth (n=16) fecal peritonitis, in the postoperative period, Remaxol (15 ml/kg) was included in the therapy. The analysis of 55 patients with acute peritonitis, operated on for acute appendicitis, perforated gastric or duodenal ulcer, acute intestinal obstruction, acute destructive cholecystitis. In the study group (n=28), Remaxol is included in the postoperative therapy. The state of the humoral and tissue (in the experiment, the tissues of the liver, intestines, kidneys, heart, lungs, pancreas, in the clinic - tissues of the resected organs) components of the hemostasis system was evaluated, a number of lipid metabolism indicators were determined, etc. RESULTS: In the early periods of all investigated urgent diseases of the abdomen, pronounced changes in the system of both humoral and tissue components of the hemostasis system were revealed. The modification of the coagulation system is registered not only in the tissues of the lesion organs, but also in the target organs (system tissue hemocoagulation modifications). The research established one of the most important processes - the trigger of the hemostatic cascade reaction - is membrane-destabilizing (the source of tissue thromboplastin), which is determined by changes in the phospholipid composition of various organs tissues (involved in the pathological process or not in it). Changes in lipid metabolism are due to the activation of phospholipases and membrane lipid peroxidation in tissues. The factual material was the scientific basis for the establishment of a new syndrome. Systemic coagulopathic distress syndrome is a set of pathological processes of the body, the most important component of which is a violation of the phospholipid bilayer of blood cell membranes and organ cells due to oxidative and phospholipase induced phenomena, leading to a coagulopathic condition. It changes understanding of the prevention of thrombohemorrhagic complications, proving the effectiveness of complex therapy, including not only anticoagulants, but also drugs with membrane-stabilizing activity, in particular, Remaxol.

[Systemic membrane-destabilizing distress syndrome in surgery: concept, pathogenesis, diagnosis]. / Sistemnyi membranodestabiliziruiushchii distress-sindrom v khirurgii: poniatie, patogenez, diagnostika.

AIM: To justify the concept of systemic membrane-destabilizing distress syndrome in surgery via analysis of phospholipid bilayer of cell membranes of various organs in urgent surgical abdominal diseases. MATERIAL AND METHODS: Experimental research on dogs (n=90) included modeling of peritonitis, pancreatitis, intestinal obstruction, obstructive jaundice, and post-hemorrhagic anemia. Clinical and laboratory studies were performed in patients (n=119) with acute peritonitis, severe pancreatitis, intestinal obstruction, post-hemorrhagic anemia, acute cholecystitis, gastrointestinal bleeding, benign mechanical jaundice. Lipid profile in tissues and blood cells was determined by extraction, fractionation and densitometry. Moreover, we assessed intensity of lipid peroxidation and phospholipase activity, endogenous intoxication, functional state of organs and blood cells. RESULTS: It was revealed that all above-mentioned acute abdominal diseases are followed by significant changes of lipid bilayer and dysfunction of tissues in target organs, blood cells and other organs (liver, kidney, colon and small intestine, heart, lungs, spleen, brain). Changes of phospholipid bilayer are correlated with severity and course of the disease. These data were used to determine a new complex in surgery - systemic membrane-destabilizing distress syndrome. Its concept, pathogenesis, and diagnosis are presented. It was analyzed its role in development and progression of dysregulation pathology and thanatogenesis. Evidence of its importance in the pathogenesis of surgical aggression was obtained.

Metabolic Restructuring in the Liver under Conditions of Endogenous Intoxication.

Significant metabolic alterations in the liver were observed in dogs with modeled acute peritonitis. These changes significantly impaired detoxification function of the liver, which was seen from the increase in the titer of toxic products in the early post-surgery period not only in the lymph, but also in the blood plasma. The key pathogenic mechanism leading to acute liver failure is destabilization of cell membrane resulting from LPO, phospholipase activity, and tissue hypoxia. Activation of LPO and increase in phospholipase activity in the liver tissues were observed within 12 h after peritonitis modeling.

[Enteral distress syndrome in surgery: definition, pathogenesis, diagnosis]. / Enteral'nyi distress-sindrom v khirurgii: ponyatie, patogenez, diagnostika.

It was performed a comprehensive experimental and clinical study of functional and metabolic status of the intestine in acute peritonitis, pancreatic necrosis, acute intestinal obstruction. We obtained objective data of impaired barrier function based on levels of toxins in arterial and mesenteric venous blood. Association of organ and organismic homeostatic changes was revealed. It was proved an important role of membrane-destabilizing processes in intestinal epithelium as a cause of enteral insufficiency. Leading trigger mechanisms of lipid metabolic disorders were determined. Enteral distress syndrome was determined as pathological response to acute abdominal surgical diseases. Enteral distress syndrome is a complex of pathological processes due to membrane-destabilizing mechanisms, impaired intestinal barrier function followed by progression of endogenous intoxication. This syndrome significantly aggravates the course of acute surgical abdominal diseases.

[Violations of oxygen transport function of hemoglobin in surgical endointoxication and their correction using remaxol].

AIM: To study the effectiveness of remaxol in erythrocytes oxygen transport function correction in patients with surgical endotoxicosis. MATERIAL AND METHODS: Two groups of patients (main (n = 25) and comparison (n = 27) groups) with acute appendicitis complicated by peritonitis were compared. All patients underwent standard postoperative treatment including infusion therapy 1600--2000 ml/day, antibiotics as combination of semi-synthetic penicillins and aminoglycosides, anesthetic and desensitizing therapy. In the main group daily intravenous infusion of remaxol 400 ml for 5 days was used. The first dose was administered intraoperatively or immediately after surgery. Patients underwent emergency surgery and destructive forms of acute appendicitis accompanied by diffuse purulent or purulent-fibrinous peritonitis were diagnosed. Removal of appendix, debridement and drainage of the abdominal cavity were performed. Observation of clinical and laboratory tests were carried out at admission and in 1, 3, 5 days after surgery. CONCLUSION: Acute peritonitis leads to changes of hemoglobin conformation and its oxygen-binding capacity according to spectroscopy that is an important factor in the development of general hypoxia. The greatest changes in the hemoglobin molecule were found in the 1st day after surgery as a result of surgical aggression. It is proved that modified conformational state of hemoglobin is associated with processes of lipid peroxidation and endogenous intoxication. Combined therapy with remaxol is effective to correct oxygen transport function of hemoglobin in acute peritonitis. Pronounced positive effect of the drug weakening manifestations of surgical aggression is noted after the first administration. Therapeutic efficacy of the drug is explained by its ability to reduce lipid peroxidation. Rapid recovery of homeostasis including decrease of general hypoxia using remaxol resulted in a clinical benefit.

[Hemoglobin oxygen transport capacity in surgical endotoxicosis ].

In surgical endointoxication hemoglobin oxygen transport capacity of red blood cells (hemoglobin affinity ligands: the ability to bind and release ligands) is reduced and is associated with the severity of endogenous intoxication. Violation of oxygen transport function of hemoglobin at endogenous intoxication is associated with conformational changes of a biomolecule, and its possible influence on reactive oxygen species, which confirmed in experiments in vitro: under the influence of oxygen-iron ascorbate ability of hemoglobin deteriorates. Largely similar structural and functional changes in hemoglobin occur in patients with surgical endotoxicosis.

Production of hyperpolarized H_{2} molecules from H[over →] atoms in gas-storage cells.

The preservation of the nuclear polarization of hydrogen atoms during the recombination to molecules was observed on different surface materials in the temperature range from 45 to 100 K and for magnetic fields up to 1 T. On a gold and a fused quartz surface, the expected molecular polarization of about 50% or lower of the atomic polarization was measured, while a surface layer of perfluoropolyether (Fomblin) shows a nearly complete preservation (at least 97%) of the atomic polarization during the recombination process. Further experiments have the possibility of storing polarized deuterium molecules and to use them in nuclear-fusion installations. Another application might be the production of polarized substances for enhanced NMR techniques.

[Rengalin, a New Efficacious and Safe Antitussive Agent. Results of a Randomized, Comparative, Multicenter Clinical Trial in Patients with Acute Respiratory Tract Infections].

UNLABELLED: Rengalin is a release-active combination antitussive drug based on antibodies to bradykinin, to histamine and morphine. It acts at various mechanisms of cough reflex by modifying endogenous target molecules and their interaction with receptors. The drug's efficacy, as demonstrated previously in experimental and clinical studies, is mediated by specific release-activity obtained as a result of the production process. METHODS: Efficacy and safety assessment of rengalin in the treatment of cough induced by acute upper respiratory tract infections (URIs) in comparison with a complex codeine-containing drug (codelac) was performed as part of a multicenter, randomized clinical trial involving 143 patients. All the participants presented with dry/non-productive cough caused by URIs (pharyngitis, laryngitis, tracheitis, tracheobronchitis, bronchitis). The duration of cough varied between 12 hours and 7 days. Rengalin was administered in 73 patients receiving 2 tablets 3 times daily for initial three days, and half reduced doses--for the subsequent four days; codelac was administered in 70 patients who were given 1 tablet 3 times daily for the entire treatment period (7 days). Primary efficacy endpoints were time to cough resolution and reduction in the severity of the cough (scored using a Cough Severity Scale). One patient in Rengalin group and three patients in Codelac group were withdrawn from the study. The article presents treatment outcomes obtained for 139 participants who completed the study in accordance with the protocol (Per Protokol-analysis). The data analysis was based on a non-inferiority (or comparability) statistical design for efficacy endpoints. RESULTS: The antitussive effect of rengalin was significantly comparable (p < 0.025) with that of codelac; the time to complete resolution of cough (both daytime and nocturnal) was 7.2 ± 1.0 days (versus 7.0 ± 1.1 in the group of codelac). Rengalin's efficacy was evidenced by a sufficiently reduced cough severity in the initial few days after treatment onset. As a result of the entire 7-day treatment, the severity score was reduced by 3.1 ± 09 (versus 3.1 ± 1.0 in the group of codelac; p < 0.05), totaling 0.2 ± 0.5 point in both groups at the end of the administration period. The frequent non-productive/dry cough was fully resolved in 76% of patients. All the participants in Rengalin group achieved either convalescent outcomes or significant improvement; none of the patients developed secondary bacterial complications. Positive changes in the patients' state over the week were finally confirmed by evaluating the total quality of life scores, including physical and mental component scores (SF-36 questionnaire), and total sleep quality scores, which were comparative between patients treated with rengalin and codelac (p < 0.025). At the end of the administration period, the effect of rengalin was rated by the physician investigators as 'pronounced'. The Clinical Global Impression Scale-Efficacy Indices (CGI-EI) in the groups of rengalin and codelac were comparable, equating a score of 3.7 ± 0.5 (p < 0.025). The safety outcomes of rengalin treatment were assessed across all 143 randomized patients. The drug's high safety profile was confirmed by the absence of adverse events that could be reliably related to the study treatment, and by monitoring of laboratory variables. Rengalin demonstrated good tolerability and favorable compatibility with other medications for URIs with concomitant pathology. The patients showed 100% treatment compliance. CONCLUSIONS: Rengalin is a new efficacious and safe drug indicated for the treatment of URI-induced cough. The severity of daytime and nocturnal cough begins to decrease as soon as on the first day after rengalin administration, with severity reduction observed throughout the whole treatment period. At the completion of the 7-day administration, cough severity is reduced by almost 100% and its changes are comparable with the outcomes of treatment with codelac. By targeting various cough reflex mediators, rengalin enables achieving an antitussive effect in the early days after URI onset (in dry, irritative cough episodes), and a protussive effect at later points of treatment. Rengalin promotes resolution of URI-induced cough without development of secondary bacterial complications.

Cryogenic distillation facility for isotopic purification of protium and deuterium.

Isotopic purification of the protium and deuterium is an important requirement of many physics experiments. A cryogenic facility for high-efficiency separation of hydrogen isotopes with a cryogenic distillation column as the main element is described. The instrument is portable, so that it can be used at the experimental site. It was designed and built at the Petersburg Nuclear Physics Institute, Gatchina, Russia. Fundamental operating parameters have been measured including a liquid holdup in the column packing, the pressure drops across the column and the purity of the product at different operating modes. A mathematical model describes expected profiles of hydrogen isotope concentration along the distillation column. An analysis of ortho-parahydrogen isomeric composition by gas chromatography was used for evaluation of the column performance during the tuning operations. The protium content during deuterium purification (≤100 ppb) was measured using gas chromatography with accumulation of the protium in the distillation column. A high precision isotopic measurement at the Institute of Particle Physics, ETH-Zurich, Switzerland, provided an upper bound of the deuterium content in protium (≤6 ppb), which exceeds all commercially available products.

Free radical lipid peroxidation in the nuclei of mouse liver cells under normal conditions and after partial hepatectomy.

The dynamics and periodicity of LPO processes in the nuclei and chromatin were detected during regenerative processes in mouse liver. LPO processes were enhanced in transcriptionally active and replicating chromatin. Phosphatidylcholine, phosphatidylinositol, esterified cholesterol, and free fatty acids were maximally oxidized during active transcription, and cardiolipin was oxidized during active replication. These processes were accompanied by periodical changes in activity of antioxidant enzymes. High activity of SOD during transcriptional activity of liver cells was typical for nuclear matrix-attached chromatin, but this parameter decreased during replication. Catalase activity significantly increased in the fractions of high salt chromatin and nuclear matrix-bound chromatin during replication.

[The directions and experiences of integration of clinical laboratory diagnostic and branch medicine].

The article considers the actual issues of teaching laboratory medicine to students of medical faculty and to physicians getting trained in different programs of postgraduate education. The major models of interaction between clinical physicians and specialists of laboratory diagnostic are considered. The proposed model of teaching of laboratory medicine is developed in collaboration with clinical chairs and is based on the principle of "clinical laboratory council of physicians". The analysis of clinical cases of specific patients and clinical analytical critiques are in the basement of the given system. The algorithm of considering one of situation tasks used in teaching is presented as example.

[Clinical, laboratory, and functional characteristic of patients with bronchial asthma and chronic obstructive pulmonary disease with disturbances of oxalic acid metabolism].

We studied the role of oxalate release through the airways as a potential injurious factor in the development of inflammation, bronchial obstruction and cough syndrome (respiratory oxalosis). Detection of oxalates in bronhcoalveolar lavage fluid and daily urine is the most valuable method for diagnostics of oxalates. Systemic effects, such as cholelithiasis, urolithiasis, and spinal osteochondrosis are characteristic clinical signs of respiratory oxalosis, besides purely respiratory symptoms.

[The treatment of patients with broncho-pulmonary pathology and concomitant disturbances of oxalic acid metabolism].

This work was aimed at estimating the role of special therapy of patients with bronchial asthma, COPD and hyperoxaluria designed to restrict the delivery or eliminate excess of oxalates and producing well apparent beneficial effect confirmed by the disappearance or decrease of clinical and functional manifestations of obstruction, reduction of requirements for broncholytic and anti-inflammatory agents.

[Consideration of the psychosomatic status as one of the conditions for effective treatment and controlled asthma].

The lecture is dedicated to the idea of a role of psychosomatic disorders in the occurrence and development of asthma, on the diagnosis and treatment of the neuropsychic type of its course, and on possibilities for psychotherapeutic correction.

[Bronchial asthma and obesity: common mechanisms].

The prevalence of bronchial asthma and obesity has grown in the recent decades. The mechanisms of these pathologies remain unclear despite a number of publications on the relationship between the two diseases. Analysis of the association of BA with obesity should take into account that both diseases develop in young children undergoing effects of breast milk and specific nutrients, intestinal colonization pattern (neonatal and early childhood), body mass at birth and it growth rate, sedentary lifestyle, and adipokine level in early ontogenesis. The available data suggest that the phenotype of BA associated with obesity is characterized by a number of clear-cut peculiarities (more severe clinical manifestations with frequent exacerbaions and impaired control of the disease). Moreover; such patients show no signs of cellular inflammation. There are several distinct mechanisms characterizing obesity-associated BA, viz. co-morbid conditions such as gastroduodenal reflux disease, sleep apnea, obesity-associated systemic inflammation (elevated cytokine (IL-6, TNF-alpha) levels), oxidative stress, production of obesity hormones (leptin. adiponektin, resistin). Thus, BA and obesity have some common potential mechanisms, including genetic factors, systemic inflammation, mechanical factors, and concomitant diseases. Understanding the common mechanisms of these diseases will promote the development of new therapeutic strategies.

[Evaluating the activity of the apoptosis-regulating genes from Bcl-2, Bax expression, and caspase-3 activity in bronchial epithelial cells in patients with asthma].

The specific features of bronchial epithelial cell apoptosis in asthma were studied, by evaluating the activity of the apoptosis-regulating genes Bcl-2, Bax, and caspase-3. Fibrobronchoscopy with target biopsy of the bronchial mucosa was carried out in 21 asthmatic patients (the latter had given informed consent). The expression of Bcl-2, Bax, and CPP32 (caspase-3 activity) was determined in the bronchial epithelial cells by the immunohistochemical technique using the DAKO kits. Allergic asthma is characterized by higher Bcl-2 and lower Bax expression than non-allergic asthma and in patients receiving systemic glucocorticosteroids. The similar nature of changes was found in the analysis of the Bcl2/Bax ratio. Regardless of the type of asthma, the expression of caspase-3 was rather high. The specific features of impaired bronchial epithelial cell apoptosis in different types of asthma can determine the pathogenetic value of apoptotic disorders in the persistence of allergic inflammation.

[Effect of pneumo 23 vaccine administration in patients with chronic obstructive pulmonary disease of intermediate severity].

AIM: To study dynamics ofclinico-immunological parameters in patients with chronic obstructive pulmonary disease (COPD) of intermediate severity after administration of Pbeumo 23 vaccine. MATERIALS AND METHODS: Forty-five patients with COPD of intermediate severity comparable to sex, age, duration of smoking and COPD history were divided on two groups: main group (I)--20 patients vaccinated with Pneumo 23 vaccine, and control group (II)--25 patients, which received only standard treatment. Complete blood count, sputum cytology, expiratory function as well as immunological parameters (levels of CD4+, CD8+, CD20+, CD25+, and IFN-gamma) were studied at baseline as well as 21 days, 3 months, and 6 months after vaccination. RESULTS: Stable remission of the disease (during 6 months) was noted in all patients in group I and in 20% of patients in group II. In group I, levels of CD4+ and CD8+ lymphocytes did not change significantly, whereas number of activated T-lymphocytes (CD25+) significantly increased. There were substantial increase of IFN-gamma level and decrease of IgE level in serum in group I that could point to predominance of Thl-dependent immune response and activation of cellular immunity. There were no such changes in group II. CONCLUSION: Administration of Pneumo 23 resulted in decrease of intensity of local inflammation and prolonged remission of COPD that allowed to recommend inclusion of vaccination to standard protocols of treatment for such patients.