[Predicting the course of urgent abdominal diseases based on intensity of catabolic phenomena]. / Prognozirovanie techeniya urgentnykh zabolevanii zhivota na osnove otsenki intensivnosti katabolicheskikh yavlenii.

OBJECTIVE: To develop a highly informative method for predicting the course of early postoperative period in urgent abdominal surgery based on indicators of lipid metabolism. MATERIAL AND METHODS: We analyzed 113 patients with acute surgical abdominal disease including 56 (49.6%) ones with acute appendicitis complicated by peritonitis, 23 (20.4%) ones with acute intestinal obstruction complicated by peritonitis and 34 (30.0%) patients with acute moderate pancreatitis (early phase). Leukocyte count, malondialdehyde, medium-weight molecules and lipid composition (phospholipid lysoforms) were analyzed throughout a 5-day period. Considering these data, we developed a method for predicting the course of early postoperative period (patent). RESULTS: Original method is highly effective in predicting the course of early postoperative period in urgent abdominal diseases. Sensitivity and specificity of this method for acute abdominal diseases complicated by acute peritonitis are 94.7% and >86.3%, for acute pancreatitis - 92.7 and 85.4%, respectively. CONCLUSION: Efficacy of original method is determined by analysis of catabolic phenomena, i.e. indicators of tissue destruction. Of course, assessment of endogenous intoxication whose toxins are components of catabolic (membrane-destructive) processes is essential.

[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.

[Problems and prospects of kinesiotaping use in clinical practice]. / Problemy i perspektivy primeneniya kinezioteipirovaniya v klinicheskoi praktike.

Currently the concept of kinesiotaping has become widespread. Kinesiotaping, which was originally implemented in sports medicine, is increasingly used in rehabilitation and various spheres of medicine, such as orthopedics, traumatology, pediatrics, etc. In recent years, the new publications about the kinesiotaping use in neurology and rheumatology have been released, where previously unknown effects, such as improved sensory feedback, have been demonstrated. Great attention is paid to comparative studies of the effects of kinesiotaping and other methods of taping, which have been used for many years. Nevertheless, despite the popularity of this physical therapy and rehabilitation method, the number of scientific studies supporting its use remains insufficient. The effects originally attributed to kinesiotaping are still controversial, and there is insufficient scientific evidence supporting them. It is not reliably determined whether the tape has a tonic or relaxing effect due to the stimulation of the mechanoreceptors and how the taping affects fascial tissue. Its effect on the reduction of pressure in subcutaneous structures, its mechanisms of action on the microcirculatory bloodstream by stimulating exteroceptors and proprioceptors is unclear. The difficulty of kinesiotaping efficacy evaluation consists in the variety of techniques and the necessity to choose the location of the tape applying, its shape, the suitable tension and adhesion time. The article represents the results of the latest scientific researches on the pathogenetic mechanisms of kinesiotaping and efficacy of this technique in various nosologies.

[Enteral protection in patients with diffuse peritonitis]. / Enteroprotektsiya v povyshenii effektivnosti lecheniya patsientov s rasprostranennym peritonitom.

OBJECTIVE: To improve treatment outcomes in patients with diffuse peritonitis via enteral protection using intestinal lavage with ozonized solution through an original tube. MATERIAL AND METHODS: We analyzed 78 patients with advanced peritonitis. The control group included 39 patients who underwent standard measures after surgery for peritonitis. The main group consisted of 39 patients who underwent early postoperative intestinal lavage with ozonized solutions through original tube for 3 days. RESULTS: Clinical and laboratory parameters, as well as ultrasound data indicated better correction of enteral insufficiency in the main group. Morbidity in the main group was lower by 33.3%, length of hospital-stay - by 3.5 days. CONCLUSION: Early postoperative intestinal lavage with ozonized solutions through original tube accelerates recovery intestinal function and improves treatment outcomes in patients with widespread peritonitis.

[Possible ways to approach the effectiveness of open abdominal interventions to laparoscopic]. / Vozmozhnye puti priblizheniya rezul'tativnosti otkrytykh abdominal'nykh vmeshatel'stv k laparoskopicheskim.

THE PURPOSE OF THE WORK: Based on the determination of the mechanisms of negative manifestations of surgical aggression in open interventions, compared with laparoscopic, to determine ways to optimize the early postoperative period when using them. MATERIAL AND METHODS: The work is based on clinical and laboratory analysis of 147 patients with acute appendicitis complicated by acute peritonitis. In the first group (n=58), patients were operated with traditional laparotomy access. In the second group (n=47) - laparoscopic interventions were used. In the first and second groups, traditional therapy was carried out according to clinical recommendations. In the third group (n=42), patients were operated with traditional laparotomy access, and in the early postoperative period, their therapy included remaxol (intravenous injections of 800.0 ml of the drug in the first two days, then within three days - 400.0 ml). Laboratory and instrumental studies were carried out in patients, including the level of hydrophilic and hydrophobic toxins in the blood, the intensity of peroxidation of membrane lipids and antioxidant enzyme potential, the activity of phospholipase A2. The functional status of the intestine and liver was assessed. RESULTS: It was found that the most important manifestation of the reduction of surgical aggression in the early stages after surgery, which is characteristic of laparoscopic operations, are significantly low phenomena of endogenous intoxication against the background of a significant decrease in the activity of peroxidation of membrane lipids and phospholipase systems - triggers of catabolic phenomena and lesions of various organs and systems, including the intestine and liver. The inclusion of remaxol in complex therapy for patients who have undergone open surgical operations leads to a number of positive clinical and laboratory effects. The most important of them is the reduction of endogenous intoxication. This beneficial effect is associated with the restoration of the functional status of the intestine and liver, as well as a decrease in the severity of catabolic phenomena. The effectiveness of complex therapy with remaxol was marked by reducing the number of postoperative complications and the length of the patient's stay in the hospital. CONCLUSION: The use of remaxol in patients with acute peritonitis complicated by peritonitis who have undergone open surgical interventions, due to the relatively rapid restoration of the functional status of the intestine and liver, reduction of catabolic phenomena, reduces the severity of endogenous intoxication syndrome, which was the basis for a significant improvement in the course of the early postoperative period, bringing it closer to that when using laparoscopic technology.

[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.

[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.

[Intensification of the organism detoxification ability under surgical endogenous intoxication]. / Povyshenie detoksikatsionnoi sposobnosti organizma pri khirurgicheskom éndotoksikoze.

The purpose of the study is to establish the effectiveness of remaxol in the correction of endogenous intoxication in patients with acute peritonitis. MATERIAL AND METHODS: The work is based on the results of clinical and laboratory studies. The clinic examined 55 patients with acute moderate peritonitis as complication of various diseases (acute appendicitis, perforated gastric or duodenal ulcer, acute intestinal obstruction, acute destructive cholecystitis). Before surgical operation and in the early postoperative period we evaluated the severity of endogenous intoxication by the level of hydrophilic and hydrophobic toxic products. The content of molecular products of lipids peroxidation - oxidative stress, phospholipase activity were determined in the blood plasma. In the study group (n = 28) in the postoperative therapy additionally included remaxol (400 ml intravenous fluids). RESULTS: Research established that the occurrence of endogenous intoxication syndrome in patients with acute peritonitis associated with the activation of oxidative stress and phospholipases, high intensity of which is maintained even after elimination of the source of peritonitis with manifestation on the 1st day after surgery. Remaxol include leads to a significant reduction in the severity of intoxication syndrome in patients with acute peritonitis. Positive effect of the drug on the correction of endogenous intoxication is largely determined by its ability to significantly reduce oxidative stress and the activity of phospholipases, as the most important membrane destabilizing agents. The greatest detoxication effect of the drug is recorded when it is applied already at the preoperative stage of patients when its ability to reduce the activity of trigger agents of catabolic processes implemented to the greatest extent. CONCLUSION: In acute moderate peritonitis, remaxol use before surgery or in the early postoperative period in complex therapy leads to a significant correction of factors contributing to the development and preservation of the intensification of catabolic processes - one of the sources of endogenous intoxication.

[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.

[Restoration of tissue reparative ability during acute pancreatitis (in Russian only)]. / Vosstanovlenie reparativnoi sposobnosti tkanei pri ostrom pankreatite.

AIM: The purpose of the study was to establish the effectiveness of Remaxol in restoring tissue reparative ability of laparotomy wound in acute severe pancreatitis. MATERIAL AND METHODS: The work is based on the results of experimental and clinical studies. Experiments were carried out using acute total pancreatic necrosis model under anesthesia on 30 dogs. Furthermore, 28 patients with acute severe pancreatitis were examined and underwent surgery on various purulent-necrotic complications. In the postoperative period, healing and metabolic processes were evaluated in the tissues along the sutures line of the laparotomy wound. Also, such parameters as endogenous intoxication, oxidative stress, and phospholipase activity were evaluated at the organism level. In the studied groups, Remaxol is included in the postoperative therapy. RESULTS: It has been established that during acute severe pancreatitis reparative potential of tissues is significantly reduced, which is caused by a significant disruption of trophism, activation of phospholipases and peroxidation of membrane lipids. Disorders of homeokinesis at the organism level play a negative role in tissue reparative potential reduction. Inclusion of Remaxol in the complex therapy of acute pancreatitis leads to a decrease in duration of wound healing by reduction in the phase of inflammation. Optimization of the healing process occurs due to complex effect of the drug at organ and body level, which results in improvement of the trophism and, what's more, stabilizes membranes of regenerating cells. CONCLUSION: In case of acute severe pancreatitis, the use of Remaxol in early postoperative period in the complex therapy leads to a significant correction of factors that adversely affect regeneration and contributes to the restoration of tissue reparative potential.

[Possibilities of tissue repair induction during mechanical jaundice of non-tumor genesis]. / Vozmozhnosti indutsirovaniia reparatsii tkanei pri mekhanicheskoi zheltukhe neopukholevogo proiskhozhdeniia.

AIM: The aim of this research was to study the effects of complex therapy with Remaxol inclusion on laparotomy wound tissue reparative process in patients with obstructive jaundice in early postoperative period. MATERIAL AND METHODS: Clinical and laboratory studies were carried out in 55 patients undergoing surgery of the biliary tract, including 35 patients with mechanical jaundice of non-tumor origin and 17 of them received Remaxol (for 5 days daily intravenous infusions of 400 ml each) in the early postoperative period. RESULTS: It has been proved that mechanical jaundice is a significant complication in the reparative process of laparotomy wound tissue structures. A significant decrease in the reparative potential of tissues can occur due to a local deterioration of the tissue metabolism of regenerating structures, and on the organism level - endogenous intoxication syndrome, hypoxia, oxidative stress, hypoalbuminemia. CONCLUSION: Remaxol is a drug with hepatoprotective, antioxidant and antihypoxant effects and its use in patients with obstructive jaundice makes it possible to correct disease pathogenetic impact on organic and organism level, which leads to optimization of reparative regeneration. A noticeable decrease in the early postoperative period of wound complications has been established as well as a significant reduction in days patients spent in the hospital.

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.

DNA methylation by wheat cytosine DNA methyltransferase: modulation by protease inhibitor E-64.

Cytosine DNA methyltransferase isolated from wheat seedlings and purified in the presence of metalloprotease and serine protease inhibitors has molecular mass and specific activity equal to about 85 kDa and 250 units/mg protein, respectively. Apparent K(m) for AdoMet and [I]50 for AdoHcy values are about 6 microM and 12 microM, respectively. The enzyme is active in wide pH range (pH 5.5-8.5) and is inhibited by NaCl. The enzyme rapidly loses its methyltransferase activity in the absence of substrates. Using the cysteine protease inhibitor E-64 it has been shown that rapid enzyme inactivation is caused by disappearance of essential enzyme SH-groups but is not due to proteolytic enzyme cleavage.

[Effect of storage conditions on the kinetic properties of myosin ATPase]. / Vliianie uslovii khraneniia na kineticheskie svoistva miozinovoi ATPazy

"Substrate inhibition", which has been described earlier for myosin Ca-ATPase in low ionic strength KCl solution [1], is found to take place also at high KCl concentration and under partial modification of enzyme thiol groups with p-CMB. "Substrate inhibition" disappeared when increasing Ca2+ concentration up to 25-40 mM. These kinetic properties are characteristic for fresh isolated enzyme and myosin preparations stored in 0.5 M KCl. They may change under storage of enzyme preparations at higher KCl concentrations: no "substrate inhibition" is observed after 6-8-day storage of myosin preparations in 3 M KCl at the presence of 4-5 mM CaCl2. The data on optical rotation dispersion and analytical ultracentrifugation have shown that the storage of myosin in 3 M KCl is accompanied by structural changes of the protein.

[Alkaline activation of myosin ATPase: some thermodynamic characteristics]. / Shchelochnaia aktivatsiia miozinovoi ATPazy; nekotorye termodinamicheskie kharakteristiki

The increase in temperature leads to a decrease in pKa of the group responsible for the activation of CaATP2- hydrolysis by myosin in the alkaline zone of pH. At 20-25 degrees the pKa value is about 9. The value of ionization heat (deltaHi) calculated from pKa temperature dependence is 7.6+/-+/-0.8 kcal/mol. These values are approximated to the values known for phenol hydroxyl of tyrosine. It has been demonstrated that the acceleration of CaATP2- hydrolysis at alkaline values of pH is accompanied by an increase in the Arrhenius energy of activation (Ea), determined from the temperature dependence of the maximal reaction rate (V). The increase of Ea at alkaline values of pH is apparent and is due to an increase in the concentration of a deprotonized form of the enzyme, having a higher activity. A comparison of activation parameters of the reaction at alkaline and neutral values of pH permits to conclude that the acceleration of CaATP2- hydrolysis at alkaline values of pH is due to the acceleration of the limiting step of the reaction. It has also been found that at alkaline values of pH the power of myosin binding with ADP, a competitive inhibitor and the reaction product, is decreased. It is assumed that the acceleration of ATP hydrolysis at alkaline values of pH is due to accelerated dissociation of the reaction products from the active centre of the enzyme, as a result of ionization of a functional group of myosin, probably of the tyrosine residue.