Kinetic modeling of demasking and hydrolysis of peptide bonds during proteolysis of ß-lactoglobulin by trypsin.

Proteolysis of ß-lactoglobulin by trypsin was studied with fluorescence spectroscopy and an empirical exponential model was engaged to describe the peptide bond hydrolysis kinetics. The shift in the fluorescence maximum of tryptophan residues, from 342 to 352 nm, in the course of ß-lactoglobulin degradation was used as an indicator of the transition of masked peptide bonds to the demasked ones, which were accessible for the enzyme action. A simple equation with only two parameters was suggested to link together the degree of demasking of peptide bonds and the degree of their hydrolysis, allowing the kinetic description of proteolysis.

[A comparison of a neuroprotective effects of hypoxic postconditioning and cerebrolysin in the experimental model].

Hypoxic postconditioning using episodes of mild hypobaric hypoxia is a new neuroprotective technique. We compared the neuroprotective efficacy of hypoxic postconditioning and cerebrolysin in a model of posthypoxic pathology in rats. Animals that survived the severe hypoxia (180 Torr, 3 h) were exposed to hypoxic postconditioning or received cerebrolysin. Postconditioning prevented the injury and loss of hippocampal (fields CA1, CA4) and neocortical neurons whereas cerebrolysin was protective only for CA4 and the neocortex. Besides that, postconditioning, unlike cerebrolysin, led to the complete functional rehabilitation from the severe hypoxia by normalizing the level of anxiety and the pituitary-adrenal axis activity. The findings demonstrate that the elaborated postconditioning technique might provide useful tool for therapy of posthypoxic pathology and stroke.

[Hypoxic postconditioning corrects behavioral abnormalities in a model of post-traumatic stress disorder in rats].

Protective effects of the novel technique of hypoxic postconditioning with a hypobaric hypoxia paradigm were studied in "stress-restress" model ofposttraumatic stress disorder in rats. It was shown that repeated (3 times) exposure of rats that survived after severe traumatic stress to mild hypobaric hypoxia (postconditioning mode) efficiently abolished the development of stress-induced anxiety state. Postconditioning had a clear anxiolytic effect both when it was delivered after traumatic stress and after restress, but the intensity of this effect depended on the period ofpathogenesis of the posttraumatic stress disorder, when postconditioning was given. The results indicate that suggested postconditioning model with repetitive mild hypobaric hypoxia exerts potent anxiolytic and stress-protective action.

[Changes in intensity of hypoxic brain damage in rats induced by hypoxic postconditioning].

The present study has been aimed to estimate a neuroprotective effect of postconditioning (PostC) by using mild hypobaric hypoxia (360 mm Hg, 2 h) in a model of severe hypoxic brain injury (180 mm Hg, 3 h) in rats. PostC was performed by three trials of mild hypoxia with 24 h intervals, according to two different protocols--PostC was started 3 h (early PostC) or 24 h (delayed PostC) following severe hypoxia. Using histological methods and computer image analysis, loss of neurons in hippocampus and neocortex was analyzed 7 days after severe hypoxia. Severe hypoxia caused loss of 24% of neurons in layer V of the neocortex, 26% of neurons in CA1 region of hippocampus and 22% of neurons in CA4 region. Early PostC prevented loss of neurons in CA1 region of hippocampus and significantly reduced loss of neurons in neocortex (to 13%) and in CA4 region (to 10%). Delayed PostC fully prevented neuronal damage in CA4 region of hippocampus and neocortex and was to a large extent but not completely protective in CA1 region (12% of neurons were lost). The results show that PostC performed by hypobaric hypoxia has a pronounced neuroprotective effect, reducing the loss of neurons in vulnerable structures of brain (hippocampus and neocortex). The efficacy of neuroprotection depends upon the time of presentation of the first PostC session.

[Comparative evaluation of the motor-evacuation function of the stomach after functional operations for complicated duodenal ulcers]. / Sravnitel'naia otsenka motorno-évakuatornoi funktsii zheludka posle funktsional'nykh operatsii pri olozhnennykh duodenal'nykh iazvakh.

Motor-evacuatory disorders (MED) of the stomach in 114 patients who have undergone functional operations for duodenal ulcers were analyzed. Clinical picture, barium contrast and ultrasonic examinations, fibrogastroduodenoscopy, pH-monitoring were used for evaluation. Many patients have MED of different degree in early postoperative period. Some patients have severe disorders that require drug therapy. US and endoscopy role in complex assessment and differential analysis of stomach evacuatory disorders is emphasized. Isolated elements of study methods are discussed.

[Classification of enterprises according to degree of accident and occupational disease risk]. / O klassifikatsii predpriiatii po stepeni riska neschastnykh sluchaev i profzabolevanii.

The authors suggested approach to classification of enterprises and economy branches according to occupational conditions. Suggestion is to classify by means of quantitative methods based on claster analysis.

Kinetics of beta-casein hydrolysis by wild-type and engineered trypsin.

Apparent rate constants of tryptic hydrolysis of amide bonds containing Arg and Lys residues in beta-casein were determined by the analysis of kinetics of accumulation of 17 major peptide components revealed by high performance liquid chromatography. When studying pH influence on Arg/Lys bond cleavage preference, averaged rate constants over several Arg&bond;X and Lys&bond;X bonds were used for analysis of kinetics of wild-type trypsin, K188H, K188F, K188Y, K188W, and of K188D/D189K mutants. The pK(a1) value of 6.5 was found for all studied trypsins. For wild-type trypsin and its K188D/D189K mutant, pK(a2) was found to be 10. The lowest among studied engineered trypsins pK(a2) = 9.3 was determined for K188Y mutant. Considerable preference for the cleavage of Arg over Lys containing peptide bonds was demonstrated for all trypsins with engineered S2 site except for K188H and K188F. The comparison of individual rate constants for various bonds showed that during the hydrolysis by wild-type trypsin, the probabilities of splitting depend on secondary specificity and local hydrophobicity of amino acid residues, which are nearest to the hydrolyzed peptide bond (P2 site). The improvement of prediction of hydrolysis rates performed by the used program was achieved after considering the presence of hydrophobic neighborhood of Lys48--Ile49 and Arg202--Gly203 bonds.

[Long-term results of endovascular treatment of metastatic renal cell cancer]. / Otdalennye rezul'taty éndovaskuliarnogo lecheniia metastaticheskogo pochechnokletochnogo raka.

The authors analyse the long-term results of treatment of 106 patients with advanced renal cell carcinoma. The patients were divided in two groups. Group 1 (42 patients) included cases with single metastatic lesion. Patients of group 2 (n = 64) had more than one site of metastases. All patients were treated by nephrectomy, embolization with chemotherapeutic agent or arterial occlusion without cytostatic drug except nine patient of group 2, who has undergone chemo and hormonal therapy. The survival according to method at treatment was studies. After occlusion satisfactory results were obtained in cases with single metastasis lesion and also in cases with many sites of metastases. Oily chemoembolization in renal cell carcinoma with distant metastases has given better results as compared with the embolization without chemodrugs. We conclude that endovascular method of treatment is an alternative to the traditional nephrectomy in palliation of renal cell carcinoma.

Quantitative comparison of casein and rapeseed proteolysis by pancreatin.

The problem of quantitative comparison of kinetic curves was solved for casein and rapeseed pancreatin hydrolysis in a membrane reactor, which ensured the measurement of proteolysis kinetics for the products with a molecular weight of less than 1000. Coordinates were derived which provided good linearization of kinetic curves and the determination of relative rate constants irrespective of reagent concentrations, E0/S0 ratio and time intervals of kinetic measurements. When the relative rate constants of the release of the individual amino acid residues in the low-weight proteolysis products were compared, trypsin-dependent constants (for Lys and Arg residues) were found to be two times less for rapeseed than for casein, and chymotrypsin-dependent constants (for Tyr and Phe residues) were approximately 1.3 times higher for rapeseed than for casein. Statistical analysis demonstrated that the distribution of constants was narrower for rapeseed than for casein. Differences between target (Arg, Lys, Tyr and Phe) and non-target constants of release in the form of peptides and free amino acids, or in the form of free amino acids only, were attributed on the differences in the peptide bond masking for casein and rapeseed proteins. Computer simulation of proteolysis kinetics was performed by PROTEOLYSIS program package to confirm the dependence of rate constant distribution on the state of masking.

[Initial kinetics of milk protein hydrolysis by chymotrypsin]. / Issledovanie nachal'noi kinetiki gidroliza belkov moloka khimotripsinom.

The kinetics of the initial stages of hydrolysis of alpha- and beta-caseins, alpha-lactalbumin, beta-lactoglobulin, and bovine serum albumin was studied quantitatively by electrophoresis. The hydrolysis rates of caseins (demasked polypeptide chains) exceeded the rates of the degradation of milk whey proteins limited by the protein globule demasking by more than two orders of magnitude. Even relatively accessible for hydrolysis globular proteins (beta-lactoglobulin and BSA) were hydrolyzed by the one-by-one mechanism. The maximum value of the ratio between the rates of the peptide chain demasking and the protein globule hydrolysis was 0.0035.

[Physical treatment methods during World War II]. / Fizicheskie metody lecheniia v gody Velikoi Otechestvennoi voiny.

The authors review the experience gained in the use of physiotherapy during World War II, specify essential principles of field physiotherapy, its stages and system. The number of the wounded and the sick who have benefited from physiotherapeutic procedures are reported. Most effective methods in management of war injuries and their sequelae which remain of importance today are analyzed.

[The informational significance of the pulse waves of an intracerebral rheoencephalogram]. / Informatsionnoe znachenie pul'sovykh voln vnutrimozgovoi reoéntsefalogrammy.

The evidence obtained on the pulse waves of intracerebral rheoencephalogram in rabbits and cats, suggests active responses of cortical vessels to the loads altering the correlation of the CSF and blood pulse volumes in the process of formation of these waves. The intracerebral rheoencephalogram seems to be able to reflect the changes of both the vascular tone and the brain tissue hydration.

[The role of the perivascular spaces in shaping the pulse waves of the intracerebral rheoencephalogram]. / O roli perivaskuliarnykh prostranstv v formirovanii pul'sovykh voln vnutrimozgovoi reoéntsefalogrammy.

The intracerebral rheoencephalogram's pulse waves were recorded in rabbits and cats with indwelling electrodes. The waves' amplitude and form were rather diverse and they were inverted in 25% cases: the systolic peak was directed to an increase in the impedance. The dynamics of the waves reflect complex hemoliquorodynamic interrelations in perivascular space.

[The local blood flow and oxygen tension in the brain of pigeons under high-altitude hypoxia]. / Lokal'nyi krovotok i napriazhenie kisloroda v mozge golubei pri vysotnoi gipoksii.

The effect of barochamber hypoxia on the local blood flow in the pigeon neostriatum caudalum, hypostriatum accessorium, ectostriatum, cerebellum cortex was studied by means of the hydrogen clearance technique. The hypoxia was shown to decrease the oxygen available in the brain tissue and to increase the blood flow. The changes were different in different brain structures. The spectral analysis of the oxygen available fluctuations revealed no regular changes in the temporal pattern of the fluctuations.

[Intracranial hemodynamics in arterial hypertension (the renal model)]. / Vnutricherepnaia gemodinamika pri arterial'noi gipertenzii (renal'naia model').

The changes of intracranial hemodynamics were studied at the early stage of vasorenal arterial hypertension in 7 rabbits. During first 4-5 weeks of the hypertension development, the AP increased to 170 mm Hg which was followed by a drop in the blood flow by 15% in the cortex and by 19% in white matter. The blood flow increment in response to inhalation of CO2 lowered from initial 120% to 106% in the cortex and from 126% to 109% in white matter. The data on the brain tissue impedance suggested an absence of the hyperhydration of extracellular space. A mathematical model of the development of cerebral hemodynamic shift was suggested for this form of arterial hypertension, and the hypothesis was formed that vasoconstrictor response of the brain resistive vessels decreased cerebral blood flow thus preventing th shift of the Starling equilibrium and the fluid outflow from the vascular bed.

[The dynamics of alcoholic psychoses in recent years in the intensified campaign against drunkenness and alcoholism]. / Dinamika alkogol'nykh psikhozov za poslednie gody v usloviiakh bor'by protiv p'ianstva i alkogolizma.

An analysis of hospital admissions for alcoholic psychoses made among males in an industrial city over the period of July-December 1984 and the corresponding period of 1985 showed that the number of admissions in 1985 decreased by one-third largely at the expense of people relatively intact from the social and clinical standpoint.