Pharmacological activity and distribution in vivo fo paramagnetic models of some psychotropic compounds.
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Biomedical subjects
Publications and source records attributed to L A Piruzyan.
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The possibility of a calorimetric determination of the number of homogeneous independent binding sites on the protein molecule surface is presented, together with the possibility of the determination of interaction heat and association constants for the binding of small molecules to one such site. Thermodynamic characteristics of interaction of 10 penicillins and methyl orange with primary and secondary binding sites of bovine serum albumin have been obtained using this technique. The data show that hydrogen bonds between the component parts of the complexes studied are absent. The main contribution to free energy change at forming these complexes is made by hydrophobic interactions. Electrostatic forces are also of some importance, their contribution into the complex formation is more significant in the case of quinacillin and carbenicillin which have an additional charged carboxyl group.
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An electron-cytochemical study of the peroxidase activity in bone-marrow eosinophils of the frog Rana temporaria revealed, in addition to peroxidase-positive granules and larger peroxidase-negative granules, many small peroxidase-negative granules.
The bone marrow of the frog was studied during the spring and winter periods. During the winter period, one type of large granules in the neutrophils of the frog proved to be peroxidase-positive. The remaining, smaller granules are peroxidase-negative. In the spring, immature and mature neutrophils are encountered in the frog. The mature neutrophils of the frog in the spring and winter periods are analogous. The immature neutrophils contain peroxidase activity in the perinuclear space, the endoplasmic reticulum and some of the granules. Some of the peroxidase-containing granules are directly associated with the canals of the endoplasmic reticulum. In the immature neutrophils, during the formation of the peroxidase-containing granules, peroxidase-negative granules smaller in size are already present in the cytoplasm. Thus, the sequence of granule formation usual for mammals is apparently not observed in the neutrophils of certain amphibia. "Annular" mitochondria, encompassing part of the cytoplasm were detected in the neutrophils. These apparently represent a section through a spherical mitochondrion enveloping and isolating a certain zone of the cell. It is proposed that the mitochondria in this way, differing from the lysosomal mode, participate in the catabolism of the cytoplasm.
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Tissues of the hollow organs of the gastrointestinal tract are crushed in order to create an anastomosis. The processes taking place in the tissues have been inadequately studied. A model of the tissue crushing process is suggested and the results of theory and experiments are compared. Dependence of the rejection time of the crushing influence on the crushing force was demonstrated experimentally. The relationship obtained can be explained on the grounds that migration of cell destruction products from the zone of crushing to the zones of healing stimulates adequate cellular immunologic processes. The views developed in this paper may prove useful for the elaboration of new surgical techniques.
A comparative analysis is given of various types of systems of selecting biologically active substances. A theoretical probability model of tests on chemical compounds for biological activity (screening) has been constructed which permits an evaluation of the efficacy of screening on the basis of fairly reasonable assumptions. It has been shown that this efficacy decreases in time with a fixed number of types of activity taken into consideration and rises sharply with an increase in the number of types of activity of chemical compounds taken into account in the tests.
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The problem of quantitative evaluation of the pharmacological influence of physiologically active substances with receptor action on the organism under conditions of screening is discussed. A vector-significant criterion, based on a functional multiparameter method (FMM), is suggested as the basic characteristic of effectiveness of action. This criterion permits an evaluation of the latitude of the permissible physiological effect, the threshold of subtoxicity, and the selectivity of the action of the substance according to the dominant activity.
On the basis of numerous results of investigations on adrenergic systems, an orientational model of the adrenoreceptor (AR) is postulated. Its active center includes low-molecular-weight components--prostaglandins (PGE, PGF), steroids (cortisone, hydrocortisone), S+-adenosylmethionine, Ca, Mg, and Mn ions. Appraisal of the stereospecific characteristics of such a functional unit of AR explains the difference in the nature and magnitude of the effects of interaction of the catecholamines, their agonists and antagonists will the so-called alpha- and beta-AR. Depending on the organ or tissue in which the AR is located, its protein subunits comprise adenylcyclase (beta-AR) or Na,K-ATPase (alpha-AR). An obligatory component of the AR is catechol-O-methyltransferase. The model elaborated describes satisfactorily the molecular mechanisms of action of many pharmacological agents, explains why attempts to isolate and reconstruct the AR have proved fruitless, and gives grounds for rejecting the hypothesis that there exist steroid, prostaglandin, and purinergic receptors, linking the exceptionally high and diverse activity of these biologically active substances with their participation in adrenoreception among other reasons. A conception of the active centers of the AR as low-molecular-weight entities permits the explanation of such phenomena as the desensitization of the AR, the "interconversion" of beta-AR into alpha-AR with a change in the parameters of the medium, and certain components of the pathogenesis of bronchial asthma, etc.
Questions of the identification of the type of pharmacological activity of physiologically active substances (PAS) with a receptor type of action under conditions of screening are examined. IN accordance with current concepts of the theory of the recognition of modes, the type of action of PAS was identified by establishing a set of criteria ("vectors of modes") characteristic of the effect of known substances and by selecting methods of comparing them with the vectors of the modes of the compounds being tested. Test parameters recorded by the the functional multiparametric method permitting identification of the type of the effects and an evaluation of their quantitative manifestations with the framework of a single experimental approach were used as the unknown set of criteria. The method of describing the relative change in the parameters from the dose as the vectors of action was used and the function of proximity (similarity).
In biological systems nonuniformity of magnetic susceptibility, magnetic heterogeneity, is a reflection of their physical-chemical and morphological heterogeneity, A characteristic value of heterogeneity is delta K approximately 10(-6)-10(-7) CGS units, a quantitative measurement of susceptibility of cells and other small objects, may give qualitatively new information about their life processes. Patterns and features of movement of small biological objects and liquids affected by magnetic forces were studied. A method was developed for measuring magnetic susceptibility of single microobjects based on observation of movement of the objects in a strong heterogeneous field with parameters (formula: see text) grad H2/2 approximately 10(9)-10(10) Oe2/cm. This method does not require knowing the distribution of the field along the path of movement of the particles, and does not require preliminary calibration. Movement of human erythrocytes, rat hepatocytes, and starch granules in liquids at a point of entry into a gap with the field was observed experimentally. With sufficiently large fields Ho approximately (1-2) x 10(4) Oe, the value of the magnetic force was enough to change the rate of sedimentation movement of the objects appreciably (up to stopping it). This made it possible to compute the value delta K for cells approximately 10(-7)-10(-8) CGS units and to obtain the value of K for starch granules (-0.80 x 10(-6) cGS units). In connection with the fact that sensitivity to gravity in plants is coupled with a disturbance of the intracellular starch granules under the influence of gravity, certain problems of stimulating the effect of gravity on plants by magnetic forces were studied. Noncontact force effect on magnetically heterogeneous biological objects is a promising instrument for biophysical studies.
The work discusses the influence of factor XIII on the molecular structure of fibrin and its properties under normal conditions and in certain forms of coagulopathies. It was shown that the reaction of stabilization is accompanied by an exothermic effect, the thermal effect of which on donor blood plasma is 15.5 kcal/mole. It was also established that the enrichment of blood plasma with fibrinogen leads to an increase in the thermal effect, which is due to the influence of the density of the terminal and lateral bonds in the fibrin molecule and the process of its covalent cross-linking. An examination of groups of patients structure of fibrin and its physiological properties, on account of a change in the number of peptide bonds formed. On the basis of the results obtained, a new energy test for the determination of the fibrin-stabilizing factor is suggested.