EFFECT OF ELECTR- AND ULTRAPHONOPHORESIS OF THE PHYTOCOMPLEX ON MICROCIRCULATORY AND BIOCHEMICAL PARAMETERS IN PATIENTS WITH KNEE JOINT OSTEOARTHRITIS.

The goal was to study the effect of modulated sinusoidal currents electrophoresis and ultraphonophoresis of the phytocomplex on disruptions in the microcirculation system in the affected joint area and on changes in connective tissue metabolism parameters, metabolic processes, and electrolyte metabolism in patients with knee joint osteoarthritis. Seventy-two patients were randomly assigned to five groups. Patients of the first group were prescribed modulated sinusoidal currents electrophoresis of the phytocomplex. The second group was prescribed ultraphonophoresis of the phytocomplex, the third group was prescribed amplipulse therapy (modulated sinusoidal currents), the fourth group was prescribed ultrasound therapy, and the fifth group was prescribed basic drug therapy. Drug therapy of patients of the fifth group was comparable to the drug treatment of patients of the first four groups. The concentration of the phytocomplex in the working composition was 10%. Electrotherapy was carried out in the full-wave modulated sinusoidal currents mode with I and IV types of operation while ultrasound therapy was carried out in continuous mode with an ultrasound intensity of 0.6 W/cm2. To assess the state of microcirculation, the laser Doppler flowmetry method was used. The pronounced anti-dystrophic effect after the use of modulated sinusoidal currents electrophoresis and ultraphonophoresis of the phytocomplex in patients with knee joint osteoarthritis was based on the correction of microcirculatory disruptions: an increase in the capillary blood flow, an increase in the blood perfusion in tissues, and a decrease in congestion effects in the venular microcirculation. The use of modulated sinusoidal currents electrophoresis of the phytocomplex (ultraphonophoresis of the phytocomplex had an even greater effect) improved the connective tissue metabolism and the content of seromucoid, fibrinogen, and mucoproteins. The use of the studied treatment methods improved magnesium and phosphorus parameters of the electrolyte metabolism. Modulated sinusoidal currents electrophoresis and ultraphonophoresis of the phytocomplex contributed to the elimination of the metabolic imbalance of acid phosphatase. Ultraphonophoresis of the phytocomplex also contributed to balancing of the alanine aminotransferase and alkaline phosphatase content. As a result of the study, the effect of modulated sinusoidal currents electrophoresis and ultraphonophoresis of the phytocomplex on disruptions in the microcirculation system in the affected joint area and on changes in connective tissue metabolism parameters, metabolic processes, and electrolyte metabolism in patients with knee joint osteoarthritis was established. The obtained results provide the basis for further studies to assess the overall effectiveness of the use of modulated sinusoidal currents electrophoresis and ultraphonophoresis of the phytocomplex in patients with knee joint osteoarthritis.

[The glutathione system in the blood of rats and morphological changes of the pancreas under experimental acute and chronic pancreatitis].

In experiment on laboratory rats the models of acute and chronic pancreatitis were developed to study the changes of lipoperoxidation-antioxidant protection system depending on morphological changes of the pancreas. The acute and chronic pancreatitis is accompanied with intensification of lipoperoxidation and gradual inhibition of antioxidant system due to development of subsequent chronization of the pathological process.

Clozapine and haloperidol differentially regulate dendritic spine formation and synaptogenesis in rat hippocampal neurons.

Antipsychotic drugs are the primary therapeutic treatment for schizophrenia. In addition to their dopaminergic/serotonergic function, atypical antipsychotics differ from conventional antipsychotics in the way they affect glutamatergic receptor function. A cellular correlate of this may be the modulation of dendritic spines (DS). Here, we demonstrate that in rat dissociated hippocampal neurons 1.0 microM clozapine administration increased DS-enriched protein spinophilin by 70%, increased post-synaptic protein shank1a puncta density by 26% and increased overall primary dendrite DS density by 59%. Filopodia and mushroom DS were particularly affected by clozapine. Conversely, 0.1 microM haloperidol decreased spinophilin protein by 40%, caused a 25% decrease in shank1a puncta and reduced the numbers of filopodia. In contrast, neither haloperidol nor clozapine induced any change in the levels of the pre-synaptic protein synapsin. This indicates that clozapine and haloperidol differentially regulate DS and post-synaptic plasticity. These findings may provide a molecular and cellular correlate to the superior therapeutic profile of clozapine when compared with haloperidol.

[Effect of masticatory load on oxygen tension in periodontal tissues]. / Vliianie zhevatel'nykh nagruzok na napriazhenie kisloroda v tkaniiakh parodonta.

Relationship between the effect of occlusional loading (weak, 10-15 H, and strong, 120-150 H) and oxygen tension (pO2) in periodontal tissues adjacent to the first molar on the working and resting sides was carried out in 57 subjects with different clinical status of the periodontium and with partial secondary adentia. pO2 decreased during exercise, the most pronounced drop (to 12 mm Hg) being observed during intensive exercise. The level of pO2 decreased greater on the resting side and in patients with periodontal diseases. The longest period of pO2 recovery (up to 50 min) was observed after intensive exercise.

Effect of ethylene oxide and propylene oxide block copolymers on the permeability of bilayer lipid membranes to small solutes including doxorubicin.

The effects of ethylene oxide and propylene oxide block copolymers (pluronics) on the permeability of several weak acids and bases through bilayer lipid membranes have been studied by the methods of monitoring (1) pH shifts near planar bilayers, (2) doxorubicin fluorescence quenching inside liposomes, and (3) current transients in the presence of hydrophobic anions. It has been shown that pluronics facilitate the permeation of comparatively large molecules (such as 2-n-undecylmalonic acid and doxorubicin) across lipid bilayers, while the permeation of small solutes (such as ammonium and acetic acid) remains unaffected. Pluronics also accelerate the translocation of large hydrophobic anions (tetraphenylborate). The effect of pluronics correlates with the content of propylene oxide units: it is enhanced when the portion of polypropylene oxide block in the copolymer is increased. The action of the pluronic on lipid membrane permeability differs from the effect of the conventional detergent Triton X-100, which does not affect doxorubicin transport if added at concentrations similar to those used for pluronics. It has been proposed that pluronics accelerate the processes of solute diffusion within lipid bilayers (in a structure-dependent manner) rather than influencing the rate of solute adsorption/desorption on the membrane surface. We suppose that the effect of pluronics on doxorubicin permeation across lipid bilayers along with the known effect on the multidrug resistance protein determines its influence on the therapeutic activity of anthracycline drugs.

Dishevelled-1 regulates microtubule stability: a new function mediated by glycogen synthase kinase-3beta.

Dishevelled has been implicated in the regulation of cell fate decisions, cell polarity, and neuronal function. However, the mechanism of Dishevelled action remains poorly understood. Here we examine the cellular localization and function of the mouse Dishevelled protein, DVL-1. Endogenous DVL-1 colocalizes with axonal microtubules and sediments with brain microtubules. Expression of DVL-1 protects stable microtubules from depolymerization by nocodazole in both dividing cells and differentiated neuroblastoma cells. Deletion analyses reveal that the PDZ domain, but not the DEP domain, of DVL-1 is required for microtubule stabilization. The microtubule stabilizing function of DVL-1 is mimicked by lithium-mediated inhibition of glycogen synthase kinase-3beta (GSK-3beta) and blocked by expression of GSK-3beta. These findings suggest that DVL-1, through GSK-3beta, can regulate microtubule dynamics. This new function of DVL-1 in controlling microtubule stability may have important implications for Dishevelled proteins in regulating cell polarity.

Molecular cloning and expression pattern of rpr-1, a resiniferatoxin-binding, phosphotriesterase-related protein, expressed in rat kidney tubules.

Bacterial phosphotriesterases are enzymes that hydrolyse phosphotriester-containing organophosphate pesticides. Resiniferatoxin is a vanilloid that desensitises nociceptive neurons. By screening a rat cDNA library with labelled resiniferatoxin, we unexpectedly isolated a novel rat phosphotriesterase homologue, here named rpr-1, that encodes a 349 amino acid, 39 kDa protein (confirmed by in vitro translation). Northern blotting and in situ hybridisation show expression primarily in proximal tubules of the kidney, in which rpr-1 distribution correlates with resiniferatoxin-binding activity. These results suggest an unsuspected link between the phosphotriesterase enzyme family and resiniferatoxin toxicity and pharmacology.

[The effect of insulin on the changes in acid phosphatase activity and cAMP level in the primary monolayer culture of hepatocytes from newborn rats during anoxia]. / Vliianie insulina na izmenenie aktivnosti kisloi fosfatazy i urovnia tsAMF v pervichnoi monosloinoi kul'ture gepatotsitov novorozhdennykh krys v usloviiakh anoksii.

Effects of insulin was studied in the monolayer hepatocyte cultures of new born rats under anoxic conditions. Insulin 10(-7) M stabilized lysosomal membranes obtained after 20 min anoxia. I hr incubation of hepatocytes with insulin in normal conditions, which was followed by anoxia, caused a significant increase of acid phosphatase activity in the fraction enriched with lysosomes. Insulin caused more distinct stabilization effect on lysosomal membranes when its action was prolonged. On the other hand, insulin caused more than 2-fold increase of cAMP content in hepatocytes within 2 min of exposition as compared with control cultures. When exposition of the cells with insulin exceeded 2 min, lowering of cAMP content was observed. These data appear to indicate that stabilizing effect of insulin was secondary towards cAMP level increase. Indirect connection between cAMP level, insulin stabilizing action and the state of lysosomal membranes were noted in the rat hepatocyte culture.

[Primary culture of hepatocytes of newborn rats as a system for modeling anoxia and metabolic ischemia]. / Pervichnaia kul'tura gepatotsitov novorozhdennykh krys kak sistema dlia modelirovaniia anoksii i metabolicheskoi ishemii.

A primary culture of hepatocytes from new born rats was used as an experimental model suitable for studies of the cell lysosomal apparatus and of molecular mechanisms involving cyclic nucleotides for initiation of lysosomal response to extremal conditions. Substrate deficiency and anoxia of the cultivated hepatocytes were found to cause distinct alterations in the state of lysosomal apparatus accompanied by an increase in free activity of acid phosphatase.

[Changes in the cAMP levels and acid phosphatase activity in a monolayer primary culture of hepatocytes from newborn rats during anoxia and substrate deprivation]. / Izmenenie urovnia tsAMF i aktivnosti kisloi fosfatazy v monosloinoi pervichnoi kul'ture gepatotsitov novorozhdennykh krys v usloviiakh anoksii i substratnogo golodaniia.

Acid phosphatase activity and cAMP level were studied in primary hepatocyte culture of new born rats under conditions of anoxia and substrate deprivation (incubation of the cells in Hanks salt solution). Incubation of hepatocytes in Hanks salt solution within one hour under conditions of anoxia caused a significant increase in free (cytosolic) enzyme activity. Substitution of Hanks salt solution by normal tissue culture medium and reoxygenation after 1 hr anoxia resulted in a decrease of free acid phosphatase activity, whereas activity of the enzyme in lysosomal fraction was increased. Content of cAMP was decreased distinctly after 15 min incubation of hepatocyte culture under conditions of anoxia and substrate deprivation and was increased above control values within 5 min of reoxygenation and substitution of Hanks salt solution by normal tissue culture media. Addition of cAMP-containing liposomes to hepatocyte culture under these experimental conditions led to a decrease in free acid phosphatase activity and to an increase of the enzyme activity in lysosomal fraction. cAMP appears to modulate the lability of hepatocyte lysosomal membrane. The mechanisms involved in these processes are discussed.