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Effect of roentgen contrast media on rheological properties of the human blood
THE MECHANISMS OF CYTOGENETIC UNSTABILITY OF BLOOD CELLS PATIENTS HAVING LUNG CANCER BEFORE AND AFTER THE ANTICANCER TREATMENT V.V. N o v i t s k i , V.E. G o l d b e r g a n d V.Yu. S e r e b r o v Pharmacology and Oncology Research Institutes of Tomsk Scientific Centre of Russian Academy of Medical Science, M e d i c a l U n i v e r s i t y o f S i b e r i a , M o s c o w s k i T r a k t A v e . 2, T o m s k , 634050, Siberia, R u s s i a .
NEPHROTOXIC ACTION OF FUROSEMIDE IN GLOMERULONEPHRITIS PATIENTS.
Yu.Milovanov, F.Dzgoeva, S.Musselius. (introduced by I.Tareyeva). Moscow Medical Academy, Moscow,: Russia. The risk factors and mechanisms of acute renal failure (ARF) due to furosemide in glomerulonephritis (GN) patients and preventive measureslwere investigatedl Furosemide-indused AIRE was seen in 2 2 of 692 GN patients:There were 16 patients with prerenal type and 6 patients wih renal type of ARF. In all prerenal type cases ARF was caused by volume and : sodium depletion induced by furosemidel (80-120 mg/d during 2-2,5 weeks). In all renal type patients furosemide (120 mg/d during 3-3,5 weeks)caused •hyperuricemia and intratubular uric acid cristall obstruction. These data suggest that ARF risk factors in GN patients are the volume and sodium depletion caused by increase fractional excretion of sodium due to furosemide and probably low ~odium diet.
The 75 adult patients (men) having lung cancer (LC) of 111-1Y stages were exarninated. It was shown that cancer process development was assisted by increasing of cells amount with cytogenetic disorders (erythrocytes and blast cells having micronucleis in cytoplasma, aberrant cells), decreasing of the intracellular activity of DNA reparation system and quantity of cells-effectors for unspecific organism resistance support. The blood cells cytogenetic disorders at patients having LC had main characteristic as chromosomes structures disorders, but this ones were unspecific for such LC localization. There were the same ceils disorders at the patients having unspecific lung diseases. The mechanism of this violations was connected with suppression of T-cells cytotoxic activity of mature killers and excision of D N A reparation. The cytogenetic unstability at patients having LC became more marked in the process of cycle polychemotherapy according to CAM programme. It was shown that the reason of depression mature cells-killers cytotoxic activity of LC patients is decreasing of this ceils amount from periphery blood and •disturbances of the cells ability for recycling.
EFFECTS OF CHRONIC TREATMENT WITH PRAVASTATIN AND SIMVASTATIN ON EXCITATION-CONTRACTION COUPLING OF RAT SKELETAL MUSCLE FIBERS S. Piemo. A. De Luca, F. Natuzzi, M. Laico* and D. Conte Camerino Unit of Pharmacology, Dept. of Pharmacobiology, Faculty of Pharmacy, University of Bari and *Division of Cardiology, Policlinico, Bari, Italy
EFFECT OF ROENTGEN CONTRAST MEDIA ON RHEOLOGICAL PROPERTIES OF THE HUMAN BLOOD. N.Shimanovsky, P.Sergeev, N.Firsov, A.Usenko, O.Smimova, E.Bolotova, S.Egorova, T.Akhadov, V.Panov Department of the Molecular Pharmacology, Medico-biology Faculty, The Moscow State Medical University, B.Pirogovskaya, Moscow, 119021, Russia.
Myopathy is the most prominent adverse effect reported after HMG-CoA reductase inhibitors therapy (Sirtori et al., Curt. Ther. Res. 46:230, 1989; Soma et al., Biochim. Biophys. Res. Comm. 200:1t43,1994). We have shown that pravastatin and simvastatin differently affect the membrane electrical properties of rat skeletal muscle fibers. Indeed a dose-dependent reduction of resting membrane chloride conductance (GC1), the parameter responsible for the electrical stability of sarcolemma, was observed in muscle fibers from 5-1050mg/kg simvastatin treated rats. In contrast 100mg/kg pravastatin treatment did not produce significant alteration of GC1 (Conte Camerino et al., Pharmacol.&Toxicol. 73:77,1993). This lack of effect may be explained by the hydrophilic nature of pravastatin, which unlike simvastatin, is less able to enter muscle cells (Komai and Tsujita, DN&P 7:279,1994). In the present study we have evaluated the effects of 2 months treatment with pravastatin (100mg/kg) or simvastatin (50mg/kg) on the excitation-contraction coupling process of rat skeletal muscle by measuring the mechanical threshold of the fibers, with the two microelectrede point voltage clamp method (De Luca and Conte Camerino, Pflligers Arch. 420:407,1992). The rheobase voltage for contraction of extensor digitorum longus (EDL) muscle fibers from simvastatin treated rats was shifted toward more negative potentials with respect to the untreated fibers, indeed at 500ms pulse duration the voltage threshold for contraction was -70±l.3mV (n=38) for simvastatin and 264±lmV (n=13) for controls. In contrast pravastatin did not alter the conlractile properties of EDL muscle fibers (-65.7±0.4mV, n=35 at 500ms). These results show that the lipophilic simvastatin affects the contractile properties of skeletal muscle while pravastatin does not. It is known that an enhancement of cytosolic calcium concentration either pathological or pharmacologically induced will shift the rheobase voltage for contraction in a negative direction (Dulhunty, Biophys. J. 53:609, 1988). In agreement it has been described that simvastatin but not pravastatin, causes cytosolic calcium elevation in cultured rat myoblasts (Nakahara et al., Muscle&Nerve (Suppl.1) 8262,1994). These data suggest that simvastatin, altering the lipid environment and microviscosity of sarcolemma, may cause an increase of cytosolic calcium concentration producing impairment of muscle function.
purpose. The aim of this study was to investigate the effect of roentgen contrast media (RCM) on human blood theology in vitro. • ods, We had investigated ionic and nonionic RCM: 1). Cholecystographye ionic RCM for oral administration: Bilimin (Russia); 2). Cholecystographyc ionic RCM for intravenous injection: Bilignost 20% and 50% (Fannac, Ukraina); 3): Angiourographyc ionic RCM: Triombrast 76% and Iedamide 380 (Farmac, Ukraina), Peritrast (Dr. Kohler Chemie OMBH, Germany); 4). Angiourograpliyc nonionic RCM: Ultravist (Schering, Germany), Melitrast (Dr. Kohler Chemic GMBH, Germany), Omnipaque (Nicomed, Norway), Metrizamid (Sigma, USA); 5). Splenogepatographyc RCM: Lipotrast (Russia). The range of concentrations was: for all intravenous RCM - 10-4-101M, for bilimin - 10-6-10"4M. The healthy donors blood was used (stabilised by 5 % solution trilon B). Macroreologieal parameters study have been done on rotational viscosimeter. The erithrocytes agregation ability have been tested on Kuvett viscosimeter by photon dispersion method and have been evaluated by Tobolsky-Muraeamy method. Gydrodinamical stability have been evaluated on kinetics of their damage after speed of displacement increasing. Defolmation ability have been evaluated by extraeytometry method. Morphology of erithrocytes have been evaluated by microscopic method. Results. Different organotropieal RCM influenced on the blood macro- and microrealogy according to their lipidosohibility and protein-binding ability. Serum albumin decreased level of negative macroreological effects of bilignost 50%, bilignost 20%, iodamide, lriombrast, metrizamide in 50-20 times. Conclusion. The effect of RCM on haman blood rheology were investigated. The main cause of theological effects of the RCM is their effect on the structure and function of erithrocytes. There was a relationship between the physico-chemical properties of RCM and the mechanism of action. The major active negative factor is the high osmolality of RCM in solution. Lipidsolubility, specific features of molecular structures and the composition of dosage played a definite role.
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NEPHROTOXIC ACTION OF FUROSEMIDE IN GLOMERULONEPHRITIS PATIENTS.
Yu.Milovanov, F.Dzgoeva, S.Musselius. (introduced by I.Tareyeva). Moscow Medical Academy, Moscow,: Russia. The risk factors and mechanisms of acute renal failure (ARF) due to furosemide in glomerulonephritis (GN) patients and preventive measureslwere investigatedl Furosemide-indused AIRE was seen in 2 2 of 692 GN patients:There were 16 patients with prerenal type and 6 patients wih renal type of ARF. In all prerenal type cases ARF was caused by volume and : sodium depletion induced by furosemidel (80-120 mg/d during 2-2,5 weeks). In all renal type patients furosemide (120 mg/d during 3-3,5 weeks)caused •hyperuricemia and intratubular uric acid cristall obstruction. These data suggest that ARF risk factors in GN patients are the volume and sodium depletion caused by increase fractional excretion of sodium due to furosemide and probably low ~odium diet.
The 75 adult patients (men) having lung cancer (LC) of 111-1Y stages were exarninated. It was shown that cancer process development was assisted by increasing of cells amount with cytogenetic disorders (erythrocytes and blast cells having micronucleis in cytoplasma, aberrant cells), decreasing of the intracellular activity of DNA reparation system and quantity of cells-effectors for unspecific organism resistance support. The blood cells cytogenetic disorders at patients having LC had main characteristic as chromosomes structures disorders, but this ones were unspecific for such LC localization. There were the same ceils disorders at the patients having unspecific lung diseases. The mechanism of this violations was connected with suppression of T-cells cytotoxic activity of mature killers and excision of D N A reparation. The cytogenetic unstability at patients having LC became more marked in the process of cycle polychemotherapy according to CAM programme. It was shown that the reason of depression mature cells-killers cytotoxic activity of LC patients is decreasing of this ceils amount from periphery blood and •disturbances of the cells ability for recycling.
EFFECTS OF CHRONIC TREATMENT WITH PRAVASTATIN AND SIMVASTATIN ON EXCITATION-CONTRACTION COUPLING OF RAT SKELETAL MUSCLE FIBERS S. Piemo. A. De Luca, F. Natuzzi, M. Laico* and D. Conte Camerino Unit of Pharmacology, Dept. of Pharmacobiology, Faculty of Pharmacy, University of Bari and *Division of Cardiology, Policlinico, Bari, Italy
EFFECT OF ROENTGEN CONTRAST MEDIA ON RHEOLOGICAL PROPERTIES OF THE HUMAN BLOOD. N.Shimanovsky, P.Sergeev, N.Firsov, A.Usenko, O.Smimova, E.Bolotova, S.Egorova, T.Akhadov, V.Panov Department of the Molecular Pharmacology, Medico-biology Faculty, The Moscow State Medical University, B.Pirogovskaya, Moscow, 119021, Russia.
Myopathy is the most prominent adverse effect reported after HMG-CoA reductase inhibitors therapy (Sirtori et al., Curt. Ther. Res. 46:230, 1989; Soma et al., Biochim. Biophys. Res. Comm. 200:1t43,1994). We have shown that pravastatin and simvastatin differently affect the membrane electrical properties of rat skeletal muscle fibers. Indeed a dose-dependent reduction of resting membrane chloride conductance (GC1), the parameter responsible for the electrical stability of sarcolemma, was observed in muscle fibers from 5-1050mg/kg simvastatin treated rats. In contrast 100mg/kg pravastatin treatment did not produce significant alteration of GC1 (Conte Camerino et al., Pharmacol.&Toxicol. 73:77,1993). This lack of effect may be explained by the hydrophilic nature of pravastatin, which unlike simvastatin, is less able to enter muscle cells (Komai and Tsujita, DN&P 7:279,1994). In the present study we have evaluated the effects of 2 months treatment with pravastatin (100mg/kg) or simvastatin (50mg/kg) on the excitation-contraction coupling process of rat skeletal muscle by measuring the mechanical threshold of the fibers, with the two microelectrede point voltage clamp method (De Luca and Conte Camerino, Pflligers Arch. 420:407,1992). The rheobase voltage for contraction of extensor digitorum longus (EDL) muscle fibers from simvastatin treated rats was shifted toward more negative potentials with respect to the untreated fibers, indeed at 500ms pulse duration the voltage threshold for contraction was -70±l.3mV (n=38) for simvastatin and 264±lmV (n=13) for controls. In contrast pravastatin did not alter the conlractile properties of EDL muscle fibers (-65.7±0.4mV, n=35 at 500ms). These results show that the lipophilic simvastatin affects the contractile properties of skeletal muscle while pravastatin does not. It is known that an enhancement of cytosolic calcium concentration either pathological or pharmacologically induced will shift the rheobase voltage for contraction in a negative direction (Dulhunty, Biophys. J. 53:609, 1988). In agreement it has been described that simvastatin but not pravastatin, causes cytosolic calcium elevation in cultured rat myoblasts (Nakahara et al., Muscle&Nerve (Suppl.1) 8262,1994). These data suggest that simvastatin, altering the lipid environment and microviscosity of sarcolemma, may cause an increase of cytosolic calcium concentration producing impairment of muscle function.
purpose. The aim of this study was to investigate the effect of roentgen contrast media (RCM) on human blood theology in vitro. • ods, We had investigated ionic and nonionic RCM: 1). Cholecystographye ionic RCM for oral administration: Bilimin (Russia); 2). Cholecystographyc ionic RCM for intravenous injection: Bilignost 20% and 50% (Fannac, Ukraina); 3): Angiourographyc ionic RCM: Triombrast 76% and Iedamide 380 (Farmac, Ukraina), Peritrast (Dr. Kohler Chemie OMBH, Germany); 4). Angiourograpliyc nonionic RCM: Ultravist (Schering, Germany), Melitrast (Dr. Kohler Chemic GMBH, Germany), Omnipaque (Nicomed, Norway), Metrizamid (Sigma, USA); 5). Splenogepatographyc RCM: Lipotrast (Russia). The range of concentrations was: for all intravenous RCM - 10-4-101M, for bilimin - 10-6-10"4M. The healthy donors blood was used (stabilised by 5 % solution trilon B). Macroreologieal parameters study have been done on rotational viscosimeter. The erithrocytes agregation ability have been tested on Kuvett viscosimeter by photon dispersion method and have been evaluated by Tobolsky-Muraeamy method. Gydrodinamical stability have been evaluated on kinetics of their damage after speed of displacement increasing. Defolmation ability have been evaluated by extraeytometry method. Morphology of erithrocytes have been evaluated by microscopic method. Results. Different organotropieal RCM influenced on the blood macro- and microrealogy according to their lipidosohibility and protein-binding ability. Serum albumin decreased level of negative macroreological effects of bilignost 50%, bilignost 20%, iodamide, lriombrast, metrizamide in 50-20 times. Conclusion. The effect of RCM on haman blood rheology were investigated. The main cause of theological effects of the RCM is their effect on the structure and function of erithrocytes. There was a relationship between the physico-chemical properties of RCM and the mechanism of action. The major active negative factor is the high osmolality of RCM in solution. Lipidsolubility, specific features of molecular structures and the composition of dosage played a definite role.
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