10-(6'-Plastoquinonyl)decyltriphenylphosphonium (SkQ1) Does Not Increase the Level of Cytochromes P450 in Rat Liver and Human Hepatocyte Cell Culture.

Mitochondria-targeted antioxidant SkQ1 did not increase the content of cytochromes P450 in livers of rats that were given SkQ1 in drinking water for 5 days in a dose (2.5 µmol per kg body weight) that exceeded 10 times the SkQ1 therapeutic dose. SkQ1 did not affect the levels of cytochrome P450 forms CYP1A2, CYP2B6, and CYP3A4 in monolayer cultures of freshly isolated human hepatocytes, while specific inducers of these forms (omeprazole, phenobarbital, and rifampicin, respectively) significantly increased expression of the cytochromes P450 under the same conditions. We conclude that therapeutic doses of SkQ1 do not induce cytochromes P450 in liver, and the absence of the inducing effect cannot be explained by poor availability of hepatocytes to SkQ1 in vivo.

[The complex of neurological symptoms of substance abuse].

Standard neurological examination was performed in 85 patients of military service age (the average age was 32,6±5,3 years - from 19 to 44 years) with a confirmed diagnosis of substance abuse, caused by the use of narcotic drugs and psychotropic substances: cocaine and amphetamine in 12 patients, opioids - in 73 patienls. Some symptoms of nervous system damage had statistically characteristic peculiarities for different forms of substance abuse. Mydriasis, signs a bilateral pyramidal insufficiency, hyperkinetic disorder are often characteristic for cocaine and amphetamine abuse. Opioid abuse is characterised by more severe symptoms of nervous system damage, disseminated neurologic symptomatic and polyneurotic disorders. Symptoms of neurasthenia and vegetative-vascular dystonia, which are usually accompanied by the; symptoms of organic lesions of the central and peripheral nervous system, were observed in all patients with substance abuse. In order to detect the symptoms of nervous system damage in patients, which are supposed to be conscribe, it is necessary to take medical history.

[Pathology of the nervous system in conscripts with drug abuse in past medical history: symptomatology, diagnostics methods].

Authors examined 60 female and male patients (average age 25.8±2.7 years) with confirmed diagnosis - drug abuse. Average duration of drug abuse was approximately 9±3.3 years. At the moment of examination patients had been fully in remission for 3 weeks. The following non-invasive procedures were undertaken: stimulation electroneuromyogrphy and brain MRI. Received results showed that drug abuse leads to diffuse lesion of the nervous system, which manifests itself as vegetative disorders, scattered neurological symptoms, polyneuropathy. Authors gave recommendations in the field of military examination with the aim of detection of nervous disorders caused by drug abuse.

[Alcohol dependence and mental adaptation disorders (the use of injectable extended-release naltrexone)].

This review of literature describes a role of chronic stress in the development of substance dependence including alcohol dependence. It is focused on neurochemical mechanisms of this dependence and approaches to its treatment in people with mental adaptation disorders. An example of treatment with injectable extended-release naltrexone is presented.

Targeting human breast tumour in xeno-grafted SCID mice with 99Tcm-glucarate.

99Tcm-glucarate accumulation in human mammary BT-20 tumours hosted in severe combined immune deficiency (SCID) mice was compared to 111In-monoclonal antibody 103D2-F(ab')2, 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) and 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA). The intracellular tumour distribution of 99Tcm-glucarate was also determined. SCID mice injected with a mixture of 99Tcm-glucarate and 111In-103D2-F(ab')2 were imaged serially up until 24 h. Computer planimetered tumour-to-blood activity (in the heart) ratios (T/BH) to 8 h were significantly greater for 99Tcm-glucarate than 111In-103D2. The mean (+/-S.D.) tumour-to-blood ratio (T/B) from biodistribution was 1.21 +/- 0.31 and 0.35 +/- 0.06 (P < 0.0001) at 5 h, and 1.526 +/- 0.29 and 0.75 +/- 0.2 (P < 0.0001) at 8 h, for 99Tcm-glucarate and 111In-103D2 respectively. At 24 h, T/B for 111In-103D2 (1.76 +/- 0.22) exceeded that of 99Tcm-glucarate (1.44 +/- 0.2, P = 0.01). 99Tcm-glucarate uptake in the tumours at 5 h (1.133 +/- 0.25 %ID g-1) and 8 h (1.213 +/- 0.23 %ID g-1) was significantly greater than that of 99Tcm-MIBI (0.340 +/- 0.09, P = 0.0002; 0.220 +/- 0.04, P = 0.0001) and 99Tcm-DTPA (0.091 +/- 0.03, P < 0.0002; 0.016 +/- 0.01, P < 0.0001) respectively. Intracellular tumour distribution of 99Tcm-glucarate was 50.91 +/- 6.55% in the nuclear fraction, 34.34 +/- 2.88% in the cytoplasmic fraction and 14.75 +/- 7.66% in the mitochondrial fraction. Thus glucarate may provide a 99Tcm-based mammary tumour imaging modality for visualization of tumours very quickly after tracer administration with maximal targeting in the nuclei of the tumour cells.

Venous thrombolysis by tissue-type plasminogen activator in conjunction with the urokinase-fibrinogen covalent conjugate. Effects of potentiation and faster action in dogs.

Conjunctive administration of the tissue-type plasminogen activator (t-PA) and the urokinase-fibrinogen covalent conjugate (UK-Fbg) was studied by the example of venous thrombosis in dogs. Comparing the effect of separate use of the two components, we observed the potentiation of thrombolytic effect induced by an i.v. bolus infusion administration of the tissue-type plasminogen activator (1 and 4 mg, respectively) combined with a bolus administration 15 min after the first injection of the 25,000 IU UK-Fbg. Faster-action and potentiation effects of thrombolysis were observed with the same administration scheme when the t-PA was used as bolus infusion (1 and 1 mg, respectively) combined with a bolus of the 250,000 IU fibrinogen-modified urokinase. The findings indicate an approach to the development of efficient thrombolytic compositions.

[The modification of Cu, Zn-superoxide dismutase by monomethoxypolyethylene glycol improves the indices of the experimental therapy of the ischemic myocardium in rats]. / Modifikatsiia Cu, Zn-superoksiddismutazy monometoksipoliétilenglikolem uluchshaet pokazateli ékpserimental'noi terapii ishemizirovannogo miokarda krys.

Mice were used to make a comparative study of the biological distribution of intravenous preparations of native and monomethoxypolyethylene glycol-modified superoxide dismutase isolated from bovine liver, as well as native and aldehyde dextran. The study demonstrated that the biodistribution of the native enzymes from various sources was, however, equal, but in the mouse liver there was a higher accumulation of SOD isolated from the rat liver. AD-SOD was found to have a longer half-life in the blood and in the liver of mice, in particular, while MPEG-SOD showed 10, 15, and 16 times longer in the lungs, blood and heart of the animals examined, respectively. The elevated accumulation of MPEG-SOD in some organs was used for their treatment, particularly for experimental therapy of rat myocardial ischemia. A rat model of ischemia demonstrated that the intravenous bolus administration of MPEG-SOD reduced the size of a myocardial necrotic area by 40% as compared to a 13% decrease when the other compounds were assayed. The findings suggest that the MPEG-SOD preparation is promising for decreasing reperfusion injuries of the cardiovascular system and the lungs.

[Antifibrotic effects of aldehyde dextran modified superoxide dismutase in experimental silicosis]. / Antifibroznoe deistvie modifitsirovannoi al'degiddekstranom superoksiddismutazy pri éksperimental'nom silikoze.

The present paper dwells on biomedical study of aldehyde dextran modified superoxide dismutase. Pharmacokinetic data demonstrated that modification of superoxide dismutase increased its half-time. A rat model of experimental silicosis showed that aldehyde dextran modified superoxide dismutase inhibited evolving fibrosis in the lungs. The same dose of native enzyme produced no therapeutic effect. Thus, superoxide dismutase can be considered as a potential agent for treatment of fibrosis due to its modification.

[Interaction of quinidine, lidocaine, tricaine and pyromecaine with heparin]. / Issledovanie vzaimodeistviia khinidina, lidokaina, trikaina i piromekaina s geparinom.

In the experiments on rabbits it was shown that quinidine administered intravenously in a dose of 5 mg/kg exerts no effect on the blood coagulability but decreases the degree and duration of the anticoagulant effect of heparin. Lidocaine, trimecaine and pyromecaine at the same dose alter neither the blood coagulability nor the anticoagulant effect of heparin.

[Interaction of the calcium salt of heparin with specific antagonists and ethacizine]. / Izuchenie vzaimodeistviia kal'tsievoi soli geparina so spetsificheskimi antagonistami i étatsizinom.

Protamine sulfate was shown to bind calcium heparinate isolated from the pig intestinal mucosa during in vitro experiments in 0.6:1 ration and during experiments on rabbits and dogs in 1.5:1 ratio. 2,5-ionen neutralizes the anticoagulant effect of calcium heparinate during in vitro and animal experiments in 0.6:1 ratio. Neutralization of calcium heparinate requires by approximately 30% more specific antagonists than neutralization of the same amount of sodium heparinate. Ethacizine was found in experiments on rabbits to decrease the anticoagulant effect of calcium heparinate to the same degree as does sodium heparinate.

[Thrombolytic action of urokinase preparation covalently bound to modified thrombin]. / Tromboliticheskoe deistvie preparata urokinazy, kovalentno sviazannoi s modifitsirovannym trombinom.

Urokinase was covalently bounded with modified thrombin. Thrombin was modified by carbodiimide and 1, 12-dodecamethylenediamine. In this conjugate thrombin is not catalytically active and does not induce platelets aggregation. The catalytic properties of modified urokinase do not essentially differ from native enzyme but its thermostability increases. The modified urokinase thrombolytic effect is at least 10-fold higher than the native one. In femoral arteries of experimental thrombosis the conjugate urokinase-thrombin brings about total thrombolytic effect as early as 1.5 hours after injection (2500 IU per 1 kg of the animals weight). The causes of the observed effect were discussed.

[Comparative study of the properties of preparations of native and modified collagenase]. / Sravnitel'noe izuchenie svoistv preparatov nativnoi i modifitsirovannoi kollagenazy.

Collagenase was gradually modified by aldehyde dextran and hyaluronidase. The modification increased enzyme stability and widened pH-optimum of its activity against specific and biological substrates. The modified complex with collagenolytic and hyaluronidase activity accumulated in the lungs of mice after intravenous injection. These results demonstrate its possible use for the treatment of lung disorders.

Magnetically driven thrombolytic preparation containing immobilized streptokinase-targeted transport and action.

Streptokinase was immobilized on the magnetic carrier at a concentration of 2,000-2,700 IU/ml of preparation. Thrombosis was induced in both canine carotid arteries by means of the vascular wall flap inverting into its lumen. The red, completely occluding thrombus was formed inside the vessel 4-5 h later. A samarium-cobalt magnet was secured externally to one of the arteries. After the clot formation the magnetically immobilized streptokinase was injected intravenously. The preparation concentrated in the region of the magnetic field action caused complete thrombus degradation and normal blood flow restoration; no effect on the clot in the control artery was observed.

[Effect of etatsizin on blood coagulability and the anticoagulant effect of heparin]. / Vliianie étatsizina na svertyvaemost' krovi i antikoaguliantnyi éffekt geparina.

Etacyzine, a new antiarrhythmic drug of the phenothiazine series, injected intravenously (1 mg/kg) does not change the blood coagulation balance of rabbits. The effect of heparin (100 Units/kg i.v.) reduces after preinjection of etacyzine (1 mg/kg). Etacyzine lowers the concentration of heparin in an aqueous medium and blood plasma.