THE INFLUENCE OF ANTIRETROVIRAL AND ANTITUBERCULOSIS AGENTS ON THE BIOCHEMICAL AND HISTOPATHOLOGICAL INDICES OF LIVER FUNCTION IN RATS

Background. Standard antituberculosis treatment and highly active antiretroviral therapy are frequently associated with hepatotoxicity leading to drugs discontinuation.Objective. This study aimed to assess the signs of hepatotoxicity in albino rats in case of simultaneous usage of tuberculostatics (TBS) and antiretroviral agents (ART).Methods. Healthy rats were divided in 4 groups: 1st control group; 2nd group was given tuberculostatics (isoniazid – 50 mg/kg, rifampicin – 50 mg/kg and pyrazinamide – 1500 mg/kg); 3rd group was given ART (efavirenz – 150 mg/kg and stavudine – 5 mg/kg); 4th group was given TBS and ART. The animals were sacrificed painlessly on the 29th day; blood and liver samples were obtained. The main biochemical and histopathological indices were determined.Conclusions. Comparing with control group, repeated usage of TBS caused the prominent liver injury with cytolysis and cholestasis signs, decreasing of CYP3A and CYP2E1 isozymes activity and dysfunction of protein synthesis by the liver. ART (efavirenz and stavudine) caused the elevation of transaminases activity with the increase of serum bilirubin level at the background of increase in cytochrome 450 isoforms 3A and 2E1 activities and total serum protein. The antiretroviral agents in case of simultaneous administration with the antituberculosis drugs diminished the hepatotoxic effects of first-line drugs for tuberculosis treatment which was confirmed by the study of liver histopathology. Such results of our experimental study give encouragement for further detailed clinical research of drug-drug interaction of both pharmacological groups due to the rising cases of HIV-associated tuberculosis in the whole world.KEY WORDS: Isoniazid, rifampicin, pyrazinamide, efavirenz, stavudine, liver, cytochrome P450

Experimental study of direct photon emission in K- --> pi- pi0 gamma decay using ISTRA+ detector

The branching ratio in the charged-pion kinetic energy region of 55 to 90 MeV for the direct photon emission in the K- --> pi- pi0 gamma decay has been measured using in-flight decays detected with the ISTRA+ setup operating in the 25 GeV/c negative secondary beam of the U-70 PS. The value Br(DE)=[0.37+-0.39(stat)+-0.10(syst)]*10^(-5) obtained from the analysis of 930 completely reconstructed events is consistent with the average value of two stopped-kaon experiments, but it differs by 2.5 standard deviations from the average value of three in-flight-kaon experiments. The result is also compared with recent theoretical predictions.Comment: 13 pages, 8 figure

Theory of traveling filaments in bistable semiconductor structures

We present a generic nonlinear model for current filamentation in semiconductor structures with S-shaped current-voltage characteristics. The model accounts for Joule self-heating of a current density filament. It is shown that the self-heating leads to a bifurcation from static to traveling filament. Filaments start to travel when increase of the lattice temperature has negative impact on the cathode-anode transport. Since the impact ionization rate decreases with temperature, this occurs for a wide class of semiconductor systems whose bistability is due to the avalanche impact ionization. We develop an analytical theory of traveling filaments which reveals the mechanism of filament motion, find the condition for bifurcation to traveling filament, and determine the filament velocity.Comment: 13 pages, 5 figure

Dynamic of indices of lipid peroxidation and antioxidant protection in muscular tissue and blood serum of rats with acute ischemia-reperfusion

Acute limb ischemia occurs as a result of sudden decrease in its perfusion, which usually occurs during the obturation of the lumen of large arteries due to acute thrombosis or embolism either impaired of vascular patency caused by trauma or compression (including the application of hemostatic tourniquets). In the case of restoration of blood supply to previously ischemic tissues, there is an ischemic-reperfusion syndrome, in which one of the main pathogenetic links of tissue alteration is the activation of lipid peroxidation. The content of diene conjugates, triene conjugates, TBA-active products, superoxide dismutase and catalase in homogenate of the muscle tissue and blood serum of 30 white rats under condition of experimental acute ischemia was determined. Acute ischemia was caused by the application of SWAT (Stretch-Wrap-And-Tuck) rubber bundles on the hind limbs of the animals for 2 hours. It was experimentally found that the maximum increase in the content of diene and triene conjugates in the injured muscle tissue of the animals occurred in the early post-ischemic period on the 2nd hour of reperfusion with a decreaseing on the 1st and 7th day and the subsequent return of indicators in the late postischemic period on the 14th day to the level of control group. The increasing of TBA-active products in the muscle tissue occurred in the first three groups of the rats and peaked in the third group (reperfusion for the 1st day), after which their level decreased in the animals during the late reperfusion period, reaching in the last group on the 14th day of reperfusion indices, close to the values of the control group. The dynamics of activity of superoxide dismutase and catalase in the muscle homogenate were to a large extent similar (as indicated by the strong positive correlation (+0,99) between them), gradually increasing and reaching the maximum on 7th day of the ischemia-reperfusion symdrome. As a result of the experiment, a decreasing in the antioxidant-prooxidant index in all experimental groups of the rats was also observed in the muscle homogenate, which was the most pronounced on the 1st day of ischemia-reperfusion. The comparative analysis of the similar parameters of lipid peroxidation and antioxidant protection in the muscle homogenate and blood serum showed a direct correlation in all the studied pairs. The strong and moderate positive correlation between analogous indices of LPO and AOP in muscle homogenate and blood serum in all five studied pairs indicates similar changes of these indicators at the local and systemic levels

Study of Radiation Damage in Lead Tungstate Crystals Using Intense High Energy Beams

We report on the effects of radiation on the light output of lead tungstate crystals. The crystals were irradiated by pure, intense high energy electron and hadron beams as well as by a mixture of hadrons, neutrons and gammas. The crystals were manufactured in Bogoroditsk, Apatity (both Russia), and Shanghai (China). These studies were carried out at the 70-GeV proton accelerator in Protvino

Observation of the radiative kaon decay K- --> mu-pi0gammanu

Using data collected with the ISTRA+ spectrometer during the 2001 run of the U-70 proton synchrotron in Protvino, we report the first observation of the radiative kaon decay K- -->mu-pi0gammanu. We find Br(Kmu3g)/Br(Kmu3) for two regions 5<Eg<30 and 30<Eg<60 MeV consistent with theoretical predictions. The measured angular distribution asymmetry for the first region, 0.093+/-0.141, is two standard deviations away from the theoretical prediction of 0.354. The measured asymmetry in the T-odd variable is -0.03+/-0.13.Comment: 15 pages, 8 figurs, submitted to Yadernaya Fizik

Prospects for Diffractive and Forward Physics at the LHC

The CMS and TOTEM experiments intend to carry out a joint diffractive/forward physics program with an unprecedented rapidity coverage. The present document outlines some aspects of such a physics program, which spans from the investigation of the low-x structure of the proton to the diffractive production of a SM or MSSM Higgs boson

CMS physics technical design report : Addendum on high density QCD with heavy ions

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