Promjene citokroma P450 jetre i mozga nakon višekratne primjene kokaina, samog ili u kombinaciji s nifedipinom

The objective of this study was to evaluate possible changes caused by multiple cocaine administration, alone and in combination with 1,4-dihydropiridine calcium channel blocker nifedipine, on cytochrome P450 levels both in the brain and liver. The experiment was done on male Wistar rats divided in four groups: control, treated with nifedipine (5 mg kg-1 i.p. for five days), treated with cocaine (15 mg kg-1 i.p. for five days), and treated with nifedipine and 30 minutes later with cocaine (also for five days). Total cytochrome P450 was measured spectrometrically in liver and brain microsomes. Multiple administration of cocaine alone and in combination with nifedipine did not change the brain P450 significantly. In the liver, nifedipine significantly increased P450 by 28 % vs. control. In contrast, cocaine significantly decreased P450 by 17 % vs. control. In animals treated with nifedipine and cocaine, cytochrome P450 increased 11 % (p<0.01) vs. control, decreased 12.5 % (p<0.001) vs. nifedipine group and increased 34 % (p<0.0001) vs. cocaine group. These results suggest that the cocaine and nifedipine interact at the metabolic level.Cilj je ovog istraživanja bio ocijeniti moguće promjene uzrokovane višestrukom primjenom kokaina kao jedinog agensa odnosno u kombinaciji s nifedipinom, 1,4-dihidropiridinskim blokatorom kalcijevih kanala, na razine citokroma P450 u mozgu i jetri štakora. Životinje (mužjaci Wistar štakora) podijeljene su u četiri skupine: kontrolnu skupinu, skupinu koja je primala nifedipin (5 mg kg-1 ip. pet dana), skupinu koja je primala kokain (15 mg kg-1 ip. pet dana) i skupinu koja je primala nifedipin te pola sata kasnije kokain (također pet dana). Ukupna količina citokroma P450 mjerena je spektrofotometrijski u mikrosomima jetre i mozga. Višestruka primjena samo kokaina odnosno u kombinaciji s nifedipinom nije značajno promijenila razine citokroma P450 u mozgu. U jetri je međutim nifedipin u odnosu na kontrolnu skupinu uzrokovao povišenje razina P450, za statistički značajnih 28 %. Kokain je uzrokovao statistički značajan pad razine P450 za 17 % u odnosu na kontrolnu skupinu. U životinja koje su primale kombinaciju nifedipina i kokaina razina citokroma P450 narasla je za 11 % (p<0.01) u odnosu na kontrolu, bila je 12.5 % (p<0.001) niža u odnosu na skupinu koja je primala nifedipin te viša za 34 % (p<0.0001) u odnosu na skupinu koja je primala samo kokain. Rezultati ovog istraživanja upućuju na interakcije ovih spojeva koje se odvijaju na razini metabolizm

Nifedipin ublažava djelovanje kokaina na enzimsku aktivnost u mozgu i jetri te smanjuje njegovo izlučivanje putem mokraće

The aim of this study was to see how nifedipine counters the effects of cocaine on hepatic and brain enzymatic activity in rats and whether it affects urinary excretion of cocaine. Male Wistar rats were divided in four groups of six: control, nifedipine group (5 mg kg-1 i.p. a day for five days); cocaine group (15 mg kg-1 i.p. a day for five days), and the nifedipine+cocaine group. Twenty-four hours after the last administration, we measured neuronal nitric oxide synthase (nNOS) activity in the brain and cytochrome P450 quantity, ethylmorphine-N-demethylase, and anilinehydroxylase activity in the liver. Urine samples were collected 24 h after the last cocaine and cocaine+nifedipine administration. Urinary cocaine concentration was determined using the GC/MS method. Cocaine administration increased brain nNOS activity by 55 % (p<0.05) in respect to control, which indicates the development of tolerance and dependence. In the combination group, nifedipine decreased the nNOS activity in respect to the cocaine-only group. In the liver, cocaine significantly decreased and nifedipine significantly increased cytochrome P450, ethylmorphine-N-demethylase, and anilinehydroxylase in respect to control. In combination, nifedipine successfully countered cocaine effects on these enzymes. Urine cocaine excretion in the cocaine+nifedipine group significantly dropped (by 35 %) compared to the cocaine-only group. Our results have confirmed the effects of nifedipine against cocaine tolerance and development of dependence, most likely due to metabolic interactions between them.Cilj je ovoga istraživanja bio utvrditi kako nifedipin ublažava djelovanje kokaina na enzimsku aktivnost u mozgu i jetri Wistar štakora te utječe li na njegovo izlučivanje putem mokraće. Mužjaci su podijeljeni u četiri skupine po šest jedinki: kontrolnu skupinu, nifedipinsku skupinu koja je pet dana intraperitonealno primala nifedipin u dozi od 5 mg kg-1; skupinu koja je pet dana primala kokain u dozi od 15 mg kg-1 na dan te skupinu koja je zajedno primala nifedipin i kokain u odgovarajućim dozama. Dvadeset i četiri sata nakon posljednje doze izmjerena je enzimska aktivnost sintaze dušičnoga oksida (nNOS) u mozgu, razina citokroma P450 te aktivnosti enzima etilmorfi n-N-demetilaze i anilinhidroksilaze u jetri štakora. Uzorci mokraće prikupljeni su 24 sata nakon posljednje doze kokaina odnosno kombinacije nifedipina i kokaina. Koncentracija kokaina u mokraći izmjerena je s pomoću vezanog sustava plinske kromatografi je i spektrometrije masa. Kokain je povećao aktivnost nNOS-a u mozgu za 55 % (p<0,05) u odnosu na kontrolnu skupinu, što upućuje na stvaranje tolerancije i ovisnosti. U kombiniranoj skupini nifedipin je značajno smanjio aktivnost nNOS-a u odnosu na skupinu koja je primila samo kokain. Kokain je značajno snizio, a nifedipin značajno povisio razinu citokroma P450 u jetri te aktivnost etilmorfi n-N-demetilaze i anilinhidroksilaze u odnosu na kontrolnu skupinu. U kombiniranoj skupini nifedipin je uspješno ublažio djelovanje kokaina na aktivnost spomenutih enzima. Izlučivanje kokaina putem mokraće u kombiniranoj skupini bilo je značajno manje (35 %) nego u skupini koja je primala samo kokain. Ovi rezultati potvrđuju da nifedipin štiti od djelovanja kokaina i stvaranja ovisnosti, najvjerojatnije zbog interakcija u metabolizmu dvaju spojeva

Forty years literature review of primary lung lymphoma

There are several unresolved issues through out the literature regarding the entity of primary lung lymphoma. Extensive literature review of this uncommon pathology is carried out

A METHOD FOR TECHNICAL ECONOMIC-ANALYSIS OF SOLAR HEATING-SYSTEMS

The necessity for technical-economic analysis of solar energy systems is obvious when assessing their feasibility vis-á-vis conventional alternative systems. Optimum magnitudes of the installation parameters should be defined under the required economic conditions. In this study, the optimization procedure was chosen so as to maximize the total accumulated saving throughout the economic lifetime of the system. The annual solar heating fraction of the system is assessed using the f-chart method which can be used for both domestic hot water and space heating. The saving produced by investing in a solar installation is obtained by taking the difference between the total discounted expenditures of the conventional and the solar systems, accumulated during their foreseen lifetimes. To this end, the present value method is applied, taking into account the initial investment costs, fuel costs, operation costs and the maintenance costs for both the solar system and its conventional alternative. Based on this technical-economic analysis, a computer program is developed. This accepts three types of input data: technical design, economic parameters and meteorological conditions, and calculates the optimum magnitudes of the design parameters. It is concluded that economic parameters are much more influential on the system economics than the technical parameters. The most significant are the payback period and the internal rate of return

Simulation of dissolution of silicon in an indium solution by spectral methods

The results of a numerical simulation of natural convection due to concentration gradients during dissolution of silicon in an indium solution in a horizontal substrate-solution-substrate system are presented. The Chebyshev-Tau spectral method has been used for the simulations. The results are in very good agreement with the experimental data available in the literature. It is concluded that the discrepancies in the dissolution depths between the previous simulations and experimental data, especially at the earlier stages of the process, are mostly due to combined effects of uncertainties in the predicted properties and insufficient numerical accuracy

Lateral heating effects on the PVT growth process of Hg2Cl2 crystals

Effects of lateral heating on flow profiles and growth rates during the growth of mercurous chloride crystals by the physical-vapour-transport process in vertical ampoules are investigated by a two-dimensional model. The growth conditions of an experimental study available in the open literature are simulated. Lateral thermal boundary condition is modelled by a spatially sinusoidal heat flux. The results of the present computations are in agreement with the earlier experimental results and indicate that an increase in the lateral heating rate can cause a significant decrease in the transport rate while the flow accelerates. In the case of flow bifurcations, the growth rates can become as low as in the case of convectionless flow conditions

Accuracy of Monte Carlo method re-examined on a box-shaped furnace problem

Monte Carlo method was applied to predictions of radiative heat flux density and source term of a box-shaped enclosure problem based on data reported previously on a large scale experimental furnace with steep temperature gradients typically encountered in industrial furnaces. The rectangular furnace under consideration has black interior walls and an absorbing emitting medium of constant properties. The predictive accuracy of the model was evaluated by comparing its predictions with exact numerical solutions produced previously for the same enclosure problem. The comparisons show that the model provides radiative heat flux and energy source term distributions in close agreement with the benchmark solutions

Comparison between performances of Monte Carlo method and method of lines solution of.discrete ordinates method

Monte Carlo method was used to predict the incident radiative heat fluxes on the freeboard walls of the METU 0.3 MWt atmospheric bubbling fluidized bed combustor based on the data reported previously. The freeboard was treated as a rectangular enclosure with gray interior walls and gray, absorbing, emitting and isotropically scattering medium. A Monte Carlo solver was developed and the performance of the solver was assessed by comparing its predictions with those of method of lines solution of discrete ordinates method and experimental measurements reported previously. Parametric studies were carried out to examine the effects of particle load and anisotropic scattering on the, predicted incident radiative heat fluxes. The comparisons show that Monte Carlo method reproduces the measured incident radiative heat fluxes reasonably well for the freeboard problem