Selective serotonine reuptake inhibitors (SSRI) are believed to be less dangerous in the treatment of depressive disorder in comparison with tricyclic antidepressants (TCA) due to their relative lack of cardiotoxicity. Thus, we investigated the effect of citalopram (SSRI) on membrane electrophysiology in rat cardiomyocytes in tissue culture. The results were compared with those from amitriptyline (TCA). The whole-cell configuration patch-clamp technique was used. Both citalopram and amitriptyline exhibited the concentration-dependent inhibition of the L-type calcium channel current (ICa). Citalopram in concentrations of 3 mM and 10 mM inhibited peak calcium current by 2.7 % and 8 %, respectively. We demonstrated the same potency of citalopram and amitriptyline to inhibit ICa. These observations led us to conclude that citalopram and amitriptyline are drugs, which exhibit a similar potency for causing concentration-dependent inhibition of ICa., J. Hamplová-Peichlová, J. Krůšek, I. Paclt, J. Slavíček, V. Lisá, F. Vyskočil., and Obsahuje bibliografii
Gel electrophoresis of DNA was used for estimation of DNA changes caused in C6 glioma cells by treatment with psychotropic drugs (imipramine, amitryptiline and fluoxetine). Some discrete bands containing a population of short DNA fragments appeared after 1 and 5 days of cultivation. Apoptotic DNA breaks were verified at single cell level using the TUNEL test in cells treated with fluoxetine.
Sodium borocaptate (BSH, Na2Bi2HnSH), a slow neutron-capture compound, was injected into the left forebrain ventricle of 1-week-old rats (150 fig BSH/3 p\ phosphate buffered saline). After 90 min, the animals were irradiated by epithermal neutrons (LVR-15 nuclear reactor in Řež near Prague, flux density 8.8 x 107 neutrons cm-2 s'1, 8 MW reactor power, 8.2 cGy/min) for 5,10 or 20 min. The brains were examined histologically 8 h after irradiation. In animals irradiated for 5 to 10 min (41 and 82 cGy-Eq, respectively) lethal damage of cells was found in the external granular layer of the cerebellum and the subependymal layer of the forebrain. Irradiation for 20 min (164 cGy-Eq) caused more extensive destruction of cell populations in these regions and, in addition, dead cells appeared also in the more differentiated postmitotic compartments, namely the deeper layers of the cerebellum, layers II/III of the cerebral cortex and corpus callosum. In the forebrain periventricular layer, the extent of cell damage was declining towards the olfactory bulbs. In intact animals, as well as in those injected only with the 150 p\ phosphate buffered saline, the radiation damage was low and limited only to the most sensitive dividing populations of the cerebellum and the forebrain. The study demonstrates a differentiation-dependent damage of the rat brain cells by alpha particles and presents a simple model for evaluation of the biological effectiveness of slow neutron beams constructed for neutron-capture therapy of tumors.
The morphology and proliferation of vascular smooth muscle cells (VSMC) were studied in cultures prepared from the aorta of newborn male and female Wistar rats. The doubling times (DT) of the male-derived population were 16.4 ±0.7 h and 30.0 ±2.2 h in the exponential and post-exponential growth phases, respectively. In the female donor cells, the corresponding DT values were significantly longer, i.e. 21.9 ± 1.8 h and 38.0 ±2.2 h. In addition, the period of growth was shorter in the female-derived cultures. The percentage of 3H-thymidine labelled cells in male cultures was 61.0±3.1, 92.8± 1.9 and 98.7±0.6 % at 2, 27 and 52 h, respectively. In the female-derived populations, only 24.6 ±4.4, 66.1 ±3.8 and 82.8 ±2.0 % of cells were labelled at the corresponding incubation intervals. As a consequence, the final population density in male cultures was 5.6 times higher. In addition, the male-derived VSMC were mainly spindle-shaped and bulgy in appearance while those from female donors were flat and polygonal which means that the cells were adhering to the growth support to a different extent. The study revealed early determination and long-term persistence of lower adhesiveness as well as higher growth potential of male VSMC, i.e. properties which may be of importance for explaining the higher incidence of vascular wall disorders in males.
Brain infections as well as peripheral challenges to the immune system lead to an increased production of interleukin-1beta (IL-1b), a cytokine involved in leukocyte-mediated breakdown of the blood-brain barrier. The effects of IL-1b have been reported to depend on whether the route of administration is systemic or intracerebral. Using 50-day-old male rats, we compared the effects of IL-1b on brain γ-glutamyl transpeptidase (GGT; an enzymatic marker of brain capillary endothelium) at 2, 24 and 96 h after either an intravenous (i.v.) injection of 5 μg IL-1β or an intracerebroventricular (i.c.v. - lateral ventricle) infusion of 50 ng IL-1β. When the i.v. route was used, the GGT activity underwent small but significant changes; decreasing in the hippocampus 2 h after the i.v. injection, increasing 24 h later and returning to control levels at 96 h. No significant changes in the hippocampal GGT activity were observed at 2 and 24 h following the i.c.v. infusion. The GGT activity in the hypothalamus remained unchanged regardless of the route of IL-1b administrations. Similar changes in GGT activity were revealed histochemically. The labeling was found mainly in the capillary bed, the changes being most evident in the hippocampal stratum radiatum and stratum lacunosum-moleculare. A transient increase in GGT activity at 24 h, together with a less sharp delineation of GGT-stained vessels, may reflect IL-1b induced increased turnover of glutathione and/or oxidative stress, that may in turn, be related to altered permeability of the blood-brain barrier in some neurological and mental disorders, including schizophrenia.