Inhibition of Human Platelet Aggregation by Amides and Ester of Salicylic Acid with Platelet-Activating Factor Analogs

The influence of acetyl salicylic acid (ASA) derivatives with platelet-activating factor (PAF) lipid analogs on PAF-induced human platelet aggregation has been studied. It was found that the ASA amide with an ethanolamine plasmalogen PAF analog (1-0-alk-1"-enyl-2-acetyl-sn-glycero-3-phospho-(N-2"-acetoxybenzoyl)ethanolamine) and the ASA ester with a choline plasmalogen PAF analog (1-0-alk-1"-enyl-2-(2"-acetoxybenzoyl)-sn-glycero-3-phosphocholine) at concentrations of 10^–7-10^–6 M effectively inhibit PAF-induced aggregation of human platelets. In contrast to these compounds, the ASA amide with an alkyl PAF analog (1-0-alkyl-2-acetyl-sn-glycero-3-phospho-(N-2"-acetoxybenzoyl)ethanolamine) did not inhibit PAF-induced platelet aggregation. As possible mechanisms of action of the studied compounds, the blockade of PAF-receptor and cyclooxygenase inhibition are proposed.     

Effect of hypothyroidism on 5-HT1A-, 5-HT2A-receptors and serotonin transporter in the rat brain

Effects of thyroid hormone deficiency on 5-HT1A receptors, 5-HT2A receptors and serotonin transporter in the brain were studied in thyroidectomised Wistar rats receiving an iodine-free diet and receiving 15 micrograms/kg of thyroxine for 21 days. Binding of 3H-8-OH-DPAT to 5-HT1A receptors and 3H-cytalopram to serotonin transporter were unchanged in hypothyroid rats as compared to the control. 3H-ketanserin binding to 5-HT2A receptors was significantly decreased in the frontal cortex in hypothyroid rats. The cortical 3H-ketanserin binding in thyroidectomised rats was normalised after thyroxine replacement. The data suggest that the decrease in the cortical 5-HT2A receptors is the main consequence of impairing effect of hypothyroidism on serotonin neurotransmission.     

Effect of new potential psychotropic drug, 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride, on the expression of serotonin-related genes in mouse brain

Study of molecular mechanisms of psychotropic drug action is the main aim of molecular psychopharmacology. New synthetic analog of variacin 8-(Trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine (TX-2153) was shown to produce anxiolytic and anticonvulsant effects on mice. Here the effect of chronic administration of TX-2153 on expression of some serotonin-related genes in mouse brain was investigated. The drug (10 mg/kg, per os, 16 days) was administered to adult males of ASC (Antidepressant Sensitive Catalepsy) mouse strain characterizing by alterations in behavior and brain serotonin system. The expression of genes encoding 1) the key enzyme of serotonin synthesis, tryptophan hydroxylase 2 (TPH2), 2) main enzyme of serotonin degradation, monoamine oxydase A (MAOA), 3) 5-HT transporter (SERT) and 4) 5-HT(1A) receptor was studied using quantitative RT-PCR. TX-2153 significantly reduced m-RNA level of 5-HT(1A) receptor and MAOA genes in the midbrain without any effect on expression of these genes in the frontal cortex and hippocampus. The drug failed to affect expression of TPH2 and SERT genes in the midbrain. The result indicates involvement of the brain 5-HT system in the molecular mechanism underlying the effect of TX-2153.     

The density of myocardial and pericardial rat mast cells in isoproterenol-induced heart failure

Myocardial mast cells (MC) respond to cardiovascular pathology. The behavior of MC population in myocardium and pericardium of rats has been studied 24 h, 14, 28 and 60 days after two isoproterenol injections (at 24 h intervals). The extent of heart failure has been estimated by supersonic inspection 28 and 60 days after isoproterenol injections. The density of MCs of different degrees of maturity was estimated on paraffin sections stained with Alcian blue--Safranin. The MC density in myocardium of intact and experimental rats was relatively low: from 4 to 6 cells/mm2. The MC density in pericardium of intact rats was several times higher than in myocardium: 48.6 +/- 13.0 cells/mm2. In 24 h and 14 days after isoproterenol injections the pericardial MC density was 1.5 times higher than in control rats (P < 0.05) at the expense of increase in the number of mature MCs with Safranine-positive granules without the increase in the number of immature cells with Alcian blue-positive granules. In 28 days the pericardial MC density was 2 times higher than in intact rats (P < 0.05) at the expense of increase in number of immature and mature cells. In 60 days after isoproterenol injections the pericardial MC density and the ratio of immature and mature cells compared with control did not reach statistical significance. The changes in pericardial MC population corresponded to severity of heart failure according to functional indices. The findings show active reaction of pericardial MCs on myocardium dysfunction that stimulates the maturation of resident immature MCs in pericardium and migration of immature cells to pericardium of damage heart.     

Food-procuring skill in rats: prolongations of the extension phase in final movements of right-handed rats

In Wistar rats with different forepaw preference trained to get food spheres from a narrow horizontal tube feeder, the duration of the paw extension phase was studied in both preliminary and final (successful) food-procuring movements. In left-handed rats, the paw extension was fastly in both preliminary and final movements than in right-handed animals. In right-handed animals, the extension phase of the final successful movements was much slower than that of preliminary movements, whereas in left-handed rats the slowing of the final extension was poorly expressed. The prolongation of the extension phase suggests a possibility of correction of the extension phase of the goal-directed movements     

Magnetic interaction of manganese with pheophytin anion-radical and chlorophyll cation-radical in reaction centers of the photosystem II

The influence of Mn on saturation curves of ESR spectra of Ph(-) and P(+)(680) at 1-200K in samples with different content of Mn has been studied. An analysis of these data and those on photoinduced changes of fluorescence yield of chlorophyll leads to the conclusion that the Mn-containing centre in Photosystem 2 is a cluster of 4 Mn atoms, two of which can be replaced by Mg(2+) or any other divalent metal. The distances between Mn Na Ph as well as between Mn and P(680) have been estimated.