Significance of cardiac cannabinoid receptors in regulation of cardiac rhythm,myocardial contractility,and electrophysiologic processes in heart

Intravenous administration of cannabinoid (CB) receptor agonists (HU-210, 0.1 mg/kg; ACPA, 0.125 mg/kg; methanandamide, 2.5 mg/kg; and anandamide, 2.5 mg/kg) induced bradycardia in chloralose-anesthetized rats irrespective of the solubilization method. Methanandamide, HU-210, and ACPA had no effect on the electrophysiological activity of the heart, while anandamide increased the duration of the QRS complex. The negative chronotropic effect of HU-210 was due to CB1 receptor activation since it was not observed after CB1 receptor blockade by SR141716A (1 mg/kg intravenously) but was present after pretreatment with CB2 receptor antagonist SR144528 (1 mg/kg intravenously). CB receptor antagonists SR141716A and SR144528 had no effect on cardiac rhythm or ECG indices. Hence, in the intact heart, endogenous CB receptor agonists are not involved in the regulation of cardiac rhythm and electrophysiological processes. The chronotropic effect of CBs was independent of the autonomic nervous system because it remained significant after autonomic ganglion blockade by hexamethonium (1 mg/kg intravenously). CB receptor activation by HU-210 (0.1 and 1 μM) in vitro decreased the rate and force of isolated heart contractions, the rates of contraction and relaxation, and end diastolic pressure. The negative chronotropic effect of HU-210 was less pronounced in vitro than in vivo. The maximum inotropic effect of HU-210 was reached at the concentration of 0.1 μM.     

Morphological discordance of the new trypanosomatid species phylogenetically associated with the genus crithidia

Three new species of monoxenous parasites from the Neotropical Heteroptera are described on the basis of the ultrastructure of cells in culture, as well as gene sequences of Spliced Leader (SL) RNA, glyceraldehyde phosphate dehydrogenase (GAPDH) and small subunit (SSU) rRNA. The results have highlighted a striking discrepancy between the morphological (dis)similarities and the phylogenetic affinities among the insect trypanosomatids. Although each of the new species is characterized by a distinct set of morphological characters, based on the predominant promastigotes observed in culture, each of them has been provisionally assigned to the genus Leptomonas pending the future revision of this genus. Yet, instead of the phylogenetic affinity with the other members of this polyphyletic genus, the new species are most closely related to Crithidia species. Thus, the extremely long promastigotes of Leptomonas acus sp. n. and the unique morphological features found in Leptomonas bifurcata sp. n. sharply contrast with their respective relatives C. fasciculata and C. deanei both of which are typical choanomastigotes. The results clearly show that the current classification at the genus level is misleading and needs to be revised. The phylogenetic clades potentially representing the candidate new genera of monoxenous trypanosomatids have started to emerge from the presented analyses.     

Reproductive Behavior of the Bug <Emphasis Type="Italic">Molipteryx fuliginosa</Emphasis> Uhler (Heteroptera,Coreidae) in the South of the Russian Far East

Reproductive behavior of Molipteryx fuliginosa (Uhler) was investigated in Primorskii Territory of Russia. From 4 to 18 repeated copulations of one female lasting from 2 to 48 hours were recorded in cages. The behavior of ovipositing females and the stages of oviposition are described for the first time. The number of eggs laid between copulations varied from 1 to 13, the number of oviposition acts, from 4 to 11, and the total female fecundity, from 21 to 38 eggs. Caged females laid eggs on plants and also on dead substrates unsuitable for nymphal feeding, such as cloth, dry branches, and a wooden pole. Copulation of M. fuliginosa was also observed under natural conditions. The preferred mating places of M. fuliginosa in anthropogenically modified habitats and in small-leaved riparian forests were plants of Rubus idaeus L., R. caesius L., and Rubus sp. After mating, females migrated in search of places for oviposition. Single eggs were found on the following plants not known previously as hosts of this bug: Solanum lycopersicum L., Carex sp., Elytrigia repens (L.) Nevski, and Taraxacum officinale Wigg. The females seemed to lack selectivity in the choice of place for oviposition, which was not always associated with host plants, despite their abundance and availability.     

mu-Opiate receptor activation and increase in heart resistance to ischemic and reperfusion injury

Stimulation of mu-opioid receptors was found to contribute to prevention of myocardial contractile dysfunction and ventricular arrhythmias in ischemia and reperfusion of the rat isolated heart. Endogenous agonists of the mu-opioid receptors were not involved in tonic regulation of the heart resistance against reperfusion disturbances of the rhythm and contractility. On the other hand, mu-opioid receptors are important for development of postischemic contracture.     

Synthesis of the alkyl-type glycerolipids with functional groups in their polar domain

A number of alkyl glycerolipids with short-chain substituents at the C2 atom of glycerol and functional groups (carboxy and amino) in the polar head were synthesized. Cationic alkyl glycerolipids with a hydroxyl function in the hydrophilic moiety were also obtained. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.     

Development of piperazine-based hydroxamic acid inhibitors against falcilysin,an essential malarial protease

The human parasite Plasmodium falciparum kills an estimated 445,000 people a year, with the most fatalities occurring in African children. Previous studies identified falcilysin (FLN) as a malarial metalloprotease essential for parasite development in the human host. Despite its essentiality, the biological roles of this protease are not well understood. Here we describe the optimization of a piperazine-based hydroxamic acid scaffold to develop the first reported inhibitors of FLN. Inhibitors were tested against cultured parasites, and parasiticidal activity correlated with potency against FLN. This suggests these compounds kill P. falciparum by blocking FLN, and that FLN is a druggable target. These compounds represent an important step towards validating FLN as a therapeutic target and towards the development of chemical tools to investigate the function of this protease.     

Nonorthogonal tight-binding model with H–C–N–O parameterisation

A parametric nonorthogonal tight-binding model (NTBM1) with the set of parameters for H–C–N–O systems is presented. This model compares well with widely used semi-empirical AM1 and PM3/PM7 models but contains less fitting parameters per atom. All NTBM1 parameters are derived based on a criterion of the best agreement between the calculated and experimental values of bond lengths, valence angles and binding energies for various H–C–N–O molecules. Results for more than 200 chemical compounds are reported. Parameters are currently available for hydrogen, carbon, nitrogen, oxygen atoms and corresponding interatomic interactions. The model has a good transferability and can be used for both relaxation of large molecular systems (e.g., high-molecular compounds or covalent cluster complexes) and long-timescale molecular dynamics simulation (e.g., modelling of thermal decomposition processes). The program package based on this model is available for download at no cost from http://ntbm.info.     

Circular dichroism of surface complexes based on quantum dots and azo dye

Chiral properties of surface complexes based on CdSe/ZnS quantum dots (QDs) and 1‐(2‐pyridylazo)‐2‐naphthol (PAN) azo dye were investigated by circular dichroism spectroscopy. The use of L‐, D‐cysteine (Lcys, Dcys) capping ligands allowed us to obtain water‐soluble chiral QD‐PAN complexes. The characterization of the complexes was performed by UV‐vis, FTIR, and CD spectroscopy. Quantum chemical TDDFT calculated CD spectra reproduced the experimentally observed sign patterns, which originate from binding Lcys or Dcys and PAN molecules to the same Zn atom on the QD surface. The resulting complex is characterized by a large circular dichroism in comparison with an ordinary QD chirality induced by cysteine molecules. The pattern of CD signal is the same for Lcys and Dcys ligands in chiral QD‐PAN complex.