Peculiar Aspects in Influence of α1-Adrenoceptor Stimulation on Isolated Rat Heart

The study examined the effect of α1-adrenoceptor stimulation with methoxamine on chronotropic function of isolated heart perfused ex vivo according to Langendorff and cardiac chronotropy in vivo. Stimulation of α1-adrenoceptors in isolated heart induced gradually developing bradycardia, which progressed during several minutes. Similar stimulation in vivo produced a short-term bradycardia probably terminated by the compensatory influences in the whole organism. Comparison of the data obtained in both experimental paradigms during α1-adrenoceptor stimulation revealed unidirectional changes in cardiac chronotropy characterized with time-related peculiarities

Effects of pyrocatechol on neuromuscular transmission

Effects of pyrocatechol on neuromuscular transmission were studied both in the frog pectoral-cutaneous muscle and in the mouse phrenic-diaphragmatic preparation by means of extracellular microelectrode recording of synaptic signals. Pyrocatechol applied in a concentration of 0.05 mM increased the frequency of miniature end-plate currents (MEPC) and the amplitude of end-plate current (EPC) by increasing its quantum content. Pyrocatechol also increased the duration of presynaptic response. When voltage-dependent potassium channels had been blocked, pyrocatechol affected neither the EPC quantum content nor the duration of presynaptic response. It is suggested that the pyrocatechol-induced enhancement of transmitter release results from modulatory effects of pyrocatechol on voltage-dependent potassium current in the membrane of a nerve terminal. © 1995 Plenum Publishing Corporation

Metastable phases and "metastable" phase diagrams

The work discusses specifics of phase transitions for metastable states of substances. The objects of condensed media physics are primarily equilibrium states of substances with metastable phases viewed as an exception, while the overwhelming majority of organic substances investigated in chemistry are metastable. It turns out that at normal pressure many of simple molecular compounds based on light elements (these include: most hydrocarbons; nitrogen oxides, hydrates, and carbides; carbon oxide (CO); alcohols, glycerin etc) are metastable substances too, i.e. they do not match the Gibbs' free energy minimum for a given chemical composition. At moderate temperatures and pressures, the phase transitions for given metastable phases throughout the entire experimentally accessible time range are reversible with the equilibrium thermodynamics laws obeyed. At sufficiently high pressures (1-10 GPa), most of molecular phases irreversibly transform to more energy efficient polymerized phases, both stable and metastable. These transformations are not consistent with the equality of the Gibbs' free energies between the phases before and after the transition, i.e. they are not phase transitions in "classical" meaning. The resulting polymeric phases at normal pressure can exist at temperatures above the melting one for the initial metastable molecular phase. Striking examples of such polymers are polyethylene and a polymerized modification of CO. Many of energy-intermediate polymeric phases can apparently be synthesized by the "classical" chemistry techniques at normal pressure.Comment: 5 pages, 4 figure

Involvement of P2Y2,4 receptors in the regulation of myocardial contractility in growing rats

Experiments with R2Y receptor blockers allowed identification of R2Y subtypes mediating the inhibitory effects of uridine triphosphate on myocardial contractility. In 100-day-old animals, the myocardial inotropic response to the administration of uridine triphosphate was mediated by R2Y2 receptors. R2Y4 receptors took part in the realization of negative inotropic response to uridine triphosphate in all age groups, but the most pronounced effects of this substance on myocardial contractility were found in 100-day-old rats. It was found that R2Y receptor blockers PPADS and reagent blue-2 affect amplitude-time parameters of myocardial contractility in rats of various ages. © 2014 Springer Science+Business Media New York

Ethyl 1,6-dimethyl-2-oxo-4-(quinolin-4-yl)-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

In the title compound, C18H19N3O3, the tetra­hydro­pyrimidone ring adopts a distorted boat conformation. In the crystal structure, inter­molecular N—H⋯O hydrogen bonds link the mol­ecules into centrosymmetric dimers, which are further linked via inter­molecular C—H⋯π inter­actions. In addition, an intra­molecular C—H⋯O hydrogen bond occurs

Human APP Gene Expression Alters Active Zone Distribution and Spontaneous Neurotransmitter Release at the Drosophila Larval Neuromuscular Junction

This study provides further insight into the molecular mechanisms that control neurotransmitter release. Experiments were performed on larval neuromuscular junctions of transgenic Drosophila melanogaster lines with different levels of human amyloid precursor protein (APP) production. To express human genes in motor neurons of Drosophila, the UAS-GAL4 system was used. Human APP gene expression increased the number of synaptic boutons per neuromuscular junction. The total number of active zones, detected by Bruchpilot protein puncta distribution, remained unchanged; however, the average number of active zones per bouton decreased. These disturbances were accompanied by a decrease in frequency of miniature excitatory junction potentials without alteration in random nature of spontaneous quantal release. Similar structural and functional changes were observed with co-overexpression of human APP and β-secretase genes. In Drosophila line with expression of human amyloid-β42 peptide itself, parameters analyzed did not differ from controls, suggesting the specificity of APP effects.These results confirm the involvement of APP in synaptogenesis and provide evidence to suggest that human APP overexpression specifically disturbs the structural and functional organization of active zone and results in altered Bruchpilot distribution and lowered probability of spontaneous neurotransmitter release

Symptomatic improvement, increased life-span and sustained cell homing in amyotrophic lateral sclerosis after transplantation of human umbilical cord blood cells genetically modified with adeno-viral vectors expressing a neuro-protective factor and a neural cell adhesion molecule

© 2015 Bentham Science Publishers. Amyotrophic lateral sclerosis (ALS) is an incurable, chronic, fatal neuro-degenerative disease characterized by progressive loss of moto-neurons and paralysis of skeletal muscles. Reactivating dysfunctional areas is under earnest investigation utilizing various approaches. Here we present an innovative gene-cell construct aimed at reviving inert structure and function. Human umbilical cord blood cells (hUCBCs) transduced with adeno-viral vectors encoding human VEGF, GDNF and/or NCAM genes were transplanted into transgenic ALS mice models. Significant improvement in behavioral performance (open-field and grip-strength tests), as well as increased life-span was observed in rodents treated with NCAM-VEGF or NCAM-GDNF co-transfected cells. Active trans-gene expression was found in the spinal cord of ALS mice 10 weeks after delivering genetically modified hUCBCs, and cells were detectable even 5 months following transplantation. Our gene-cell therapy model yielded prominent symptomatic control and prolonged life-time in ALS. Incredible survivability of xeno-transpanted cells was also observed without any immune-suppression. These results suggest that engineered hUCBCs may offer effective gene-cell therapy in ALS

ВЛИЯНИЕ СЕРОВОДОРОДА НА СОКРАТИТЕЛЬНУЮ АКТИВНОСТЬ ПРЕДСЕРДИЯ МЫШИ В КОНТРОЛЕ И В УСЛОВИЯХ МОДЕЛИРОВАНИЯ САХАРНОГО ДИАБЕТА

Hydrogen sulfide (H2S) is endogenously synthesized gasotransmitter that has a regulatory effect in cardiovascular system. Diabetes mellitus leads to an increased risk of hypertension and cardiovascular diseases, so the purpose of the study was to analyze the contractility of the atria mice after application of L-cysteine and H2S. Contractile activity of the myocardium was investigated in the experiment on isolated mouse atria. Alloxan was used for modeling diabetes. Intraperitoneal injection of alloxan resulted in a significant increase of glucose concentration in blood, whereas the concentration of glucose didn’t change at the injection of physiological solution. In control, the addition of NaHS resulted in a significant dose-dependent decrease of the amplitude of contraction of the myocardium, whereas the negative inotropic effect of NaHS was significantly lower in terms of modeling diabetes compare to control conditions. In the control, L-cysteine reduced the amplitude contractions significantly, whereas L-cysteine did not lead to significant changes in the amplitude of contractions in terms of modeling diabetes. These data indicate that the sensitivity of mice’s atria reduced for H2S and L-cysteine in diabetes mellitus.Сероводород (H2S) является эндогенно синтезируемым газообразным посредником, который был обнаружен в качестве регулятора сердечно-сосудистой системы. Сахарный диабет (СД) ведет к увеличению риска развития гипертензии и сердечно-сосудистых заболеваний, поэтому целью исследования явился анализ сократительной функции предсердий мыши в ответ на аппликацию L-цистеина и H2S. Сократительную активность миокарда в эксперименте in vitro исследовали на изолированных предсердиях мыши. Для моделирования СД использовали аллоксан. Внутрибрюшинная инъекция аллоксана приводила к достоверному повышению концентрации глюкозы в крови, которая при инъекции физиологического раствора достоверно не увеличивалась. В контроле добавление NaHS приводило к достоверному дозозависимому снижению амплитуды сокращения миокарда, тогда как в условиях моделирования СД отрицательный инотропный эффект NаHS был достоверно ниже, чем в контрольных условиях. В контроле L-цистеин достоверно уменьшал амплитуду сокращения, тогда как в условиях моделирования СД L-цистеин в тех же концентрациях не приводил к достоверным изменениям амплитуды сокращения. Полученные данные свидетельствуют о том, что чувствительность предсердия мыши к H2S и субстрату его синтеза L-цистеину заметно снижается в условиях моделирования СД

Transcriptional Analysis of Blood Lymphocytes and Skin Fibroblasts, Keratinocytes, and Endothelial Cells as a Potential Biomarker for Alzheimer's Disease

© 2016 - IOS Press and the authors. All rights reserved.Alzheimer's disease (AD) is a devastating and progressive form of dementia that is typically associated with a build-up of amyloid-β plaques and hyperphosphorylated and misfolded tau protein in the brain. Presently, there is no single test that confirms AD; therefore, a definitive diagnosis is only made after a comprehensive medical evaluation, which includes medical history, cognitive tests, and a neurological examination and/or brain imaging. Additionally, the protracted prodromal phase of the disease makes selection of control subjects for clinical trials challenging. In this study we have utilized a gene-expression array to screen blood and skin punch biopsy (fibroblasts, keratinocytes, and endothelial cells) for transcriptional differences that may lead to a greater understanding of AD as well as identify potential biomarkers. Our analysis identified 129 differentially expressed genes from blood of dementia cases when compared to healthy individuals, and four differentially expressed punch biopsy genes between AD subjects and controls. Additionally, we identified a set of genes in both tissue compartments that showed transcriptional variation in AD but were largely stable in controls. The translational products of these variable genes are involved in the maintenance of the Golgi structure, regulation of lipid metabolism, DNA repair, and chromatin remodeling. Our analysis potentially identifies specific genes in both tissue compartments that may ultimately lead to useful biomarkers and may provide new insight into the pathophysiology of AD