Selective blockade of α<inf>2</inf>-adrenoceptor subtypes modulates contractility of rat myocardium

© 2016 Springer Science+Business Media New York.The study examined the dose-dependent effects of selective antagonists of α2A/D-, α2B-, and α2C-adrenoceptors applied in concentrations of 10-9-10-5 M on atrial and ventricular contractility of rat myocardium in vitro. Selective blockade of each α2-adrenoceptor subtype affected the contractile force of the atrial and ventricular strips. Various concentrations of α2A/D-and α2C-adrenoceptor antagonists produced positive inotropic effect on ventricular strips and negative effect on atrial strips. α2B-Adrenoceptor blocker in the majority of the tested concentrations produced a positive inotropic effect in both atria and ventricles

Effect of α2-adrenoceptor stimulation on cardiac activity in rats

We studied the effect of α2-adrenoceptor stimulation with clonidine on BP and cardiac activity in rats. Variations in BP and chronotropism of the heart were studied in vivo after bolus injection of clonidine. In vitro experiments were performed to evaluate a dose-dependent change in myocardial contractility of the atria and ventricles after treatment with clonidine in concentrations of 10-9-10-5 M. α2- Adrenoceptor stimulation with clonidine had a negative chronotropic and inotropic effect and induced the decrease in systolic BP of rats. © 2014 Springer Science+Business Media

Peculiar Effects of Selective Blockade of α2-Adrenoceptor Subtypes on Cardiac Chronotropy in Newborn Rats

© 2015, Springer Science+Business Media New York. We studied the effects of selective blockade of various subtypes of α2-adrenoceptors on cardiac chronotropy in newborn rats. This period in rats is characterized by the absence of adrenergic regulation of heart function. Blockade of α2A/D- and α2B-adrenoceptors in 1-weekold rats provoked tachycardia. In contrast, blockade of α2C-adrenoceptors in newborn rats had no effect on heart rate

Selective Blockade of α<inf>2</inf>-Adrenoceptor Subtypes Modulates Contractility of Rat Myocardium

© 2016 Springer Science+Business Media New YorkThe study examined the dose-dependent effects of selective antagonists of α2A/D-, α2B-, and α2C- adrenoceptors applied in concentrations of 10—9-10—5 M on atrial and ventricular contractility of rat myocardium in vitro. Selective blockade of each α2-adrenoceptor subtype affected the contractile force of the atrial and ventricular strips. Various concentrations of α2A/D- and α2C-adrenoceptor antagonists produced positive inotropic effect on ventricular strips and negative effect on atrial strips. α2B-Adrenoceptor blocker in the majority of the tested concentrations produced a positive inotropic effect in both atria and ventricles

Optogenetics and photopharmacology - effective tools for managing cell activity using light

Contemporary research has been enriched by the new directions in which the light plays a key role as a tool for modulation of cellular activity and invasive monitoring of intracellular ions and other components. The main advantages of these approaches are the possibilities to precisely control the intensity, spectral characteristics and durations of light signals in space and time. This review summarizes the key areas, optogenetics and photopharmacology, - directions that allow to control cellular activity with light. Optogenetics is the use of light-sensitive transmembrane proteins capable of exciting or inhibiting cellular activity under illumination by different wavelengths. In 2003 a light-sensitive protein canalo-rodopsine was isolated and cloned which is capable of inducing ion currents and changing cellular rest potential with its excitation under the blue light when embedded into the neurons or other cell types. Inhibition of cellular activity is caused by expression of other lightsensitive proteins - chloride or hydrogen pumps, or anion-selective ion channels. These principles turns out to be efficacious for the study of the functions of solitary cells and neural nets as well as for the control of living organisms behavior but their use in medicine is complicated because of necessary genetic manipulations. Photopharmacology is based on creating and using of chemical compounds changing conformations and/or activity under the light. Photochromic compounds with the use of photosensitive switches are capable of selective activation or inhibition of the activity of functionally important proteins - receptors, ion channels, enzymes, etc. The principles and the potential use of optogenetics and photopharmacology in the analysis of the neuronal functions and the perspectives for new approaches to treat some diseases of the nervous system are discussed

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

Reação adaptativa do sistema simpático de adrenalina de meninas em atividade física

The study of the functional state of the sympatho-adrenal system in girls of 11-16 years old undergoing graduated physical activity was performed on the basis of excretion rates of epinephrine, norepinephrine, dopamine and DOPA. As a functional test, a graduated cycloergometric load of 50% of the individually determined PWC170 was used. The results obtained made it possible to establish the heterochronic nature of the maturation of the hormonal and mediator links of the sympathetic adrenal system. The highest reactivity of the adrenal link of SAS is observed in girls of 12 years old, the lowest – in senior schoolgirls (15-16 years old). In girls of 12-13 years old, the reaction of urgent adaptation to the graduated physical activity is carried out against a background of high excretion of epinephrine (E), norepinephrine (NE), but without sufficient replenishment of the reserve capabilities of SAS, which is confirmed by minimal shifts in the excretion of dopamine (DA) and DOPA in these age groups. At 14-16 years, moderate shifts of E and NE as a reaction to activity are noted against the background of a significant increase in the excretion of precursors, which characterizes the SAS response to the functional test as more saving, with increasing reserve capacities.El estudio del estado funcional del sistema simpato-adrenal en niñas de 11-16 años sometidas a actividad física graduada se realizó sobre la base de las tasas de excreción de epinefrina, norepinefrina, dopamina y DOPA. Como prueba funcional, se utilizó una carga cicloergométrica graduada del 50% de la PWC170 determinada individualmente. Los resultados obtenidos permitieron establecer la naturaleza heterócrona de la maduración de los enlaces hormonales y mediadores del sistema adrenal simpático. La mayor reactividad del enlace suprarrenal de SAS se observa en niñas de 12 años, la más baja - en niñas de escuela secundaria (15-16 años). En niñas de 12-13 años de edad, la reacción de adaptación urgente a la actividad física gradual se lleva a cabo en un contexto de alta excreción de epinefrina (E), norepinefrina (NE), pero sin un reabastecimiento suficiente de las capacidades de reserva de SAS. que se confirma por cambios mínimos en la excreción de dopamina (DA) y DOPA en estos grupos de edad. A los 14-16 años, se observan cambios moderados de E y NE como reacción a la actividad en el contexto de un aumento significativo en la excreción de precursores, que caracteriza la respuesta SAS a la prueba funcional como más ahorro, con el aumento de la capacidad de reserva.O estudo do estado funcional das raparigas do sistema simpático-envelhecido 11-16 anos, submetidos a actividade física realizada classificados com base em taxas de excreção de epinefrina, norepinefrina, dopamina e DOPA. Como teste funcional, utilizou-se uma carga cicloergométrica graduada de 50% do PWC170 individualmente determinado. Os resultados obtidos permitiram estabelecer a natureza heterocrônica da maturação dos laços hormonais e mediadores do sistema adrenal simpático. A reatividade mais alta do elo adrenal de SAS observa-se em meninas de 12 anos, o mais baixo - em meninas de escola secundária (15-16 anos). Em raparigas com idades entre 12-13, reacção urgente de adaptação gradual da actividade física ocorre em um contexto de elevada excreção de adrenalina (E), norepinefrina (NE), mas sem capacidades de reabastecimento suficientes Reserva SAS. o que é confirmado por alterações mínimas na excreção de dopamina (DA) e DOPA nestes grupos etários. Aos 14-16 anos, E e NE variações moderadas em resposta à actividade no contexto de um aumento significativo da excreção de precursores, o que caracteriza a resposta SAS para um teste funcional, mais economia, com o aumento observado a capacidade de reserva

State-of-the-Art Technologies for Studying Cellular and Molecular Mechanisms Underlying Alzheimer's Disease

Alzheimer's disease (AD) is the most common neurodegenerative disease and cause of dementia. It is associated with progressive cognitive decline due to the development of cortical and hippocampal atrophy. We reviewed key factors in AD pathogenesis, such as synaptic dysfunction, accumulation and aggregation of amyloid beta (A) peptide, tau phosphorylation causing neurofibrillary tangles, mitochondrial dysfunction, and neuroinflammation. We studied the dysbiosis role in AD development and demonstrated how much the bidirectional communication between the gut and brain sheds new light on some pathogenic processes underlying AD. We reviewed state-of-the-art biomedical technologies for studying AD: transgenic models, electrophysiological techniques, optogenetics, multi-omics approaches, neuroimaging, etc. New biomedical technologies significantly expanded our current knowledge of the AD pathogenesis and laid the groundwork for state-of-the-art treatment approaches

ГАЗОМЕДИАТОРЫ: ОТ ТОКСИЧЕСКИХ ЭФФЕКТОВ К РЕГУЛЯЦИИ КЛЕТОЧНЫХ ФУНКЦИЙ И ИСПОЛЬЗОВАНИЮ В КЛИНИКЕ

Nitric oxide II (NO), carbon monoxide (СО) and hydrogen sulfide (H2S) for many decades were described as the toxic gases inducing damaging action in man’s organisms. Recently it was found that NO, CO and H2S endogenously synthesized and served as signaling molecules of autocrine and paracrine regulation in many systems. The properties, mechanisms of synthesis and action in excitable systems are presented in this paper. Besides we also descried our results concerning the effects and mechanisms of action of gaseous messengers in peripheral nervous system – in neuromuscular junction. В течение многих десятилетий оксид азота (II) (NO), монооксид углерода (СО) и сероводород (H2S) описывались как токсичные газы, оказывающие повреждающие эффекты на организм человека. Недавно было обнаружено, что NO, CO и H2S эндогенно синтезируются и являются сигнальными молекулами, выполняющими как аутокринную, так и паракринную регуляцию во многих системах организма. В настоящей статье представлены данные о свойствах, ферментах синтеза и механизмах действия газообразных посредников в возбудимых системах. Кроме того, описываются результаты собственных исследований по выявлению эффектов и механизмов действия NO, СО и H2S в периферической нервной системе – в области нервно-мышечного синапса

Human cognitive and neuro-psychiatric bio-markers in the cardiac peri-operative patient

© 2014 Bentham Science Publishers. Some of the complexities of surgical interventions include neurological and psychiatric disturbances. Prompt identification and early treatment of these complications are pivotal in achieving excellent clinical results. Recognizing major adverse events such as stroke, seizure or delirium is usually straight-forward, however the discovery of less frequent or more subtle post-operative changes such as cognitive dysfunction might be delayed due to lack of appropriate diagnostic tools. This review summarizes biological markers that can be utilized as surrogates in evaluating surgery-related neuro-psychiatric disorders