The infarct-limiting efficacy of deltorphin-II in old rats with diet-induced metabolic syndrome

Background. The discovery of new pharmacological agents for myocardial protection during reperfusion injury is an urgent goal of modern physiology and pharmacology.The aim of the study. To identify the potential for protecting the myocardium from reperfusion injury by administering the delta-2 opioid receptor agonist deltorphin-II prior to reperfusion in old rats with diet-induced metabolic syndrome.Materials and methods. The study was performed on Wistar rats aged 60 days (young rats) and 450 days (old rats) before the onset of a study. Metabolic syndrome (MetS) was modeled for 84 days with a high-carbohydrate high-fat diet (16 % protein, 21 % fat, 46 % carbohydrate) with the replacement of drinking water with 20 % fructose solution. Myocardial infarction was performed by 45-min coronary occlusion followed by 120-min reperfusion; the size of the area of the necrotic myocardium was determined relative to the size of the hypoperfusion zone. The delta-2 opioid receptor agonist deltorphin-II was administered once intravenously 5 minutes before the end of ischemia.Results. It was found that coronary occlusion and subsequent reperfusion both in groups of young and old rats led to the formation of myocardial infarction (necrosis), the size of which was 45 % of the size of the risk zone. Administration of deltorphin-II in old rats led to a limitation of infarct size to 30 % of the size of the risk zone, i. e. 1.7-fold. The use of deltorphin-II in old rats with MetS contributed to a decrease in infarct size to 27 % of the size of the risk zone (1.5 times). The obtained results demonstrate the cardioprotective efficacy of the delta-2 opioid receptor agonist deltorphin-II in aging and metabolic syndrome in rats.Conclusions. These data may serve as a basis for conducting preclinical studies of deltorphin-II as a drug for treatment of acute myocardial infarction

Volcanic glass from the 1.8 ka Taupō eruption (New Zealand) detected in Antarctic ice at ~ 230 CE.

Chemical anomalies in polar ice core records are frequently linked to volcanism; however, without the presence of (crypto)tephra particles, links to specific eruptions remain speculative. Correlating tephras yields estimates of eruption timing and potential source volcano, offers refinement of ice core chronologies, and provides insights into volcanic impacts. Here, we report on sparse rhyolitic glass shards detected in the Roosevelt Island Climate Evolution (RICE) ice core (West Antarctica), attributed to the 1.8 ka Taupō eruption (New Zealand)-one of the largest and most energetic Holocene eruptions globally. Six shards of a distinctive geochemical composition, identical within analytical uncertainties to proximal Taupō glass, are accompanied by a single shard indistinguishable from glass of the ~25.5 ka Ōruanui supereruption, also from Taupō volcano. This double fingerprint uniquely identifies the source volcano and helps link the shards to the climactic phase of the Taupō eruption. The englacial Taupō-derived glass shards coincide with a particle spike and conductivity anomaly at 278.84 m core depth, along with trachytic glass from a local Antarctic eruption of Mt. Melbourne. The assessed age of the sampled ice is 230 ± 19 CE (95% confidence), confirming that the published radiocarbon wiggle-match date of 232 ± 10 CE (2 SD) for the Taupō eruption is robust

Research in the area of preparing activated alumina. Part 4. new technological approaches for synthesis of ultrafine α-Al₂O₃

Results of new integrated technological approaches to synthesis of ultrafine -alumina using commercially available metallurgical alumina as a raw material are presente

The role of reactive oxygen species and redoxsensitive protein kinases in the infarction-limiting effect of opioid peptide deltorphin II in cardiac reperfusion in rats

Background. Mortality from acute myocardial infarction with ST-segment elevation in cardiac hospitals ranges from 4.5 to 7 %, and these data has not decreased in recent years. The most common cause of death in patients is cardiogenic shock, the likelihood of which directly depends on infarct size. It is quite clear that there is an urgent need to create drugs to limit the size of infarction and prevent the occurrence of cardiogenic shock.The aim. To evaluate the role of reactive oxygen species and redox-sensitive protein kinases in the infarction-limiting effect of opioid peptide deltorphin II in cardiac reperfusion in rats.Materials and methods. Coronary occlusion (45 min) and reperfusion (120 min) were performed in rats anesthetized with α-chloralose. The selective δ2-opioid receptor agonist deltorphin II, a hydroxyl radical scavenger 2-mercaptoprpionyl glycine (2-MPG), a superoxide radical scavenger tempol, the protein kinase Cδ (PKCδ) inhibitor rottlerin, the PI3-kinase inhibitor wortmannin, the inhibitor of ERK1/2 kinase PD98059 were injected before of reperfusion of the heart.Results. Deltorphin II contributed to a two-fold decrease in infarction size. Injection of 2-MPG, tempol, rottlerin, wortmannin, PD98059 alone had no effect on infarction size in rats. 2-MPG and tempol did not affect the infarction-reducing effect of deltorphin II. Rottlerin, wortmannin, and PD98059 eliminated the cardioprotective effect of deltorphin II.Conclusion. The infarction-reducing effect of deltorphin II does not depend on the production of superoxide radical and hydroxyl radical. Superoxide radical and hydroxyl radical do not play a significant role in reperfusion injury of the heart after coronary occlusion (45 min). PKCδ, PI3-kinase, and ERK1/2 kinase are involved in the infarction-limiting effect of deltorphin II in myocardial reperfusion

Влияние возраста, высокоуглеводной и высокожировой диеты на развитие артериальной гипертензии и поражения почек в эксперименте

Aim. To identify the structural foundations of the pathogenesis of arterial hypertension and kidney disease associated with a high-fat, high-carbohydrate diet and age.Materials and methods. The study was carried out on male Wistar rats aged 60 and 450 days. The animals were divided into 4 groups: group 1 (n = 14) – intact rats (60 days old) fed with a standard diet for 90 days; group 2 (n = 14) – rats (aged 60 days) receiving a high-fat, high-carbohydrate diet for 90 days; group 3 (n = 14) – intact rats (aged 450 days) receiving a standard diet for 90 days; group 4 (n = 14) – rats (aged 450 days) fed with a high-fat, high-carbohydrate diet for 90 days. Clinical and instrumental research methods, enzyme-linked immunosorbent assay, and immunohistochemistry and histology techniques were used in the study.Results. Feeding 60-day-old animals with a high-fat, high-carbohydrate diet resulted in an increase in body weight and abdominal fat, a rise in systolic blood pressure, and moderately pronounced histologic changes in the kidneys. In intact 450-day-old rats, age-related changes prevailed: changes in the myocardial mass, an increase in TGF-β1, morphological changes in the renal tubules and glomeruli. In 450-day-old rats receiving a high-fat, highcarbohydrate diet, the most pronounced increase in both systolic and diastolic blood pressure, a significant rise in serum fibronectin, and destructive changes in the renal tissue were noted.Conclusion. Functional and biochemical signs of arterial hypertension and morphological changes in the kidneys were the most pronounced in 450-day-old rats fed with a high-fat, high-carbohydrate diet.Цель: выявить структурные основы патогенеза артериальной гипертензии и поражения почек, связанных с высокоуглеводной высокожировой диетой (ВУСЖД) и возрастом у крыс линии Wistar.Материал и методы. Исследование проводили на самцах крыс линии Wistar в возрасте 60 и 450 сут. Животных распределяли на четыре группы: 1-я (n = 14) – интактные крысы (возраст 60 сут), содержащиеся на стандартном рационе в течение 90 сут; 2-я (n = 14) – крысы (возраст 60 сут), содержащиеся на ВУВЖД в течение 90 сут; 3-я (n = 14) – интактные крысы (возраст 450 сут), содержащиеся на стандартном рационе в течение 90 сут; 4-я (n = 14) – крысы (возраст 450 сут), содержащиеся на ВУВЖД в течение 90 сут. Использовались клинико-инструментальный, иммуноферментный, иммуногистохимический и гистологический методы исследования.Результаты. Высокоуглеводная высокожировая диета приводила у 60-дневных животных к увеличению массы тела и абдоминального жира, нарастанию систолического артериального давления, появлению умеренно выраженных гистологических изменений почек. У интактных 450-дневных крыс преобладали изменения, связанные с возрастом: увеличение массы миокарда, увеличение TGF-β1 в сыворотке крови, морфологические изменения почечных канальцев и клубочков. У 450-дневных крыс, содержащихся на ВУВЖД, отмечалось наиболее выраженное нарастание как систолического, так и диастолического артериального давления, значительное увеличение концентрации фибронектина в сыворотке крови, выраженные деструктивные изменения в почечной паренхиме.Заключение. Функциональные и биохимические признаки артериальной гипертензии и морфологические изменения в почках были наиболее выражены у 450-дневных крыс, содержавшихся на ВУВЖД

Роль вегетативной нервной системы в стресс-индуцированном повреждении сердца

 Aim. To identify the role of the autonomic nervous system in stress cardiomyopathy in an experimental model of Takotsubo syndrome.Materials and methods. The study was carried out on 120 female Wistar rats. Stress modeling was performed by immobilizing animals on the back for 24 hours. Intact rats were used as controls. The rats were decapitated after termination of immobilization under general anesthesia with ether. Stress cardiomyopathy (SCM) was quantified by accumulation of 99mTc pyrophosphate radiopharmaceutical (99mTc PP) in the myocardium. The pharmacological agents used included the ganglionic blocker hexamethonium, administered five times at a dose of 20 mg / kg; guanethidine (50 mg / kg) administered subcutaneously once a day for three days, the last injection was performed 24 hours before immobilization; the muscarinic receptor antagonist atropine methyl nitrate (1 mg / kg); the α1-AR (adrenergic receptor) antagonist prazosin (2 mg / kg); the α2-AR antagonist yohimbine, administered at a dose of 2 mg / kg; the β1-AR antagonist nebivolol (1.2 mg / kg); the β2-AR antagonist ICI 118,551 (0.3 mg / kg); and the β3-AR antagonist L-748337 (0.1 mg / kg).Results. Three-day administration of guanethidine caused a decrease in the degree of 99mTc-PP accumulation in the heart by 35.9%. Hexamethonium did not affect the degree of SCM. The blockade of the muscarinic receptor caused an increase in accumulation of 99mTc-PP by 26.5%. Inhibition of α1-AR did not affect SCM. The blockade of α2-AR caused a 2.2-fold increase in the accumulation compared with stress control. The blockade of β1-AR reduced 99mTc-PP accumulation by 2.5 times. The blockade of β2-AR by ICI 118,551 increased the degree of 99mTcPP accumulation by 34.6%. Inhibition of β3-AR had no effect on SCM.Conclusion. The adrenergic system and β1-adrenergic receptor play an important role in the development of SCM. The parasympathetic nervous system ensures resistance of the heart to stress.Цель. Оценка роли вегетативной нервной системы в стресс-индуцированном повреждении сердца в экспериментальной модели синдрома такотсубо.Материалы и методы. Исследование выполнено на 120 самках крыс линии Вистар. Каждая группа животных состояла из 12 особей. Моделирование стресса осуществляли с помощью иммобилизации животных на спине в течение 24 ч. В качестве контроля использовали интактных особей. Крыс декапитировали после прекращения иммобилизации под общим эфирным наркозом. Количественную оценку стресс-индуцированного повреждения сердца (СИПС) осуществляли по аккумуляции радиофармпрепарата 99mTc-пирофосфата (99mTc-ПФ) в миокарде. Фармакологические агенты вводили внутрибрюшинно: ганглиоблокатор гексаметоний вводили пятикратно в дозе 20 мг/кг; гуанетидин (50 мг/кг) – подкожно 1 раз/сут в течение 3 сут, последнюю инъекцию делали за 24 ч до иммобилизации. Остальные препараты (антагонист М-холинорецепторов атропина метилнитрат (1 мг/кг); антагонист α1-адренорецепторов (АР) празозин (2 мг/кг); антагонист α2-АР йохимбин (2 мг/кг); антагонист β1-АР небиволол (1,2 мг/кг); антагонист β2-АР ICI 118,551 (0,3 мг/кг); антагонист β3-АР L-748337 (0,1 мг/кг)) вводили 2 раза/сут с интервалом 12 ч.Результаты. Трехдневное введение гуанетидина вызвало уменьшение степени аккумуляции 99mTc-ПФ в сердце на 35,9%. Гексаметоний не оказал влияние на степень СИПС. Блокада М-холинорецепторов вызвала усиление аккумуляции 99mTc-ПФ на 26,5%. Ингибирование α1-АР не оказало влияния на СИПС. Блокада α2-АР вызывала усиление аккумуляции в 2,2 раза по сравнению со стресс-контролем. Блокада β1-АР снизила степень аккумуляции 99mTc-ПФ в 2,5 раза. Блокада β2 АР ICI 118,551 увеличила степень аккумуляции 99mTc-ПФ на 34,6%. Ингибирование β3-АР не оказало эффекта на СИПС.Заключение. Симпатоадреналовая система и, в частности, β1-адренорецепторы играют важную роль в развитии СИПС. Парасимпатическая нервная система обеспечивает устойчивость сердца к стрессу

Measurement of the Spin-Dependence of the pbar-p Interaction at the AD-Ring

We propose to use an internal polarized hydrogen storage cell gas target in the AD ring to determine for the first time the two total spin-dependent pbar-p cross sections sigma_1 and sigma_2 at antiproton beam energies in the range from 50 to 450 MeV. The data obtained are of interest by themselves for the general theory of pbar-p interactions since they will provide a first experimental constraint of the spin-spin dependence of the nucleon-antinucleon potential in the energy range of interest. In addition, measurements of the polarization buildup of stored antiprotons are required to define the optimum parameters of a future, dedicated Antiproton Polarizer Ring (APR), intended to feed a double-polarized asymmetric pbar-p collider with polarized antiprotons. Such a machine has recently been proposed by the PAX collaboration for the new Facility for Antiproton and Ion Research (FAIR) at GSI in Darmstadt, Germany. The availability of an intense stored beam of polarized antiprotons will provide access to a wealth of single- and double-spin observables, thereby opening a new window on QCD spin physics.Comment: 51 pages, 23 figures, proposal submitted to the SPS committee of CER

Forward K+ production in subthreshold pA collisions at 1.0 GeV

K+ meson production in pA (A = C, Cu, Au) collisions has been studied using the ANKE spectrometer at an internal target position of the COSY-Juelich accelerator. The complete momentum spectrum of kaons emitted at forward angles, theta < 12 degrees, has been measured for a beam energy of T(p)=1.0 GeV, far below the free NN threshold of 1.58 GeV. The spectrum does not follow a thermal distribution at low kaon momenta and the larger momenta reflect a high degree of collectivity in the target nucleus.Comment: 4 pages, 3 figure

The Ross Sea Dipole-temperature, snow accumulation and sea ice variability in the Ross Sea region, Antarctica, over the past 2700 years

High-resolution, well-dated climate archives provide an opportunity to investigate the dynamic interactions of climate patterns relevant for future projections. Here, we present data from a new, annually dated ice core record from the eastern Ross Sea, named the Roosevelt Island Climate Evolution (RICE) ice core. Comparison of this record with climate reanalysis data for the 1979-2012 interval shows that RICE reliably captures temperature and snow precipitation variability in the region. Trends over the past 2700 years in RICE are shown to be distinct from those in West Antarctica and the western Ross Sea captured by other ice cores. For most of this interval, the eastern Ross Sea was warming (or showing isotopic enrichment for other reasons), with increased snow accumulation and perhaps decreased sea ice concentration. However, West Antarctica cooled and the western Ross Sea showed no significant isotope temperature trend. This pattern here is referred to as the Ross Sea Dipole. Notably, during the Little Ice Age, West Antarctica and the western Ross Sea experienced colder than average temperatures, while the eastern Ross Sea underwent a period of warming or increased isotopic enrichment. From the 17th century onwards, this dipole relationship changed. All three regions show current warming, with snow accumulation declining in West Antarctica and the eastern Ross Sea but increasing in the western Ross Sea. We interpret this pattern as reflecting an increase in sea ice in the eastern Ross Sea with perhaps the establishment of a modern Roosevelt Island polynya as a local moisture source for RICE