The significance of ACTH for the process of formation of complex heparin compounds in the blood during immobilization stress

Adrenocorticotropin (ACTH) was administered to rats at different times following adrenalectomy. Adrenocorticotropin caused a significant increase in the formation of heparin complexes even in the absence of stress factor. When ACTH secretion is blocked, immobilization stress is not accompanied by an increase in the process of complex formation. The effect of ACTH on the formation of heparin complexes was mediated through its stimulation of the adrenal cortex

The role of ACTH and glucocorticoids in nonenzymatic fibrinolysis during immobilization stress in animals

The role of the altered hormonal status of an organism in the activation of the anticoagulative system during stress is investigated. The 30 minute immobilization stress was shown to raise significantly the nonenzymatic fibrinolytic activity of blood in rats. Combined with adrenocorticotropin (ACTH) the effect is still greater. Intravenous administration of 0.2 m1 0.01 percent solution of protamine sulphate prevented the nonenzymatic fibrinolysis induced by the stress. Administration of ACTH after protomine sulphate again raised the fibrinolysis. This suggests that ACTH stimulates the release of heparin

The effects of adrenalectomy and corticsteroid injection on the fibrinolytic activity of complex heparin compounds in the blood during immobilization

Total non-enzymatic fibrinolytic activity in the blood of rats increased three times in response to stress caused by 30 minute immobilization, and the activity of epinephrine-heparin complex increased nine times. In adrenalectomized animals, which showed a weak response to the same stress, intraperitoneal injection of hydrocortisone 30 minutes prior to immobilization normalized the response. Obtained results indicate that adrenalectomy leads to sharp reduction of heparin complexing with thromogenic proteins and epinephrine, while substitution therapy with hydrocortisone restores anticoagulation system function

Effects of hirudin-induced activation of nonenzymatic fibrinolysis during immobilization stress

The specific inhibitor of thrombin, hirudin, was used for studying the mechanism of the activating effect of ACTH and adrenalin on nonenzymatic fibrinolytic activity (NEFA), the latter characterizing the function of the anticoagulation system (ACS). Simultaneous administration of ACTH and hirudin to animals subjected to immobilization stress did not reduce the effect of ACTH on NEFA, while simultaneous administration of adrenalin and hirudin revealed a diminished effect of the former. This suggests different mechanisms of ACTH and adrenalin effects upon NEFA: the stimulating effect of norepinephrine is realized through throminogenesis followed by activation of the ACS function and by increased NEFA and therefore inhibitable by hirudin which forms an inactive complex with thrombin. In fact the stimulating effect of ACTH upon NEFA is brought about specifically by another route than thrombinogenesis and thus occurs in the presence of hirudin. Hirudin itself has no effect upon NEFA

Blood fluidity during physical exertion of various types

This paper presents data from the literature and own results on the study of blood fluidity (or rheological properties) when performing physical exercises. It is shown that the rheology of blood depends on the functional state of the haemostasis system. It has been established that in the physiological state of the organism, physical exertion of any strength can lead to changes in the reactions of primary and plasma haemostasis and, accordingly, the rheological properties of blood. The review describes the study of factors related to blood flow in humans and animals before and after physical exercise (running, swimming, etc.) in the normal physiological state of the organism, with overstrain and with certain types of pathology (cardiovascular and metabolic diseases). Data on blood flow in conditions of physical activity restriction are presented. Special attention is paid to the corrective role of physical exercises on the rheology (fluidity) of blood in violation of homeostasis of the organism. Possible mechanisms of action of physical exertion on blood flow are considered

Leucine-glycine and carnosine dipeptides prevent diabetes induced by multiple low-dose streptozotocin in experimental model of adult mice

Aims/Introduction Peptides are considered as quasi‐hormones and effective molecules for regulation of the cells function and metabolic disorders prevention. Di‐ and tripeptides with the ability to gastrointestinal absorption have been proposed to prevent diabetes progression. Materials and Methods Small peptides with different sequences of specific amino acids were synthesized based on a solid phase peptide synthesis (SPPS) protocol as well as carnosine (A) and glutathione (B) were examined for the prevention of diabetes induced by multiple low‐dose of streptozotocin (MLDS) in mice. Results The peptides A, Leu‐Gly (D) and Pro‐Pro (F) exhibited a preventive effects on blood glucose elevation and impairment of the signaling and performance of beta cells. The beta cells function assessed by immunofluorescence and blood glucose level in mice exposed to diabetes treated by the peptides A and D was similar to the normal mice. The peptide D prevented from body weight loss caused by diabetes induction. The use of D and A peptides dramatically prevents the incidence of disruption in beta cells signaling by maintaining the natural balance of intracellular Akt‐2 and cAMP. Conclusions The results proved that peptide D (Leu‐Gly) named Hannaneh inhibits the body weight loss caused by diabetes induction. The Hannaneh and carnosine dipeptides with preservation of normal beta cell signalling and anti DPP‐4 activity were prevented from increasing the blood glucose in mice at risk of diabetes. These dipeptides may be regarded as the pharmaceutical agents for the prevention of diabetes

Особенности ранней реабилитации пациентов после коррекции приобретенных пороков сердца

Aim. To develop and evaluate the safety/efficacy of an early rehabilitation program with physical aerobic training in patients after surgical repair of acquired valvular heart disease.Methods. The study included 45 patients with valvular heart disease undergoing surgical repair. Patients in the group (n = 30) underwent a standard cardiac rehabilitation after the surgery; on the 8th day after the surgery patients in the main group (n = 15) in addition to the standard cardiac rehabilitation were involved in personalized aerobic physical training on a treadmill prescribed according to the cardiopulmonary exercise testing results (spiroveloergometry). The duration of the training on a treadmill was 14 days.Results. The rhythm changing, life-threatening heart rhythm disorders, episodes of ischemia, desaturation were not recorded during the training. The main reason to stop the training was the weakness and fatigue of the patients. There were no disturbances of intracardiac hemodynamic after the course of physical training. In the main group there was a significant increase in exercise tolerance from 50.0 [25.0; 75.0] to 75.0 [50.0; 100.0] W (p = 0.04), close to significant increase in VO2peak from 10.9 [9.6; 13.3] to 12.3 [10.6; 14.9] ml/kg/min (p = 0.07).Conclusion. The 14-days program of early rehabilitation with aerobic training after surgical repair of valvular heart disease has demonstrated its safety and influenced the increase in exercise tolerance, peak oxygen consumption. Цель. Оценить безопасность и эффективность программы ранней реабилитации пациентов с физическими аэробными тренировками после коррекции приобретенных пороков сердца.Материалы и методы. В исследование включены 45 больных с пороками клапанов сердца, подвергшихся кардиохирургическому вмешательству. Пациентам группы контроля (n = 30) после операции проведена стандартная кардиореабилитация; пациентам основной группы (n = 15) помимо традиционных реабилитационных мероприятий на 8-е сут после вмешательства инициированы физические тренировки на тредмиле с персонифицированным выбором программы тренировок с учетом результатов спировелоэргометрии. Продолжительность тренировок составила 14 дней.Результаты. В период тренировок не зарегистрированы смена ритма, жизнеугрожающие нарушения ритма сердца, эпизоды ишемии, десатурации. Основным поводом для прекращения тренировки явились слабость и усталость пациентов. На фоне курса тренировок по данным эхокардиографии не выявлено ухудшения параметров внутрисердечной гемодинамики. В основной группе отмечен достоверный прирост толерантности к физической нагрузке – с 50,0 [25,0; 75,0] до 75,0 [50,0; 100,0] Вт (p = 0,04), близкое к достоверному увеличение VO2peak – с 10,9 [9,6; 13,3] до 12,3 [10,6; 14,9] мл/кг/мин (p = 0,07).Заключение. 14-дневная программа ранней реабилитации с аэробными тренировками после коррекции клапанной патологии сердца не ухудшает параметры гемодинамики, при этом увеличивает толерантность к физической нагрузке и пиковое потребление кислорода.

«Портрет» пациентов c легочной гипертензией на фоне приобретенного порока митрального Клапана сердца до хирургической коррекции

Aim. To study “the portrait” of patients with acquired mitral valve (MV) heart disease of various origins and pulmonary hypertension hospitalized for surgical correction of the defect.Methods. The study included 97 patients with acquired diseases of mitral valve and pulmonary hypertension. The assessment of demographic, clinical and anamnestic data, indicators of transthoracic echocardiography, quality of life before the correction of MV defect was carried out.Results. The studied cohort is mostly represented by female patients (n = 70; 72.2%). The most common cause of mitral valve disease was rheumatic heart disease (n = 40; 41.2%). Overweight, hypertension (n = 76; 78.4%) and atrial fibrillation (n = 62; 63.9%) were the most common comorbidities. The mean pressure level in the pulmonary artery according to echocardiography was 35.5 (29.0; 40.0) mm Hg, with no significant difference among the patients, regardless the mitral defect etiology. Less pronounced remodeling of the left ventricle was noted in patients with rheumatic heart disease, which is caused by a lesion of the MV by the type of stenosis in contrast to patients with connective tissue dysplasia syndrome or against the background of detachment of MV chords with MV damage in the form of its insufficiency. There were no significant differences in the systolic function of the right ventricle depending on the etiology of MV defect.Conclusion. The “portrait” of a patient with pulmonary hypertension associated with an acquired mitral valve defect before its correction is the predominance of female, overweight, with II or III functional class of chronic heart failure, more frequent rheumatic genesis of MV defect, the presence of concomitant pathology in the form of hypertension and persistent atrial fibrillation, and increased size of the left atrium and left ventricle, reduced systolic function of the right ventricle according to the data of Echocardiography. Цель. Изучить «портрет» больных приобретенным пороком митрального клапана (МК) различного генеза и легочной гипертензией, госпитализированных для хирургической коррекции патологии.Материалы и методы В исследование включены 97 пациентов с приобретенными пороками МК и легочной гипертензией. Оценены демографические, клинико-анамнестические данные, показатели трансторакальной эхокардиографии, качества жизни до коррекции порока МК. Результаты Исследуемая когорта представлена в большей степени больными женского пола (n = 70; 72,2%). Чаще всего причиной порока МК была ревматическая болезнь сердца (n = 40; 41,2%). Избыточная масса тела, гипертоническая болезнь (n = 76; 78,4%) и фибрилляция предсердий (n = 62; 63,9%) – наиболее частые сопутствующие патологии. Уровень среднего давления в легочной артерии по данным эхокардиографии составил 35,5 (29,0; 40,0) мм рт. ст., значимо не различаясь у пациентов независимо от этиологии митрального порока. Менее выраженное ремоделирование левого желудочка отмечено у лиц с ревматической болезнью сердца, что обусловлено поражением МК по типу стеноза, по сравнению с пациентами с синдромом соединительно-тканной дисплазии или на фоне отрыва хорд МК, имеющих поражение МК в виде его недостаточности. Значимых различий в систолической функции правого желудочка в зависимости от этиологии порока МК не выявлено.Заключение. «Портрет» пациента с легочной гипертензией, ассоциированной с приобретенным пороком МК до его коррекции, включает: преобладание женского пола, избыточную массу тела, II–III функциональный класс хронической сердечной недостаточности, более частый ревматический генез порока МК, наличие сопутствующей патологии в виде гипертонической болезни и персистирующей формы фибрилляции предсердий, увеличенные размеры левого предсердия и левого желудочка, сниженную систолическую функцию правого желудочка по данным эхокардиографии.

CSN-mediated deneddylation differentially modulates Ci155 proteolysis to promote Hedgehog signalling responses

The Hedgehog (Hh) morphogen directs distinct cell responses according to its distinct signalling levels. Hh signalling stabilizes transcription factor cubitus interruptus (Ci) by prohibiting SCFSlimb-dependent ubiquitylation and proteolysis of Ci. How graded Hh signalling confers differential SCFSlimb-mediated Ci proteolysis in responding cells remains unclear. Here, we show that in COP9 signalosome (CSN) mutants, in which deneddylation of SCFSlimb is inactivated, Ci is destabilized in low-to-intermediate Hh signalling cells. As a consequence, expression of the low-threshold Hh target gene dpp is disrupted, highlighting the critical role of CSN deneddylation on low-to-intermediate Hh signalling response. The status of Ci phosphorylation and the level of E1 ubiquitin-activating enzyme are tightly coupled to this CSN regulation. We propose that the affinity of substrate–E3 interaction, ligase activity and E1 activity are three major determinants for substrate ubiquitylation and thereby substrate degradation in vivo

Uncovering Ubiquitin and Ubiquitin-like Signaling Networks

Microscopic imaging and technolog