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

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

Phenotype of a modern patient with valvular heart diseases: literature review

In modern conditions, valvular heart diseases (VHD) are one of the most common pathologies among cardiovascular diseases with a dynamic change in the phenotype of patients. An increase in the prevalence of VHD is currently observed due to the active implementation of diagnostic methods in cardiology. Geographical differences in the genesis of the development of valvular heart defects are noted, and the portrait of patients also changes as a result of aging and the addition of comorbid pathology. The purpose of the literature review was to present current trends in changing phenotype of patients with VHD, to study current data on the epidemiology of valve pathology, the contribution of various cardiovascular risk factors and comorbidity of patients on the course of the disease. Current data on the number of surgical interventions performed for VHD based on Russian, European, American, Australian and other studies, data on patient survival and mortality, as well as differences in these indicators in age groups of different countries are presented. The review will be useful for doctors to understand the modern portrait of a patient with VHD, trends in cardiovascular risk factors that influence the course of the disease and prognosis in patients with VHD

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

Динамика приверженности лечению и качества жизни больных с протезами клапанов сердца при участии в образовательных программах (10 лет наблюдения)

Highlights. Patient education program developed for patients with prosthetic heart valves, which includes information on the anticoagulant therapy, prevention of prosthetic valve endocarditis, and physical and psychological rehabilitation, helps to improve adherence to treatment and quality of life immediately upon completion of training (6 months). The quality of life and adherence to treatment were higher at 10-year follow-up in patients undergoing full course of training, in inpatient and outpatient settings, compared with patients undergoing training in inpatient setting only.Aim. To evaluate the efficacy of the training program for patients with prosthetic heart valves in improving treatment adherence and quality of life at 10-year follow-up.Methods. Patient education program entitled “School for patients with prosthetic heart valves” was developed and implemented at the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo) in 2010. The program provides knowledge and training regarding anticoagulant therapy, prevention of prosthetic valve endocarditis, physical and psychological rehabilitation. The training group consisted of 92 patients who completed a full course of training (6 months). The control group included 56 patients who completed training in inpatient setting only. Long-term efficacy of the developed education program was assessed at 10-year follow-up via evaluation of the indicators of adherence to treatment (questionnaire for determining the integral indicator of adherence to treatment (IIAT)) and the quality of life (using Short-Form 36-item questionnaire (SF-36)).Results. Initially, data analysis showed no statistically significant differences between the groups in the quality of life and adherence to treatment. Six months later the IIAT score in the training group (full course of training) was 9.15±1.16, in controls the score was 6.20±1.05 (р = 0.0001). Highest IIAT scores in the training group remained similar (8.10±1.20 points) at 10-year follow-up, in the control group it was lower - 5.19±1.09 (р = 0.0001). After 6 months, physical component summary score increased by 24% over baseline in controls (р = 0.0001) and by 25% in the training group (р = 0.0001). After 6-month follow-up, there was an improvement in the psychological component summary score by 14.5% (р = 0.0001) in the control group and by 42.8% in the training group (р = 0.0001). 10 years after completion of training, physical component and mental component summary scores were higher in patients undergoing full training course - 8.3% (р = 0.0001) and 14.3% (р = 0.0001), respectively.Conclusion. Patient education program “School for patients with prosthetic heart valves” via full course of training increases levels of adherence to treatment and quality of life mainly due to improvement of psychological component summary score in the early period (6 months) and at 10-year follow-up.Основные положения. Обучающая программа для пациентов с протезами клапанов сердца, посвященная основным аспектам режима и контроля антикоагулянтной терапии, профилактики протезного эндокардита, физической и психологической реабилитации, способствует повышению приверженности лечению и качества жизни непосредственно после ее завершения (6 мес.). При полном курсе обучения, включающем стационарный и амбулаторный этапы, через 10 лет наблюдения зарегистрированы более высокие показатели качества жизни и соблюдения рекомендаций лечащего врача, чем при обучении больных только в условиях стационара.Цель. Оценить эффективность обучающей программы для пациентов с протезами клапанов сердца в повышении приверженности лечению и качества жизни через 10 лет наблюдения.Материалы и методы. С 2010 г. в НИИ КПССЗ (Кемерово, Россия) разработана и внедрена обучающая программа «Школа для больных с протезированными клапанами сердца». В программу обучения входят особенности антикоагулянтной терапии, профилактики протезного эндокардита, физической и психологической реабилитации. Основную группу составили 92 пациента, завершивших полный курс обучения, включавший стационарный и амбулаторный этапы. В контрольную группу вошли 56 больных, прошедших обучение только в условиях стационара. Отдаленную эффективность разработанной программы анализировали через 10 лет при сравнении показателей соблюдения врачебных рекомендаций (опросник для определения интегрального показателя приверженности лечению (ИППкЛ)) и качества жизни (опросник SF-36).Результаты. Исходно статистически значимые различия в группах сравнения отсутствовали. Через 6 мес. у пациентов с полным курсом обучения ИППкЛ составил 9,15±1,16 балла, при неполном - 6,20±1,05 балла (р = 0,0001). В основной группе больных через 10 лет наблюдения сохранялось высокое значение ИППкЛ (8,10±1,20 балла), в контрольной группе этот показатель был ниже - 5,19±1,09 (р = 0,0001). Через 6 мес. физический компонент здоровья увеличился на 24% от исходного значения (р = 0,0001) в контрольной группе и на 25% (р = 0,0001) в основной. Через 6 мес. наблюдения выявлено улучшение психологического компонента здоровья на 14,5% (р = 0,0001) в контрольной и на 42,8% в основной (р = 0,0001) группах. Через 10 лет после завершения обучения показатели физического и психологического компонентов здоровья оказались на 8,3% (р = 0,0001) и 14,3% (р = 0,0001) выше при полном курсе обучения.Заключение. Полный курс обучения больных с протезированными клапанами сердца обеспечивает высокий уровень приверженности лечению и качества жизни преимущественно за счет психологического компонента здоровья в ранние сроки (6 мес.) и через 10 лет наблюдения

JAMM: A Metalloprotease-Like Zinc Site in the Proteasome and Signalosome

The JAMM (JAB1/MPN/Mov34 metalloenzyme) motif in Rpn11 and Csn5 underlies isopeptidase activities intrinsic to the proteasome and signalosome, respectively. We show here that the archaebacterial protein AfJAMM possesses the key features of a zinc metalloprotease, yet with a distinct fold. The histidine and aspartic acid of the conserved EX(n)HS/THX(7)SXXD motif coordinate a zinc, whereas the glutamic acid hydrogen-bonds an aqua ligand. By analogy to the active site of thermolysin, we predict that the glutamic acid serves as an acid-base catalyst and the second serine stabilizes a tetrahedral intermediate. Mutagenesis of Csn5 confirms these residues are required for Nedd8 isopeptidase activity. The active site-like architecture specified by the JAMM motif motivates structure-based approaches to the study of JAMM domain proteins and the development of therapeutic proteasome and signalosome inhibitors

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.