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Aim: Assessment of WNT1, WNT3a, and LRP6 concentrations in patients with ischemic heart disease (IHD) and obstructive and non-obstructive coronary artery (CA) disease., Material and Methods: This cross-sectional observational study included 50 IHD patients (verified by coronary angiography, CAG), of which 25 (50%) were men, mean age 64.9±8.1 years; 20 patients had non-obstructive CA disease (stenosis <50%), and 30 patients had hemodynamically significant stenosis. Concentrations of WNT1, WNT3a and LRP6 were measured in all patients., Results: The concentrations of WNT1 and WNT3a proteins were significantly higher in patients with IHD and obstructive CA disease (p < 0.001), while the concentration of LRP6 was higher in the group with non-obstructive CA disease (p = 0.016). Data analysis of the group with obstructive CA disease showed a moderate correlation between WNT1 and LRP6 (ρ=0.374; p=0.042). Correlation analysis of all groups of patients with CA disease revealed a moderate association between the concentrations of WNT1 and uric acid (ρ=0.416; p=0.007). Regression analysis showed that risk factors for the development of IHD, such as increased body mass index, age, smoking, dyslipidemia, and hypertension, did not significantly influence the type of CA disease in IHD patients. According to ROC analysis, the obstructive form of IHD was predicted by a WNT3a concentration higher than 0.155 ng/ml and a LRP6 concentration lower than 12.94 ng/ml., Conclusion: IHD patients with non-obstructive CA disease had the greatest increase in LRP6, while patients with obstructive CA disease had significantly higher concentrations of the canonical WNT cascade proteins, WNT1 and WNT3a. According to the ROC analysis, a WNT3a concentration >0.155 ng/ml can serve as a predictor for the presence of hemodynamically significant CA stenosis in IHD patients (sensitivity 96.7%; specificity 70%), whereas a LRP6 concentration >12.94 ng/ml can predict the development of non-obstructive CA disease (sensitivity 76.7%; specificity 65%).

Aim: To assess the levels of matrix metalloproteinases (MMP), vascular endothelial growth factor (VEGF), and miRNA-34a expression in patients with ischemic heart disease (IHD) and obstructive and nonobstructive coronary artery (CA) disease., Material and Methods: This cross-sectional observational study included 64 patients with IHD (diagnosis verified by coronary angiography or multislice computed tomography coronary angiography), of which 33 (51.6%) were men aged 64.9±8.1 years. 20 patients had nonobstructive CA disease (stenosis <50%), and 44 had hemodynamically significant stenoses. The control group consisted of 30 healthy volunteers. MMP-1, -9, -13, and -14, miRNA-34a, and VEGF were measured in all patients., Results: The concentration of MMP-1 was significantly higher in patients with ischemia and nonobstructive CA disease (INOCAD) (p=0.016), and the concentration of MMP-9 was the highest in the group with obstructive CA disease (p<0.001). The concentrations of MMP-13 and MMP-14 did not differ significantly between the groups. The highest VEGF concentrations were observed in the INOCAD group (p<0.001). The expression of miRNA-34a significantly differed between the IHD groups with different types of CA disease and controls (p <0.001). Patients with hemodynamically significant stenosis showed moderate relationships between the concentrations of MMP-14 and VEGF (ρ=0.418; p=0.024), as well as between VEGF and miRNA-34a (ρ=0.425; p=0.022). Patients with INOCAD had a significant negative correlation between the concentrations of MMP-13 and VEGF (ρ= -0.659; p=0.003). Correlation analysis showed in all IHD patients a moderate relationship of the concentrations of MMP-1 and MMP-14 with VEGF (ρ=0.449; p=0.002 and p=0.341; p=0.019, respectively). According to ROC analysis, a MMP-9 concentration above 4.83 ng/ml can be a predictor for the presence of hemodynamically significant CA obstruction in IHD patients; a VEGF concentration higher than 27.23 pg/ml suggests the absence of hemodynamically significant CA stenosis., Conclusion: IHD patients with INOCAD had the greatest increase in MMP-1, whereas patients with obstructive CA disease had the highest level of MMP-9. According to our data, concentrations of MMP-9 and VEGF can be used to predict the degree of CA obstruction. The expression of miRNA-34a was significantly higher in IHD patients with INOCAD and CA obstruction than in the control group, which suggested a miRNA-34a contribution to the development and progression of coronary atherosclerosis. In the future, it may be possible to use this miRNA as a diagnostic marker for IHD.

Abstract: Endocrine tumors are a heterogeneous cluster of malignancies that originate from cells that can secrete hormones. Examples include, but are not limited to, thyroid cancer, adrenocortical carcinoma, and neuroendocrine tumors. Many endocrine tumors are relatively slow to proliferate, and as such, they often do not respond well to common antiproliferative chemotherapies. Therefore, increasing attention has been given to targeted therapies and immunotherapies in these diseases. However, in contrast to other cancers, many endocrine tumors are relatively rare, and as a result, less is understood about their biology, including specific targets for intervention. Our limited understanding of such tumors is in part due to a limitation in model systems that accurately recapitulate and enable mechanistic exploration of these tumors. While mouse models and 2D cell cultures exist for some endocrine tumors, these models often may not accurately model nuances of human endocrine tumors. Mice differ from human endocrine physiology and 2D cell cultures fail to recapitulate the heterogeneity and 3D architectures of in vivo tumors. To complement these traditional cancer models, bioengineered 3D tumor models, such as organoids and tumor-on-a-chip systems, have advanced rapidly in the past decade. However, these technologies have only recently been applied to most endocrine tumors. In this review we provide descriptions of these platforms, focusing on thyroid, adrenal, and neuroendocrine tumors and how they have been and are being applied in the context of endocrine tumors.

Background: Progressive myocardial remodeling (MR) in chronic heart failure (CHF) leads to aggravation of systolic dysfunction (SD) and clinical manifestations. Identification of metabolomic markers of these processes may help in the search for new therapeutic approaches aimed at achieving reversibility of MR and improving prognosis in patients with CHF., Methods: To determine the relationship between plasma acylcarnitine (ACs) levels, MR parameters and clinical characteristics, in patients with CHF of ischemic etiology (n = 79) and patients with coronary heart disease CHD (n = 19) targeted analysis of 30 ACs was performed by flow injection analysis mass spectrometry., Results: Significant differences between cohorts were found for the levels of 11 ACs. Significant positive correlations (r > 0.3) between the medium- and long-chain ACs (MCACs and LCACs) and symptoms (CHF NYHA functional class (FC); r = 0.31-0.39; p < 0.05); negative correlation (r = -0.31-0.34; p < 0.05) between C5-OH and FC was revealed. Positive correlations of MCACs and LCACs (r = 0.31-0.48; p < 0.05) with the left atrium size and volume, the right atrium volume, right ventricle, and the inferior vena cava sizes, as well as the pulmonary artery systolic pressure level were shown. A negative correlation between C18:1 and left ventricular ejection fraction (r = -0.31; p < 0.05) was found. However, a decrease in levels compared to referent values of ACs with medium and long chain lengths was 50% of the CHF-CHD cohort. Carnitine deficiency was found in 6% and acylcarnitine deficiency in 3% of all patients with chronic heart disease., Conclusions: ACs may be used in assessing the severity of the clinical manifestations and MR. ACs are an important locus to study in terms of altered metabolic pathways in patients with CHF of ischemic etiology and SD. Further larger prospective trials are warranted and needed to determine the potential benefits to treat patients with CV diseases with aberrate AC levels.

Adrenocortical carcinoma (ACC) has a poor prognosis, and no new drugs have been identified in decades. The absence of drug development can partly be attributed to a lack of preclinical models. Both animal models and 2D cell cultures of ACC fail to accurately mimic the disease, as animal physiology is inherently different than humans, and 2D cultures fail to represent the crucial 3D architecture. Organoids and other small 3D in vitro models of tissues or tumors can model certain complexities of human in vivo biology; however, this technology has largely yet to be applied to ACC. In this study, we describe the generation of 3D tumor constructs from an established ACC cell line, NCI-H295R. NCI-H295R cells were encapsulated to generate 3D ACC constructs. Tumor constructs were assessed for biomarker expression, viability, proliferation, and cortisol production. In addition, matrix metalloproteinase (MMP) functionality was assessed directly using fluorogenic MMP-sensitive biosensors and through infusion of NCI-H295R cells into a metastasis-on-a-chip microfluidic device platform. ACC tumor constructs showed expression of biomarkers associated with ACC, including SF-1, Melan A, and inhibin α. Treatment of ACC tumor constructs with chemotherapeutics demonstrated decreased drug sensitivity compared to 2D cell culture. Since most tumor cells migrate through tissue using MMPs to break down extracellular matrix, we validated the utility of ACC tumor constructs by integrating fluorogenic MMP-sensitive peptide biosensors within the tumor constructs. Lastly, in our metastasis-on-a-chip device, NCI-H295R cells successfully engrafted in a downstream lung cell line-based construct, but invasion distance into the lung construct was decreased by MMP inhibition. These studies, which would not be possible using 2D cell cultures, demonstrated that NCI-H295R cells secreted active MMPs that are used for invasion in 3D. This work represents the first evidence of a 3D tumor constructs platform for ACC that can be deployed for future mechanistic studies as well as development of new targets for intervention and therapies., (© 2023. Springer Nature Limited.)

Aim      To evaluate functional changes in the heart in the long-term following COVID-19 in patients with chronic heart failure (CHF).Material and methods  Case reports of 54 patients aged 69.1±9.7 years who had COVID-19 from January 2021 through January 2022 and had been previously diagnosed with NYHA functional class II-III CHF were studied. Two comparison groups were isolated: HF with LV EF &gt;50 % (n=39) and &lt;50 % (n=15). Echocardiography was used to evaluate changes in LV EF and pulmonary artery systolic pressure (PASP) 5-6 months following COVID-19.Results In all CHF patients after COVID-19 at 5.8 months on average, LV EF decreased (median difference, 2.5 %; 95 % confidence interval (CI): 6.99×10-5- 4.99) and PASP increased (median difference, 8 mm Hg; 95 % CI: 4.5-12.9). In the HF group with LV EF &lt;50 %, the decrease in EF was greater than in the group with LV EF &gt;50 % (6.9 and 0.7 %, respectively; p=0.037); furthermore, the CHF phenotype did not influence the change in PASP (p=0.4). The one-factor regression analysis showed that the dynamics of LV EF decrease was significantly influenced by the baseline decrease in LV EF, whereas the change in PASP was influenced by the dynamics of LV EF decrease, presence of dyslipidemia, and statin treatment. Furthermore, the multifactorial analysis showed that prognostically significant factors for long-term changes in LV EF following COVID-19 were male gender (odds ratio (OR), 5.92; 95 % CI: 1.31-26.75; p=0.014), LV EF at baseline &lt;50 % (OR, 0.88; 95 % CI: 0.8-0.96; p&lt;0.001); changes in PASP depended on the presence of dyslipidemia (OR, 0.08; 95 % CI: 0.01-0.84; p=0.018).Conclusion      This study showed that COVID-19 in the long term can influence the course of CHF; in this process, HF patients with EF &lt;50 % have progression of systolic dysfunction and PASP, whereas patients with EF &gt;50 % have an isolated increase in PASP.

The recommended tactics for prevention of thromboembolic complications of atrial fibrillation (AF) is the oral anticoagulant (OAC) treatment. The drugs of choice for preventing stroke for most patients with AF, excluding some valvular defects, are direct OACs (DOACS). Regardless of the drug class, all anticoagulants, even at appropriate doses, increase the risk of bleeding. However, the development of minor bleedings is not an absolute indication for DOAC withdrawal. This review presents a tactics for management of patients with minor bleeding associated with the DOAC treatment.

A central component of the epigenome is the pattern of histone post-translational modifications that play a critical role in the formation of specific chromatin states. Following DNA replication, nascent chromatin is a 1:1 mixture of parental and newly synthesized histones and the transfer of modification patterns from parental histones to new histones is a fundamental step in epigenetic inheritance. Here we report that loss of HAT1, which acetylates lysines 5 and 12 of newly synthesized histone H4 during replication-coupled chromatin assembly, results in the loss of accessibility of large domains of heterochromatin, termed HAT1-dependent Accessibility Domains (HADs). HADs are mega base-scale domains that comprise ∼10% of the mouse genome. HAT1 globally represses H3 K9 me3 levels and HADs correspond to the regions of the genome that display HAT1-dependent increases in H3 K9me3 peak density. HADs display a high degree of overlap with a subset of Lamin-Associated Domains (LADs). HAT1 is required to maintain nuclear structure and integrity. These results indicate that HAT1 and the acetylation of newly synthesized histones may be critical regulators of the epigenetic inheritance of heterochromatin and suggest a new mechanism for the epigenetic regulation of nuclear lamina-heterochromatin interactions., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The replisome is a protein complex on the DNA replication fork and functions in a dynamic environment at the intersection of parental and nascent chromatin. Parental nucleosomes are disrupted in front of the replication fork. The daughter DNA duplexes are packaged with an equal amount of parental and newly synthesized histones in the wake of the replication fork through the activity of the replication-coupled chromatin assembly pathway. Histone acetyltransferase 1 (HAT1) is responsible for the cytosolic diacetylation of newly synthesized histone H4 on lysines 5 and 12, which accompanies replication-coupled chromatin assembly. Here, using proximity ligation assay-based chromatin assembly assays and DNA fiber analysis, we analyzed the role of murine HAT1 in replication-coupled chromatin assembly. We demonstrate that HAT1 physically associates with chromatin near DNA replication sites. We found that the association of HAT1 with newly replicated DNA is transient, but can be stabilized by replication fork stalling. The association of HAT1 with nascent chromatin may be functionally relevant, as HAT1 loss decreased replication fork progression and increased replication fork stalling. Moreover, in the absence of HAT1, stalled replication forks were unstable, and newly synthesized DNA became susceptible to MRE11-dependent degradation. These results suggest that HAT1 links replication fork function to the proper processing and assembly of newly synthesized histones., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Agudelo Garcia et al.)

Histone acetyltransferase 1 (Hat1) is responsible for the acetylation of newly synthesized histone H4 on lysines 5 and 12 during the process of chromatin assembly. To understand the broader biological role of Hat1, we have generated a conditional mouse knockout model of this enzyme. We previously reported that Hat1 is required for viability and important for mammalian development and genome stability. In this study, we show that haploinsufficiency of Hat1 results in a significant decrease in lifespan. Defects observed in Hat1 +/- mice are consistent with an early-onset aging phenotype. These include lordokyphosis (hunchback), muscle atrophy, minor growth retardation, reduced subcutaneous fat, cancer, and paralysis. In addition, the expression of Hat1 is linked to the normal aging process as Hat1 mRNA and protein becomes undetectable in many tissues in old mice. At the cellular level, fibroblasts from Hat1 haploinsufficient embryos undergo early senescence and accumulate high levels of p21. Hat1 +/- mouse embryonic fibroblasts (MEFs) display modest increases in endogenous DNA damage but have significantly higher levels of reactive oxygen species (ROS). Consistently, further studies show that Hat1 -/- MEFs exhibit mitochondrial defects suggesting a critical role for Hat1 in mitochondrial function. Taken together, these data show that loss of Hat1 induces multiple hallmarks of early-onset aging., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Non-vitamin K antagonist oral anticoagulants (NOACs) - direct oral anticoagulants - are getting the ever-broadening use in clinical practice. However, many problems related to optimal use of NOACs in specific clinical situations remain unresolved. European Heart Rhythm Association in April 2018 issued the renovated recommendations on the use of NOACs in patients with atrial fibrillation. The authors of recommendations presented some specific clinical variants for which they formulated practical advices based on the evidence obtained in randomized clinical trials. They also outlined the indications for use of NOACs, formulated practical start-program and scheme of subsequent follow-up management of patients taking NOACs. Recommendations contain information on pharmacokinetics of NOACs and their interactions with other drugs, consideration of feasibility of NOACs use in patients with chronic renal insufficiency or advanced liver disease. Many other practical problems are covered as well.

Non-vitamin K antagonist oral anticoagulants (NОАСs) are highly effective drugs that prevent venous thrombosis and stroke in atrial fibrillation. Their use has difficulties that are associated with the need for laboratory control and with the influence of many factors on the activity of these medications. The emerged direct oral anticoagulants have some advantages over NOACs. Nevertheless, there are a number of pathological conditions, in which NOACs remain first-line drugs. These include prosthetic mechanical heart valves, a glomerular filtration rate less than 60 mL/min/1.73 m2, and left atrial thrombus.

Platelets are important components of hemostasis and play a key role in the formation of atherothrombosis. Rupture or erosion of atherosclerotic plaque gives rise to a thrombus with the involvement of platelets. Antiplatelet agents are instrumental in preventing the development of atherothrombosis of different localization, including coronary arteries.

The growing occurrence of thrombophilic conditions in recent years, the discovery of new forms of thrombophilia, the involvement of intravascular microcoagulation in the development of many diseases make their study of primary importance especially in patients with chronic obstructive pulmonary disease and atherothrombosis. Such investigations would facilitate a deeper understanding of the detailed mechanisms of thrombosis in these patients and thereby contribute to the optimization of their treatment and prevention.

Modern concepts of thrombophilia, its role in pathogenesis of arterial and venous thrombosis are discussed. The author's view of further development of this issue is expounded.

The stroke resulting in serious neurologic deficit is the third most frequent cause of death and loss of working ability. In 60-65% of the cases, it is provoked by atherothrombosis located in aortic arch, common and internal carotid arteries. Thromboembolism of cerebral vessels originating in heart cavities is responsible for 15-18% of the cases. Stroke prevention is an interdisciplinary problem encountered not only by neurologists but also by many other physicians. A major preventive tool for the stroke is healthy lifestyle while therapy with antithrombotic drugs (antiaggregants, oral anticoagulants) is the main component of secondary prevention. The choice of therapy depends on the cause and degree of stroke.

81 patients were included in the research into study of acute myocardial infarction (AMI) clinical course features in patients with various polymorphism of gene. These patients besides traditional examination, received genetic examination for determination of of NO-synthase gene in intron 4 (eNOS 4a/4b polymorphism) and mutation in position 298 of protein sequence leading to replacement of rest of glutamine acid by asparaginic acid (Glu298Asp). Patients with allele 4a polymorphism of endothelial NO-synthase gene in intron 4 (genotypes 4a/4a and 4a/4b) had low level of high-density lipoprotein cholesterol (HDLC) in comparison with 4b homozygote patients. Inverse association of 4a allele with HDLC did not depend on the AMI therapy character. Besides, it was detected that AMI patients with 4a/4a polymorphism had bronchial asthma and chronic hepatitis more frequently than patients with 4b/4b genotype. AMI patients with 4a allele had early postinfarction angina and gastroesophagoreflux disease. The relation of allele 4a carriage with development of early postinfarction angina depended on presence of bronchial asthma in AMI patients. AMI patients with Glu298Asp polymorphism Asp/Asp genotype did not have significant differences in AMI and concomitant pathology course in comparison with Glu/Glu genotype patients.

Acute ischemia resulting from arterial lesions poses a real threat to mankind. The concept of atherothrombosis aims to unite doctors of different specialities to combat this pathology; it suggests active exchange of experience in the management of aherothrombosis between representatives of different medical disciplines. The concept is expected to promote treatment of the patients. The common pathogenetic mechanism of ischemic disorders of the heart, brain, and lower extremities provides a basis for the recommendation of active antithrombotic therapy for their prevention. The current approach to the management of atherothrombosis is prone to further improvement despite certain reports of successful inpatient treatment of acute myocardial infarction. Prevention of blood clot formation, i.e. prophylaxis of atherosclerosis, remains a challenging problem. Statins may prove of great help in this respect. Studies of the effect of infectious factors on the integrity of the fibrous envelope of an atherosclerotic plaque are currently underway.

Coronary artery calcinosis was measured with ECG-gated multislice spiral CT in 68 patients, mean age 57.54+/-1.04 (M+/-m), including 47 men (69.1%) and 21 women (30.9%). Vascular reactivity of microcirculatory bed was assessed with laser Doppler flowmetry after acetylcholine and histamine administration. Coronary artery calcinosis correlated negatively with vascular susceptibility to acetylcholine (r=-0.380, p=0.002). This correlation did not depend on sex, age and concomitant drug therapy. Smoking was shown to affect significantly microvascular reactivity to histamine in persons free from coronary atherosclerosis. History of smoking determined the disturbances of vascular reactivity to histamine in patients with coronary artery calcinosis.

Venous thrombosis (VT) is a frequent pathology associated with a high mortality. A high risk of VT is associated with a variety of diseases, syndromes, and situations, connected with a congenital predisposition (thrombophilia) or not. Clinical and instrumental data in VT are non-specific. The diagnosis of these conditions is very difficult. Correct and timely treatment decreases mortality associated with pulmonary arterial thromboembolism (PATE). Unfortunately, this index is still very high: a lot of patients die within first minutes and even seconds of the moment of pulmonary arterial obturation with a thrombus. All this suggests that PATE belongs to diseases that are easier to prevent than to treat. In connection with this, a doctor examining a patient must always keep the possibility of VT and PATE in mind and evaluate the risk of their development, thus taking a decision concerning the necessity, duration, and a method of preventive treatment.

Aim: To examine diagnostic potential of arthrosonography (ASG) in diagnosis of tendenitis in combination with synovitis in patients with gonarthrosis stage I-III by Kellgren's classification., Material and Methods: A total of 40 patients with gonarthrosis exacerbation were examined with x-ray and ultrasound scanning (80 joints). ASG was made on Aloka-SSD-630 device using two-dimentional scanning in 4 longitudinal and 4 transverse positions., Results: Clinical symptoms of synovitis were predominant in patients with gonarthrosis x-ray stage II (68.3%). In ASG synovitis was detected in 41 (51.25%) of 48 knee joints with clinical picture of synovitis. Ultrasound detected such synovitis signs as increased amount of water in the knee joint cavity and b. suprapatellaris, thickening of the synovial membrane more than 0.3 cm and changes in its structure. Six (7.5%) joints were affected with subclinical synovitis diagnosed only in ASG. Ultrasound visualized Baker's cyst in 5 patients and in 5 knee joints. Periarthritis was detected in 77.5% joints, in 46.25% joints it combined with synovitis, ASG provided differential diagnosis of synovitis with periarthritis. Thinning of the cartilage was detected in most of the joints both in synovitis and in its absence but it was more significant in synovitis (62.5 and 40%, respectively)., Conclusion: ASG is an informative diagnostic method in periarthritis and synovitis, including subclinical, and give additional information for x-ray diagnosis in gonarthrosis stage I-III.

Aim: To examine the relationship between the vascular response of the microcirculatory bed to vasoactive agents and lipid peroxidation (LPO) and antioxidative defense in patients with unstable angina pectoris., Materials and Methods: Thirty male patients (mean age 58.0 +/- 2.4 years) were examined. The patients were divided into 2 groups: 1) those with high alpha-cholesterolemia alone and 2) those with high alpha-cholesterolemia concurrent with hyperglyceridemia and elevated total cholesterol levels. Photoplethysmographic determination was used to evaluate vascular responses to norepinephrine (vasopressor function) and histamine (vasodilating function), the blood levels of cortisol, LPO products, antioxidative protection components, histamine, and serotonin., Results: Vascular dilating function was found to be most pronounced in Group 1. Moreover, Group 1 patients had a significant depression of the antioxidative defense system and the highest blood levels of cortisol, and serotonin. The levels of LPO products did not differ significantly in both groups though they were significantly higher than those in healthy individuals., Conclusion: Impairment in the antioxidant system and in coordination of vasodilating function to histamine stimulation are typical of patients with unstable angina.

As many as 56 patients with stage-II hypertensive disease (HD) as per the WHO classification were examined. On day 30 of myocardial infarction (MI) the left ventricular myocardium mass was calculated and six months later exercise tolerance was evaluated using bicycle ergometer. The evaluation done showed that the presence of hypertrophy of the Left ventricle in HD patients by day 30 of MI was a prognostic sign of low exercise tolerance in postinfarction period, which fact permits exercise tolerability to be foreseen, and issues related to the patients' fitness for work to be settled as early as the hospital stage of rehabilitation of MI patients.

Seventy patients with hypertonic disease (HD) in the IInd stage were examined echocardiographically 30 days and 6 months after macrofocal myocardial infarction with the view to study contractility of myocardium of the left ventricle depending on its mass. Increase of the left ventricle mass (LVM) in patients with HD after infarction was established to be associated with rise of myocardial contractility. Fall of the LVM occurs at the account of thinning of ventricular wall without changes in volumic parameters of the left ventricle.

It is concluded on the basis of probability analysis about the necessity of including esophagogastroduodenoscopy in the complex of preoperative examination of patients with calculous cholecystitis. Data of 1050 consecutive esophagogastroduodenoscopies for calculous cholecystitis confirm from clinical positions the expediency of the mathematically based tactics.

Analysis is done of the work of the inpatient department of a polyclinic belonging to the VPO "Orenburggazprom". In that department, the treatment is mainly given to the persons of a capable age with different visceral diseases. The authors have worded indications for referral of the patients to the indicated department, evaluated the social and economic advantages of that form of rendering medical services.

A new method for radionuclide measurement of gastric juice proteolytic activity (GJPA) is described. GJPA is determined according to the time of dissolution of the protein capsule filled with 99mTc-pertechnetate solution. In vitro experiments made with 342 samples of gastric juice revealed a correlation (p1 less than 0.01) between the time of dissolution of the 99mTc-pertechnetate capsule and proteolytic activity measured according to Metta's method. No correlation was established between GJPA (measured by Metta's method and by radionuclide method) and gastric juice acidity (p greater than 0.05). In 63 patients examined, the time of capsule dissolution was 15 to 18 minutes with GJPA being normal, 8 to 14 minutes (p less than 0.01) with elevated parameters of GJPA, and 19 to 37 minutes (p less than 0.01) with GJPA being reduced. The given method is a physiological one, sufficiently precise and can be recommended for a screening analysis of GJPA.

A possibility of the use of a radionuclide tubeless rapid method for measuring gastric content proteolytic activity (GCPA) with the help of a protein (gelatin) RP containing capsule was demonstrated in experiments in vitro. There was correlation between the time of dissolution of RP containing capsules and GCPA determined after Mett's method. Reference time intervals were established for normal, raised and lowered proteolytic activity. The method was shown to be physiological, simple and time-saving.

Changes in skin vascular responsiveness (VR) to six vasoactive agents were examined in 25 patients with myocardial infarction during its acute period. In small myocardial infarction, there was a synchronous increase in all VR types on days 1-7 followed by its normalization on day 14. VR synchronization was also observed in transmural myocardial infarction, yet increased VR to vasoconstrictive agents such as noradrenaline, adrenaline, and angiotensin II remained until the end of the fourth week without showing a tendency to normalization. Abnormal VR was seen in the most severe fatal cases. The synchronous and cyclic VR changes observed in myocardial infarction were absent in patients with unstable angina that did not result in myocardial infarction.

The authors described clinical testing of a new tubeless radionuclide rapid method for measuring gastric content proteolytic activity (GCPA) using a protein (gelatin) capsule filled with a radiopharmaceutical (RP). The solution time of a capsule with a radiotracer determined by its clearance, corresponded to GCPA measured after Mett's method. The testing has shown that the above method is physiological, causes no complications and unpleasant sensations in patients, is simple to perform, and can be recommended for a wide clinical use in gastroenterology.