The Role of Neprilysin Inhibitors in the Treatment of Heart Failure with Preserved Ejection Fraction.

Clinical and hemodynamic aggravation of heart failure with preserved ejection fraction (HFpEF) is largely due to progression of left ventricular (LV) diastolic dysfunction. The key role in the normal maintenance of diastolic function is played by a high level of activity of the intracellular signaling axis, cyclic guanosine-monophosphate-protein kinase G, the activity of which is significantly reduced in HFpEF. The activity of this axis can be increased by increasing the bioavailability of natriuretic peptides by blocking the enzyme neutral endopeptidase (neprilisin), which is responsible for the destruction of natriuretic peptides.This review presents experimental and clinical data on the use of neprilysin inhibitors in HFpEF and addresses prospects of this treatment.

[EVALUATION OF CARDIOVASCULAR RISKS WITH THE USE OF MORPHOGENETIC KLOTHO PROTEIN IN PATIENTS WITH CHRONIC RENAL DISEASE].

The aim: of the study was to explore the Klotho protein significance in patients with different stages of chronic kidney disease (CKD) and to assess the influence of antihypertensive therapy on Klotho protein serum levels. Materials and methods: 130 patients with stage 5 CKD1 were included in the study. Serum PTH, calcium and phosphorus were measured. ELISA was used to determine serum soluble alpha Klotho. Blood pressure including brachial and central (aortic) pressure was measured in all patients together with pulse wave velocity (using a «Sfigmokor¼ device); in addition, echocardiography (EchoCG), and X-ray examination of the abdominal aorta by Kauppila method were performed. Results: The dynamic study of serum Klotho level showed that it changes with decreasing glomerular filtration rate faster than a rise in phosphate and PTH levels starting from stage 3A of CKD. The two later variables increased at stages 4-5.According to the ROC analysis, the values of serum Klotho below 387 pg /ml suggested enhanced risk of myocardial calcification with 80% sensitivity and 76% specificity. In addition, the highest Klotho serum levels were observed in patients whose target BP values were achieved with angiotensin receptor blockers (ARB) compared to those who used other drugs [р<0,01] or failed to reached target BP levels [p=0,008]. Conclusion: The study showed the possibility of practical use of Klotho protein as an early diagnostic marker of cardiovascular risk. Reduced serum Klotho was less pronounced in patients who used ARB for correction of high blood pressure. Normal Klotho protein levels in serum have been associated with a lower frequency of heart and vessels calcification in CKD patients.

[MORPHOGENETIC PROTEINS--FIBROBLAST GROWTH FACTOR AND KLOTHO, IN THE SERA OF PATIENTS WITH CHRONIC RENAL DISEASE].

The aim of the study was to evaluate the role of morphogenetic proteins--fibroblast growth factor-23 (FGF-23) and extracellular form (alpha) of Klotho protein, present in the sera of patients with chronic renal disease (CRD) as markers of cardiovascular risk. The study included 130 patients (64 men and 66 women) with stage I-VD CRD. The patients'age was 20-65 (mean 41 ± 6.7) years. 30 of them had chronic glomerulonephritis, 23 chronic tubulointerstitial nephritis, 28 hypertensive nephrosclerosis, 22 polycystic kidneys, 27 type 2 diabetes mellitus. Inclusion and exclusion criteria were standardfor clinical studies of CRD patients. Control group contained 30 healthy volunteers matched for age and sex. The patients were uniformly distributed by stages of CRD in terms of age and sex (18-20 per group). All of them were followed up during 1 year Standard clinical and laboratory examination was supplemented by the measurement of the parathyroid hormone (PTH), Ca and P levels. Serum FGF-23 and Klotho levels were determined by ELISA before and 1 year after onset of the study. Blood pressure including brachial (peripheral) and aortic (central) one as swell as the pulse wave velocity was measured by a Sphygocorr apparatus (Australia). Other studies included ECG, EchoCG, and X-ray of abdominal aorta in the lateral projection using the Kaupilla method. Comparison of FGF-23 and Klotho levels in patients at different stages of CRD revealed their decrease with decreasing glomerular filtration rate that started before (at IIIA stage) a rise in the serum P and PTG levels (IV-V stage). Negative relationship was documented between the Klotho level and the degree of cardiac calcinosis estimated from a semi-quantitative scale (r = 0.64; p < 0.01). Serum FGF-23 significantly correlated wiht myocardial remodeling (r = 0.612; p < 0.01). Multiple regression analysis showed that patients with elevated FGF-23 and P levels, high central systolic pressure and pulse wave velocity had greater left ventricular myocardium mass. ROC-analysis demonstrated that FGF-23 level over 412 pg/ml is indicative of left ventricular hypertrophy with sensitivity 80% and specificity 76%. Patients undergoing hemodialysis who died within 1 year after the onset of the treatment had a higher FGF-23 level than survivals on hemodialysis. The risk of death during the first year on hemodialysis correlated with the FGF-23 level (r = 0.564, p < 0.01). ROC-analysis showed that Klotho levels below 387 pg/ml suggested an increased risk of myocardiym calcification with sensitivity 80% and specificity 75%. It is concluded that morphogenetic proteins, fibroblast growth factor and Klotho, not only play an important role in mineral metabolism in patients with CRD but also produce pleiotropic effects on the development of cardiovascular complications (via involvement in cardiac and vascular calcification and remodeling). It provides a basis for the use of these proteins as early markers of cardiovascular risk in CRD patients.

[Two technologies for designing digital X-ray image detectors].

The goal of this work was to discuss the problem of replacement of conventional devices for film roentgenography with modern digital X-ray image detectors. Several types of digital detectors are considered. The material presented in this work makes it possible to draw some conclusions on the prospects of development of X-ray detectors and transducers, their advantages and disadvantages.

[Digital X-ray unit ARC-01-"OKO"]. / Tsifrovoi rentgenovskii apparat ARTS-01-"OKO".

Presented is a description of a new roentgenographic unit ARC-01-"OKO" designed by the "Electron" Research and Design Company Ltd. for digital roentgenography (with X-ray transparent deck) of patients in the standing, sitting and lying positions. The unit enhances the capacity of X-ray examination room and makes almost unnecessary the use of X-ray films and chemicals. According to its medicals trials, the structural elements of the thorax, lungs, mediastinum, diaphragm, skull, lower and upper extremities, vertebral column, abdominal cavity and pelvis, when examined in different projections, are reproduced by the unit with good and excellent quality both at health and disease.

[Failures and complications of transcatheter coil occlusion of patent ductus arteriosus]. / Neudachi i oslozhneniia chreskateternoi spiral'noi okkliuzii otkrytykh arterial'nykh protokov.

An analysis of fails and complications of transcatheter coil occlusion of patent ductus arteriosus (PDA) was made. An attempt to close PDA with Gianturco coils was undertaken in 132 patients. Fails were noted in 4 (3.1%) children, 3 of them failed to hold the coil in PDA due to its greater width, and in 1 patient the catheter could not be delivered through a narrow duct. Complications were noted in 9 patients (7%): migration of the coils into the pulmonary artery branches took place in 8 patients, and in 1 patient there appeared haemolysis due to a large residual shunt. Snare-assisted removal of the migrating coils was carried out in 7 children, in 1 girl the coil could not be extracted from the peripheral branch of the left pulmonary artery. In 7 patients reocclusion of PDA was made, in 1 case no reembolization was performed. Haemolysis was liquidated by an additional implantation of the coils in repeated procedure. Risk of fail and complications was associated with great minimal diameter of patent ductus arteriosus.

[Surgical treatment in chronic gastroduodenal ulcers]. / Khirurgicheskoe lechenie pri khornicheskikh gastroduodenal'nykh iazvakh.

Operative treatment was carried out in 1197 patients with chronic gastroduodenal ulcers. Among the most frequent complications of the ulcers there were penetration of the III-IV degree, compensated, subcompensated and decompensated pyloroduodenal stenosis. The operative interventions included Billroth-II resections of the stomach in modification of Hofmeister-Finsterer, Billroth-I, with saving the pyloric sphincter, after Roux and gastrectomies. Postoperative complications developed in 127 (10.6%) patients, postoperative lethality was 0.7%. Excellent and good long-term results were noted in 846 (94.5%) patients, in 14 (1.6%) patients they were estimated as satisfactory and in 35 (3.9%) as unsatisfactory. The causes of unsatisfactory results were recurrent ulcers (0.7%), peptic ulcer of the gastroenteroanastomosis (0.6%), dumping-syndrome of a severe and medium degree (1.5%), diarrhea of a severe degree (0.3%) and erosive-ulcerous reflux-esophagitis (0.3%).

[The TsFK-1 digital camera for fluorography and roentgenography]. / Tsifrovaia kamera TsFK-1 dlia fliuorografii i rentgenografii.

Digital X-ray apparatuses have been designed to substitute for film fluorographs, which are noted for smaller radiation loads and high image quality. The paper describes one of such apparatuses, whose distinctive feature is the use of a low-noise CCD matrix having high-resolution matrix and a high performance luminescence screen. It outlines prospective variants of the use of the apparatus, describes the basic set supplied and its operation, gives its technical data and dimensions.

[A device for studying liminal and supraliminal indices of the state of the olfactory analyzer]. / Ustroistvo dlia issledovaniia porogovykh i nadporogovykh pokazatelei sostoianiia oboniatel'nogo analizatora.

An universal device (olfactoadaptometer) permitting to carry out threshold and suprathreshold olfaction assessment in suggested. Use of odorous substances of different receptor orientation increases the possibilities of differential diagnosis of olfactory analyzer diseases. The construction of the device is simple. Units, which are in industrial production can be used for its manufacture. The olfactometer is portable, simple in attendance and self-reacting.