Interim Results of the BYHEART Observational Study: Exogenous Phosphocreatine Effect on the Quality of life of Patients with Chronic Heart Failure.

Aim      Improvement of quality of life is one of the most important goals for the treatment of patients with chronic heart failure (CHF). This study searched for ways to increase the efficiency of CHF treatment based on parameters of quality of life in CHF patients during and after the treatment with exogenous phosphocreatine (EP).Material and methods  The effect of a single course of EP treatment on quality of life of patients with functional class (FC) II-IV CHF with reduced or mid-range left ventricular ejection fraction was studied as a part of the all-Russia prospective observational study BYHEART. The presence of FC II-IV CHF and a left ventricular ejection fraction <50 % were confirmed by results of 6-min walk test (6MWT) and findings of echocardiography after stabilization of the background therapy.Results An interim data analysis showed that the course of EP treatment was associated with a significant improvement of quality-of-life indexes as determined by the Minnesota Living with Heart Failure Questionnaire (LHFQ) total score. These indexes significantly increased and remained at a satisfactory level for 6 mos. following completion of the treatment course. Also, the treatment significantly beneficially influenced the clinical condition of patients (heart failure severity scale), results of 6MWT, and the increase in left ventricular ejection fraction.Conclusion      The conclusions based on results of the interim analysis should be confirmed by results of the completed study. Complete results are planned to be published in 2022.

Chronic obstructive pulmonary disease and diabetes: a look at the epidemiology, pathogenetic mechanisms, treatment.

Lately, increasingly studied the negative impact of diabetes type 2 on chronic obstructive pulmonary disease (COPD). According to literary data diabetes type 2 is more often diagnosed in patients with COPD in comparison with the general population: diabetes type 2 occur among patients with COPD in 18.7%, in comparison with patients without COPD - in 10,5%. The complexity of this association is primarily that chronic obstructive lung disease is regarded as a risk factor for diabetes type 2. The results of some researches show existence of close connection between the glycemic status and spirometric indicators - forced expiratory volume 1-second, forced vital capacity. Obstructive, restrictive, mixed ventilatory lung dysfunction observed in the states prior to the beginning of diabetes, such as impaired glucose tolerance and / or in patients with metabolic syndrome. The associations between lungs function and diabetes type 2 is explained by biochemical changes in airways, in lungs tissue. In patients with diabetes type 2 the decrease of lungs function is considered as a result of diabetes type 2 and as risk of development and progressing of COPD. Communication between the two complex nosologies - COPD and diabetes type 2 is confirmed by epidemiological data, common pathogenetic mechanisms - chronic systemic inflammation, oxidative stress, hypoxia, chronic hyperglycemia, side effects of drugs used in the treatment of two diseases - inhaled and / or systemic corticosteroids, inhaled bronchodilators, oral hypoglycemic agents. However, the pathogenetic mechanisms underlying the high prevalence of diabetes type 2 in patients with COPD is still unclear and requires a detailed study. Thus, it is actually and reasonable to conduct scientific and clinical work on identifying and better understanding of the exact mechanisms of the association between COPD and diabetes type 2 to develop methods for their correction, prevention and selection of adequate combination regimens in patients with these comorbid pathologies.

STED nanoscopy reveals molecular details of cholesterol- and cytoskeleton-modulated lipid interactions in living cells.

Details about molecular membrane dynamics in living cells, such as lipid-protein interactions, are often hidden from the observer because of the limited spatial resolution of conventional far-field optical microscopy. The superior spatial resolution of stimulated emission depletion (STED) nanoscopy can provide new insights into this process. The application of fluorescence correlation spectroscopy (FCS) in focal spots continuously tuned down to 30 nm in diameter distinguishes between free and anomalous molecular diffusion due to, for example, transient binding of lipids to other membrane constituents, such as lipids and proteins. We compared STED-FCS data recorded on various fluorescent lipid analogs in the plasma membrane of living mammalian cells. Our results demonstrate details about the observed transient formation of molecular complexes. The diffusion characteristics of phosphoglycerolipids without hydroxyl-containing headgroups revealed weak interactions. The strongest interactions were observed with sphingolipid analogs, which showed cholesterol-assisted and cytoskeleton-dependent binding. The hydroxyl-containing headgroup of gangliosides, galactosylceramide, and phosphoinositol assisted binding, but in a much less cholesterol- and cytoskeleton-dependent manner. The observed anomalous diffusion indicates lipid-specific transient hydrogen bonding to other membrane molecules, such as proteins, and points to a distinct connectivity of the various lipids to other membrane constituents. This strong interaction is different from that responsible for forming cholesterol-dependent, liquid-ordered domains in model membranes.

[Synthesis, structure, and biological properties of some 8alpha-analogues of steroid estrogens with fluorine in position 2].

A total synthesis of 8alpha analogues of steroid estrogens with fluorine in position 2 was achieved. Structural features of these compounds were studied by the example of 17beta-acetoxy-2-fluoro-3-methoxy-8alpha-estra-1,3,5(10)-triene. It was shown that the 8alpha analogues of 2-fluorosubstituted steroid estrogens have a low uterotropic activity and retain the osteoprotective and hypocholesterolemic activities.

Spirocyclopropanated bicyclopropylidenes: straightforward preparation, physical properites, and chemical transformations.

Perspirocyclopropanated bicyclopropylidene (6) was prepared in three steps from 7-cyclopropylidenedispiro[2.0.2.1]heptane (4) (24% overall) or, more efficiently, through dehalogenative coupling of 7,7-dibromo[3]triangulane (15) (82%). This type of reductive dimerization turned out to be successful for the synthesis of (E)- and (Z)-bis(spiropentylidene) 14 (67%) and even of the "third-generation" spirocyclopropanated bicyclopropylidene 17 (17% overall from 15). Whereas the parent bicyclopropylidene 1 dimerized at 180 degrees C to yield [4]rotane, dimerization of 6 at 130 degrees C under 10 kbar pressure occured only with opening of one three-membered ring to yield the polyspirocyclopropanated (cyclopropylidene)cyclopentane derivative 19 (34% yield), and at the elevated temperature the polyspirocyclopropanated 2-cyclopropylidene[3.2.2]propellane derivative 20 (25 % yield). Perspirocyclopropanated bicyclopropylidene 6 and the "third-generation" bicyclopropylidene 17 gave addition of bromine, hydrogen bromide, and various dihalocarbenes without rearrangement. The functionally substituted branched [7]triangulane 28 and branched dichloro-C2v-[15]triangulane 32 were used to prepare the perspirocyclopropanated [3]rotane (D3h-[10]triangulane) 49 (six steps from 6, 1.4% overall yield) and the C2v-[15]triangulane 51 (two steps from 17, 41% overall). Upon catalytic hydrogenation, the perspirocyclopropanated bicyclopropylidene 6 yielded 7,7'-bis(dispiro[2.0.2.]-heptyl) (52) and, under more forcing conditions, 1,1'-bis(2,2,3,3-tetramethylcyclopropyl) (53). The bromofluorocarbene adduct 33 of 17 reacted with butyllithium to give the unexpected polyspirocyclopropanated 1,4-di-n-butyl-2-cyclopropylidenebicyclo[2.2.0]hexane derivative 37 as the main product (55% yield) along with the expected "third-generation" perspirocyclopropanated dicyclopropylidenemethane 38 (21% yield). Mechanistic aspects of this and the other unusual reactions are discussed. The structures of all new unusual hydrocarbons were proven by X-ray crystal structure analyses, and the most interesting structural and crystal packing features are presented.