New opportunities of renal denervation Agaeva, R A; Danilov, N M; Shelkova, G V ...
Terapevtic̆eskii arhiv,
2020-Jul-09, Volume:
92, Issue:
6
Journal Article
Peer reviewed
Open access
Radiofrequency renal artery denervation (RND) was introduced as a method of interventional treatment of resistant hypertension almost ten years ago. The first studies demonstrated the effectiveness ...of this procedure. This has led to growing interest in this area and the rapid development of the method. However, the results of the first randomized trial of SYMPLICITY HTN-3 questioned the role of RND in the treatment of resistant hypertension, this fact conducted to the decrease in the recommendation class and level of evidence in the Guidelines of the European Society of Cardiology and the European Society of Hypertension in 2018. To date, the medical community is actively discussing the results of recently published trials such as SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED, RADIANCE-HTN SOLO and RADIOSOUND-HTN.
We report on facile method of graphene nanoplatelets synthesis by electrochemical method using multi‐walled carbon nanotubes (MWCNTs). For the synthesis procedure we utilize standard redox potential ...of the carbon atom belonging to carboxyl groups. The graphene oxide was obtained by anodic oxidation of MWCNTs in 80% sulfuric acid at optimum oxidation potential +3.0 V for 4 h. The subsequent electrochemical reduction of the obtained material was carried out in an alkaline medium. The successful electrochemical production of the graphene nanoplatelets from MWCNTs was confirmed by different experimental techniques, in particular TEM, XRD, XPS, XES, FTIR and Raman spectroscopy. The current‐voltage characteristics of the oxygen electrodes produced from the electrochemically obtained graphene nanoplatelets were investigated. It was shown that the graphene nanoplatelets produced by electrochemical method is a promising material for fuel cell electrodes.
Angiotensin I-converting enzyme (ACE) metabolizes a range of peptidic substrates and plays a key role in blood pressure regulation and vascular remodeling. Thus, elevated ACE levels may be associated ...with an increased risk for different cardiovascular or respiratory diseases. Previously, a striking familial elevation in blood ACE was explained by mutations in the ACE juxtamembrane region that enhanced the cleavage-secretion process. Recently, we found a family whose affected members had a 6-fold increase in blood ACE and a Tyr465Asp (Y465D) substitution, distal to the stalk region, in the N domain of ACE.
HEK and CHO cells expressing mutant (Tyr465Asp) ACE demonstrate a 3- and 8-fold increase, respectively, in the rate of ACE shedding compared to wild-type ACE. Conformational fingerprinting of mutant ACE demonstrated dramatic changes in ACE conformation in several different epitopes of ACE. Cell ELISA carried out on CHO-ACE cells also demonstrated significant changes in local ACE conformation, particularly proximal to the stalk region. However, the cleavage site of the mutant ACE--between Arg1203 and Ser1204--was the same as that of WT ACE. The Y465D substitution is localized in the interface of the N-domain dimer (from the crystal structure) and abolishes a hydrogen bond between Tyr465 in one monomer and Asp462 in another.
The Y465D substitution results in dramatic increase in the rate of ACE shedding and is associated with significant local conformational changes in ACE. These changes could result in increased ACE dimerization and accessibility of the stalk region or the entire sACE, thus increasing the rate of cleavage by the putative ACE secretase (sheddase).
The quality of the blade material and specimens cast from a ZhS3DK-VI heat-resistant nickel alloy with 50% returns in the charge (after preliminary remelting), subject to hot isostatic pressing (HIP) ...and standard heat treatment, was evaluated. It is established that the chemical composition, macroand microstructure, mechanical and heat-resistant properties of the casting material meet the requirements of standard specifications and engineering documentation. The bending angle on the blades was found to be within 88–126° (according to the OST 1.90.126-85 requirements, it should be no less than 20°). Hot isostatic pressing of the blades at 1210°C and 160 MPa brings about the healing of microporosity and looseness that do not come out at the surface of the componenti (located in the bulk of the metal). The structure of the turbine blades after HIP is practically free of micropores, which contributes to the stabilization of the structure and properties of the material. Single micropores detected after HIP are more than 40 times smaller compared to those revealed in the cast blades before HIP. Thus, it supports the feasibility of fabricating the turbine blades with 50% returns in the charge. Hot isostatic pressing before standard heat treatment is shown to positively influence the complex of physical, mechanical, and service properties of critical cast products from heatresistant nickel alloys for aviation and power plants.
Angiotensin-converting enzyme (ACE) is highly expressed in renal proximal tubules, but ACE activity/levels in the urine are at least 100-fold lower than in the blood. Decreased proximal tubular ACE ...has been associated with renal tubular damage in both animal models and clinical studies. Because ACE is shed into urine primarily from proximal tubule epithelial cells, its urinary ACE measurement may be useful as an index of tubular damage.
We applied our novel approach-ACE phenotyping-to characterize urinary ACE in volunteer subjects. ACE phenotyping includes (1) determination of ACE activity using two substrates (ZPHL and HHL); (2) calculation of the ratio of hydrolysis of the two substrates (ZPHL/HHL ratio); (3) quantification of ACE immunoreactive protein levels; and (4) fine mapping of local ACE conformation with mAbs to ACE.
In normal volunteers, urinary ACE activity was 140-fold less than in corresponding plasma/serum samples and did not differ between males and females. However, urinary ACE immunoreactivity (normalized binding of 25 mAbs to different epitopes) was strongly sex-dependent for the several mAbs tested, an observation likely explained by differences in tissue ACE glycosylation/sialylation between males and females. Urinary ACE phenotyping also allowed the identification of ACE outliers. In addition, daily variability of urinary ACE has potential utility as a feedback marker for dieting individuals pursuing weight loss.
Urinary ACE phenotyping is a promising new approach with potential clinical significance to advance precision medicine screening techniques.
—A technique is proposed for estimating the parameters of spatial orientation of the
vectors of distances between the components in wide binary stars (BS) in open star clusters (OCs). An analysis of ...the orientation features of these vectors for 36 wide BSs previously discovered in Pleiades based on Gaia DR2 data shows that the largest number of vectors
of wide BSs in Pleiades are oriented in direction close to the perpendicular to cluster center. This result agrees with earlier estimates that yielded positive total energies for wide BSs in Pleiades and with the conclusion that the disruption of wide binaries can occur mostly in the direction perpendicular to the direction of the cluster center. Two groups are distinguished by the value of their
parameter—the ratio of the mass of the component of the binary that is closest to the cluster center to the mass of the more distant component: with
and
, each consisting of 18 stars. Different dependence on the orientation parameters of the vectors
for these groups is indicative of different tidal constraints from the regular cluster field. Equations are derived for estimating the tidal distances
between the components of wide BSs in OCs in terms of two models of mass density distribution: an OC model with a uniform-density core and density decreasing as
outside this core, where
is the clustercentric distance, and a point-mass cluster model. The equations were derived using the integral of the energy of the system of three gravitating bodies and the condition of the balance of the attraction on the BS component by the cluster and the other two bodies of the system. Tidal constraints on wide BSs in Pleiades are analyzed. It is shown that
in the cluster core is mostly determined by the regular force field of the cluster. Outside the core and at the cluster periphery, the most likely hitherto studied formation mechanism of wide BSs (and hence of the
value) is “pulling” components of such BSs into resonance with oscillations of the regular cluster field. Therefore, the presence of wide BSs in Pleiades can be considered as one of the signs of the nonstationarity of Pleiades in the field of regular forces. Formulas are derived for estimating
for wide BSs moving in circular orbits in a non-uniform cluster, which take into account the effect on
of the cluster mass distributed between the components of the wide BS. The distances
at the cluster periphery (
pc) are shown to increase by about a factor of three when passing from radial to circular BS orbits.
—
The parameters of scintillator veto detectors that should be installed in an intermediate water Cherenkov detector of the Hyper-Kamiokande project have been measured. The veto detectors are disc ...scintillators with embedded wavelength-shifting fibers and with compact photosensors, i.e., silicon photomultipliers. It is shown that the detection efficiency of these detectors for cosmic muons is larger than 99%.
—The paper analyzes the estimates of the parameters of wide binary stars (BSs) in the Pleiades open star cluster, obtained in 2020 from Gaia DR2 data. To this end a model of a gravitating system was ...used, consisting of two stars connected in the total force field of these stars and a homogeneous gravitating sphere simulating a star cluster. The existence of two “tidal” distances
between the components of the BS is shown for its distances from the center of the cluster sphere greater than a certain critical value. The lesser of the “tidal” distances
decreases with increasing distance from the center of the cluster sphere, since the force of attraction to the center of a homogeneous cluster sphere within its limits increases with distance from its center. The larger of the “tidal” distances
is due to the difference in the magnitudes of the cluster force field at the location points of the BS component stars and increases with increasing distance of the BS from the cluster center, reaching values of several parsecs at the periphery of the cluster sphere. The condition for gravitational coupling of wide BSs with zero relative velocities of their components in the common force field of a moving BS and the cluster sphere has been written down and investigated. It is shown that the decay of wide BSs can occur mainly in the direction perpendicular to the direction towards the center of the cluster. This slows down the decay of wide BSs observed in the nearest open clusters. In the case of the cluster sphere mass equal to the total mass of the member stars of the Pleiades cluster with magnitudes
, estimates were obtained for the decay time
and the formation of wide BSs for characteristic Pleiades values of the oscillation parameters of the regular cluster field (at
pc, the values of
decrease from 1.25 to
Myrs as the distance of the BSs from the center of the cluster sphere increases from 0.34 to 0.45 pc). Estimates of the “tidal” distances
between the BS components in the model of an inhomogeneous cluster also show the existence of two values of
at the cluster periphery for BS distances from the cluster center greater than a certain critical value. It is shown that changes in the regular force field in the core of a collapsing cluster destroy wide BSs more actively than their encounters with groups of several stars. Estimates of the distances of the kinematic groups of stars from the center of the cluster in the Pleiades were obtained. Kinematic groups of three stars are located mainly at distances
–
pc and
–
pc from the center of the cluster. Kinematic groups of four stars in the Pleiades are located near the distances
pc and
pc from the center of the cluster. Possible mechanisms of formation for such groups in the Pleiades are discussed.
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