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Aim To evaluate long-term safety and efficacy of anatomically optimized distal renal denervation (RDN). Methods We assessed major adverse cardiovascular and renal events; changes in BP (office, ambulatory), and renal function (serum creatinine, eGFR) over 3 year follow-up extension of our double blind, randomized controlled study of the efficacy and safety of distal RDN versus conventional main trunk treatment in patients with true resistant hypertension (NCT02667912). Results Of 55 randomized patients (28/27, distal/main trunk RDN, respectively), 47 (23/24) were assessed at 1 year, and 39 (21/18) - at 3-year post-procedure. During 3-year follow-up 2 fatal and 2 non-fatal strokes were observed in distal RDN group versus one heart failure death and 2 non-fatal strokes in group of main trunk treatment. In distal RDN arm BP remained powerfully and significantly lowered both at 1 and 3 years post-procedure: −18.0 (95% CI −27.6; −8.5) and −16.9 (95% CI −27.3; −6.5) mmHg, 24h ambulatory systolic. During 1st year this potent BP lowering effect was accompanied by moderate eGFR decrease: −8.9 (95% CI −14.8; −3.1) ml/min/sq.m, however, this decrease was later reduced to non-significant −6.5 (95% CI −13.2; 0.3) ml/min/sq.m at 3 year post-procedure signaling some improvement in renal function after 1st year despite sustained strong BP lowering. In group of main trunk intervention BP only moderately decreased at 1 year −12.1 (95% CI −19.2; −5.0) mmHg, in parallel with small non-significant change in eGFR: −1.3 (95% CI −6.6; 4.0) ml/min/sq.m. Subsequently, BP lowering effect weakened and lost significance at 3 years post-procedure: −8.5 (95% CI −19.7; 2.2) mmHg. In contrast, eGFR continued to decline and reached significant −5.0 (95% CI −9.6; −0.3) ml/min/sq.m at the end of the study. Five patients developed new onset chronic kidney disease after main trunk RDN versus 3 patients – after distal RDN. The number of concomitant antihypertensive medications did not significantly changed in either group. Conclusion Our data demonstrate strong long-term BP lowering efficacy of distal RDN and, also, the potential of this procedure to prevent the decline of renal function in patients with resistant hypertension. Funding Acknowledgement Type of funding sources: None.

Objective To assess whether electrode temperature and impedance change that are typically monitored during radiofrequency renal denervation (RDN) for safety reason may also be used as measures of the procedural success of the intervention. Methods We conducted a prospective clinical study of the radiofrequency RDN in patients meeting criteria of true resistant hypertension. The RDN treatment included the trunk and major branches of the renal artery. To obtain simple easy-to-use electrophysiology measures of the procedural success of RDN we averaged the maximal values of the temperature and change of impedance across all single treatments with a full duration. Then we assessed the relation of the average change in impedance and average maximal electrode temperature during RDN to blood pressure (BP) lowering 6 month post-procedure using a linear regression analysis. Also, we compared the groups with “successful” and “unsuccessful” procedures according to whether the impedance decreased, on average, ≥10% during RDN, and, alternatively, on whether the average maximal temperature of the electrode was ≥50 C. Results Of 65 treated patients 52 with quality recordings of the electrophysiology parameters during RDN completed 6-month follow-up. The mean 24-h systolic BP decreased significantly after RDN by −14.3 mmHg [95% CI: −8.7; −19.9]. The BP lowering was positively and significantly related to the decrease in impedance during RDN, r=0.35, p=0.013 and to less extent to the maximal electrode temperature, r=0.29, p=0.044. The 10% average drop in impedance predicted -9.9 mmHg decrease in 24-h mean systolic BP. According to group analysis the decrease of mean 24-h systolic BP was powerful in those with average decrease in impedance ≥10% during RDN (“successful” procedure), but almost zero otherwise: −19.9 [95% CI: −13.7; −24.5] vs −0.5 [95% CI: −11.9; 12.9] mmHg, respectively (raw estimates), p=0.003. The difference in BP lowering was less pronounced and non-significant when the procedural “success” was defined according to the average maximal electrode temperature. Conclusions The impedance decrease during radiofrequency RDN treatment may be an effective criterion of the procedural success of the intervention. Guiding radiofrequency RDN by the impedance drop 10% or greater may significantly improve the efficacy of the procedure. Funding Acknowledgement Type of funding source: None

Background Experimental studies of radiofrequency renal denervation (RDN) have shown a strong relation of the depth of structural lesions and completeness of renal nerve injury to the relative drop in impedance during the treatment caused by the increased permeability of the cell membranes. Thus, the otherwise successful treatments but with low impedance drop may be, in fact, totally ineffective. Objective We assessed the relation between impedance drop during single radiofrequency treatments and local structural changes of vascular wall at the electrode positions using optical coherence tomography. Methods Optical coherence tomography of the treated segments was performed during radiofrequency RDN in 14 patients with resistant hypertension. The parameters of contrast injection depended on the position of the guiding catheter: for selective branch imaging 15 ml volume was injected at 8 ml/sec speed; otherwise 30 ml of contrast was injected at the speed 15 ml/sec to flush the whole renal artery. Automatic pullback of the sensor was done with the standard speed 20 mm/sec. In total, 423 mm of treated segments in 22 renal vessels (mostly distal branches) had sufficient quality of imaging and were studied for structural changes. Results There was almost no local structural changes of the arterial wall after the treatments with low impedance drop Conclusion Our study shows that variable efficacy of radiofrequency RDN may be explained by a significant proportion of the small-depth point treatments ineffective in terms of renal nerve injury, and, thereby, may be significantly improved if the procedure is guided by the impedance drop during the treatment. Funding Acknowledgement Type of funding source: None

The study aims at the investigation of the morphology and topography of the ternary Fe-Co-Mo electrolytic coatings. Compositions and morphology of the alloys are examined by scanning electron microscopy and X-ray analysis. Both topography and surface roughness are studied by an atomic force microscopy AFM using a NT–206 microscope. The Fe-Co-Mo coatings with an iron content of 47 at.%, cobalt 28 at.% and molybdenum 25 at.% are deposited on mild steel substrate by pulse electrolysis mode from citrate bath with the ratio of concentrations с(Fe 3+ ):с(Co 2+ ):с(MoO 4 2– ) = 2.5:3:1. Atomic force microscope analysis topography of the coatings Fe-Co-Mo at the scanning area 39.9×39.9 μm show that their surface is more developed compared with the substrate material. Moreover the AFM analysis of the coatings morphology and surface topography indicates the parts with a globular structure with an average conglomerates size of 0.2–0.5 μm and singly located sharp grains. Within the same scan area, sites with a developed surface are detected the topography of which is identical to the crystal structure of cobalt with the crystallite size in the range of 0.2–1.75 μm. The parameters R a and R q for parts with different morphology as well as average characteristics of coatings demonstrated the low roughness of the surface. Electrolytic deposits Fe-Co-Mo can be attributed to 8–9-th class of roughness. The study tested the magnetic behavior of Fe-Co-Mo coatings. The coercive force of 7–10 Oe confirms the soft magnetic properties of materials which in combination with high microhardness open prospects for usage of Fe-Co-Mo systems in the production of magnetic head elements for recording and reproducing information .

Background/Introduction Distal renal denervation (RD) of the segmental branches beyond the bifurcation of the main renal artery is considered more effective treatment than conventional RD of the trunk renal artery. Evidence accumulated over the last decade has shown that global longitudinal strain (GLS) from speckle-tracking analysis of 2-dimensional echocardiography may represent a sensitive parameter of the left ventricular (LV) dysfunction. Purpose We compared cardiac function, structure, and GLS parameters after distal and conventional RD in the double-blind randomized prospective study. Methods The study (NCT01499810) compromised 55 patients who met criteria for resistant hypertension and signed informed consent. Patients were randomized to either endovascular conventional RD of the main renal artery (group 1, n=27) or to distal treatment applied to the segmental branches after the bifurcation of the main renal artery (group 2, n=28). Parameters of GLS from speckle-tracking echocardiography, ejection fraction, thickness of the interventricular septum (IVS) and LV posterior wall (PW), as well as the parameters of the diastolic function of the heart were assessed at baseline and at 12-months follow-up. Reference echocardiographic values were adapted from the ASE/ESC guidelines. Baseline parameters of heart and drug intake did not significantly differ between patients at the time of randomization. Results Drug treatment consisted in combination therapy in the maximum tolerated doses. Patients used different types of drugs, but the number of drug classes did not significantly differ between groups (4.1 in group 1 vs. 4.2 in group 2). Reduction of systolic blood pressure was significantly greater after distal RD vs. conventional RD: −22.1 vs. −11.5 mm Hg, respectively (p Conclusion(s) Compared to conventional RD, distal RD treatment applied to the segmental branches beyond the bifurcation of the main renal artery significantly greater attenuated the LV wall thickness and the number of patients with diastolic dysfunction. At 12-month follow up, the global longitudinal LV function also improved in distal RD patients.

Effective treatment of uncontrolled hypertension using catheter-based percutaneous renal denervation may depend strongly on the anatomic strategy applied when delivering therapy. We hypothesized that concentering renal denervation treatment in the distal region of the artery would improve clinical response.We conducted a single-center, double-blind, randomized, controlled, and parallel group study (ClinicalTrials.gov NCT02667912). Fifty-one treatment-resistant hypertensive patients meeting guideline indications were randomized either to 'conventional' treatment restricted to the main renal artery (n = 26) or to 'distal' treatment applied mainly in the distal branches beyond the main bifurcation (n = 25). Computer-based treatment assignment was performed in the catheterization laboratory at the time of the procedure by the interventional radiologist and remained unknown to patients, investigators, and other outcomes assessors for the entire study period. Six months after randomization, the distal therapy group (n = 24) had a significantly greater decrease in the primary outcome, 24-h mean ambulatory SBP, as compared with the conventionally treated group (n = 21): -22.6 ± 20.0 vs -9.4 ± 18.7 mmHg; P less than 0.05. No major safety issues were observed in either group.Percutaneous renal denervation treatment was significantly less effective at lowering 24-h blood pressure in treatment-resistant hypertensive patients when therapy was applied conventionally in the trunk of renal artery as compared with when applied to distal segmental branches. This observation is in accordance with previous surgical and anatomical findings showing that most renal nerve fibers are distant from the lumen proximally and become available for endovascular treatment mainly in the distal portion of the vessel.

The condensation of dinitromethane with glyoxal has been investigated and it has been demonstrated that 1,1,4,4-tetranitro-2,3-butandiol, α-hydroxy-β,β-dinitropropionic acid or their mixture may be formed. Interaction of 1,1,4,4-tetranitro-2,3-butandiol or 1,4-dibromo-1,1,4,4-tetranitro-2,3-butanediol diacetates with sodium azide leads to bis(5-nitro-1,2,3-triazol-4-yl) via intermediate 1,1,4,4-tetranitro-1,3-butadiene.

Several chemoselective syntheses have been developed for 4-nitro-1,2,3-triazoles from sodium azide and gem-dinitroethylenes prepared from readily available transformation products of dinitroacetic acid ester: N-(β,β-dinitroethyl)-N,N-dialkylamines, 2,2-dinitroethanol acetate, a mixture of dinitroacetic acid ester with aliphatic aldehydes, or 1,1,1-trinitroalkanes. Hitherto-unknown 4-nitro-5-amino- and 4,5-dinitro-1,2,3-triazoles have been synthesized via successive transformations of the CH3 groups in 5-nitro-4-methyltriazole. Nitration of 4-nitro-1,2,3-triazole with nitronium fluoroborate or acetyl nitrate gave an unknown 2,4-dinitro-1,2,3-triazole.

Exposure of a small skin area (400 cm2) of volunteers to visible incoherent polarized (VIP) light (400 - 2000 nm) in therapeutic doses is accompanied by rapid appearance in the circulating blood of soluble factors able to restore proliferation of X-ray-damaged autologous lymphocytes and to decrease frequency of chromosome breaks. The appearance of a such activity in blood can also be induced without skin irradiation, by in vitro modeling of mixing in the circulation of a small amount of transcutaneously VIP- irradiated blood with the intact blood (one volume of the directly VIP-irradiated blood was added to 10 volumes of the intact blood). Hence, the blood (not the skin) is a major source of the active factors. The data obtained indicate a possibility of release of them from photomodified platelets; moreover, the activity restoring chromosome structure in X- damaged cells has been found in the platelet-derived growth factor and epidermal growth factor (which are known to be associated with platelets) when they were added to physiological concentrations to the culture medium. We assume that activation of cell proliferation based on the effective repair of DNA damaged in situ by endogenous and exogenous factors could be one of the mechanisms of photostimulation of wound healing.© (1998) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Hydrogen halides (HCl and HF) react with α-polynitroalkylsulfides and α-polynitroalkylselenides as electrophilic or as nucleophilic reagents depending on the conditons, forming accordingly products of electrophilic or nucleophilic substitution at the α-carbon atom. In contrast to this, halogen ions (Cl−, F−) always bond to the α-carbon. The use of dipolar aprotic solvents and activators (Lewis acids or strong mineral acids) facilitates the formation of products of nucleophilic substitution at the α-carbon.

A modified scheme was proposed for the synthesis of 1-benzyl-4, 5-diamino-1,2,3-triazole involving the use of high pressure (5–6 kbar) which permits a significant increase in the yield of this product.