Aim . The aim of our study was to investigate the influence of polymorphic markers of CYP3A4*22 CYP3A4*22 ( c.522-191C>T, rs35599367 ), CYP3A5*3 ( c.219 237A>G, rs776746 ), ABCB1 rs1045642 ( ...c.3435T>C ) and rs4148738 ( c.2692-2236C>T ) genes on the plasma concentration of apixaban, on changes in prothrombin time (PT), activated partial thromboplastin time (APTT), and bleeding development in patients taking apixaban. Material and methods. The study included 108 patients with non-valvular atrial fibrillation and deep vein thrombosis receiving apixaban in therapeutic doses. Genotyping was performed by real-time polymerase chain reaction. Apixaban concentrations were measured using an electrospray ionization mass spectrometer in positive ionization mode. Because the daily dose of apixaban was different (5, 10, and 20 mg daily), the residual equilibrium concentration (Cmin,ss) of apixaban was adjusted relative to the daily drug dose (Cmin,ss/D). PT and APTT were determined using an automatic coagulometer analyzer Destiny Max (Tcoag, Ireland). Statistical processing was performed in SPSS Statistics 20.0 program. Results . We found that patients with CT ABCB1 ( rs4148738 ) C>T genotype had higher Cmin,ss /D value than patients with TT genotype (6.23 4;13 vs 5.77 4;17, p=0.018). No statistically significant associations were found between carriage of CYP3A4*22 (rs35599367) C>T, CYP3A5*3 A>G, ABCB1 (rs1045642) C>T gene polymorphisms and Cmin,ss /D value of apixaban. Also, there was no significant effect of carrying polymorphisms rs35599367, rs776746, rs4148738,rs4148642, and the above genes on the risks of hemorrhagic complications. However, the influence of ABCB1 (rs1045642) C>T polymorphism on the PT value was found ( TT ABCB1 ( rs1045642 ) C>T genotype carriers the CT value wassignificantly higher than in CT genotype (17.0 40;112 vs. 14.9 35;132) p=0.044). Conclusion . It was found that the Cmin,ss /D value was higher in patients with CT ABCB1 (rs4148738) C>T genotype than in patients with TT genotype. At the same time, carriage of polymorphisms of CYP3A4*22 (rs35599367) C>T , CYP3A5*3 A>G , ABCB1 (rs1045642) C>T genes did not affect the pharmacokinetics of apixaban and the risk of bleeding. We also identified the effect of ABCB1 (rs1045642) C>T gene polymorphism on the PT value.
Introduction.
Insufficient sensitivity and specificity of existing methods for diagnosing urethral stricture require more accurate methods, which may include magnetic resonance imaging (MRI).
...Objective.
To study the possibilities of MRI to assess the extent of bulbous urethral stricture and spongiofibrosis grade.
Materials & methods
. The study included six men with bulbous urethral stricture, who underwent non-transecting anastomotic urethroplasty via ventral approach. Before surgery, all patients underwent retrograde urethrography according to the standard method and urethral MRI according to their own method, and their data were compared with intraoperative parameters.
Results.
The length of the stricture according to retrograde urethrography averaged 11.5 ± 6.3 mm, MRI — 17.8 ± 10.9 mm, intraoperative measurement — 16.7 ± 9.1 mm. There was a significant difference between the mean length of the stricture according to retrograde urethrography and the mean length according to intraoperative data (p = 0.028). There was no significant difference between the mean stricture length according to MRI data and the mean stricture length according to intraoperative data (p = 0.085). The length of spongiofibrosis according to MRI was 15.8 ± 13.6 mm on average, and 16.7 ± 12.9 mm according to intraoperative measurements. There was no significant difference between the average length of spongiofibrosis according to MRI and the average length according to intraoperative data (p = 0.092).
Conclusions.
MRI provides information comparable to intraoperative data on the extent of urethral stricture, location, and spongiofibrosis grade.
The effective sorption method for melanin isolation and purification from fermentation solutions of
Bacillus thuringiensis
serovar
galleriae
K1 has been elaborated, the principle process flowsheet is ...presented. The identification of obtained pigment with the samples of natural and synthetic melanin was done by IR-spectroscopy, and the intensity ratio of optical absorption at 650 and 500 nm allows to refer the isolated melanin to eumelanin class. By thermal treatment it was determined, that melanin’s amorphous sediment is steady at up to 120°C) the concentration of paramagnetic centers being changed from 0.053 × 10
18
spin/g (48°C) to 0.25 × 10
18
spin/g (120°C). The rising of the temperature of treatment up to 210°C brings to substantial increase of the concentration of unpaired electrons, and at 280°C its sharp growth is observed. At 350°C growth stops, then sharp decrease is observed. The obtained results were confirmed by methods of IR spectroscopy and derivatographic analysis.
Aim
. To investigate the effect of ABCB1 gene carriage and interdrug interactions on apixaban pharmacokinetics and clinical outcomes in patients with atrial fibrillation and deep vein thrombosis.
...Material and methods
. Patients hospitalized at Yudin State Clinical Hospital participated in the study. A total of 92 patients (50 patients received apixaban and 42 – rivaroxaban) with non-valvular atrial fibrillation and deep vein thrombosis were included. Genotyping was performed by real-time polymerase chain reaction. Direct oral anticoagulants concentrations were measured using an electrospray ionization mass spectrometer in positive ionization mode.
Results
. In our study we found that in patients carrying the CT+TT ABCB1 (rs4148738) C>T genotype encoding the carrier protein (P-gp), the plasma concentration of rivaroxaban was statistically significantly higher p= 0.026. In addition, we found that patients taking apixaban together with a CYP3A4/P-gp inhibitor were 3.5 times more likely to have hemorrhagic complications than those without inhibitors p = 0.004.
Conclusion
. Our study revealed that the plasma concentration of rivaroxaban was higher in patients carrying the ABCB1 (rs4148738) C>T polymorphism T allele. And patients taking apixaban together with CYP3A4/P-gp inhibitor had higher risk of hemorrhagic complications in comparison with patients not taking such drugs. Further studies are needed on the influence of pharmacogenetics and pharmacokinetics on the safety and efficacy profile of apixaban and rivaroxaban, taking into account the trend of systemic approach to optimization of anticoagulant therapy of direct oral anticoagulants based on pharmacokinetic, pharmacogenetic biomarkers.
In this paper the stability of a rectangular plate in a supersonic flow in the presence of a temperature field, inhomogeneous across the thickness, is investigated. The temperature field ...inhomogeneity across the thickness leads to the buckling of the plate, and this buckled state is considered as the initial unperturbed state. Governing equations and boundary conditions are obtained for the unperturbed and perturbed states. The corresponding linear analysis leads to the stability conditions of unperturbed state of the thermal-fluid-elastic structure system. The stability boundary is determined as function of the flow speed, the middle surface temperature, and the temperature gradient normal to the plane. It is shown that the temperature field and the flow speed have interdependencies and regulate the stability process. It is also shown that the temperature field significantly affects the critical flutter speed. The nonlinear stability is also investigated, both cubic geometrical non-linearity and aerodynamic non-linearity of both quadratic and cubic types are considered. Compared with the case without thermal field, this study shows for the first time the existence of new types of "amplitude-frequency" limit cycles.
In this review we present comparison of pharmacokinetics of novel oral anticoagulants (NOAC) dabigatran, rivaroxaban, apixaban, and edoxaban, principles of selection of a regimen of their dosing for ...phase III clinical trials in patients with atrial fibrillation. Multiplicity of administration of NOAC depends on required level of anticoagulation, ability to maintain anticoagulation for 24 hours, relationship between minimal and maximal levels of equilibrium concentrations, efficacy and safety. Once a day administration of some drugs of this group is reasonable from positions of clinical pharmacology. It can provide not only better adherence to treatment but greater safety relative to development of bleeding.
Background. The first day-care hospital (DCH) in the Russian Federation with 30 beds was established in the departments of general surgery, urology, and gynecology of the Botkin Hospital in 2016 in ...Moscow.
Aim. To analyze the six-year experience of the gynecological DCH based on the Botkin Hospital.
Materials and methods. The six-year experience (20162021) of the gynecological DCH based on the Botkin Hospital was analyzed.
Results. The number of patients treated in the DCH increased progressively from 2016 to 2019. Due to the gain in the experience of DCH, patients with a broader spectrum of diseases can receive care in DCH settings, the number of hospitalized patients with a higher anesthetic risk has increased, and the proportion of patients over 65 years of age has also increased.
Conclusion. Analysis of the activities of the DCH based on the Botkin Hospital showed that the pilot project can be considered successful due to good clinical and economic indicators. This activity format can be widely implemented, and it is optimal to establish such hospitals in multidisciplinary clinics.
A technique is proposed for estimating the signal-to-noise ratio in fiber-optic transmission systems with spectral multiplexing, multiplexing of orthogonal and non-orthogonal channel subcarriers in ...the case of cross-channel interference due to four-wave mixing in the fiber. It is shown that it is possible to estimate the signal-to-noise ratio of a system with any number of sub-carriers of channels from the results of measurements of this ratio for a four-channel transmission system.
To determine the most feasible treatment strategy for malignant colonic obstruction.
There were 427 patients with malignant colonic obstruction who were hospitalized for emergency indications. 30 of ...them were treated with medical therapy; 286 - underwent acute resection; 43 - stoma construction; 68 - stents deployment. 64 out of 427 patients underwent elective restorative/radical surgery and radio- or chemotherapy in 1-8 months. 3-year Kaplan-Meier survival was assessed.
Complications occurred in 58% after acute resection and in 32.6% and 8.8% after stoma and stent deployment, respectively. Postoperative mortality was significantly lower after palliative surgery (stent or stoma) compared with acute resection: 2.9%, 18.6%, 29.37%, respectively. 3-year survival was higher after elective resections compared with emergency resection group: 0,81 и 0,68 respectively.
Bridging strategy (stoma/stents) may be a valid alternative in some patients with malignant colonic obstruction due to significantly reduced postoperative mortality. Acute surgery for malignant colonic obstruction should only be carried out by appropriately trained surgeons at multi-field hospital.
Ability for selective extraction of copper and zinc from zinc concentrate using association of chemolithotrophic bacteria was investigated. In the presence of bacterial association, the rate of ...leaching of zinc, copper, and iron was increased 3-fold, 4–5-fold, and 2-fold, respectively. The results indicate the maximum dissolution rate for zinc, then followed by copperand iron. It was revealed that addition of Fe
3+
2 g/l resulted in reduction of iron leaching and in 3-fold increase of leaching rate of copper at constant dissolution rate of mineral zinc. It is suggested that the intensification of copper leaching is connected with the activity of sulfur-oxidizing bacteria able to activate the mineral surface via elimination of passivation layer of elemental sulfur. It was concluded that sulfur-oxidizing bacteria play a significant role in copper leaching from zinc concentrate. A unique strain of mesophile sulfur-oxidizing bacteria was isolated from leaching pulp of zinc concentrate; in the perspective, it may serve as efficient candidate for performing of selective extraction of copper from zinc concentrate.
