[Herpesviruses in patients after renal transplantation].

AIM: To estimate graft function after kidney transplantation during active herpesviruses or superinfection Materials and methods. The study included 32 patients (men 21, women 11) with end-stage chronic kidney disease. The median age was 43 years. Cytomegalovirus (CMV), EpsteinBarr virus (EBV) and human herpes virus 6 (HHV-6) DNAs were screened by RT-PCR in the donor's transplant biopsy, and recipients peripheral blood and urine after kidney transplantation (KT) on 0, 1, 2, 4, 6, 12 months. Antiviral antibodies (IgM and IgG) were also screened by Enzyme-linked immunoassay analysis (ELISA) along with PCR. The 500 or less copies of viral DNA per 105 nuclear cells or 1 ml of urine was considered as low, more than 1000 copies high. RESULTS: On the first month after KT CMV DNA was detected in 50% of pts., EBV DNA in 40% and HHV-6 DNA in 33%. During first year after KT two or three viruses simultaneously were found in 12 recipients: CMV, EBV, and HHV-6 were detected in 5 recipients; CMV and EBV in 4 patients; CMV and HHV-6 in 2 pts; EBV and HHV-6 in 1 pt. Graft dysfunction was observed in 9 patients with a high concentration of viral DNA of one, two or three viruses simultaneously. An upraise of the concentration of virus DNA (CMV, EBV and HHV 6) was detected primarily in the urine, while in the blood its concentration was less than 500 cop or undetectable. Renal dysfunction was not observed on the background of low concentrations of viral DNA in urine and blood. However, with an increase of DNA concentration, an impaired graft function in 8 of 12 patients appeared. Low viral DNA level proved to be a background for another virus activation or bacterial/fungal superinfection. CONCLUSION: Graft dysfunction occurs at high viral DNA levels detection during mono-or superinfection. Low viral load can serve as a background for another virus activation and/or bacterial/fungal superinfection.

[Simultaneous laparoscopic bilateral nephrectomy as a preparation for kidney transplantation in patients with autosomal dominant polycystic kidney disease].

AIM: to study the possibility and safety of performing simultaneous bilateral laparoscopic nephrectomy in symptomatic patients with autosomal dominant polycystic kidney disease (ADPKD) as a preparation for kidney transplantation. MATERIALS AND METHODS: From May 2018 to September 2019, six symptomatic patients with end-stage renal disease caused by ADPKD, who had hemodialysis, underwent simultaneous bilateral laparoscopic nephrectomy. The mean vertical kidney size according to CT data was 211.67+/-37.15 mm, the mean horizontal size was 145.36+/-19.53 mm. In 5 cases, the hand-assisted procedure was performed. RESULTS: The average duration of the procedure was 225.1+/-40.37 minutes. Postoperative complications were recorded in 2 (33.2%) patients. The average length of stay was 8.83+/-2.13 days. There were no clinical manifestations of adrenal insufficiency. All patients are alive. In two patients, cadaveric kidney transplantation was performed after laparoscopic bilateral nephrectomy. CONCLUSION: Laparoscopic bilateral nephrectomy in patients with chronic renal failure associated with ADPKD is feasible, safe and is associated with a short length of stay. This procedure improves the quality of life of patients and facilitates subsequent kidney transplantation.

[EBV-positive central nervous system lymphoproliferative disease associated with immunosuppression after organ transplantation: Long-term remission without chemotherapy]. / Limfoproliferativnoe EBV-pozitivnoe zabolevanie s porazheniem tsentral'noi nervnoi sistemy, assotsiirovannoe s immunosupressiei posle organnoi transplantatsii: dlitel'naia remissiia posle khimioterapevticheskogo lecheniia.

Primary central nervous system (CNS) lymphomas account for 13-20% of the posttransplant lymphoproliferative disorders (PTLD) and rank among the most aggressive conditions. Reduction of immunosuppressive therapy should be mandatory to treat PTLD, but this is rarely used as the only therapy option. Chemotherapy regimens for PTLD involving the CNS most commonly include high-dose rituximab and high-dose methotrexate and/or cytarabine. The efficiency only of discontinuation of immunosuppressive therapy for PTLD does not exceed 5-10%, but there are no literature data on its efficiency for PTLD involving the CNS. The paper describes a clinical case of achieving long-term remission in a female patient with Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma involving the central nervous system, associated with immunosuppression after kidney transplantation from a related donor, in the absence of chemotherapy during immunosuppressive therapy discontinuation and transplantectomy.

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (CC-RCC) is the most lethal of all genitourinary cancers. The functional loss of the von Hippel-Lindau (VHL) gene occurs in 90% of CC-RCC, driving cancer progression. The objective of this study was to identify chemical compounds that are synthetically lethal with VHL deficiency in CC-RCC. An annotated chemical library, the library of pharmacologically active compounds (LOPAC), was screened in parallel on VHL-deficient RCC4 cells and RCC4VHL cells with re-introduced VHL. The ROCK inhibitor, Y-27632, was identified and validated for selective targeting of VHL-deficient CC-RCC in multiple genetic backgrounds by clonogenic assays. Downregulation of ROCK1 by small interfering RNA (siRNA) selectively reduced the colony-forming ability of VHL-deficient CC-RCC, thus mimicking the effect of Y-27632 treatment, whereas downregulation of ROCK2 had no effect. In addition, two other ROCK inhibitors, RKI 1447 and GSK 429286, selectively targeted VHL-deficient CC-RCC. CC-RCC treatment with ROCK inhibitors is cytotoxic and cytostatic based on bromodeoxyuridine (BrdU) assay, propidium iodide (PI) staining and growth curves, and blocks cell migration based on transwell assay. On the one hand, knockdown of hypoxia-inducible factor (HIF) ß in the VHL-deficient CC-RCC had a protective effect against Y-27632 treatment, mimicking VHL reintroduction. On the other hand, CC-RCCVHL cells were sensitized to Y-27632 treatment in hypoxia (2% O2). These results suggest that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC.

[Some aspects of clinical kidney transplantation from marginal cadaver donors].

The results of kidney transplantation from marginal donors were compared in two groups of patients who had received high-dose dopamine (10-35 mcg/kg/min). Group 1 consisted of 652 patients with grafts from stable donors given dopamine in doses from 0 to 10 mcg/kg/min, group 2--of 112 patients with grafts from donors given high-dose dopamine (10-35 mcg/kg/min). Mean follow-up was 52 +/- 19 months. The following parameters were compared: percent of delayed graft function, primary nonfunction transplants, acute graft rejection, graft survival, biopsy-proven ischemic-reperfusion graft injury. The rate of delayed graft function, primary non function transplants was higher in group 2 (59 and 51%, 7 and 4%, respectively). Five-year survival of the transplants and recipients was less in group 2 (68 vs. 73% and 78 vs. 71%, respectively, p < 0.05). At the end of the follow-up the level of serum creatinine was 151 +/- 50 in group 1 and 165 +/- 80 mcmol/l in group 2 (p > 0.05). Thus, despite worse results in group 2, kidney transplantation from such marginal donors can be used.

Coherent synchrobetatron beam-beam modes: experiment and simulation.

Analytic calculation and numerical simulations reveal a multiline structure in the spectrum of coherent dipole oscillations in the colliding beam system due to coupled synchrobetatron beam-beam modes. The model employed in the analysis involves linearization of the beam-beam kick and takes into account the fact that the length of the colliding bunches is finite. In the present paper, we discuss the behavior of the synchrobetatron beam-beam modes, obtained both analytically and numerically, and compare it with the experimental results for the VEPP-2M collider. A particular case of the betatron tune close to the half-integer resonance is considered on the basis of the presented models.

Direct measurement of the phi(1020) leptonic branching ratio.

The process e(+)e(-)-->mu(+)mu(-) has been studied by the SND detector at the VEPP-2M e(+)e(-) collider in the phi(1020)-resonance energy region. The measured effective phi meson leptonic branching ratio B(phi-->l(+)l(-)) identical with square root of B(phi-->e(+)e(-))B(phi-->mu(+)mu(-))] = (2.89 +/- 0.10 +/- 0.06) x 10(-4) agrees well with the Particle Data Group value B(phi-->e(+)e(-)) = (2.91 +/- 0.07) x 10(-4), confirming mu-e universality. Without additional assumption of mu-e universality the branching ratio B(phi-->mu(+)mu(-)) = (2.87 +/- 0.20 +/- 0.14) x 10(-4) was obtained.

Experiments with longitudinally polarized electrons in a storage ring using a siberian snake

We report on first measurements with polarized electrons stored in a medium-energy ring and with a polarized internal target. Polarized electrons were injected at 442 MeV (653 MeV), and a partial (full) Siberian snake was employed to preserve the polarization. Longitudinal polarization at the interaction point and polarization lifetime of the stored electrons were determined with laser backscattering. Spin observables were measured for electrodisintegration of polarized 3He, with simultaneous detection of scattered electrons, protons, neutrons, deuterons, and 3He nuclei, over a large phase space.

[Use of plasmapheresis in intensive therapy of acute steroid-resistant rejection reaction in renal transplants]. / Primenenie plazmafereza v intensivnoi terapii ostroi steroidrezistentnoi reaktsii ottorzheniia renal'nykh transplantatov.

For many years the treatment of steroid-resistant rejection (SSR) remains a common problem od renal transplantation. We used plasmapheresis (PPH) in the treatment of SRR in 29 renal transplant recipients. All patients had progressive deterioration of renal function and compatible biopsy histology. The first group (15 patients) was administered PPH with methylprednisolone (MP). The second group (14 patients) was treated by intravenous MP. There was no significant difference in the time of beginning and severity of rejection. In the PPH group the results were better: a significant increase in SSR reversion was attained (73.3%) in comparison with the control (42.8%), the number of grafts lost during the first year was less (26.7 versus 57.2%). Better results were observed in patients with high levels of serum anti-HLA antibodies. Their transplants functioned well during 12 months after SSR. Hence, PPH can be used in patients with SSR with high levels of anti-HLA antibodies.