A NEW APPROACH TO IMMUNOSUPPRESSIVE THERAPY IN PATIENTS WITH GLOMERULONEPHRITIS WITH NEPHROTIC SYNDROME

Glomerulonephritis (GN) is a group of immuno–inflammatory kidney diseases with predominant glomerular lesions that are difficult to treat.  The greatest problems are caused by the treatment of GN with nephrotic syndrome, which often has a recurrent course. The aim of the research was to study the effectiveness of the inclusion of recombinant interleukin–2 (rIL-2) in the treatment of GN with nephrotic syndrome.   62 patients with a nephrotic form of primary GN with frequent relapses, hospitalized in the nephrology department, were selected for the research. The age of patients is from 18 to 65 years. The patients underwent a standard examination, as well as immunological studies before the appointment of anti-relapse treatment and 12 months after the start of the treatment: immunophenotyping of lymphocytes with identification of T- and B-lymphocytes, immunoregulatory and activated subpopulations of T–lymphocytes, determination of urine levels of immunoglobulins IgM, IgG, IgA by immunoturbidimetric method, proinflammatory cytokines - IL-1ß, IL-8, IL-17A and anti-inflammatory cytokine IL-10 by enzyme immunoassay. As a result of the research, the examined patients showed an increase in the content of T-helper, activated T-lymphocytes (CD8+HLA-DR+CD45+, CD3+CD8brightCD38+) against the background of a decrease in the number of Treg cells and an increased content of proinflammatory cytokines IL-1ß, IL-8, IL-17A and immunoglobulins of all three classes in the urine.The cohort of patients with GN selected for the research was divided into two groups (the main group and the compared group). In addition to nephroprotective and steroid therapy, the treatment regimen of patients in the main group included rIL-2 and in the compared group – Cyclophosphane. Regardless of the method used, as a result of the treatment, the levels of protein, IgG and IL-17A in the urine decreased relative to the initial values, the content of B cells and HLA-DR+ -cytotoxic T-lymphocytes in the blood decreased. The noted changes were more pronounced in the main group of patients and 12 months after the start of the treatment, the listed indicators of the main group began to differ significantly from those in the compared group. Serum creatinine levels, the number of T-helper cells and Treg cells, the level of IL-1ß in urine did not undergo significant changes in the compared group, while in the main group of patients there was a decrease in serum creatinine and IL-1ß in urine, decreased the number of T-helpers and increased the number of Treg cells. In the main group of patients treated with rIL-2, the average number of relapses per year decreased by 4 times, while in the compared group only by 1.2 times.  Low-dose therapy with rIL-2 can be considered as an effective and safe alternative to traditional immunosuppressive therapy and as a new option for targeted treatment of GN with frequent recurrence of nephrotic syndrome

Biomarker Associations with Efficacy of Abiraterone Acetate and Exemestane in Postmenopausal Patients with Estrogen Receptor–Positive Metastatic Breast Cancer

Purpose: Abiraterone may suppress androgens that stimulate breast cancer growth. We conducted a biomarker analysis of circulating tumor cells (CTCs), formalin-fixed paraffin-embedded tissues (FFPETs), and serum samples from postmenopausal estrogen receptor (ER)þ breast cancer patients to identify subgroups with differential abiraterone sensitivity. Methods: Patients (randomized 1:1:1) were treated with 1,000 mg/d abiraterone acetate þ 5 mg/d prednisone (AA), AA þ 25 mg/d exemestane (AAE), or exemestane. The biomarker population included treated patients (n = 293). The CTC population included patients with 3 baseline CTCs (n = 104). Biomarker [e.g., androgen receptor (AR), ER, Ki-67, CYP17] expression was evaluated. Cox regression stratified by prior therapies in the metastatic setting (0/1 vs. 2) and setting of letrozole/anastrozole (adjuvant vs. metastatic) was used to assess biomarker associations with progression-free survival (PFS). Results: Serum testosterone and estrogenlevels werelowered and progesterone increased with AA. Baseline AR or ER expression was not associated with PFS in CTCs or FFPETs for AAE versus exemestane, but dual positivity of AR and ER expression was associated with improved PFS [HR, 0.41; 95% confidence interval (CI), 0.16–1.07; P = 0.070]. For AR expression in FFPETs obtained <1 year prior to first dose (n = 67), a trend for improved PFS was noted for AAE versus exemestane (HR, 0.56; 95% CI, 0.24–1.33; P = 0.19). Conclusions: An AA pharmacodynamic effect was shown by decreased serum androgen and estrogen levels and increased progesterone. AR and ER dual expression in CTCs and newly obtained FFPETs may predict AA sensitivity

Disturbed Lands Reclamation Statement in the Territory of the Mokhovsky Coal Mine

The national project “Ecology” sets to bring up to date the ecological policy of the environment-geared laws of the Russian Federation which must preserve biodiversity and afford the involvement of all participants in the process. Revegetation, as part of the program, sets to restore disturbed lands to a condition suitable for their use in the national economy and prevent their anthropogenic impact on the adjacent areas. The quality of reclamation works is not always at an adequate level, which creates difficulties in the remediated lands development. This is a consequence of insufficient information at the design stage, specifically data on the composition and properties of the soil cover and worked-out rock mass, lack of special technical support for the implementation of remediation measures at the proper level, the landscape of the deposit is not taken into account during the work with disturbed soils. Intensive use of the studied territories of the Sartakinsky, Karakansky and Mokhovsky fields both in agricultural and mining industries led to changes in the natural biocenos. This paper presents the study of soil-agrochemical characteristics (granulometric and structural structure of soil, the humus content, hydrogen index, the content of food elements, hydrolytic acidity, the sum of absorbed bases, absorption capacity, etc.) on different genetic horizons of zonal soils of Mokhovsky coal mine, and specifically unbroken soils of Mokhovsky, Sartakinsky and Karakansky fields on possibility of their use at carrying out of biological reclamation