Atherosclerosis of brachiocephalic arteries and arterial stiffness in patients with breast cancer.

Cardiovascular toxicity is one of the important problems of clinical oncology. Atherosclerosis progression was demonstrated in patients with cancer and chemotherapy.Te aim - to evaluate the vascular wall characteristics and to determine the predictors of AS of brachiocephalic arteries progression during anticancer therapy in patients with breast cancer. METHODS: Te study involved 43 patients with newly diagnosed breast cancer (BC) (II-III stage) with overexpression of HER2; median age 50 (40;57) years. All patients underwent neoadjuvant drug therapy with antracyclines, taxanes and trastuzumab followed by surgery, radiation and hormone therapy according to the indications. Before anticancer therapy the general clinical examination was conducted and lipid profle, plasma lipoprotein (a) [Lp(a)] level, titres of autoantibodies IgM and IgG to lipoproteins and their oxidized derivatives were estimated. Te vascular wall stiffness (pulse wave velocity on the carotid-femoral (PWVcf) and shoulder-ankle (PWVsa) segments, the central pressure, carotid intima-media thickness (CIMT) and the degree of stenosis of the brachiocephalic arteries) were determined at baseline and at each stage of anticancer therapy. Te atherosclerosis progression was determined if the new stenosis (≥15%) or increase of preexisting stenosis (≥5%) were revealed; CIMT increase ≥ 0.1 mm. Te parameters of cellular immunity (peripheral blood lymphocyte phenotyping via direct immunofluorescence and flow cytometry), lipid spectrum parameters, serum concentration of Lp (a), autoantibodies IgM and IgG against lipoproteins and their oxidized derivatives, as well as PWVсf and PWVsa were assessed in 17 BC patients before the onset of neoadjuvant therapy and in 20 healthy women. RESULTS: BC patients and healthy women were comparable in traditional cardiovascular risk factors but differed in PWVsa and PWVcf levels (p<0.05). In BC patients the activation of T-cell immunity with the stimulation of both subpopulations with pro-inflammatory and regulatory properties was observed (p<0.05). Te direct correlations between the content of activated T-lymphocytes (T-act), T-helpers (T) 1 and PWVsa (p<0.05), as well as T-act, T1 and T2 and PWVcf (p<0.05) were revealed in the general group. Te decrease of systolic blood pressure (SBP), central SBP (SBPc), central diastolic blood pressure (DBPc), PWVcf and PWVsa levels accompanied with a temporary heart rate increase were observed during anticancer therapy; SBP, SBPc, PWVcf levels restored by the end of the follow-up period. Te CIMT increase was detected in 22 (51%), and the atherosclerosis progression in 26 (60%) BC patients during anticancer therapy. Lp (a) level above 12.8 mg/dl was associated with CIMT increase (p<0.05). Age > 48 years and radiation therapy were risk factors for CIMT increase and atherosclerosis progression (p<0.05), respectively. CONCLUSIONS: Te vascular stiffness is increased in BC patients, which is associated with the activation of effector subpopulations of T-lymphocytes and the elevation of circulating level of both pro-atherogenic and anti-atherogenic T-cells. Te level of Lp (a) above 12.8 mg/dl is associated with atherosclerosis progression, which requires further research. Age and radiation therapy are the risk factors for atherosclerosis progression during anticancer therapy.

[The effect of high-molecular weight chitosans on the antioxidant and immune systems of the honeybee].

High-molecular weight chitosan (200 kDa, 75% deacetylated) and N-succinoyl chitosan (300 kDa, 75% deacetylated) were shown to have a preadaptive effect and increase the lifespan of honeybees due to the induction of protective antioxidant and immune mechanisms. Chitosan with a molecular weight of 200 kDa had a fungistatic effect on a pathogenic fungus that causes ascospherosis, a disease of bee larvae and pupae.

Analysis of circulating tumor cells in patients with triple negative breast cancer during preoperative chemotherapy.

The presence of circulating tumor cells in the blood of patients with triple negative breast cancer (early and locally advanced cancer) before and after preoperative chemotherapy was assessed using expression markers. Before therapy, circulating tumor cells were detected in 5 of 13 (38%) patients with early cancer and in 7 of 17 (41.2%) patients with locally advanced cancer. After therapy, the circulating immune cells were detected in one patient with locally advanced cancer, who had no circulating cells before therapy. The tumor was resistant to chemotherapy and the disease progressed. The detected circulating tumor cells were HER-2-positive, while the primary tumor was HER-2-negative. It was concluded that the circulating immune cells can be a potential marker of the efficiency of therapy and predictors of the disease course, while their phenotype can differ from the phenotype of the primary tumor.

[The effect of adaptation to the periodic action of hypoxia on the indices of the immunity system and on the course of allergic diseases]. / Vliianie adaptatsii k periodicheskomu deistviiu gipoksii na pokazateli sistemy immuniteta i techenie nekotorykh allergicheskikh zabolevanii.

The authors studied the effect of adaptation to periodical exposure to hypoxia on the organism's immune status and the values of neurohumoral regulation in children with bronchial asthma and adults suffering from allergic dermatoses and autoimmune thyroiditis. It was found that adaptation facilitated normalization of humoral values of immunity in allergic and autoimmune disorders (the content of serum immunoglobulins increased while the level of circulating immune complexes reduced) and was attended by a stable therapeutic effect. The revealed changes of the immune values occurred in increase of the reserve potency of the hypothalamo-hypophyseal-adrenal and sympathoadrenal systems and reduction of the blood histamine level.

[Experimental basis of a new principle for purifying antilymphocyte serum]. / Eksperimental'noe obosnovanie novogo printsipa ochistki antilimfotsitarnoi syvorotki.

The experiment has demonstrated a higher immunosuppressive activity of antilymphocytic serum, purified with the use of a placental immunoadsorbent, in comparison with the preparations exhausted by red blood cells and plasma. This fact experimentally substantiates the use of the immunoadsorbent prepared from human placenta for the purification of antilymphocytic immunoglobin preparations. Rabbit immunoglobulin to human lymphocytes obtained by means of the new method corresponds to the technical specifications for such preparations and is less reactogenic than antilymphocytic immunoglobulin prepared in accordance with the routine technology.

[Immunological indices in acquired heart defects after heart valve replacement with bioprostheses]. / Immunologicheskie pokazateli u bol'nykh s priobretennymi porokami serdtsa posle zameny klapanov serdtsa bioprotezami.

The indices of cellular and humoral immunity were studied in 46 patients with heart diseases of rheumatic origin prior to and alter operation for replacement of the heart valves with synthetic prostheses (in 19) and pig aortic valves treated with glutaraldehyde and methaperiodate solutions ater Karpantje (in 27). The indirect fluorescence method and the leukocyte migration inhibition test to the myocardial antigens showed that the operation for valve prosthetics causes an increase in the content of antibodies and activation of specific leukocyte sensitization to the antigens of the myocardium and heart valves. These changes do not depend on the type of the valve prosthesis and are normalized by the 6th month. The activation of immunological processes encountered in some patients in late periods after the operation (1-8 years) corresponded to an aggravation of their clinical condition which in most cases was not associated with impaired functioning of the biological prosthesis. The implantation of xenogenous valve prostheses treated by Karpantje's method did not cause the development of immunological processes which could have induced destruction of the prostheses.

[Suppression of humoral antibody synthesis on exposure to hyperbaric oxygenation]. / Podavlenie sinteza gumoral'nykh antitel pod deistviem giperbaricheskoi oksigenatsii.

The influence of hyperbaric oxygenation (HBO) on the immune response in mice, immunized intraperitoneally with sheep red blood cells, was studied. HBO was shown to reduce hemagglutinin and hemolysin titres in peripheral blood as well as to decrease the amount of antibody-forming cells in the spleen. The most pronounced immunodepressant HBO effect is seen when hyperbaric oxygenation is carried out under toxic conditions before immunization of the animals with low antigen doses. Relationship is shown between the immunodepressant HBO effect and reduced leucocyte and lymphocyte counts in peripheral blood of the animals.

[Enhancement phenomenon in mice with a heterotopic heart transplant]. / Fenomen usileniia u myshei s geterotopicheskim transplantatom serdtsa.

A possibility of enhancement induction with the aid of a preparation of lymphocyte membranes of the spleen of donor specificity in its combination with antimouse horse globulin was studied on mice with heterotopic graft of the heart. As shown, in recipients with prolongation of the graft electrical activity lymphocytes retained their reaction to donor antigens, whereas the blood serum produced an enhancement effect in its administration to syngeneic recipients.

[Lymphocyte reactions at early periods after heart transplantation]. / Reaktsiia limfotsitov v rannie sroki posle peresadki serdtsa.

The authors determined the quantitative and qualitative composition of the white blood and dehydrogenase activity of lymphocytes in the blood from the afferent and afferent vessels of the transplanted heart at the early postoperative periods in dogs. There was noted a reduction of the lymphocyte count in the blood flowing from the transplanted heart on account of retention of these cells in the transplant, and also an inversion of the mitochondrial dehydrogenases activity due to the lymphocyte contact with foreign antigens of the transplanted heart. A hypothesis is put forward that the inversion mechanism was connected with the lymphocyte functions in the capacity of immunocompetent cells.

[Lysosome activity in mice during rejection of a heterotopic heart implant]. / Izmenenie aktivnosti lizosom pri ottorzhenii geterotopicheskogo implantata serdtsa u myshei.

Allotransplantation of the heart from newborn mice C57B1/6 into the pinna of adult CBA mice on the 3rd day after operation led to increased acid phosphatase activity and activation of the Golgi apparatus. Numerous lysosomes whose membrane became disrupted on the 7th-9th day from the time of implantation appeared later. At the same time histochemical study demonstrated local loss of acid phosphatase activity and a diffuse staining (brown) of the cytoplasm. No destruction of the lysosome membranes or release of the enzymes into the cytoplasm occurred in case of heart isografts (CBA-GBA).

[Experimental study of cellular immunity after administration of inactivated and live virus vaccine]. / Z Eksperimental'noe izuchenie kletochnogo immuniteta pri vvedenii inaktivirovannogo i zhivogo virusa vaktsiny.

Experiments were conducted on guinea pigs with the use of cell migration inhibition test of the peritoneal exudate; stimulation of a definite level of cell immunity in response to the administration of both live and of inactivated vaccine virus was shown. The results obtained are used for the interpretation of the action mechanism of the inactivated preparation in two-stage smallpox vaccination.

[Antigenic properties of 1-asparaginases isolated from different species and strains of bacteria]. / Antigennye svoistva 1-asparaginaz, vydelennykh iz razlichnykh vidov i shtammov bakterii

Immunological relation of L-aspariginase isolated from different strains of E. coli and Ervinia carotovera was investigated by the method of specific neutralization of the asparaginase effect on asparagin in the presence of immune antiasparaginase serum and the method of microprecipitation in agar. It was found that there was immunological relation between asparaginases of different strains of the same microbial species. At the same time common antigens were absent in asparaginases synthesized by different bacterial species.

[Mechanism of changes in lymphocyte dehydrogenase activity during heart transplantation]. / O mekhanizme izmeneniia degidrogenaznoi aktivnosti limfotsitov pri transplantatsii serdtsa

A study was made of the activity of succinic dehydrogenase (SDH) and of the alpha-glycerophosphoric dehydrogenase (alpha-GPDH) in the peripheral blood lymphocytes and the transplant myocardium in the CBA mice in transplantation to them of the heart of newborn C57BL/6 mice into the pinna, subcutaneously. It appeared that the (see article) ratio in the myocardium and the lymphocytes of intact animals and also in the recipients of the isolinear transplant of the heart was greater than 1, but in allogenous transplantation this ratio became less than 1 on account of alpha-GPDH activation in the blood lymphocytes, which preceded the inversion in the transplant myocardium. It is supposed that the mentioned phenomenon was associated with the development of the immunological conflict.