Effect of antiserotonin drug on the development of lung fibrosis and blood system reactions after intratracheal administration of bleomycin.

The effects of antiserotonin preparation on the development of the connective tissue in the lungs, reaction of the blood system, and the content of hemopoietic stem cells, committed hemopoietic and stromal precursors in BM, spleen, and peripheral blood were studied on C57Bl/6 mice with experimental toxic lung fibrosis caused by intratracheal administration of bleomycin. It was demonstrated that the antiserotonin drug inhibits the growth of the connective tissue in the lungs and attenuates the course inflammatory process primarily due to inhibition of the granulocytic lineage, which was related to suppression of hemopoietic stem cells. Reduced content of the stromal precursor cells in BM and spleen was noted.

[Effects of granulocyte colony-stimulating factor on experimental bleomycin-induced pulmonary fibrosis].

The influence of granulocyte colony-stimulating factor (G-CSF) has been studied on a model of bleomycin-induced pulmonary fibrosis. It is established that G-CSF significantly increases infiltration of alveolar and alveolar duct interstitium by inflammation cells (lymphocytes, neutrophils, plasmocytes) and increases collagen deposition in lung under conditions of bleomycin introduction. Simultaneously with profibrotic and anti-inflammation effects, G-CSF increased the content of granulocyte cells in the bone marrow and peripheral blood, which was related to the stimulation of committed granulocyte precursors in the bone marrow.

Effect of hyaluronidase immobilized using electron-beam synthesis nanotechnology on sensitivity of progenitor cells to regulatory factors.

In vitro experiments demonstrated increased colony-forming capacity of erythroid, granulomonocytic, and mesenchymal progenitors of the bone marrow and parenchymal progenitor elements of the liver after treatment with immobilized hyaluronidase. Increased sensitivity of these progenitor cells to erythropoietin, granulocyte colony-stimulating factor, fibroblast growth factor, and stem cell factor, respectively, was demonstrated. Immobilized hyaluronidase enhanced the formation of tissue-specific hepatic CFU against the background of reduced yield of stromal precursors in liver tissue culture containing insulin.

Reactions of granulocytic lineage of hemopoiesis and mechanisms of their development in combined treatment with adriablastin and taxotere.

We studied myelotoxic effects of adriablastin and taxotere combination on granulocytic lineage cells and processes of their recovery in patients with stage III-IV breast cancer. Intensive maturation of granulocytic CFU provided regeneration of the hemopoiesis even under conditions of reduced proliferative activity of these cells, which, in turn, led to accumulation of mature and immature neutrophilic granulocytes in the bone marrow and improved reserve capacities of the neutrophil pool in the bone marrow.

[Influence of taxan-containing cytostatic preparations on the progeny].

In experiments designed to study effect of taxan-containing agents on the progeny of Wistar rats, one of the parents was given a single intravenous injection of the antineoplastic drug paclitaxel 1, 3 and 6 months before crossing with the untreated partner. The number of systemic pathological changes in the off-springs of paclitaxel-treated females was significantly greater and their spectrum wider than in those of the treated males. Severity of toxic effects depended on the time of crossing after drug administration. The optimal time for obtaining less affected off-springs of treated females and males was 3 and 6 months after administration of paclitaxel.

Mechanisms of stimulation of granulocytopoiesis with neupogen in patients with breast cancer during chemotherapy.

The mechanisms of granulocytopoiesis stimulation with granulocytic CSF (neupogen), added to chemotherapy protocol (adriablastine+taxotere) in patients with stages III-IV breast cancer, were studied. The hemostimulatory effect of granulocytic CSF preparation is based on stimulation of proliferation and differentiation of granulomonocytopoisis precursor cell in the hemopoietic tissue, due to neupogen effects on hemopoietic elements and on the hemopoiesis-inducing microenvironment cells.

Reaction of bone marrow hematopoiesis to the toxic effect of paclitaxel.

Intraperitoneal injection of paclitaxel (Mitotax) in a single dose of 40 mg/kg was followed by an increase in the number of mitotic granulocytic and erythroid cells, hypoplasia, and pancytopenia of the bone marrow in CBA/CaLac mice. The test preparation decreased the number of hematopoietic precursor cells for erythropoiesis and granulocytopoiesis, but increased the count of polyploid cells and incidence of structural and genomic abnormalities in bone marrow cells. These changes were reversible.

Toxic effect of an antitumor drug paclitaxel on morphofunctional characteristics of the liver in rats.

Single intravenous injection of paclitaxel to rats in a maximum tolerated dose of 4.6 mg/kg was accompanied by permanent structural and functional changes in the liver. The observed changes were typical of nonspecific reactive hepatitis: infiltration with lymphocytes and macrophages, pyknosis, and focal fatty degeneration of hepatocytes. Liver enzyme activity increased in blood plasma.

The stage of offspring of female rats after treatment with cytostatics of various groups.

We examined the offspring of female rats that were mated with intact males in the delayed period after administration of cytostatic drugs Farmorubicin, platidiam, carboplatin, etoposide, and paclitaxel (1, 3, and 6 months post-treatment). Toxicity of these drugs in the offspring decreased in the following order: paclitaxel > etoposide > carboplatin > platidiam > Farmorubicin. The toxic effect depended not only on the type of cytostatic treatment, but also on the period of conception.

Pharmacological correction of etoposide ovariotoxicity.

The possibility of reducing the ovariotoxicity of antitumor drug etoposide with buserelin, a hypothalamic regulator of pituitary function, was studied in female Wistar rats. Quantitative analysis of ovarian structural and functional elements on serial sections through the entire organ showed that 3 months after combined treatment with etoposide and buserelin, the morphological picture of the ovarian glands did not differ from that in intact animals of the same age, while etoposide monotherapy led to earlier development of atrophic processes. Six months after treatment, the number of bi- and multilayer follicles was significantly higher in rats receiving combined therapy compared to animals treated with etoposide alone.

Evaluation of the progeny of rats treated with topoisomerase II inhibitor vepesid.

Progeny of Wistar rats treated with vepesid 1, 3, and 6 months before mating is characterized by common pathological changes. These changes were more pronounced and more diverse in animals descending from females receiving the cytostatic compared to the progeny of treated males. The severity of toxic effects depended on the period between mating and vepesid treatment. Cytostatic treatment 3 months before mating was associated with minimum toxicity for the progeny.

Morphological and functional state of rat ovaries in the early and late periods after injection of vepesid.

Morphological and functional state of the ovaries in female Wistar rats was assessed in the early and late periods after administration of antitumor drug vepesid in a single maximum tolerated dose. In the early period, the drug pronouncedly decreased the number of primordial follicles, bi- and multilayer follicles, and the total number of generative elements. The number of graafian vesicles and corpora lutea did not decrease. In the late period, exhaustion of the reserved potencies of gonads was more pronounced than in the control. Morphological alterations in the ovaries were accompanied by inhibition of the functional state of the female reproductive system in the period corresponding to the action on mature and primordial follicles. This inhibition manifested in increased postimplantation mortality.

Effect of vepeside on the function of reproductive system in rats.

Experiments on adult rats showed that a single intravenous injection of antitumor drug vepeside in a MTD (maximum tolerable dose) reduced the reproductive status during periods corresponding to exposure of mature sex cells, spermatocytes, and spermatogonia in male rats and exposure of oocytes in ovulating, mature, and primordial follicles in female rats. Reduction of the male and female reproductive function manifested in increased antenatal mortality of the progeny. The toxic effects of the drug on mature male sex cells caused temporary partial infertility.

Function of hemopoietic stem cells under conditions of cytostatic myelosuppression and treatment with hemostimilators.

We compared the function of hemopoietic stem cells under conditions of cytostatic myelosuppression (cyclophosphamide treatment) and during treatment with granulocytopoiesis stimulators. It was found that unipotent hemopoietic precursor cells are most sensitive to cyclophosphamide. Different effects of hemostimulators on stem cells are determined by different proportions between proliferation and differentiation processes.

State of central and peripheral pools of hemopoietic precursor cells in patients with malignant neoplasms during chemotherapy.

We studied toxic effects of various schemes of cytostatic treatment on central and peripheral pools of hemopoietic precursor cells in patients with III-IV stages of lung cancer and breast cancer. It was found that erythro- and granulomonocytopoietic precursors are characterized by high resistance to cytostatic treatment compared to morphologically discernible bone marrow elements, which is probably a evolutionary developed property of this cell type aimed at rapid recovery of the hemopoietic tissue.

[The effect of antitumor polychemotherapy on the structural, metabolic, and functional status of erythrocytes in patients with head and neck tumors]. / Vliianie protivoopukholevoi polikhimoterapii na strukturno-metabolicheskii status i funktsional'noe sostoianie eritrotsitov u bol'nykh s opukholiami golovy i shei.

The structure, metabolic status, and functional properties of erythrocytes in patients with stage III-IV head and neck tumors in the course of antineoplastic cytostatic chemotherapy (platidiam, 5-fluorouracil, methotrexate) were studied. In the course of this treatment, disorders of the morphology and functional state of erythrocytes (reduced dry mass, decreased content of sulfohydryl grups and lipoproteins, increased number of transformed cells and the cells with violated ultrastructure, enhanced reversible aggregation of erythrocytes) were retained or became more pronounced.

Tartrate-resistant acid phosphatase as a marker of bone metastases in patients with breast cancer and prostate cancer.

Serum activity of tartrate-resistant acid phosphatase 5b (TRAP 5b) in patients with breast cancer and prostate cancer having bone metastases was much higher than in healthy donors and patients without skeletal injuries. TRAP 5b activity in patients with breast cancer and multiple bone metastases surpassed that in patients with single bone metastases. The mean activity of TRAP 5b and range of enzyme activity in women treated with bisphosphonates were significantly lower than in patients not receiving antiresorptive therapy. Diagnostic sensitivity and specificity of TRAP 5b as a marker of skeletal metastases in patients with breast cancer were 82 and 87%, respectively. In patients with prostate cancer these indexes were 71 and 83.4%, respectively. Detection of this marker in tumor patients holds much promise for early diagnostics of bone metastases, estimation of the severity of skeletal metastases, and monitoring of the efficiency of bisphosphonate therapy.

[Protein composition of erythrocyte membranes in patients with stomach, colon and rectal cancer]. / Belkovyi sostav membran éritrotsitov u bol'nykh rakom zheludka, tolstoi i priamoi kishki.

Examinations of the protein composition of erythrocyte membrane in patients with cancer of the stomach, large intestine and rectum by using the method of disc-electrophoresis in polyacrylamide gel revealed the changing contents of protein fractions, which consisted in a lower share of high-molecular polypeptides with, simultaneously, higher quantity of low-molecular peptides. A comparison of the studied parameters of the protein spectrum of erythrocyte membrane as observed in patients with cancer of the stomach, on the one hand, and in patients with tumors of the large intestine and rectum, on the other hand, led to defining the reliable difference only for the content of the fraction-5 proteins.

Typical changes of erythrocytes in chronic inflammation.

Structural and metabolic status and function of erythrocytes were studied in patients with chronic bronchitis, chronic inflammatory diseases of the upper airways, and chronic colitis. Complex study of the peripheral component of the erythron showed that disorders in erythrocyte morphology and function (decreased erythrocyte dry weight, low concentration of sulfhydryl groups and lipoproteins, decreased content of high molecular weight polypeptides in parallel with increased content of low molecular weight proteins, increased number of transformed cells, and enhanced reversible aggregation) were nonspecific and did not depend on the location of the inflammatory process.

[Chronic bronchitis: participation of red cells in the pathologic process]. / Khronicheskii bronkhit: uchastie éritrotsitov v patologicheskom protzesse.

To study characteristics of structural-metabolic status and function of erythrocytes in patients with chronic bronchitis (CB), the examination was made of 53 CB patients (39 male and 14 female). A complex study of morphofunctional state of peripheral erythron included investigation of protein and lipid composition, microviscosity of the lipid phase of erythrocyte membrane, surface architectonics, ultrastructure, reversible aggregation of red cells, concentrations of sulfhydric groups, lipoproteins and dry cell mass in erythrocytes. CB patients were found to have prominent defects in membrane structure and metabolism of mature red cells (reduced dry mass and concentration of sulfhydric groups and lipoproteins, abnormal protein composition and lipid membrane spectrum, increased viscosity of membrane lipid bilayer), alterations of surface architectonics, shape, ultrastructure of erythrocytes. Disorders in structural-metabolic status of erythrocytes in CB patients affected their functional features, the ability for reversible aggregation, in particular. Functional disturbances of erythrocytes in CB patients aggravate the course of the disease and need correction with membrane-stabilizing and membrane-repairing drugs.