Preparation and Mechanism of the Antitumor Action of a 4H-Aminochromene Compound

Pharmaceutical Chemistry Journal - We report here studies of the antitumor action of a 4H-aminochromene compound in a xenograft model of ALK-expressing lung adenocarcinoma in humanized nude BALB/c...     

Angiogenesis after Transplantation of Auto- and Allogenic Cells

Neoangiogenesis after transplantation of auto- and allogenic mononuclears and multipotent stromal cells from the bone marrow was studied on the model of inflammatory angiogenesis. Transplanted auto- and allogenic cells stimulate the formation of new blood vessels in the granulation tissue, this manifesting in an increase in the quantity and volume density of blood vessels. The most pronounced angiogenesis was observed after transplantation of allogenic mononuclears and multipotent stromal cells. It was associated with intense inflammatory infiltration, with less numerous and mature collagen fibers in the granulation tissue. Injection of allogenic cells led to stimulation and chronization of inflammation, infiltration with inflammatory and poorly differentiated cells, and more pronounced and lasting angiogenesis. However, neither auto-, nor allogenic transplanted labeled cells were detected in the walls of new blood vessels. Hence, it seems that bone marrow mononuclears and multipotent stromal cells stimulated angiogenesis mainly at the expense of production of angiogenic factors, and after transplantation of allogenic cells also by stimulating the inflammation.     

Regeneration of skull bones in adult rabbits after implantation of commercial osteoinductive materials and transplantation of a tissue-engineering construct

We performed a comparative study of reparative osteogenesis in rabbits with experimental critical defects of the parietal bones after implantation of commercial osteoinductive materials "Biomatrix", "Osteomatrix", "BioOss" in combination with platelet-rich plasma and transplantation of a tissue-engineering construct on the basis of autogenic multipotent stromal cells from the adipose tissue predifferentiated in osteogenic direction. It was found that experimental reparative osteogenesis is insufficiently stimulated by implantation materials and full-thickness trepanation holes were not completely closed. After transplantation of the studied tissue-engineering construct, the defect was filled with full-length bone regenerate (in the center of the regenerate and from the maternal bone) in contrast to control and reference groups, where the bone tissue was formed only on the side of the maternal bone. On day 120 after transplantation of the tissue-engineering construct, the percent of newly-formed bone tissue in the regenerate was 24% (the total percent of bone tissue in the regenerate was 39%), which attested to active incomplete regenerative process in contrast to control and reference groups. Thus, the study demonstrated effective regeneration of the critical defects of the parietal bones in rabbits 120 days after transplantation of the tissue-engineering construct in contrast to commercial osteoplastic materials for directed bone regeneration.     

Fragility of telomeres after bleomycin and cisplatin combined treatment measured in human leukocytes with the Comet-FISH technique

THE AIM of the present study was the comparative investigation of action of widely applied anticancer preparations: cisplatin (cis-DDP) and bleomycin (BLM) on total DNA and telomeres damage in human blood cells. METHODS: The "Comet-FISH technique" -- single cell gel electrophoresis ("comet assay") in combination with fluorescent in situ hybridization (FISH) was used for this purpose. This newly applied combined approach permits to detect on the same specimen the total DNA damage in individual cells and evaluate specific DNA sequences as well. Telomere -- specific -- PNA (peptide nucleic acid) probes were used for the localization of telomeres in the comet's head and their migration to the tail. THE RESULTS obtained indicate that in control variants, due to DNA metabolism and handling, approximately 7% of the DNA and 17% of the telomeres were found in the tail. In cells treated with BLM alone, telomeres leak out with equal probability as total DNA. In turn, the combination of cis-DDP with BLM reduces telomere migration more than the migration of total DNA due to cis-DDP crosslinking effect. Thus, preferentially telomeric action of the cis-DDP can be concluded. CONCLUSION: The Comet-FISH approach permitted us to reveal the induction of DNA breaks with BLM and its modification due to platinum-crosslink formation, using telomeric PNA probes.     

Transferable clastogenic activity in plasma from persons exposed as salvage personnel of the Chernobyl reactor

Clastogenic factors were first described in the plasma of people who had been accidentally or therapeutically irradiated. They were found also in A-bomb survivors, where they persisted for many years after the irradiation. The present study searched for these factors in the plasma of 32 civil workers from Armenia, who had been engaged as liquidators around the Chernobyl atomic power station in 1986. It also included 15 liquidators who had emigrated from the ex-Soviet Union to Israel. Reference plasma samples were obtained from 41 blood donors from the Armenian Blood Center in Yerevan. The samples were tested for their clastogenic activity in blood cultures from healthy donors. The majority of results from the liquidators exceeded those from the unexposed reference samples. The samples from the first Armenian group, with the higher average irradiation dose (0.6±0.6 Gy), were more clastogenic than those from the second group exposed to 0.2±0.2 Gy. The number of aberrations in the test cultures was 17.9±2.9% and 10.5±3.8% respectively, compared to 5.7±3.2% in the cultures exposed to the reference ultrafiltrates from Armenian blood donors. The samples from the Israeli liquidators also induced significantly increased aberration rates (14.0±3.9% aberrant cells). The clastogenic activity was regularly inhibited by superoxide dismutase, indicating that the chromosome-damaging effects of radiation-induced clastogenic factors are exerted via the intermediation of superoxide radicals, as is known for clastogenic factors of different origin.     

Responses of Respiratory Neurons in the Medulla Oblongata to Stimulation of the Septal Nuclei during Hypoxia

Dynamic studies were performed in conditions of hypoxia on the effects of stimulation of the ventral, lateral, and medial nuclei of the septum on the spike activity of bulbar respiratory neurons and respiration. The various phases of hypoxia provided a model experiment over which the overall effects of the septal neurons were summed. Electrical stimulation of these septal nuclei in conditions of normal atmospheric pressure had both facilitatory and inhibitory effects on the spike activity of respiratory neurons in the respiratory center of the medulla oblongata, inhibitory effects being predominant. The ventral nucleus had the most effective inhibitory effect on the activity of respiratory neurons. Electrical stimulation of the septal nuclei in the initial phase (4000-5000 m) of hypoxia, on the background of activation, had a predominantly inhibitory influence on the activity of respiratory neurons. During the phase of severe hypoxia (7500-8000 m), on the background of marked hypoxic suppression of respiratory neuron activity, stimulation of the septal nuclei produced no characteristic changes in the activity of these neurons.     

Effect of thyrotoxicosis on skeletal muscle proprioceptor activity

The effect of prolonged administration of thyroid hormones on the discharges from muscle spindles of the cat soleus was investigated. In animals with thyrotoxicosis the response of the primary spindle endings to a constantly acting and to a sudden rapid stretching increased considerably in both the dynamic and the static phase. The discharge frequency of the secondary endings remained substantially unchanged. It is postulated that the observed changes in activity of the primary endings are connected with disturbances of metabolism in the muscle and also with its atrophy.Group for Evolution of Motor Activity, Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Laboratory of Pathological Physiology, Institute of Experimental Endocrinology and Hormone Chemistry, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éxperimental'noi Biologii i Meditsiny, Vol. 82, No. 10, pp. 1187–1189, October, 1976.     

Effect of Chronic Inhalation of Toluene and Dioxane on Activity of Free Radical Processes in Rat Ovaries and Brain

The effects of toluene and dioxane inhalations on the intensity of free radical oxidation in rat ovaries and brain cortex were studied. Both toxins in a dose 10-fold surpassimg the maximum permissible concentration increased activity of glutathione peroxidase in brain tissue; moreover, toluene increased chemiluminescence intensity, which attested to activation of free radical processes. In ovarian tissue toluene increased activities of glutathione peroxidase and catalase and the intensity of lipid peroxidation. These changes were associated with the appearance of normally absent circadian rhythm.