Effect of somatostatin on repair of ionizing radiation-induced DNA damage in pituitary adenoma cells GH3.

Ionizing radiation and somatostatin analogues are used for acromegaly treatment to achieve normalization or reduction of growth hormone hypersecretion and tumor shrinkage. In this study, we investigated a combination of somatostatin (SS14) with ionizing radiation of (60)Co and its effect on reparation of radiation-induced damage and cell death of somatomammotroph pituitary cells GH3. Doses of gamma-radiation 20-50 Gy were shown to inhibit proliferation and induce apoptosis in GH3 cells regardless of somatostatin presence. It has been found that the D(0) value for GH3 cells was 2.5 Gy. Somatostatin treatment increased radiosensitivity of GH3 cells, so that D(0) value decreased to 2.2 Gy. We detected quick phosphorylation of histone H2A.X upon irradiation by the dose 20 Gy and its colocalization with phosphorylated protein Nbs-1 in the site of double strand break of DNA (DSB). Number of DSB decreased significantly 24 h after irradiation, however, clearly distinguished foci persisted, indicating non repaired DSB, after irradiation alone or after combined treatment by irradiation and SS14. We found that SS14 alone triggers phosphorylation of Nbs1 (p-Nbs1), which correlates with antiproliferative effect of SS14. Irradiation also increased the presence of p-Nbs1. Most intensive phosphorylation of Nbs1 was detected after combined treatment of irradiation and SS14. The decrease of the number of the DSB foci 24 h after treatment shows a significant capacity of repair systems of GH3 cells. In spite of this, large number of unrepaired DSB persists for 24 h after the treatment. We conclude that SS14 does not have a radioprotective effect on somatomammotroph GH3 cells.

Primary hemostasis in patients treated with LDL-apheresis for severe familiar hypercholesterolemia: a prospective pilot trial using PFA-100 analysis to rationalize therapeutic LDL-apheresis procedure.

UNLABELLED: LDL-apheresis is a method of extracorporeal elimination of serum LDL-cholesterol used for treating patients with severe hyperlipidemia resistant to diet and pharmacotherapy. A practically applicable marker that may possibly be used to ascertain the efficacy of this treatment in lowering the activity of atherosclerosis are still to be found and remains an unresolved problem. Activity of primary hemostasis plays an important role in the process of developing atherosclerotic complications. This fact led us to hypothesize that the investigation of primary hemostatic activity might be a useful marker for monitoring LDL-apheresis efficacy. The aim of this work was to verify this hypothesis. METHODS AND PATIENTS: Commercial analyzer Dade Behring PFA-100, Germany (PFA, platelet function analysis) was used for all investigations. This analyzer enables quantitative measurement of platelet-mediated hemostasis in uncoagulated (citrated) blood. The method simulates platelet activation by mechanical stress (shear stress), and also simulates contact of platelets with collagen. A total of nine long-term treated patients with familial hypercholesterolemia were included in the study group (4 females and 5 males). Ages ranged from 17 to 59 years (average 46.4, median 55). Two patients had homozygous hypercholesterolemia. Eighteen sample pairs were examined using collagen/epinephrine (COL/EPI) membrane and 17 pairs were examined using collagen/ADP (COL/ADP) membrane, the total number of samples amounted to 70. RESULTS: Closure time (CT) values were prolonged after separation in all cases but CT prolongation was not statistically significant (p < 0.14). No differences between homozygous and heterozygous patients were found (p < 0.05). CONCLUSION: Investigation of primary hemostasis using PFA-100 analyzer is not a suitable marker and should not be used to determine the optimal intensity of individual LDL-apheresis procedures.

[Polycyclic aromatic hydrocarbons. II. Toxic effects]. / Polycyklické aromatické uhlovodíky. II. Toxické úcinky.

Polycyclic aromatic hydrocarbons (PAH) represent dangerous environmental pollutants. Many of them have toxic and carcinogenic potential. Presented work summarizes most of available data on the absorption, metabolism and elimination of PAH. The second part of article contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. In the third part of article, the populations with higher susceptibility to exposure to PAH are described and the influences of chemical interaction of PAH to biological effects are mentioned.

[Polycyclic aromatic hydrocarbons. Biological indicators of exposure and possibilities of prevention]. / Polycyklické aromatické uhlovodíky. III. Biologické ukazatele expozice a moznosti prevence.

Polycyclic aromatic hydrocarbons (PAH) represent an extensive group of ubiquitous environmental pollutants disposing of a considerable toxic and carcinogenic potential. According to the IARC data (International Agency for Research on Cancer), PAH represent the largest group of chemical carcinogens produced during combustion, pyrolysis and pyrosynthesis of organic matter. PAH can be identified in atmosphere, water, soil, food and other materials which are in daily contact which the general population. Presented work summarizes most of available data on the biological markers used to identify or quantify the exposure to PAH and on the biological markers used to characterize the effects caused by PAH. The digest of possibilities of reduction toxic effects of PAH concludes the work.

[Polycyclic aromatic hydrocarbons. I. Environmental contamination and environmental exposure]. / Polycyklické aromatické uhlovodíky I. Kontaminace prostredí a expozice osob.

Polycyclic aromatic hydrocarbons (PAHs) represent danger ubiquitous environmental pollutants. A lot of them have toxic and carcinogenic potential. Presented work summarises most of available data describing properties, origin and occupational and non-occupational sources of PAHs. Contamination of environment is described separately for air, water, soil, sediments and food. Possibilities of occupational and non-occupational exposure of persons are discussed and populations with potentially high exposures to PAHs are defined. The work is concluded by digest of regulations and guidelines regarding environmental contamination of PAHs.