Ciliary activity under normal conditions and under viscous load

Ciliary metachronism and motility were examined optically in muco-ciliary tissue cultures from three different systems: a) frog's palate epithelium, b) frog's oesophagus, and c) human nasal polyps. In addition, lateral cilia of Mytilus edulis (water transporting cilia) were examined. It was revealed that the degree of synchronization between muco-ciliary systems is lower than that of water transporting cilia. There are no significant differences between different muco-ciliary systems, within the accuracy of our measurement although relatively large statistical ensembles were used. In addition the wavelength and wave direction of the metachronal wave was examined. All four systems exhibit similar wavelength. The metachronal parameters of muco-ciliary systems exhibit fluctuations (as was demonstrated by the degree of synchronization), however, the magnitude and repetitivity of these fluctuations, is dependent on the loading of the ciliary system. We have loaded the system by increasing the viscosity of the medium. Under viscous load the frequency of the beating decreased. The metachronal wavelength became longer and the metachronal coordination type more orthoplectic.     

Hemodynamics (general and cerebral) and mental activity under normal conditions

Interrelations between the mental work efficiency and changes in total and cerebral hemodynamics during mental activity are considered. Five subgroups of the efficiency are distinguished. Changes in the vegetative reactions considerably differ in the type as well. Basic four types of such reactions are distinguished with allowance for changes in the character of minute blood circulation volume and cerebral blood flow. Comparison of changes in the efficiency of the activity with vegetative changes shows that in the process of the mental activity the vegetative changes are determined by interrelation between the intensity of the mental activity and its efficiency. It was concluded that the higher the activity efficiency, the lower the mental intensity and changes in the total and cerebral hemodynamics and, vice versa.     

Mutagenic potential of anti-herpes agents

A number of anti-herpes agents which are either licensed for clinical use (acyclovir) or subject of clinical studies (bromovinyldeoxyuridine, fluoroiodoaracytidine, dihydroxypropoxymethylguanine) or under preclinical investigation (i.e., fluoroiodoarauridine), fluoromethylarauridine, dihydroxybutylguanine, bromovinyldeoxycytidine, bromovinylarauridine and carbocyclic bromovinyldeoxyuridine) were evaluated for their ability to induce sister chromatid exchange (SCE), an indicator of mutagenesis. SCE was scored on metaphase chromosomes of human lymphocytes which had been exposed to 5-bromo-2'-deoxyuridine and varying concentrations of the test compounds. The antiviral assays were based on the inhibition of the cytopathogenicity of herpes simplex virus for human diploid fibroblasts. Most compounds, i.e. acyclovir, bromovinyldeoxyuridine or carbocyclic bromovinyldeoxyuridine, did either not induce SCE or only so at concentrations far above their minimum antiviral concentrations. However, fluoroiodoaracytidine and dihydroxypropoxymethylguanine were found to affect the SCE rate at a concentration (greater than or equal to 4.5 micrograms/ml) that is readily achievable in blood following intravenous injection.     

Level of dehydrogenase activity in chipmunks under normal conditions and during chronic external gamma-irradiation

Chipmunks were chronically exposed to gamma-radiation at an average dose rate of 46 pA/kg. Changes in activity of succinate dehydrogenase (EC 1.3.99.1), pyruvate dehydrogenase (EC 1.2, 4.1) and lactate dehydrogenase (EC 1.1.1.27) were detected in the homogenates of the cardiac muscle, liver and brain at different physiological periods (before, during and after hibernation). The changes observed were related to the impairment of coordination between the processes of tissue respiration and glycolysis.     

Mutagenic activity of radiosensitizers

Seven radiosensitizers, six derivatives of nitroimidazole (coded P1 to P5 and one imidazole derivative--P6 were investigated for mutagenicity using 3 short-term tests: Ames test, prophage lambda induction and tryptophan reversion test. Out of seven investigated compounds five were not mutagenic. Only P1 derivative induces base pair substitutions. Another derivative of nitroimidazole: metronidazole induces base pair substitution and frameshift mutations. Its positive response in the prophage lambda induction test suggests that metronidazole provokes also epigenetic changes.     

Handling of injectable antineoplastic agents.

Although the clinical toxicity of antineoplastic drugs has been well documented there is little or no information on the problems that may arise on the handling and mishandling of such agents. This paper attempts to highlight the importance of taking precautions to prevent adverse effects resulting from contact with cytotoxic drugs during handling and to suggest a practical guide for the handling of such agents.     

Mutagenic activity of chloramines

Mutagenesis by chloramines and hypochlorous acid (HOCl) was studied to determine whether these agents could contribute to the mutagenic and potentially carcinogenic activity of stimulated leukocytes and whether environmental exposure to these agents is a cause for concern. Mutagenic activity was measured using the S. typhimurium TA97a, TA100 and TA102 tester strains. Because chloramines and HOCl are bactericidal, react rapidly with cell components, and can destroy the histidine and biotin required for the mutagenesis assay, activity can't be compared directly with that of less toxic or reactive agents. Nevertheless, chloramines were mutagenic when tested under appropriate conditions. TA100 was the most sensitive strain, and the most active mutagens were lipophilic dichloramines (RNCl2) including derivatives of histamine, ethanolamine and putrescine. Lipophilic monochloramines (RNHCl) such as histamine-monochloramine and NH2Cl were less active. Hydrophilic chloramines such as taurine-chloramines had low activity, and HOCl was inactive. The metabolic state of the bacteria was critical. Chloramines were mutagenic when added to bacteria with glucose at 37 degrees C, but killing predominated when chloramines were added at 4 degrees C or 25 degrees C, or at 37 degrees C without glucose. Production of chloramines and HOCl by leukocytes in vivo could contribute to the association of chronic inflammation and cancer as a result of: (1) the entry of membrane-permeable chloramines into normal cells followed by attack on intracellular components including DNA, and (2) the production of secondary mutagens such as compounds with carbonyl groups or carbon-chlorine bonds. On the other hand, chlorination of water supplies is perhaps more likely to destroy than create mutagens, and chloramines from the environment are unlikely to penetrate the skin and mucous membranes.     

Measurement of the sequence specificity of covalent DNA modification by antineoplastic agents using Taq DNA polymerase.

A polymerase stop assay has been developed to determine the DNA nucleotide sequence specificity of covalent modification by antineoplastic agents using the thermostable DNA polymerase from Thermus aquaticus and synthetic labelled primers. The products of linear amplification are run on sequencing gels to reveal the sites of covalent drug binding. The method has been studied in detail for a number of agents including nitrogen mustards, platinum analogues and mitomycin C, and the sequence specificities obtained accord with those obtained by other procedures. The assay is advantageous in that it is not limited to a single type of DNA lesion (as in the piperidine cleavage assay for guanine-N7 alkylation), does not require a strand breakage step, and is more sensitive than other primer extension procedures which have only one cycle of polymerization. In particular the method has considerable potential for examining the sequence selectivity of damage and repair in single copy gene sequences in genomic DNA from cells.     

Pyridoxal kinase activity and pyridoxal-P concentration in mammalian tissues under normal and experimental conditions]

The activity and the distribution of pyridoxal kinase in rat and mouse tissues are studied. The data obtained testify the presence of a relative excess of pyridoxal kinase in all the organs studied, which probably causes a high rate of pyridoxalphosphate (PLP) biosynthesis under comparatively low vitamin B6 concentration. A correlation between the level of pyridoxal kinase activity and the content of PLP in rat brain and liver during ontogenesis is observed. The activity of pyridoxal kinase and the content of PLP are shown to be sharply increased in liver of rats received a protein-rich diet. Bilateral adrenalectomy resulted in the decrease of absolute and specific enzyme activities in rat liver by 20--30%. The content of PLP in mouse brain and liver was sharply decreased under experimental B6-avitaminosis while the content of pyridoxal kinase practically did not change. The injection of vitamin B6 rapidly normalized the PLP content in mouse tissues. The data obtained show that under physiological conditions the functional activity of pyridoxal kinase may be regulated in tissues by enzyme and substate contents. Some aspects of vitamin B6 metabolism in mammals are considered. It is concluded that in body the pyridoxal catabolism connected with its phosphorylation by pyridoxal kinase and the formation of pyridoxalphosphate.