Retro-and prospective evaluation of dynamics of some mutational events

Summary The dynamics of some mutational events were studied in a Siberian town with a chemical industry. Retro-and prospective evaluations of the frequency of spontaneous abortions, multiple congenital malformations, and Down syndrome were carried out. Mutational components of these end-points were summarized and provisionally termed units of mutational events (UME). The results show that the frequencies of UME have not changed in 14 years.     

Radioautographic study of cell proliferation in the pigment epithelium of tritons after transplantation into the cavity of a lens-free eye

The proliferative activity of the pigment epithelium cells transplanted in the lens-less eyes was studied in the adult crested newt. The cells of transplanted pigment epithelium incorporated 3H-thymidine injected intraperitoneally. Within 10 days after explantation, the index of labelled nuclei equaled 27.8-34.0% and within 20 days the number of labelled cells doubled. By that time the proliferating transplant cells were depigmented and formed 2-3 rows of cells of retinal rudiment. In response to the removal of lens from the of recipients eyes their regeneration proceeded. Irrespective of participation (dorsal iris) or nonparticipation in lens regeneration (ventral iris), the index of labelled nuclei in these regions of iris had similar values. The eyes of recipients were also characterized by a local proliferation of pigment epithelium cells in the zones of retinal detachment. In these zones the index of labelled nuclei in the pigment epithelium equaled 11.0-31.3%.     

Disorders in the system of cyclic nucleotides in atherosclerosis: cyclic AMP and cyclic GMP content and activity of related enzymes in human aorta

Cyclic AMP and cyclic GMP content and activities of cyclic nucleotide metabolic enzymes were determined in intima and media of atherosclerotic and unaffected human aorta obtained shortly after death due to myocardial infarction. Cyclic AMP content in fatty streaks and atherosclerotic plaques was lower by three- and five-fold, respectively, as compared with uninvolved intima. Cyclic GMP level in atherosclerotic lesions was estimated to be three-fold higher than in grossly normal area. Basal activity of adenylate cyclase in fatty streaks and plaques was two- to six-fold lower than in unaffected intima. Besides, the ability of adenylate cyclase to be stimulated by the stable analogue of prostacyclin, carbacyclin, was suppressed in plaques. Guanylate cyclase activity in fatty streaks was 1.5- to three-fold higher than in normal tissue. The thiol-reducing agent, dithiothreitol, decreased the enzyme activity to normal level, suggesting the oxidative nature of guanylate cyclase activation in the lesion zone. There were no significant changes in cyclic AMP phosphodiestease activity in the regions of the atherosclerotic lesion. Cyclic GMP phosphodiesterase activity in atherosclerotic plaques was two-fold lower than in the intima of unaffected areas. We did not find differences in the content of cyclic nucleotides or related enzyme activities in the media of uninvolved areas of human aorta nor in the media underlying atherosclerotic lesions. Our findings suggest that development of human atherosclerotic lesions is accompanied by dramatic changes in the cyclic nucleotide metabolism featuring gradual hormonal receptor uncoupling from adenylate cyclase, activation of guanylate cyclase in fatty streaks and inhibition of cyclic GMP phosphodiesterase in plaques.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional Role of Cerebellar Purkinje Cells in Ontogenesis of Postural-Motor Reactions in Mature- and Immature-Born Mammals

In experiments on guinea pigs, cats, and rats of different ages, from newborns to adults, the postural and stato-kinetic reflexes were studied with subsequent recording of electrical activity of identified cerebellar Purkinje cells (PC) in the same animals. Simultaneously in same age group of the animals, a morphometrical study of the shape and size of Purkinje cells and their nuclei was carried out. The first signs of manifestation of reflexes of standing and of the support reaction were observed in mature-born guinea pigs as early as at the first day after birth. At this time the PC fire has an irregular and low-frequency character with long inhibitory pauses and a great dispersion of the frequency-time characteristics. In the course of postnatal ontogenesis the parameter of the ratio of frequencies of simple and complex spikes increased in all the studied animals, guinea pigs, rat puppies, and kittens, but to different degrees. The complete maturation of the PC activity in the mature-born guinea pigs took 3–4 weeks after birth, whereas in the immature-born rat puppies and kittens this process took, on average, 5–6 and 8–9 weeks, respectively. By this time, all the studied postural-motor reactions were formed. The comparison of the course of formation of the frequency-time characteristics of the Purkinje cell activity in mature- (guinea pigs) and immature-born (rats and cats) animals allowed establishing that the highest rate of maturation of the Purkinje cell activity in the mature-born animals is observed during the first half, whereas in immature-born animals, during the second half of postnatal ontogenesis. A similar rate of changes also took place at maturation of postural-motor reflexes. The complete functional maturity of the Purkinje cell occurred, as a rule, at the time period when the shape and size of the Purkinje cell body became close to the definitive ones, and their vertical and horizontal diameters reached the values characteristic of adult animals.     

Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 4. Age-related eye disease. SkQ1 returns vision to blind animals

Mitochondria-targeted cationic plastoquinone derivative SkQ1 (10-(6′-plastoquinonyl) decyltriphenylphosphonium) has been investigated as a potential tool for treating a number of ROS-related ocular diseases. In OXYS rats suffering from a ROS-induced progeria, very small amounts of SkQ1 (50 nmol/kg per day) added to food were found to prevent development of age_induced cataract and retinopathies of the eye, lipid peroxidation and protein carbonylation in skeletal muscles, as well as a decrease in bone mineralization. Instillation of drops of 250 nM SkQ1 reversed cataract and retinopathies in 3-12-month-old (but not in 24-month-old) OXYS rats. In rabbits, experimental uveitis and glaucoma were induced by immunization with arrestin and injections of hydroxypropyl methyl cellulose to the eye anterior sector, respectively. Uveitis was found to be prevented or reversed by instillation of 250 nM SkQ1 drops (four drops per day). Development of glaucoma was retarded by drops of 5 μM SkQ1 (one drop daily). SkQ1 was tested in veterinarian practice. A totally of 271 animals (dogs, cats, and horses) suffering from retinopathies, uveitis, conjunctivitis, and cornea diseases were treated with drops of 250 nM SkQ1. In 242 cases, positive therapeutic effect was obvious. Among animals suffering from retinopathies, 89 were blind. In 67 cases, vision returned after SkQ1 treatment. In ex vivo studies of cultivated posterior retina sector, it was found that 20 nM SkQ1 strongly decreased macrophagal transformation of the retinal pigmented epithelial cells, an effect which might explain some of the above SkQ1 activities. It is concluded that low concentrations of SkQ1 are promising in treating retinopathies, cataract, uveitis, glaucoma, and some other ocular diseases. Electronic Supplementary Material  Supplementary material is available for this article at and is accessible for authorized users. Published in Russian in Biokhimiya, 2008, Vol. 73, No. 12, pp. 1641–1654.     

Different effects of the immunostimulatory drug Stimforte on infections of hepatitis C virus and herpes simplex virus type 1

Stimforte, an immune response-stimulating preparation, is active with respect to hepatitis C virus (HCV) and herpes simplex virus type I (HSV-1). The effects of Stimforte in animals infected with either HCV or HSV-1 are fundamentally different. In mice with acute herpes virus infection, Stimforte administration leads to a higher activity of natural killer cells and cytotoxic lymphocytes, and the amount of interferon (IFN) λ grows. In mice infected with HCV, Stimforte administration results in a significant increase in IFN-β but not IFN-λ in blood and affected organs. Stimforte has been found to affect directly HCV reproduction that causes the infected cell death, but it does not affect HSV-1 reproduction in the Vero cells (V).     

Comparative analysis of spontaneous unit activity of the cerebellum fastigial nucleus' neurons in different periods of vibration influence

In conditions of acute experiment on white rats anaesthetized with Nembutal (40 mg/kg, interperitonially) recording and analysis of spontaneous impulse activity of the fastigial nucleus' neurons in norm and after 5, 10 and 15 days of vibration influence on the organism were carried out. Distribution of the neurons was evaluated by the dynamics of neuronal current flow and the modality of the interspike interval hystograms, as well as the statistical parameters: the average discharge frequency and the coefficient of the interspike interval variation. It is shown that more significant changes in neuronal activity of fastigial nucleus cells are formed during the first 10 days of vibration influence. On the 15th day, there was a tendency towards return to control levels of the parameters under study.     

Electromagnetic fields of millimeter range: effect on the structure and functional properties of erythrocyte membranes

The effect of coherent and non-coherent electromagnetic fields of millimetre range on biophysical and biochemical indices of blood erythrocytes and plasma of the animals totally exposed to radiation at various periods of observation (day 1, 5, 10) was studied. The following structure-functional shifts were revealed: deviations in the content of separate phospholipid fractions of erythrocyte membranes, the changes of lipid peroxidation products in erythrocyte membranes and blood plasma of the irradiated animals, statistically significant increase of K ions out-flow from the erythrocytes, as well as the alteration of the value of membrane potential of erythrocytes.     

The study of interhemispheric asymmetry in spatial-perceptive problem solving

Features of brain interhemispheric asymmetry during solving the spatial figurative task (maze model) were studied in men and women with different intelligence quotients (IQ). It was shown that during task solving the rate of information processing was higher in the right brain hemisphere, and amplitude characteristics of the event-related potentials were higher in the left hemisphere. No gender and IQ differences in the character of interhemispheric interaction were found during the realization of the maze-model task. The results testify that the character of hemispheric interaction depends om the task rype rather than gender and intelligence level.