Epidemiological problems of ozena and the means for controlling this infection

Clinical, bacteriological, serological and epidemiological studies of ozena morbidity among the population of Minsk were carried out in 1970-1980. On January 1, 1981, the ozena morbidity rate among the inhabitants of Minsk was 26.72%. Ozena was found to affect mainly children and women. A wide spread of the family foci of this disease (31.68%) was revealed. The results of this study indicate that the source of K. ozaenae is a sick person who begins to excrete the bacteria in the prodromal period of the disease and may continue to excrete them for many years. The transfer of K. ozaenae occurs probably by droplet or contact infection. The droplet infection is less active in the absence of symptoms (coughing, sneezing) facilitating excretion of the infective agent into the air and in cases of the low susceptibility of persons to ozena. The main measures for controlling ozena are the timely detection and sanitation of the sources of ozena, as well as the current disinfection of the infection foci in apartments.     

The EPR spectra of the ribonucleotide reductase in the tumorous tissues and organs of tumor-bearing animals

Ribonucleotide reductase activity (RRA) has been studied in various tumors and spleens of tumor-bearing animals using EPR technique and biochemical methods. The effect of a number of biologically active compounds on RRA has also been studied. RRA in tumor and spleen increases during tumor growth. Inhibitory effect of irradiation, hydroxyurea, nitrosomethylurea and activatory effect of 5-nitrofurans and nitroimidazole derivatives on RRA has been observed. Regulatory factors of RRA and DNA synthesis in vivo have been discussed.     

Relation between the changes in the structure and synthesis of DNA in the cells of mouse leukemia L1210 induced by 1-methyl-1-nitrosourea and 1,3-bis(2-chloroethyl)-1-nitrosourea

The damage of DNA structure and synthesis in murine leukemia L1210 cells upon single administration in therapeutic doses of antitumour agents of N-nitrosourea type, such as 1-methyl-1-nitrosourea (MNU) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was studied. MNU and BCNU were characterized by stronger inhibitory effects on de novo DNA synthesis compared to additional pathway of DNA synthesis in leukemia L1210 cells in vivo. Centrifugation in alkaline sucrose density gradients of L1210 cell lysates has revealed persistent single-strand breaks and alkaline-labile sites in newly replicated DNA. Parental DNA structure was more stable to damaging drug effects than that of newly replicated DNA. The results are consistent with our previous data on the differences in the mechanisms of MNU and BCNU action and the absence of complete cross resistance between the drugs.     

Excitotoxic Insult Results in a Long-Lasting Activation of CaMKIIα and Mitochondrial Damage in Living Hippocampal Neurons

Over-activation of excitatory NMDA receptors and the resulting Ca²⁺ overload is the main cause of neuronal toxicity during stroke. CaMKII becomes misregulated during such events. Biochemical studies show either a dramatic loss of CaMKII activity or its persistent autonomous activation after stroke, with both of these processes being implicated in cell toxicity. To complement the biochemical data, we monitored CaMKII activation in living hippocampal neurons in slice cultures using high spatial/temporal resolution two-photon imaging of the CaMKIIα FRET sensor, Camui. CaMKII activation state was estimated by measuring Camui fluorescence lifetime. Short NMDA insult resulted in Camui activation followed by a redistribution of its protein localization: an increase in spines, a decrease in dendritic shafts, and concentration into numerous clusters in the cell soma. Camui activation was either persistent (> 1–3 hours) or transient (~20 min) and, in general, correlated with its protein redistribution. After longer NMDA insult, however, Camui redistribution persisted longer than its activation, suggesting distinct regulation/phases of these processes. Mutational and pharmacological analysis suggested that persistent Camui activation was due to prolonged Ca²⁺ elevation, with little impact of autonomous states produced by T286 autophosphorylation and/or by C280/M281 oxidation. Cell injury was monitored using expressible mitochondrial marker mito-dsRed. Shortly after Camui activation and clustering, NMDA treatment resulted in mitochondrial swelling, with persistence of the swelling temporarily linked to the persistence of Camui activation. The results suggest that in living neurons excitotoxic insult produces long-lasting Ca²⁺-dependent active state of CaMKII temporarily linked to cell injury. CaMKII function, however, is to be restricted due to strong clustering. The study provides the first characterization of CaMKII activation dynamics in living neurons during excitotoxic insults.     

Viability and proliferative activity of a Chinese hamster cell culture exposed to nitrosoureas in exponential and stationary growth phases

The lethal effect of antitumor nitrosourea chloroethyl derivatives on proliferating (exponential phase of growth) and non-proliferating (stationary phase of growth) cells is observed at a concentration 5-fold less than that of methyl derivatives revealed by the colony-formation technique. 1,3-bis(2-chlororoethyl)-1-nitrosourea is equally effective towards proliferating and non-proliferating cells, but chlorozotocin exerts a primary cytotoxic effect on proliferating cells. 1-methyl-1-nitrosourea at low concentration causes death more readily of proliferating cells than non-proliferating ones. However, studies on proliferative activity during the first hours after treatment with 1-methyl-1-nitrosourea revealed drug sensitivity in cells being at the early stationary phase of growth.     

A study of the effects of flocalin on respiration and potassium transport of rat-heart and liver mitochondria

The effects of the drug flocalin, which possesses cardioprotective properties, on the respiration rates of rat-heart and liver mitochondria in different functional states, the efficiency of oxidative phosphorylation, as well as the transport of potassium ions in these organelles, were studied. It was found that flocalin at concentrations of 7–30 μm stimulated respiration of rat-heart and liver mitochondria in V ₂ and V ₄ states in the presence of succinic add as a respiration substrate in a potassium-containing medium. In the absence of potassium ions in the incubation medium, flocalin had no effect on mitochondrial respiration in these states. Studying the functioning of the potassium transport system revealed that flocalin at these concentrations dose-dependently activated the ATP-dependent transport of potassium ions in rat-heart and liver mitochondria. The data we obtained indicate that the cardioprotective effect of flocalin can be associated with activation of the ATP-dependent potassium channel of the inner mitochondrial membrane.     

Effect of enteropeptidase on survival of cultured hippocampal neurons under conditions of glutamate toxicity

The effects of full-size bovine enteropeptidase (BEK) and of human recombinant light chain enteropeptidase (L-HEP) on survival of cultured hippocampal neurons were studied under conditions of glutamate excitotoxicity. Low concentrations of L-HEP or BEK (0.1–1 and 0.1–0.5 nM, respectively) protected hippocampal neurons against the death caused by 100 μM glutamate. Using the PAR1 (proteinase-activated receptor) antagonist SCH 79797, we revealed a PAR1-dependent mechanism of neuroprotective action of low concentrations of enteropeptidase. The protective effect of full-size enteropeptidase was not observed at the concentrations of 1 and 10 nM; moreover, 10 nM of BEK caused death of 88.9% of the neurons, which significantly exceeded the cell death caused by glutamate (31.9%). Under conditions of glutamate cytotoxicity the survival of neurons was 26.8% higher even in the presence of 10 nM of L-HEP than in the presence of 10 nM BEK. Pretreatment of cells with 10 nM of either form of enteropeptidase abolished the protective effect of 10 nM thrombin under glutamate cytotoxicity. High concentrations of BEK and L-HEP caused the death of neurons mainly through necrosis.     

Organization of the cortical bioelectric activity at different stages of a relaxation session

The dynamics of electroencephalographic (EEG) parameters in adults were studied during active relaxation (which involved simple psychological techniques) and passive relaxation (without using any techniques). The experiment included four stages: background 1, active relaxation, passive relaxation, and background 2. During the experiment, the EEG was recorded in the occipital, parietal-temporal-occipital, central, and frontal regions of both hemispheres of the brain. Comparative analysis of the dynamics of EEG parameters during changing experimental conditions was performed in the frequency range from 5 to 40 Hz divided into ten frequency subranges. It was possible to establish the general pattern in the dynamics of EEG parameters at different relaxation stages, as well as differences in system-level brain performance in the active and passive relaxation states.     

A new approach for study of structural and functional properties of proteins with unknown functions

Selected proteins were produced in Escherichia coli bacterial expression system--three proteins from extremophil bacteria: a putative monooxygenase from Deinococcus radiodurans, a putative nucleotidyltransferase from Thermotoga maritima, a putative oxidoreductase from Exiguobacterium sibiricum; and a shaperon from Homo sapiens DJ-1. The protocol of isolation & purification of recombinant proteins were developed that allowed to obtain expression products with the purity of no less than 96%. Conditions for the crystallization have been selected that allowed a stable growth of crystals. Preliminary x-ray experiments were conducted in order to confirm the quality of produced crystals; the resolution of obtained structural data was from 1.2 to 1.8 angstrom.