The problem of the radiosensitivity of bone marrow cellular elements and assessments of the postradiation kinetics of myelopoiesis (an analysis based on data on the sequelae of the accident at the Chernobyl Atomic Electric Power Station]

On the basis of the data obtained from 61 cases of accidental exposure (0.1-12.5 Gy) at the Chernobyl A.P.S. the kinetics of acute radiation bone-marrow syndrome was analyzed and radiosensitivity of the entire spectrum of human granulocytic compartment cells was estimated. The radiosensitivity estimates were made by a "functional" criterion, developed by the authors, which was based on the comparative ability of irradiated and nonirradiated bone marrow cells of different maturity to produce peripheral blood neutrophils. Changes were found in physiology of myeloid cells during their maturation: the maturation mechanism, for cells of the committed pool, was "attached" to the division process, whereas these processes were independent for cells of the dividing and maturing pool. It is once again confirmed that the transit time of a maturing myeloid cell, to begin with the primarily committed one and to end with a peripheral blood neutrophil, is not constant and lasts normally for 32 days.     

Nonhomogeneity of the distribution of the absorbing substance in cytophotometry]

Results of two-wavelengths cytophotometry may be used to calculate m--the quantity of light absorbing substance, and gamma--the degree of non-homogeneity of distribution of the substance on a preparation. Formula (1) is almost free from any distributional error. Optical density limits of applicability of formula (3) for gamma are shown on fig. 2. An algorithm for calculation of gamma at higher optical densities is proposed.     

Model of regulation of the proliferation rate of bone marrow stem cells]

A mathematical model of speed regulation of the reproduction of bone marrow stem cells has been constructed and investigated, Two possible regulation mechanisms of proliferative activity of stem cells have been compared: at tissue level and at subtissual units level. The comparison of calculation results and experimental data has shown that the latter regultaion mechanism of stem cells proliferation would take place.     

Diversity of Eukaryotic Microorganisms in the Drainage Waters of a Coal Open-Cast Mine

Microbiology - The composition of the microbiome of acid drainage water of a quarry used for the mining of brown coal was studied. The water had a pH of 5.15 and contained 1.4 g/L of sulfate....     

The Cytochrome P450 Epoxygenase Pathway Regulates the Hepatic Inflammatory Response in Fatty Liver Disease

Fatty liver disease is an emerging public health problem without effective therapies, and chronic hepatic inflammation is a key pathologic mediator in its progression. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs), which have potent anti-inflammatory effects. Although promoting the effects of EETs elicits anti-inflammatory and protective effects in the cardiovascular system, the contribution of CYP-derived EETs to the regulation of fatty liver disease-associated inflammation and injury is unknown. Using the atherogenic diet model of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH), our studies demonstrated that induction of fatty liver disease significantly and preferentially suppresses hepatic CYP epoxygenase expression and activity, and both hepatic and circulating levels of EETs in mice. Furthermore, mice with targeted disruption of Ephx2 (the gene encoding soluble epoxide hydrolase) exhibited restored hepatic and circulating EET levels and a significantly attenuated induction of hepatic inflammation and injury. Collectively, these data suggest that suppression of hepatic CYP-mediated EET biosynthesis is an important pathological consequence of fatty liver disease-associated inflammation, and that the CYP epoxygenase pathway is a central regulator of the hepatic inflammatory response in NAFLD/NASH. Future studies investigating the utility of therapeutic strategies that promote the effects of CYP-derived EETs in NAFLD/NASH are warranted.     

EH3 (ABHD9): the first member of a new epoxide hydrolase family with high activity for fatty acid epoxides

Epoxide hydrolases are a small superfamily of enzymes important for the detoxification of chemically reactive xenobiotic epoxides and for the processing of endogenous epoxides that act as signaling molecules. Here, we report the identification of two human epoxide hydrolases: EH3 and EH4. They share 45% sequence identity, thus representing a new family of mammalian epoxide hydrolases. Quantitative RT-PCR from mouse tissue indicates strongest EH3 expression in lung, skin, and upper gastrointestinal tract. The recombinant enzyme shows a high turnover number with 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid (EET), as well as 9,10-epoxyoctadec-11-enoic acid (leukotoxin). It is inhibited by a subclass of N,N'-disubstituted urea derivatives, including 12-(3-adamantan-1-yl-ureido)-dodecanoic acid, 1-cyclohexyl-3-dodecylurea, and 1-(1-acetylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea, compounds so far believed to be selective inhibitors of mammalian soluble epoxide hydrolase (sEH). Its sensitivity to this subset of sEH inhibitors may have implications on the pharmacologic profile of these compounds. This is particularly relevant because sEH is a potential drug target, and clinical trials are under way exploring the value of sEH inhibitors in the treatment of hypertension and diabetes type II.     

Genetic disruption of soluble epoxide hydrolase is protective against streptozotocin-induced diabetic nephropathy

Cytochrome P-450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important roles in regulating cardiovascular functions. The anti-inflammatory, antiapoptotic, proangiogenic, and antihypertensive properties of EETs suggest a beneficial role for EETs in diabetic nephropathy. Endogenous EET levels are maintained by a balance between synthesis by CYP epoxygenases and hydrolysis by epoxide hydrolases into physiologically less active dihydroxyeicosatrienoic acids. Genetic disruption of soluble epoxide hydrolase (sEH/EPHX2) results in increased EET levels through decreased hydrolysis. This study investigated the effects of sEH gene disruption on diabetic nephropathy in streptozotocin-induced diabetic mice. Streptozotocin-induced diabetic manifestations were attenuated in sEH-deficient mice relative to wild-type controls, with significantly decreased levels of Hb A(1c), creatinine, and blood urea nitrogen and urinary microalbumin excretion. The sEH-deficient diabetic mice also had decreased renal tubular apoptosis that coincided with increased levels of antiapoptotic Bcl-2 and Bcl-xl, and decreased levels of the proapoptotic Bax. These effects were associated with activation of the PI3K-Akt-NOS3 and AMPK signaling cascades. sEH gene inhibition and exogenous EETs significantly protected HK-2 cells from TNFα-induced apoptosis in vitro. These findings highlight the beneficial role of the CYP epoxygenase-EETs-sEH system in the pathogenesis of diabetic nephropathy and suggest that the sEH inhibitors available may be potential therapeutic agents for this condition.     

Analysis of activity of neuron pairs in the cat caudate nucleus

Activity of neuron pairs in the caudate nucleus, derived simultaneously by a single microelectrode, was investigated in experiments on lightly anesthetized, immobilized cats. Strong temporal correlation was shown to be characteristic of the spontaneous activity of a neuron pair if grouped discharges were present in that activity. If, however, spontaneous activity was characterized by impulses randomly distributed in time, temporal correlation was observed in only 50% of cases, it was weaker, and it reflected excitatory and inhibitory interactions equally. In many cases negative correlation was observed in discharges of neurons within the time interval of 0–4 msec. Electrical stimulation of the various afferent inputs of the caudate nucleus not only did not cause correlation to appear in the discharges of the neurons but, on the contrary, it abolished correlation which existed for that same pair of neurons discharging spontaneously. Comparison of the results with data in the literature indicates that, by the character of interaction of its neurons, the caudate nucleus is one of the group of associative nuclei of the brain.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 5, pp. 486–493, September–October, 1978.     

Polymorphism of essential oils in thyme species growing in European part of North-East Russia and Ural

Essential oils of thyme species growing in the European part of North-East Russia and Ural were shown to contain azulene, trans-isopropyl-1-methyl-2-cyclohexene-1-ol, trans-4,5-epoxycarane, 1,3,5-tri-methylene cycloheptane, eudesm-7(11)-en-4-ol, and isoaromadendrene epoxide. Detection in the plants of the genus Thymes of uncharacteristic compounds could be accounted for by the beginning of investigation of earlier unexplored species or by the biosynthesis of these compounds induced by environmental conditions. All species of the genus Thymus growing in the European part of North-East Russia and Ural (T. hirticaulis, T. talijevii, T. paucifolius, T. guberlinensis, and T. punctulosus) belong to nonphenolic chemotype characteristic of the way of their adaptation to low temperatures. In three species (T. talijevii, T. paucifolius, and T. punctulosus), essential oils were rich in bicyclic sesquiterpenes.