Synchrotron single-crystal XRD, IR-, Raman spectroscopy and high pressure study of synthetic krieselite.

Spontaneous crystals of krieselite (Ge analogue of topaz) with the chemical formula Al2[(Ge0.75Si0.25)O4](F1.63OH0.37) were synthesized using a thermo-gradient hydrothermal method at a temperature of 600/650 °C and pressure of 100 MPa. The unit cell parameters are: a = 8.9732(8) Å, b = 8.4823(7) Å, c = 4.7379(5) Å, V = 360.62(6) Å3, space group Pnma. The F-/OH- content of the samples was refined by FTIR spectroscopy method. Raman spectroscopy showed the main differences between the spectra of krieselite and topaz at the ambient conditions. The assignment of observed and calculated Ag bands (cm-1) for non-polarized Raman spectra was carried out. Using in situ Raman spectroscopy at high pressures, the dependence of the shift in the position of the main bands of the krieselite Raman spectrum on the pressure was established, and the corresponding paths of pressure induced distortion of crystal structure was assumed. According to the data of Raman spectroscopy, it was revealed that krieselite does not undergo the phase transitions up to 30 GPa. The probable way of crystal structure distortion within the space group Pnma was proposed based on simulation of high-pressure Raman spectra.

Synthetic brunogeierite Fe2GeO4: XRD, Mössbauer and Raman high-pressure study.

We present complex spectroscopic data of the synthetic brunogeierite (Fe2+)2Ge4+O4 with space group Fd3¯m of spinel structure: a = 8.3783 (6) Å, V = 588.12 (13) Å3. Brunogeierite crystals up to 200 µm in size were crystallized by the interaction of a boric acid solution on a metal iron wire in the presence of germanium oxide (GeO2) at 600/650 °C and 100 MPa. Mössbauer spectrum of synthetic brunogeierite consists of the symmetric doublet with the parameters IS = 1.104(1) mm/s and QS = 2.845(1) mm/s, that corresponds to the octahedral position of iron ions ([VI]Fe2+). The Raman spectra of Fe2GeO4 crystal consist of an intense main band at 756 cm-1 and four less intense bands at ∼644, 472, 302, and ∼205 cm-1 at ambient conditions. All five bands inherent in the spectrum of cubic spinel are present and gradual change in high pressure spectra up to 30 GPa. The color of the crystal changes from brown-orange to reddish at the center at 22.7 GPa and became opaque black up to 30.2 GPa. Herewith, in the high pressure spectra, we observed the splitting of some bands and the appearance of additional bands in a wide pressure range (from 1.6 to 30 GPa). The factor group analysis with the lattice dynamics calculation of potential crystal structure distortions shows the decreasing of the structure symmetry to tetragonal or rhombohedral in this pressure range.

Exploring photochemistry of p-bromophenylsulfonyl, p-tolylsulfonyl and methylsulfonyl azides by ultrafast UV-pump-IR-probe spectroscopy and computations.

The photochemistry of p-bromophenylsulfonyl azide (BsN3), p-tolylsulfonyl azide (TsN3) and methylsulfonyl azide (MsN3) was studied by femtosecond time-resolved infrared spectroscopy with CH2Cl2 and CCl4 as solvents along with quantum chemical calculations. The photolysis of these azides after 267 nm light excitation leads to the population of each respective azide S1 excited state. Decay of the S1 excited state gives rise to singlet nitrene formation. In the case of BsN3, the decay was found to correlate with the formation of a pseudo-Curtius photoproduct (PCP) BrC6H4NSO2. Transient electronic ground states of the three azides on their way to singlet nitrenes and PCPs were shown by locating the corresponding transition states on the potential energy surfaces. The lifetime of singlet (1)(BsN) and (1)(TsN) nitrenes is τ(S) = ∼20 ps in CH2Cl2 and ∼700 ps in CCl4. Singlet (1)(MsN) was not detected. Due to fast intersystem crossing (ISC), singlet nitrenes are converted into the triplet spin isomers lying lower in energy, the formation time constants being equal to the corresponding singlet nitrene lifetime. The formation of (3)(MsN) was shown and the formation time constant in CH2Cl2 was found to be τ(ISC) = 34 ± 3 ps. Internal conversion of the S1 excited state to the ground state of the azide was low (Φ ≈ 0.15) for BsN3 and TsN3 and was not found in the case of MsN3.

Role of nicotinic and muscarinic cholinoreceptors in the realization of the cholinergic anti-inflammatory pathway during the early phase of sepsis.

Stimulation of nicotinic and muscarinic cholinoreceptors (nAChR, mAChR) in outbred albino mice with nicotine and aceclidine, respectively, in single equilethal doses 0.5 DL(50)6 h before sepsis induction significantly reduced animal mortality due to a decrease in blood concentrations of proinflammatory cytokines IL-1ß, IL-6, and MIP-2. Stimulation of mAChR (injection of aceclidine) stimulated the neutrophilic phagocytic and metabolic activity. Realization of the cholinergic anti-inflammatory pathway (stimulation of the peripheral nicotinic cholinoreceptors (α7nAChR) and central muscarinic cholinoreceptors (mAChR) was modulated by stimulation of the muscarinic cholinoreceptors of the phagocytic monocytic system cells.

Effects of reversible inhibition of cholinesterase and nicotine on mouse mortality and blood levels of proinflammatory cytokines during the early phase of sepsis.

Experiments on outbred albino mice have shown that proserine (reversible cholinesterase inhibitor) and nicotine (nicotinic receptor agonist) in a equivalent dose of 0.2 DL(50)injected 2 h before sepsis induction significantly reduced animal mortality from experimental infection due to reduction of blood concentrations of proinflammatory cytokines TNF-α, IL-1ß, and IL-6.

Mechanisms of immune status disorders in chronic ethanol intoxication.

Experiments of outbred albino rats showed that chronic ethanol intoxication (20 days, summary dose 5 LD(50)) inhibited immune reactions mainly mediated by Th1-cells, increased blood corticosterone concentration, reduced T-lymphocyte acetylcholinesterase activity, blood concentrations of IFN-γ, IL-2, IL-4, IL-10, and increased IL-6 level.

Role of cholinergic and cytokine regulation of T cell function in stimulation and inhibition of immune reactions in intoxication by organophosphorus compounds in different doses.

Experiments on outbred albino rats showed that administration of acetylcholine and aceclidine in a dose of 0.1 LD50 for 3 days and of dimethyl dichlorovinyl phosphate (organophosphorus compound) in a single dose of 0.05 LD50 stimulated the function of Th1 and Th2 lymphocytes and cytokine production by these cells. Dimethyl dichlorovinyl phosphate in a single dose of 0.5 LD50 produced an opposite effect. Acetylcholine and aceclidine stimulated activity of acetylcholinesterase in T cells, while dimethyl dichlorovinyl phosphate in a single dose of 0.5 LD50 inhibited it. During acute intoxication, the organophosphorus compound, depending on the dose, can stimulate (acetylcholine effect) and inhibit the immune reactions (acetylcholinesterase inhibition of T cells).

Blood concentrations of persistent toxic substances in the indigenous communities of the Russian Arctic.

OBJECTIVES: Investigation was carried out within the framework of the large-scale international project "Persistent Toxic Substances (PTS), Food Security and Indigenous People of the Russian North" under RAIPON/AMAP/GEF aegis. Objectives of the project are to obtain comprehensive information on exposure of indigenous populations to contaminants through food chains (and other sources), and to investigate the possible health effects connected to this exposure. Four regions of Russia are involved in the project: Kola Peninsula (Murmansk oblast), Nenetsk okrug (Pechora river basin), Taimyr Peninsula, Chukotka Peninsula. METHODS: Questionnaire and paired sampling of maternal/cord blood among indigenous women at childbirth (more than 250 persons) as well as among general indigenous population (more than 1,400 persons), additionally breast milk sampling of lactating women (more than 50 persons) in Chukotka was conducted. About 700 blood samples have been analyzed at the Center for Environmental Chemistry, SPA "Typhoon" (Obninsk, Russia), the Regional Center "Monitoring of the Arctic", RCMA (St. Petersburg, Russia), the Norwegian Institute for Air Research, NILU (Tromso, Norway) and at INSPQ (Sainte-Foy, Quebec, Canada). RESULTS AND CONCLUSIONS: On the whole, PTS in human blood of the Russian Arctic natives are similar to those in the coastal areas of Greenland and Canada, and for some POPs such as toxaphenes and mirex, these levels are lower.

Chaos-assisted instanton tunneling in one-dimensional perturbed periodic potential.

For the system with a one-dimensional spatially periodic potential we demonstrate that small periodic in-time perturbation results in the appearance of chaotic instanton solutions. We estimate the parameter of local instability, the width of the stochastic layer, and the correlator for perturbed instanton solutions. The application of the instanton technique enables us to calculate the amplitude of the tunneling, the form of the spectrum, and the lower bound for the width of the ground quasienergy zone.

Influence of buprenorphine, butorphanol and nalbuphine on the initiation of intravenous cocaine self-administration in drug naive mice.

The influence of different mixed mu-kappa-opioid receptor agonists-antagonists on cocaine reinforcement was studied using the method of initiation of intravenous cocaine self-administration in naive mice. Self-administration of cocaine was readily initiated according to an inverted U-shaped unit dose-response curve. Buprenorphine, butorphanol and nalbuphine tested against the optimal unit dose of cocaine (0.8 microg per infusion), inhibited initiation of cocaine self-administration in a dose-dependent manner. When tested against a scale of cocaine unit doses (0.2 -1.6 microg per infusion) buprenorphine (0.1 mg/kg, s.c.) and nalbuphine (2 mg/kg, s. c.) produced a shift of the optimal cocaine dose from 0.8 to 0.4 microg/inf, while butorphanol (1 mg/kg, s.c.) shifted the optimal unit dose of cocaine to the right along the cocaine unit doses axis. Co-administration of naloxone (0.1 mg/kg, s.c.) significantly reduced the effect of buprenorphine but failed to influence the effect of nalbuphine and butorphanol on cocaine intake. Taken together, these results suggest that nalbuphine is capable of affecting cocaine's reinforcing properties in the same manner as buprenorphine during the initiation phase of cocaine self-administration behavior, while butorphanol causes the opposite effect. Although the exact opioid profile of action of the mixed opioid receptor agonists-antagonists is as yet not precisely known, the present findings suggest that multiple opioid receptor systems (i.e. mu and kappa) play a role in reinforcing properties of cocaine and that a co-operative interaction between mu- and kappa-opioid systems may be of importance during initiation of cocaine self-administration.

Kappa-opioid receptor blockade with nor-binaltorphimine modulates cocaine self-administration in drug-naive rats.

The modulation of the reinforcing effects of cocaine by the kappa-opioid receptor antagonist, nor-binaltorphimine was studied by using the initiation of intravenous self-administration in drug-naive Wistar rats. Treatment with nor-binaltorphimine (3.0 mg/kg s.c.) 48 h before the start of the first of five daily self-administration sessions significantly decreased the intake of cocaine when offered in a threshold unit dose (30 micrograms per infusion), but had no effect on cocaine intake when it was offered in a higher unit dose (60 micrograms per infusion). It is concluded that blockade of the kappa-opioid receptor by nor-binaltorphimine may produce a rightward shift of the unit dose-response relationship of cocaine reward, thus decreasing the sensitivity to cocaine reward. These data suggest an involvement of endogenous kappa-opioid systems in the mechanisms underlying the initiation of cocaine self-administration behaviour.

Kappa-opioid receptor agonist U50,488H modulates cocaine and morphine self-administration in drug-naive rats and mice.

Modulation of the reinforcing effects of cocaine and morphine by the kappa-opioid receptor agonist U50,488H (trans-3,4-dichloro-N-methyl-N-(2-1-pyrrolidinyl)-cyclohexyl-benzeace tamide) was studied by using the method of intravenous (i.v.) self-administration in drug-naive Wistar rats and DBA/2 mice. Self-administration of cocaine (by rats) and morphine (by mice) was readily initiated and showed an inverted U-shaped unit dose-response curve. Treatment with the kappa-opioid receptor agonist U50,488H dose dependently decreased the intake of both cocaine and morphine when offered in doses that readily initiated and sustained self-administration behavior. Interestingly, treatment with U50,488H induced self-administration behavior with lower sub-threshold doses of cocaine and morphine. With regard to the inverted U-shaped relation between the dose of the drug and the number of self-infusions, it seems that activation of the kappa-opioid receptor with U50,488H produced an almost parallel shift to the left, indicating an increased sensitivity of the animals for the reinforcing effects of cocaine and morphine. These data demonstrate an involvement of kappa-opioid systems in the neurobiological mechanisms underlying drug addiction in general, and sensitivity for drug reward in particular. Furthermore, the dual effect of kappa-opioid receptor agonists on drug self-administration may prompt further research into the mechanisms underlying the role of endogenous opioids in drug self-administration.

Naloxone inhibits the reinforcing and motivational aspects of cocaine addiction in mice.

The opioid receptor antagonist naloxone is known to influence a wide range of behavioral effects of cocaine, including its addictive property. In the present study the effects of different doses of naloxone and naloxone-methyl-iodide, a methylated analogon of naloxone that does not penetrate the blood-brain barrier, on the action of cocaine in the intravenous self-administration and conditioned place preference (CCP) paradigm were assessed. Systemic naloxone, but not naloxone-methyl-iodide, dose-dependently suppressed cocaine intake during self-administration and decreased the preference for the cocaine-associated compartment in the CCP paradigm. A significant blockade of cocaine's effects was only present at a relatively high dose of NLX (1.0 mg/kg, s.c.). In addition, NLX produced a rightward shift in the inverted U-shaped dose-response curve for cocaine reward during self-administration, indicating a decrease in sensitivity for the reinforcing effects of cocaine. These data demonstrate that blockade of opioid receptors in the brain block both the reinforcing and conditioned motivational effects of cocaine. An interaction between endogenous opioid systems and local dopaminergic systems is suggested in mediating the effects of NLX on cocaine.

Intracerebroventricular La3+ but not Gd3+ inhibits cocaine-induced motor activation in rats.

In the present work the effects of i.c.v. administration of La3+ and Gd3+ on the motor stimulant effect of cocaine in rats were studied. Both La3+ and Gd3+ failed to influence basal motor activity. However, the two metal ions differ in modulation of cocaine-induced activation of motor activity. While Gd3+ (10.0, 20.0 and 40.0 mM/1 ml) did not influence significantly the cocaine effect, La3+ (0.1, 1.0 and 10 mM/1 ml) inhibited cocaine-induced motor activation in a dose-dependent manner. The results suggest the possible involvement of La(3+)-but not Gd(3+)-sensitive calcium channels in the locomotor stimulant effect of cocaine.

Analgesic and reinforcing effects of morphine in mice. Influence of Bay K-8644 and nimodipine.

The aim of the present work was to clarify the role of calcium influx through L-type calcium channels in the rewarding and analgesic effects of morphine. Therefore the effects of Bay K-8644 and nimodipine, dihydropyridine calcium agonist and antagonist, respectively, on the analgesic and rewarding effects of morphine in mice were studied. Morphine-induced analgesia was measured with the aid of writhing test, hot plate test and tail clip test. The rewarding properties of morphine were studied using i.v. self-administration in drug-naive mice. Bay K-8644 potentiated morphine-induced analgesia in all the tests. The influence of nimodipine on morphine analgesia was more complicated and depended on the dose of morphine and test used. In self-administration experiments morphine exhibited the bell-shaped concentration-response curve. Bay K-8644 produced a shift of the curve to the left, while nimodipine had the opposite action indicating, respectively, facilitating and inhibitory influence on morphine rewarding effect. It is concluded that nimodipine exhibits partial antagonistic properties towards the rewarding action of morphine and slightly potentiates morphine-induced analgesia while Bay K-8644 increases either the rewarding or the analgesic effects of morphine.

Combination ethacizin and ethmozin treatment of resistant ventricular ectopy: theoretical, experimental, and clinical study.

Ethmozin (Moricizine HCl) and ethacizin are two class I antiarrhythmic drugs with different rate constants of interaction with the sodium channel. Computer simulation using the "guarded-receptor" model predicted that the combination of ethacizin and ethmozin should exert a greater decrease in excitability and conduction at short coupling intervals, but little effect at normal heart rates (HR). To test this prediction, we measured intraventricular conduction delay in canine hearts in vivo. In agreement with the model, the combination more potently prolonged the delay only at intervals < 600 ms as compared with ethacizin alone. Combination therapy was tested in 6 patients with idiopathic ventricular ectopic depolarizations (VEDs). Three patients were resistant to either ethmozin or ethacizin monotherapy, and three could not tolerate effective doses because of side effects. Quantitative continuous ECG monitoring showed that total VEDs in the resistant group decreased 0 and 17 +/- 13% for 400 and 800 mg/day ethmozin and 18 +/- 12 and 55 +/- 12% for 100 and 200 mg/day ethacizin, respectively. Combined therapy with ethmozin (400 mg/day) and ethacizin (100 mg/day) reduced the number of VEDs by 78 +/- 2% in these patients without side effects. In the "nonresistant" but intolerant group of patients, use of the combination allowed relief of symptomatic ectopy without side effects. A theoretical model correctly predicted an effective combination of class I antiarrhythmic drugs, one with "fast-off" and one with "slow-off" kinetics, which may provide a general rationale for choosing drug combinations.

Cocaine, amphetamine and cathinone, but not nomifensine and pargyline increase calcium inward current in internally perfused neurons.

The influence of cocaine, amphetamine, cathinone, pargyline and nomifensine on inward calcium current was studied using internally perfused neurons of the snail Lymnaea stagnalis. While nomifensine and pargyline inhibited inward calcium current in the concentrations 10(-7)-10(-4) M and did not affect them in the concentrations 10(-9)-10(-8) M, cocaine, amphetamine and cathinone had a biphasic action on inward calcium current, causing activation (10-30 percent) at 10(-9)-10(-7) M, and inhibition at higher concentrations. Only cathinone caused a shift of the I-V characteristics of the membrane along the potential axis. It is suggested that drugs of abuse affect membrane excitability and inward calcium current in neurons directly.

Low concentrations of A23187 increase calcium uptake by cardiac sarcoplasmic reticulum.

The divalent cation ionophore A23187 at a concentration of 1 nM produced an increased rate of oxalate-supported calcium uptake by isolated cardiac sarcoplasmic reticulum as determined by absorbance changes of the calcium-sensitive dye murexide. Addition of a higher concentration of A23187 (0.1 microM) produced a decreased rate of calcium uptake. Measurement of the time during which ATPase was activated by calcium addition also suggested an increased rate of calcium uptake in the presence of 1 nM A23187 and an inhibition of calcium uptake at a higher concentration of the ionophore (0.1 microM). Ca2+-stimulated ATPase activity and incorporation of 32Pi from [gamma-32P]ATP into sarcoplasmic reticular proteins were increased by A23187 at concentrations of 1 nM or greater. An increased coupling of calcium uptake to ATP hydrolysis was observed at 1 nM A23187, while concentrations of the ionophore greater than or equal to 10 nM produced a decreased coupling. Addition of an inhibitor of cyclic AMP-dependent protein kinase decreased the rate of calcium uptake, and this inhibition was reversed in a concentration-dependent manner by 0.01-1 nM A23187. These data suggest that A23187 can activate a mechanism involving the calcium-dependent phosphorylation of protein that may regulate the activity of the calcium uptake system of the sarcoplasmic reticulum. These observations appear to provide an explanation for some of the contractile effects of A23187 in intact cardiac muscle that suggest that treatment with the ionophore results in an increased sequestration of calcium from the cytoplasm.

The cardiac relaxing system. Its nature, calcium ion capacity, and influence of hydrogen and magnesium ions on initial velocity of calcium binding.

The functional and structural properties of Ca2+ ATPases isolated from heart and skeletal muscles were compared. The pH and Ca2+ dependences of the activities as well as amino acid and phospholipid composition of the enzymes are similar. On the other hand, specific activities of Ca2+ ATPases and their abilities to pump calcium in the reconstituted proteoliposomes differ. The sarcoplasmic reticulum (SR) extracted completely from 1 g of pigeon and guinea pig hearts is able to bind up to 65 and 76 nmol Ca2+/sec, respectively, at 37 degrees (24 microM concentration of free Ca2+ ions). In the absence of oxalate, the process of calcium binding is nonlinear in a time interval of 100 msec to 5 min. One-third and half of the quantity of calcium consumed at 1 sec is bound at 100 and 200 msec, respectively. Judging by steady-state levels of the phosphorylated intermediate of Ca2+ ATPase in highly purified and completely extracted preparations of SR, an estimate was made that 1 g of heart contains from 2 to 3 mg of SR protein. The rate of energy-dependent calcium binding by isolated cardiac SR depends on pH and the concentrations of free calcium and magnesium. At calcium concentrations above 5 microM, the rate of calcium accumulation is higher at pH 6.2 than at pH 7.2. Increase in magnesium ion concentration from 0.5 to 6.0 mM leads to a significant inhibition of calcium binding at calcium concentrations 0.1 to 10 microM. The data obtained show that at physiological concentrations of calcium, the ability of SR to accumulate calcium is close to that postulated for a system of calcium transport providing relaxation for heart muscle.