Relationship between analgesia and extracellular morphine in brain and spinal cord in awake rats

Extracellular concentrations of morphine from the dorsal spinal cord, the periaqueductal gray (PAG) including the dorsal raphé, and the lateral hypothalamus were measured by microdialysis in awake rats after intraperitoneal (i.p.) administration of 2.5, 5.0 and 10 mg/kg morphine. Morphine concentrations in all areas showed similar time courses: morphine was detected in the first dialysate sample (13-15 min) and maximal concentrations were reached at 45 min after injection. When in vivo recoveries of morphine from the spinal cord and brain areas were taken into account, no significant differences between morphine concentrations in the various areas were found. The relationship between extracellular morphine concentrations and morphine-induced analgesic behavior was investigated by simultaneously measuring morphine in the dialysate and its analgesic effect in the paw-withdrawal and tail-flick tests. In all areas sampled, the extracellular concentrations of morphine at different times after i.p. injection, significantly correlated with the magnitude of behavioral analgesia assessed by either test. The highest correlation was obtained between extracellular concentrations of morphine in the spinal cord and PAG and behavioral analgesia assessed in the paw-withdrawal test. Our data indicate that, after systemic injection, morphine is evenly distributed throughout the spinal cord and brain including potential anatomical sites of morphine's analgesic action. We estimate that the minimal extracellular morphine concentration in spinal cord that is required to produced a significant increase in nociceptive threshold is approximately 100 pg/25 microl, which corresponds to a tissue concentration of about 100 mg/g of morphine.     

Etude de la reaction du carbone avec le sulfure d'hydrogene H2S a hautes temperatures et sous basses pressions

Reaction of carbon with hydrogen sulfide at high temperature (1000–2000°C) and low pressure (10^?4–10^?2 Torr) exhibits the following features:—carbon disulfide CS₂ is the only carbonaceous reaction product. There is no indication that CS₂ would originate from a secondary reaction of the unstable carbon monosulfide CS. Some decomposition of H₂S into its elements is also observed (Figs. 1–3).—as already observed in other high temperature carbon gasification reactions, the intrinsic reactivity of the sample surface is temperature and pressure dependent. Consequently, transitory or stationary rates are observed, depending respectively upon a changing or a stationary surface state of the carbon sample (Fig. 4). The changes in the surface state are more marked for amorphous than for graphitized samples (Fig. 5).—below 1700°C, the true reaction order is smaller than one, as a consequence of the high stability of the carbon-sulfur surface complexes.—for ungraphitized samples, the carbon surface loses slowly and irreversibly its ability to change with changes in pressure and temperature.All these features were previously observed in the reaction of carbon with sulfur vapor: consequently hydrogen sulfide appears to behave simply as a gaseous sulfur carrier. The kinetic behaviour is in agreement with former interpretations assuming presence of peculiar reactive sites, which originate from chemical attack of the solid but disappear due to a surface thermal heating process.Confirming also previous assumptions, sulfur chemisorption strongly affects the reaction kinetics, as shown by the influence of H₂S traces on the kinetics of the C-O₂ reaction (Fig. 10):—at lower temperatures (< 1300°C) there is an important inhibiting effect on the CO production: H₂S is adsorbed strongly on the reactive sites which become inaccessible to O₂ molecules.—in the intermediate temperature range an enhancing effect is observed which is attributed to a hindrance of thermal healing (caused by chemisorption still present).Finally, the kinetic features as a whole are tentatively summarized in a comprehensive diagram where the consistency of experimental results appears clearly.     

Design,analysis and fabrication of high frequency piezoelectric transducers

Applicability of the finite element method to optimize high frequency transducers is reported. Two recent studies on piezoelectric transducers or systems are presented, in which the FEM algorithm is used for the optimization of transducers performance. They provide resonance frequencies from greater than 1 MHz to below 10 kHz. First, miniature multimode monolithic flextensional transducers, with active shells, are described. They combine the advantages of small size and low-cost manufacturing with control of the shape of the acoustic radiation/receive pattern. Then, linear arrays are studied and a technique is developed to reduce cross-coupling in acoustical arrays. In each case, numerical results are compared to experiments and show how the finite element tool is used to improve the understanding of the physical behavior of the system.     

Piezoelectric PZT films for MEMS and their characterization by interferometry

Piezoelectric films can be used in micro-electro-mechanical system (MEMS) devices because the piezoelectric effect can provide high forces with relatively low energy losses. The energy output by a piezoelectric film per unit area is proportional to the film thickness, so it is desirable to have relatively thick films. Chemical solution deposition (CSD) techniques were used to prepare lead zirconate titanate (PZT) thin films with Zr/Ti ratios of 30/70 and 52/48. Usually CSD processing is restricted to making crack-free single layer films of ca 70 nm thick, but modifications to the sol-gel process have permitted the fabrication of dense, crack-free single layers up to 200–300 nm thick, which can be built-up into layers up to 3 μm thick. Thicker PZT films (> 2 μm single layer) can be produced by using a composite sol-gel/ceramic process. Knowledge of the electro-active properties of these materials is essential for modeling and design of novel MEMS devices and accurate measurement of these properties is by no means straightforward. A novel double beam common path laser interferometer has been developed to measure the piezoelectric coefficient in films and the results were compared with the values obtained by Berlincourt method. A laser scanning vibrometer was also used to measuring the longitudinal (d ₃₃) and transverse (d ₃₁) piezoelectric coefficients for PZT films and ceramics and the results were compared to those obtained by the other methods. It was found that for thin film samples, the d _33,f values obtained from the Belincourt method is usually larger than those obtained from the interferometer method but smaller than those from the vibrometer method and the reasons for this are discussed.     

Enteric methane emission,milk production,and composition of dairy cows fed 3-nitrooxypropanol

This study examined the effect of 3-nitrooxypropanol (3-NOP), an investigational substance, on enteric methane emission, milk production, and composition in Holstein dairy cows. Following a 3-wk covariate period, 48 multi- and primiparous cows averaging (± standard deviation) 118 ± 28 d in milk, 43.4 ± 8 kg/d milk yield, and 594 ± 57 kg of body weight were blocked based on days in milk, milk yield, and enteric methane emission and randomly assigned to 1 of 2 treatment groups: (1) control, no 3-NOP, and (2) 3-NOP applied at 60 mg/kg feed dry matter. Inclusion of 3-NOP was through the total mixed ration and fed for 15 consecutive weeks. Cows were housed in a freestall barn equipped with a Calan Broadbent Feeding System (American Calan Inc., Northwood, NH) for monitoring individual dry matter intake and fed ad libitum once daily. Enteric gaseous emissions (methane, carbon dioxide, and hydrogen) were measured using 3 GreenFeed (C-Lock Inc., Rapid City, SD) units. Dry matter intake, cow body weight, and body weight change were not affected by 3-NOP. Compared with the control group, 3-NOP applied at 60 mg/kg feed dry matter decreased daily methane emission, emission yield, and emission intensity by 26, 27, and 29%, respectively. Enteric emission of carbon dioxide was not affected, and hydrogen emission was increased 6-fold by 3-NOP. Administration of 3-NOP had no effect on milk and energy-corrected milk yields and feed efficiency, increased milk fat and milk urea nitrogen concentrations, and increased milk fat yield but had no other effects on milk components. Concentration of C6:0 and C8:0 and the sum of saturated fatty acids in milk fat were increased by 3-NOP. Total trans fatty acids and the sum of polyunsaturated fatty acids were decreased by 3-NOP. In this experiment, 3-NOP decreased enteric methane daily emission, yield, and intensity without affecting dry matter intake and milk yield, but increased milk fat in high-producing dairy cows.     

Neither human immunodeficiency virus-1 (HIV-1) nor HIV-2 infects most-primitive human hematopoietic stem cells as assessed in long-term bone marrow cultures

Phenylglyoxylate (benzoylformate) is an intermediate in the anoxic metabolism of phenylalanine and phenylacetate. It is formed by alpha-oxidation of phenylacetyl-CoA. Phenylglyoxylate is oxidatively decarboxylated by phenylglyoxylate-oxidoreductase to benzoyl-CoA, a central intermediate of anaerobic aromatic metabolism. The phenylglyoxylate oxidizing enzyme activity in the denitrifying bacterium Azoarcus evansii was induced during anaerobic growth with phenylalanine, phenylacetate and phenylglyoxylate, but not with benzoate. The new enzyme phenylglyoxylate:acceptor oxidoreductase was purified and studied. The oxygen-sensitive enzyme reduced both NAD+ and viologen dyes. It was composed of five subunits of approximately 50, 48, 43, 24, and 11.5 kDa; the native mass as determined by gel filtration was 370 kDa, suggesting an alpha2 beta2 gamma2 delta2 epsilon2 composition. Phenylglyoxylate:acceptor oxidoreductase exhibited an ultraviolet/visible spectrum characteristic for an iron-sulfur protein and contained 35 +/- 4 mol Fe, 36 +/- 4 mol acid-labile sulfur, and 1.1 +/- 0.2 mol FAD/mol. The enzyme was specific for phenylglyoxylate (Km 45 microM) and coenzyme A (Km 55 microM); 2-oxoisovalerate was oxidized with 15% of the rate. The turnover number with benzyl viologen at 37 degrees C was 46 s(-1) at the optimal pH of 8. The enzyme catalyzed a NAD(P)H:viologen dye transhydrogenation reaction, NAD(H) being the preferred coenzyme. It also catalyzed an isotope exchange between CO2 and the carboxyl group of the substrate. The data are consistent with the following hypothesis. The enzyme complex consists of a core enzyme of four subunits with the composition alpha2 beta2 gamma2 delta2, as reported for archaeal 2-oxoacid:ferredoxin oxidoreductases; this complex is able to reduce viologen dyes. The holoenzyme contains in addition an epsilon2 unit that catalyzes the transfer of electrons from a small ferredoxin-like subunit of the core complex to NAD+; this unit also catalyzes the transhydrogenase reaction, carries FAD and resembles ferredoxin:NAD(P)+-oxidoreductase.     

Effects of 3-nitrooxypropanol on methane emission,digestion, and energy and nitrogen balance of lactating dairy cows

The objective was to measure effects of 3-nitrooxypropanol (3NP) on methane production of lactating dairy cows and any associated changes in digestion and energy and N metabolism. Six Holstein-Friesian dairy cows in mid-lactation were fed twice daily a total mixed ration with maize silage as the primary forage source. Cows received 1 of 3 treatments using an experimental design based on two 3 × 3 Latin squares with 5-wk periods. Treatments were a control placebo or 500 or 2,500 mg/d of 3NP delivered directly into the rumen, via the rumen fistula, in equal doses before each feeding. Measurements of methane production and energy and N balance were obtained during wk 5 of each period using respiration calorimeters and digestion trials. Measurements of rumen pH (48 h) and postprandial volatile fatty acid and ammonia concentrations were made at the end of wk 4. Daily methane production was reduced by 3NP, but the effects were not dose dependent (reductions of 6.6 and 9.8% for 500 and 2,500 mg/d, respectively). Dosing 3NP had a transitory inhibitory effect on methane production, which may have been due to the product leaving the rumen in liquid outflow or through absorption or metabolism. Changes in rumen concentrations of volatile fatty acids indicated that the pattern of rumen fermentation was affected by both doses of the product, with a decrease in acetate:propionate ratio observed, but that acetate production was inhibited by the higher dose. Dry matter, organic matter, acid detergent fiber, N, and energy digestibility were reduced at the higher dose of the product. The decrease in digestible energy supply was not completely countered by the decrease in methane excretion such that metabolizable energy supply, metabolizable energy concentration of the diet, and net energy balance (milk plus tissue energy) were reduced by the highest dose of 3NP. Similarly, the decrease in N digestibility at the higher dose of the product was associated with a decrease in body N balance that was not observed for the lower dose. Milk yield and milk fat concentration and fatty acid composition were not affected but milk protein concentration was greater for the higher dose of 3NP. Twice-daily rumen dosing of 3NP reduced methane production by lactating dairy cows, but the dose of 2,500 mg/d reduced rumen acetate concentration, diet digestibility, and energy supply. Further research is warranted to determine the optimal dose and delivery method of the product.     

Semisynthesis and screening of a small library of pro-apoptotic squamocin analogues: selection and study of a benzoquinone hybrid with an improved biological profile

Acetogenins of Annonaceae, including squamocin (1), exert spectacular cytotoxicity and the most potent inhibition of NADH:ubiquinone oxidoreductase known so far. Cell death induced by these natural products was identified as apoptosis and was thought to be linked to alterations in mitochondrial function. Quinone-squamocin hybrid compounds were semisynthesized and evaluated for their pro-apoptotic properties with a screening method based on dissipation of the mitochondrial transmembrane potential (DeltaPsim). Herein, we report a short one-step synthesis of a squamocin carboxylic acid analogue. For the first time on a natural product, the radical decarboxylation and quinone addition reaction has enabled preparation of a library of squamocin-quinone hybrids and four other analogues. Squamoquinone, tenfold more potent than squamocin as an inducer of apoptosis, emerged as a promising compound, as it induces apoptosis through a mitochondrial caspase-dependent pathway.     

Experimental characterization of the intragranular strain field in columnar ice during transient creep

A digital image correlation (DIC) technique has been adapted to polycrystalline ice specimens in order to characterize the development of strain heterogeneities at an intragranular scale during transient creep deformation (compression tests). Specimens exhibit a columnar microstructure so that plastic deformation is essentially two-dimensional, with few in-depth gradients, and therefore surface DIC analyses are representative of the whole specimen volume. Local misorientations at the intragranular scale were also extracted from microstructure analyses carried out with an automatic texture analyzer before and after deformation. Highly localized strain patterns are evidenced by the DIC technique. Local equivalent strain can reach values as much as an order of magnitude larger than the macroscopic average. The structure of the strain pattern does not evolve with strain in the transient creep regime. Almost no correlation between the measured local strain and the Schmid factor of the slip plane of the underlying grain is observed, highlighting the importance of the mechanical interactions between neighboring grains resulting from the very large viscoplastic anisotropy of ice crystals. Finally, the experimental microstructure was introduced in a full-field fast Fourier transform polycrystal model; simulated strain fields are a good match with experimental ones.