Occurrence of Lipid Peroxidation in Brain Microsomes in the Presence of NADH and Vanadate

Oxidation of NADH by rat brain microsomes was stimulated severalfold on addition of vanadate. During the reaction, vanadate was reduced, oxygen was consumed, and H2O2 was generated with a stoichiometry of 1:1 for NADH/O2, as in the case of other membranes. Extra oxygen was found to be consumed over that needed for H2O2 generation specifically when brain microsomes were used. This appears to be due to the peroxidation of lipids known to be accompanied by a large consumption of oxygen. Occurrence of lipid peroxidation in brain microsomes in the presence of NADH and vanadate has been demonstrated. This activity was obtained specifically with the polymeric form of vanadate and with NADH, and was inhibited by the divalent cations Cu2+, Mn2+, and Ca2+, by dihydroxy-phenolic compounds, and by hemin in a concentration-dependent fashion. In the presence of a small concentration of vanadate, addition of an increasing concentration of Fe2+ gave increasing lipid peroxidation. After undergoing lipid peroxidation in the presence of NADH and vanadate, the binding of quinuclidinyl benzylate, a muscarinic antagonist, to brain membranes was decreased.

Effect of undernutrition on the metabolism of phospholipids and gangliosides in developing rat brain

1. Phospholipid content of brains of 3- or 8-week-old undernourished rats was 7--9% less than that for the corresponding control animals and this deficit could not be made up by rehabilitation. Phosphatidyl ethanolamine and plasmalogen were the components most affected in brains of undernourished rats. 2. Incorporation of 32P into phospholipids by brain homogenates was 28% higher in 3-week-old undernourished rats. It is suggested that enhanced phospholipid metabolism in undernourished animals may be related to behavioural alterations noted previously (Sobotka, Cook & Brodie, 1974). 3. Ganglioside concentrations in 3- and 8-week-old undernourished animals were 14% and 11.5% less respectively than those of the control animals and this difference could be made up by rehabilitation. [14C]Glucosamine incorporation in vivo into brain gangliosides was not affected by undernutrition.

Effect of phenyl and phenolic acids on mevalonate-5-Phosphate decarboxylase if the brain

Phenyl and phenolic acids are known to inhibit metabolism of mevalonate in rat brain. The site of inhibition has been found to be mevalonate-5-pyrophosphate decarboxylase. Phenolic acids also inhibited mevalonate-5-phosphate kinase on preincubation. The kinetics showed that p-coumaric acid and isoferulic acid were competing with substrates, mevalonate-5-phosphate or mevalonate-5-pyre phosphate, whereas others showed an uncompetitive type of inhibition. Chlorophenoxyisobutyrate, a hypocholesterolaemic drug, had no effect on these enzymes. An improved method for the synthesis of mevalonate-5-phosphate and mevalonate-5-pyrophosphate, labeled at carbon-1, is described.

Numerical simulation of solidification of liquid aluminum alloy flowing on cooling slope

Preparation of semisolid slurry using a cooling slope is increasingly becoming popular, primarily because of the simplicity in design and ease control of the process. In this process, liquid alloy is poured down an inclined surface which is cooled from underneath. The cooling enables partial solidification and the incline provides the necessary shear for producing semisolid slurry. However, the final microstructure of the ingot depends on several process parameters such as cooling rate, incline angle of the cooling slope, length of the slope and initial melt superheat. In this work, a CFD model using volume of fluid (VOF) method for simulating flow along the cooling slope was presented. Equations for conservation of mass, momentum, energy and species were solved to predict hydrodynamic and thermal behavior, in addition to predicting solid fraction distribution and macrosegregation. Solidification was modeled using an enthalpy approach and a volume averaged technique for the different phases. The mushy region was modeled as a multi-layered porous medium consisting of fixed columnar dendrites and mobile equiaxed/fragmented grains. The alloy chosen for the study was aluminum alloy A356, for which adequate experimental data were available in the literature. The effects of two key process parameters, namely the slope angle and the pouring temperature, on temperature distribution, velocity distribution and macrosegregation were also studied.

Cooling of a composite slab in a two-fluid medium

A mixed boundary value problem associated with the diffusion equation that involves the physical problem of cooling of an infinite parallel-sided composite slab in a two-fluid medium, is solved completely by using the Wiener-Hopf technique. An analytical solution is derived for the temperature distribution at the quench fronts being created by two different layers of cold fluids having different cooling abilities moving on the upper surface of the slab at constant speedv. Simple expressions are derived for the values of the sputtering temperatures of the slab at the points of contact with the respective layers, assuming the front layer of the fluid to be of finite width and the back layer of infinite extent. The main problem is solved through a three-part Wiener-Hopf problem of a special type and the numerical results under certain special circumstances are obtained and presented in the form of a table.

Solution structure of Am2766: A highly hydrophobic d-conotoxin from Conus amadis that inhibits inactivation of brain voltage gated sodium channels

The three-dimensional (3D) NMR solution structure (MeOH) of the highly hydrophobic δ-conotoxin δ-Am2766 from the molluscivorous snail Conus amadis has been determined. Fifteen converged structures were obtained on the basis of 262 distance constraints, 25 torsion-angle constraints, and ten constraints based on disulfide linkages and H-bonds. The root-mean-square deviations (rmsd) about the averaged coordinates of the backbone (N, Cα, C) and (all) heavy atoms were 0.62±0.20 and 1.12±0.23 Å, respectively. The structures determined are of good stereochemical quality, as evidenced by the high percentage (100%) of backbone dihedral angles that occupy favorable and additionally allowed regions of the Ramachandran map. The structure of δ-Am2766 consists of a triple-stranded antiparallel β-sheet, and of four turns. The three disulfides form the classical ‘inhibitory cysteine knot’ motif. So far, only one tertiary structure of a δ-conotoxin has been reported; thus, the tertiary structure of δ-Am2766 is the second such example.Another Conus peptide, Am2735 from C. amadis, has also been purified and sequenced. Am2735 shares 96% sequence identity with δ-Am2766. Unlike δ-Am2766, Am2735 does not inhibit the fast inactivation of Na+ currents in rat brain Nav1.2 Na+ channels at concentrations up to 200 nM.

Analysis of conjugate laminar mixed convection cooling in a shrouded array of electronic components

The temperature variation in the insulation around an electronic component, mounted on a horizontal circuit board is studied numerically. The flow is assumed to be laminar and fully developed. The effect of mixed convection and two different types of insulation are considered. The mass, momentum and energy conservation equations in the fluid and conduction equation in the insulation are solved using the SIMPLER algorithm. Computations are carried out for liquid Freon and water, for different conductivity ratios, and different Rayleigh numbers. It is demonstrated that the temperature variation within the insulation becomes important when the thermal conductivity of the insulation is less than ten times the thermal conductivity of the cooling medium.

Cooling of an infinite slab in a two-fluid medium

A mixed boundary-valued problem associated with the diffusion equation, that involves the physical problem of cooling of an infinite slab in a two-fluid medium, is solved completely by using the Wiener-Hopf technique. An analytical solution is derived for the temperature distribution at the quench fronts being created by two different layers of cold fluids having different cooling abilities moving on the upper surface of the slab at constant speed. Simple expressions are derived for the values of the sputtering temperatures of the slab at the points of contact with the respective layers, assuming one layer of the fluid to be of finite extent and the other of infinite extent. The main problem is solved through a three-part Wiener - Hopf problem of a special type, and the numerical results under certain special circumstances are obtained and presented in the form of a table.

Specific-heat measurements during cooling through the glass-transition region

In this paper we report the measurements of specific heats of five glass formers as they are cooled through the glass-transition region. The measurements are compared with other specific-heat measurements such as adiabatic-calorimetry and ac-calorimetry measurements. The data are then analyzed using a model of enthalpy relaxation and nonequilibrium cooling, which can track the nonequilibrium relaxation time tau(S). The relevant parameters that describe tau(S) are obtained, allowing us to compare the enthalpy-relaxation times obtained from this method with other methods. We display the clear connection of the unrelaxed enthalpy with the nonequilibrium relaxation time and also show the role played by the delayed heat release from the unrelaxed enthalpy in the glass-transition region. We have also made certain definite observations regarding the equilibrium configurational specific heat and the Vogel-Fulcher law, which describes tau(S).

High level stable expression of rat brain type IIA sodium channel ?-subunit in CHO cells

The neuronal sodium channels are responsible for the rising phase of action potential and are composed of three subunits, of which the alpha-subunit has been shown to be adequate for most of its functional properties. We have stably expressed the rat brain type IIA sodium channel alpha-subunit in CHO cell tine using a CMV promoter-based vector. The expression was confirmed by detecting a 6.5 kb RNA corresponding to sodium channel alpha-subunit using Northern hybridization. The cells stably expressing the alpha-subunit, yield isolated sodium currents of amplitudes greater than 4nA when studied in whole-cell configuration of the patch-clamp technique. The sodium currents are characterized by activation and inactivation properties similar to neuronal sodium channels, and are blocked by the voltage gated sodium channel blocker tetrodotoxin (TTX).

In vitro and in vivo effects of methyl isocyanate on rat brain mitochondrial respiration

The present study deals with the in vitro and in vivo effects of methyl isocyanate (MIC) on rat brain mitochondrial function. Addition of MIC to tightly coupled brain mitochondria in vitro resulted in a mild stimulation of state 4 respiration, abolition of respiratory control, decrease in ADP/0 ratio, and inhibition of state 3 oxidation. The oxidation of NAD+-linked substrates (glutamate + malate) was more sensitive (fourfold) to the inhibitory action of MIC than succinate while cytochrome oxidase was unaffected. Administration of MIC subcutaneously at a lethal dose affected respiration only with glutamate + malate as the substrate (site I) and caused a 20% decrease in state 3 oxidation leading to a significant decrease in respiratory control index while state 4 respiration and ADP/O ratio remained unaffected. As both the malondialdehyde and iron contents of brain mitochondria were not altered, it may be inferred that the observed in vivo inhibition of state 3 oxidation is induced by MIC through systemic stagnant hypoxia leading to ischemia of brain, which further contributes to the cerebral hypoxia.

Regulation of diacylglycerol kinase in rat brain membranes by docosahexaenoic acid

The effect of docosahexaenoic acid (DHA) on the diacylglycerol kinase (DG kinase) activity in rat brain membranes was investigated. DHA at 500 mu M concentration, stimulated the enzyme activity by about 2 fold. This effect was concentration-and time-dependent and was observed after very short periods of incubation (one min). DHA stimulation of DG kinase was observed only with rat brain membranes, and not with rat brain cytosol or rat liver membranes. Treating the rat brain membranes with phospholipase A(2) which released free fatty acids including DHA, significantly stimulated the DG kinase activity. It is concluded that DHA through its stimulatory effect on DG kinase may regulate the signalling events in growth-related situations in the brain such as synaptogenesis.

Injection cooling of blunt bodies flying at high Mach numbers

A study of transpiration cooling of blunt bodies such as a hemicylinder is made by solving Navier-Stokes equations. An upwind, implicit time-marching code is developed for this purpose. The study is conducted for both perfect-gas and real-gas (chemical equilibrium) flows. Investigations are carried out for a special wall condition that is referred to as no heat flow into the wall condition. The effects of air injection on wall temperature are analyzed. Analyses are carried out for Mach numbers ranging between 6-10 and Reynolds numbers ranging between 10(6)-10(7). Studies are made for spatially constant as well as spatially varying mass injection rate distributions, White cold air injection reduces the wall temperature substantially, transpiration cooling is relatively less effective when the gas is in chemical equilibrium.