Modeling the effects of anesthesia on the electroencephalogram

Changes to the electroencephalogram (EEG) observed during general anesthesia are modeled with a physiological mean field theory of electrocortical activity. To this end a parametrization of the postsynaptic impulse response is introduced which takes into account pharmacological effects of anesthetic agents on neuronal ligand-gated ionic channels. Parameter sets for this improved theory are then identified which respect known anatomical constraints and predict mean firing rates and power spectra typically encountered in human subjects. Through parallelized simulations of the eight nonlinear, two-dimensional partial differential equations on a grid representing an entire human cortex, it is demonstrated that linear approximations are sufficient for the prediction of a range of quantitative EEG variables. More than 70 000 plausible parameter sets are finally selected and subjected to a simulated induction with the stereotypical inhaled general anesthetic isoflurane. Thereby 86 parameter sets are identified that exhibit a strong “biphasic” rise in total power, a feature often observed in experiments. A sensitivity study suggests that this “biphasic” behavior is distinguishable even at low agent concentrations. Finally, our results are briefly compared with previous work by other groups and an outlook on future fits to experimental data is provided.

G-protein-coupled-receptor-mediated presynaptic inhibition in the cerebellum

Throughout the central nervous system a dominant form of inhibition of neurotransmitter release from presynaptic terminals is mediated by G-protein-coupled receptors (GPCRs). Neurotransmitter release is typically induced by action potentials (APs), but can also occur spontaneously. Presynaptic inhibition by GPCRs has been associated with modulation of voltage-dependent ion channels. However, electrophysiological recordings of spontaneous, AP-independent (so-called ‘miniature’) postsynaptic events reveal an additional, important form of GPCR-mediated presynaptic inhibition, distinct from effects on ionic conductances and consistent with a direct action on the vesicle release machinery. Recent studies suggest that such miniature events might be of physiological relevance not only in signalling but also in development. In the cerebellum, neurotransmitter release onto Purkinje cells occurs by AP-dependent and AP-independent pathways. Here, I focus on inhibitory synapses between interneurons and Purkinje cells, which are subject to strong, identifiable regulation by endogenous GPCR agonists, to consider mechanisms of GPCR-mediated presynaptic inhibition.

Plant uptake of non-ionic organic chemicals

Plant uptake of organic chemicals is an important process when considering the risks associated with land contamination, the role of vegetation in the global cycling of persistent organic pollutants, and the potential for industrial discharges to contaminate the food chain. There have been some significant advances in our understanding of the processes of plant uptake of organic chemicals in recent years; most notably there is now a better understanding of the air to plant transfer pathway, which may be significant for a number of industrial chemicals. This review identifies the key processes involved in the plant uptake of organic chemicals including those for which there is currently little information, e.g., plant lipid content and plant metabolism. One of the principal findings is that although a number of predictive models exist using established relationships, these require further validation if they are to be considered sufficiently robust for the purposes of contaminated land risk assessment or for prediction of the global cycling of persistent organic pollutants. Finally, a number of processes are identified which should be the focus of future research

Measurement of ionic calcium, pH and soluble divalent cations in milk at high temperature

Dialysis and ultrafiltration were investigated as methods for measuring pH and ionic calcium and partitioning of divalent cations of milk at high temperatures. It was found that ionic calcium, pH, and total soluble divalent cations decreased as temperature increased between 20 and 80°C in both dialysates and ultrafiltration permeates. Between 90 and 110°C, ionic calcium and pH in dialysates continued to decrease as temperature increased, and the relationship between ionic calcium and temperature was linear. The permeabilities of hydrogen and calcium ions through the dialysis tubing were not changed after the tubing was sterilized for 1h at 120°C. There were no significant differences in pH and ionic calcium between dialysates from raw milk and those from a range of heat-treated milks. The effects of calcium chloride addition on pH and ionic calcium were measured in milk at 20°C and in dialysates collected at 110°C. Heat coagulation at 110°C occurred with addition of calcium chloride at 5.4mM, where pH and ionic calcium of the dialysate were 6.00 and 0.43mM, respectively. Corresponding values at 20°C were pH 6.66 and 2.10mM.

Ionic calcium and pH as predictors of stability of milk to UHT processing

This paper describes the use of pH and calcium ion electrodes for investigating factors affecting the heat stability of UHT milk with added calcium chloride. Calcium chloride was added to raw milk to manipulate ionic calcium and pH to within the range that may be typically encountered in raw milk of different compositions and microbial quality. Addition of only 5 mM calcium chloride was sufficient to induce considerable changes in pH, ionic calcium and ethanol stability and alter its stability to UHT treatment. There was a strong relationship between pH decrease and increase in ionic calcium when pH was reduced, whether by addition of calcium chloride or by acidification. Calcium chloride addition was found to increase sediment formation in UHT treated milk. However, sediment could be reduced by addition of stabilizers. Those most effective were ones which decreased ionic calcium and increased pH, such as trisodium citrate and disodium hydrogen phosphate. Sediment formation following UHT treatment was only slight for milk samples whose ethanol stability was greater than 80%.

Inhibition of human mesangial cell proliferation by targeting T-Type calcium channels

Background: Aberrant glomerular mesangial cell (MC) proliferation is a common finding in renal diseases. T-type calcium channels (T-CaCN) play an important role in the proliferation of a number of cell types, including vascular smooth muscle cells. The hypothesis that T-CaCN may play a role in the proliferation of human MC was investigated. Methods: The presence of T-CaCN in primary cultures of human MC was examined using voltage clamping and by RT-PCR. The effect of calcium channel inhibitors, and of siRNA directed against the Cav3.2 T-CaCN isoform, on MC proliferation was assessed using the microculture tetrazolium assay and nuclear BrdU incorporation. Results: Human MC express only the Cav3.2 T-CaCN isoform. Co-incubation of MC with a T-CaCN inhibitor (mibefradil, TH1177 or Ni2+) results in a concentration-dependent attenuation of proliferation. This effect cannot be attributed to direct drug-induced cytotoxicity or apoptosis and is not seen with verapamil, an L-type channel blocker. Transfection of MC with siRNA results in knockdown of T-CaCN Cav3.2 mRNA and a clear attenuation of MC proliferation. Conclusions: These results demonstrate for the first time an important role for T-CaCN in human MC proliferation. This could potentially lead to a novel therapy in the treatment of proliferative renal diseases.

Unexpectedly superior enantioselectivity for trans-stilbene cis-dihydroxylation over anchored triosmium carbonyl species in confined Al-MCM-41 channels

Superior enantioselectivity in the dihydroxylation of trans-stilbene catalysed by anchored triosmium carbonyl species without using a chiral modifier is observed inside sterically congested MCM-41 channels; this effect is more pronounced through the introduction of surface Al sites into the silicate.

Aqueous gels of mixtures of ionic surfactant SDS with pluronic copolymers P123 or F127

Gel diagrams based on tube inversion and oscillatory rheometry are reported for Pluronic copolymers F127 (E98P67E98) and P123 (E21P67E21) in mixtures with anionic surfactant sodium dodecyl sulfate (SDS). Total concentrations (e, SDS+copolymer) were as high as 50 wt% with mole ratios SDS/copolymer (mr) in the ranges 1-5 (F127) a lid 1-7 (PI 23). Temperatures were its high as 90 degrees C. Determination of the temperature dependences of the dynamic moduli served to confirm the gel boundaries from tube inversion and to reveal the high elastic moduli of the gels, e.g., compared at corn parable positions in the gel phase, a 50 wt% SDS/P123 wit h mr = 7 had G' three times that of a corresponding gel of P123 alone. Sin all-angle X-ray scattering (SAX S) was used to show that the structures of all the SDS/F127 gels were bee and that the structures of the SDS/P123 gels with mr = I were either fcc(c = 30 wt%) or hex (c = 40 wt%). Assignment of structures to SDS/P123 gels with values of mr in the range 3-7 was more difficult, as high-order scattering peaks Could be very weak, and at the higher values of c and mr, the SAXS peaks included multiple reflections.

Design of a new foldamer turn-linker-turn in acyclic hexapeptides and formation of channels through self-assembly

Single crystal X-ray diffraction studies and solvent dependent NMR titration reveal that the designed pepticles I and 11, Boc-Xx(1)-Aib(2)-Yy(3)-NH(CH2)(2)NH-Yy(3)-Aib(2)-Xx(1)-Boc, where Xx and Yy are lie and Leu in peptide I and Leu and Val in peptide 11, respectively, fold into a turn-linker-turn (T-L-T) conformation both in the solid state and in solution. In the crystalline state the T-L-T foldamers; of peptide I and II self-assemble to form a three-dimensional framework of channels. The insides of the channels are hydrophilic and found to contain solvent CHCl3 hydrogen bonded to exposed C=O of Aib located at the turn regions. (c) 2008 Elsevier B.V. All rights reserved.

Synthesis of multicarboxylic acid appended imidazolium ionic liquids and their application in palladium-catalyzed selective oxidation of styrene

A series of multicarboxylic acid appended imidazolium ionic liquids ( McaILs) with chloride [ Cl](-) or bromide [ Br](-) as anions have been synthesized and characterized. Deprotonation of these ionic acids gives the corresponding zwitterions. Re-protonation of the zwitterions with strong Bronsted acids gives a series of new ionic acid-adducts, many of which remained as room-temperature ionic liquids. A new catalytic system, McaIL/PdCl2 for the selective catalytic oxidation of styrene to acetophenone with hydrogen peroxide as an oxidant has been attempted. In the presence of McaILs, it is found that the quantity of palladium chloride PdCl2 used can be greatly reduced while the activity ( TOF) and selectivity towards acetophenone are enhanced sharply. It is also shown that the catalytic properties of this system could be finely tuned through the molecular design of the McaILs. The best TOF value obtained so far is 146 h(-1) with 100% conversion of styrene at 93% selectivity to acetophenone. In addition, the catalytic activity has been maintained for at least ten catalytic cycles.

Ultrasonic chemical oxidative degradations of 1,3-dialkylimidazolium ionic liquids and their mechanistic elucidations

A highly efficient process for oxidative degradation of 1,3-dialkylimidazolium ionic liquids in hydrogen peroxide/acetic acid aqueous medium assisted by ultrasonic chemical irradiation is, for the first time, described. It is shown that more than 93% of the 1,3-dialkylimidazolium cation with the corresponding Cl-, Br-, BF4- and PF6- counter-anions at a concentration of 2.5 mM can be degraded at 50 degrees C within 12 h while at 72 h the conversions approach 99%. A tentative mechanism for the degradation of these ILs is for the first time proposed through a detailed kinetic analysis of several characteristic transients and/or immediate products, which are identified during the ILs degradation using GC-MS. The results clearly indicate that three hydrogen atoms in the imidazolium ring are the first sites preferably oxidized, followed by cleavage of the alkyl groups attached to the N atoms from the ring. The nature of the alkyl chain length on the imidazolium ring and the type of counter anion do not seem to affect the degradation process. Further, selective fragmentations of C-N bonds of the imidazolium or derived ring lead to ring opening, forming degraded intermediates. It is also shown that acetoxyacetic acid and biurea are the final kinetically stable degraded products from the ILs under the degradation conditions.