High-capacity Component Research Articles

ZnCl2-based activation for converting spent coffee grounds into a robust anode for Li-ion batteries

Achieving a net-zero target via a circular economy approach necessitates maximizing the recycling of waste into higher-value materials. In the present study, spent coffee grounds (SCG) from industrial food processing biomass waste are converted into a high-performance anode material used in lithium-ion batteries via one-step carbonization of ZnCl2 at 550 °C. The hybrid composites (HCs) are collected after the process contained C- and Zn-based mixed oxides, such as zinc silicate (Zn2SiO4) and zinc ferrate (ZnFe2O4). The content of Zn-based mixed oxides in HCs increases with the initial ZnCl2:SCG mass ratio and reaches its maximum at a ratio of 2:1 wt/wt (HCs_2). The electrochemical performance of the HC-based anodes is proportional to the loaded Zn content when the ZnCl2:SCG mass ratio increases from 0 to 2. The optimized anode (HCs_2) exhibits a charge capacity of 692 mAh g−1 and capacity retention of 86 % at the 100th cycle, whereas the corresponding values for HCs_0 anode (without ZnCl2 treatment) are 311 mAh g−1 and 73.3 %. The superior electrochemical performance of the optimized anode is attributed to the nanosized Zn2SiO4 and ZnFe2O4, stabilization effect of activated carbon matrices, and a strategy that increases the proportions of high-capacity components.

Towards high-capacity lithium ion batteries:constructing hollow-structured SiOx-based nanocube anode via a sequential coating strategy

Reserving void space for silicon oxide-based (SiOx-based) anodes has proved highly efficient in tackling their volume expansion and contraction upon lithiation/delithiation. Specially, hollow structure featured with sufficient internal spaces shows great promise in buffering the volumetric effect of SiOx. However, constructing a hollow structure, containing high-capacity SiOx components and high-conductivity carbon components, still remains a great challenge. In this work, we design a sequential coating strategy to initially construct sandwich hollow-structured high-capacity SiOx anode (NC@SiOx@m-C) that consists of an innermost nitrogen-doped porous carbon network (NC), a middle mesoporous SiOx layer, and outermost mesoporous carbon (m-C) layer. The incorporation of high-capacity component SiOx (x < 2) via sequential coating process greatly improves the specific capacity of NC@SiOx@m-C. Both of NC and m-C layers synergistically enhance the overall electronic conductivity of the anode. Moreover, the outermost m-C layer retards the direct contact between SiOx and electrolyte and effectively reduces the side reactions. As a result, the NC@SiOx@m-C nanocubes delivers a capacity as high as 583 mAh g−1 at a high current density of 1 Ag-1 after 500 cycles, giving an excellent electrochemical performance.

Efficient Lithium/Sodium-Ion Storage by Core-Shell Carbon Nanospheres@TiO2 Decorate by Epitaxial WSe2 Nanosheets Derived from Bimetallic Polydopamine Composites.

Metal-polydopamine coordination chemistry attracts great attention owing to the synergistic effect of adjustable components and advantageous structures. However, few efforts have been devoted to exploring bimetal-polydopamine composites, especially for multistructural composites with high-capacity components and high stability. In this regard, the TiO2 @C-WSe2 core-shell nanospheres are designed and fabricated based on Ti-W-polydopamine composites after selenization, in which the TiO2 nanoparticles are encapsulated or embedded in the carbon nanospheres and the external WSe2 nanosheets are grown epitaxially on the carbon surfaces, featuring multiple channels for ion diffusion and abundant active edges for electrochemical reactions. The introduction of WSe2 not only greatly improves the capacity but also results in exponential growth of the active edge. As a result, the as-prepared TiO2 @C-WSe2 displayed long-term cycling performance in lithium-ion batteries. Furthermore, the anode is assembled into sodium-ion batteries, manifesting a stable capacity of 352mA h g-1 at 1.0 A g-1 even after 2000 cycles, one of the best performances for polydopamine-based composites. Enhanced performance can be attributed to the synergies of high-capacity components and different dimensional materials. This work highlights that the rational design of functional structures provides a novel inspiration for electrodes with effective nanoarchitectures.

Enhanced Structural Stability and Volumetric Capacity of a 3D Pyknotic Graphene Conductive Network via a Pillar Effect of Sn Nanoparticles for Sodium-Ion Batteries

High volumetric capacity and durability anode materials for sodium ion batteries have been urgently required for practical applications. Herein, we reported a Sn-pillared pyknotic graphene conductive network with high-level N-doping. This densely stacked block offers high volumetric Na-ion storage capacity, rapid electrochemical reaction kinetics, and robust structural stability during cycling owing to the high capacity component (metallic Sn ≈847 mAh g-1), high tap density (≈2.63 g cm-3), high conductivity (N doping ≈5 at. %), and strong spatially confined and pillared structure. Moreover, theoretical simulations have indicated that the charge accumulation around the N-doped region is more pronounced compared to the pristine one, and electrons accumulate around the N atom while loss occurs at the Na atom. These studies also suggest that it might possibly contribute to higher conductivity and stronger electrophilic reactivity, thereby resulting in enhanced Na-ion storage performance. As a result, the as-obtained electrode material exhibits competitive volumetric capacity (1462 mAh cm-3 at 0.1 A g-1), cycling performance (1207 mAh cm-3 after 100 cycles), and promising rate behavior simultaneously.

Cut of OPEX—Sophisticated Technical Solutions for Hot Strip Mills

The yield and economy during hot strip rolling depend on developing high capacity components fulfilling further the increasing customers’ demands for cost and resource effective production figures. The paper gives an overview of the latest developments for high capacity components and tools of the SMS group for conventional hot strip mills and CSP® plants. The SMS components cover the fields’ mill mechanics, electric, and automation as well as mill reliability and customer strip quality figures in case of modernization tasks as well as erection of new mills.

New insight into the mechanism of accumulation and intraerythrocytic compartmentation of albitiazolium, a new type of antimalarial.

Bis-thiazolium salts constitute a new class of antihematozoan drugs that inhibit parasite phosphatidylcholine biosynthesis. They specifically accumulate in Plasmodium- and Babesia-infected red blood cells (IRBC). Here, we provide new insight into the choline analogue albitiazolium, which is currently being clinically tested against severe malaria. Concentration-dependent accumulation in P. falciparum-infected erythrocytes reached steady state after 90 to 120 min and was massive throughout the blood cycle, with cellular accumulation ratios of up to 1,000. This could not occur through a lysosomotropic effect, and the extent did not depend on the food vacuole pH, which was the case for the weak base chloroquine. Analysis of albitiazolium accumulation in P. falciparum IRBC revealed a high-affinity component that was restricted to mature stages and suppressed by pepstatin A treatment, and thus likely related to drug accumulation in the parasite food vacuole. Albitiazolium also accumulated in a second high-capacity component present throughout the blood cycle that was likely not related to the food vacuole and also observed with Babesia divergens-infected erythrocytes. Accumulation was strictly glucose dependent, drastically inhibited by H+/K+ and Na+ ionophores upon collapse of ionic gradients, and appeared to be energized by the proton-motive force across the erythrocyte plasma membrane, indicating the importance of transport steps for this permanently charged new type of antimalarial agent. This specific, massive, and irreversible accumulation allows albitiazolium to restrict its toxicity to hematozoa-infected erythrocytes. The intraparasitic compartmentation of albitiazolium corroborates a dual mechanism of action, which could make this new type of antimalarial agent resistant to parasite resistance.

Role of H 2O 2 on the kinetics of low-affinity high-capacity Na +-dependent alanine transport in SHR proximal tubular epithelial cells

The presence of high and low sodium affinity states for the Na +-dependent [ 14C]- l-alanine uptake in immortalized renal proximal tubular epithelial (PTE) cells was previously reported (Am. J. Physiol. 293 (2007) R538–R547). This study evaluated the role of H 2O 2 on the Na +-dependent [ 14C]- l-alanine uptake of ASCT2 in immortalized renal PTE cells from Wistar Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). Na + dependence of [ 14C]- l-alanine uptake was investigated replacing NaCl with an equimolar concentration of choline chloride in vehicle- and apocynin-treated cells. Na + removal from the uptake solution abolished transport activity in both WKY and SHR PTE cells. Decreases in H 2O 2 levels in the extracellular medium significantly reduced Na +- K m and V max values of the low-affinity high-capacity component in SHR PTE cells, with no effect on the high-affinity low-capacity state of the Na +-dependent [ 14C]- l-alanine uptake. After removal of apocynin from the culture medium, H 2O 2 levels returned to basal values within 1 to 3 h in both WKY and SHR PTE cells and these were found stable for the next 24 h. Under these experimental conditions, the Na +- K m and V max of the high-affinity low-capacity state were unaffected and the low-affinity high-capacity component remained significantly decreased 1 day but not 4 days after apocynin removal. In conclusion, H 2O 2 in excess is required for the presence of a low-affinity high-capacity component for the Na +-dependent [ 14C]- l-alanine uptake in SHR PTE cells only. It is suggested that Na + binding in renal ASCT2 may be regulated by ROS in SHR PTE cells.

Kinetic analysis of agonist-induced down-regulation of the beta(2)-adrenergic receptor in BEAS-2B cells reveals high- and low-affinity components.

We examined the interrelationships of internalization and down-regulation of the beta(2)-adrenergic receptor in response to treatment of the BEAS-2B human epithelial cell line with both a series of agonists at high occupancy and with various concentrations of fenoterol that gave occupancies from 0.93 to 0.001. We found that the extent of internalization measured after a 30-min treatment increased as a function of coupling efficiency, with ephedrine, dobutamine, albuterol, fenoterol, and epinephrine giving 0, 7, 17, 48, and 55% internalization, respectively. With the exception of dobutamine, the rates of down-regulation (k(deg)) also showed a dependence on agonist coupling efficiency, giving (in terms of fraction of receptors lost/h) 0.082 with ephedrine, 0.250 with dobutamine, 0.148 with albuterol, 0.194 with fenoterol, and 0.212 with epinephrine. Comparison of down-regulation to internalization showed that weak agonists caused down-regulation in the absence of significant internalization. The extent of internalization caused by fenoterol over a 1000-fold range of occupancy was proportional to agonist occupancy. However, although no internalization was observed with the low concentrations (0.2 and 2 nM fenoterol), these concentrations did cause significant down-regulation. Thus, as with partial agonists, it was clear that down-regulation occurred in the absence of measurable internalization. The kinetics of agonist-induced down-regulation are consistent with a scheme in which down-regulation proceeds by two pathways; a high-affinity, low-capacity component (EC(50) = 0.5 nM) clearly dissociated from internalization and a low-affinity, high-capacity component (EC(50) = 160 nM) closely correlated with internalization.

Electrogenic sodium-sodium exchange carried out by Na,K-ATPase containing the amino acid substitution Glu779Ala.

Na,K-ATPase containing the amino acid substitution glutamate to alanine at position 779 of the alpha subunit (Glu779Ala) supports a high level of Na-ATPase and electrogenic Na+-Na+ exchange activity in the absence of K+. In microsomal preparations of Glu779Ala enzyme, the Na+ concentration for half maximal activation of Na-ATPase activity was 161 +/- 14 mM (n = 3). Furthermore, enzyme activity with 800 mM Na+ was found to be similar in the presence and absence of 20 mM K+. These results showed that Na+, with low affinity, could stimulate enzyme turnover as effectively as K+. To gain further insight into the mechanism of this enzyme activity, HeLa cells expressing Glu779Ala enzyme were voltage clamped with patch electrodes containing 115 mM Na+ during superfusion in K+-free solutions. Electrogenic Na+-Na+ exchange was observed as an ouabain-inhibitable outward current whose amplitude was proportional to extracellular Na+ (Na+(o)) concentration. At all Na+(o) concentrations tested (3-148 mM), exchange current was maximal at negative membrane potentials (V(M)), but decreased as V(M) became more positive. Analyzing this current at each V(M) with a Hill equation showed that Na+-Na+ exchange had a high-affinity, low-capacity component with an apparent Na+(o) affinity at 0 mV (K0(0.5)) of 13.4 +/- 0.6 mM and a low-affinity, high-capacity component with a K0(0.5) of 120 +/- 13 mM (n = 17). Both high- and low-affinity exchange components were V(M) dependent, dissipating 30 +/- 3% and 82 +/- 6% (n = 17) of the membrane dielectric, respectively. The low-affinity, but not the high-affinity exchange component was inhibited with 2 mM free ADP in the patch electrode solution. These results suggest that the high-affinity component of electrogenic Na+-Na+ exchange could be explained by Na+(o) acting as a low-affinity K+ congener; however, the low-affinity component of electrogenic exchange appeared to be due to forward enzyme cycling activated by Na+(o) binding at a Na+-specific site deep in the membrane dielectric. A pseudo six-state model for the Na,K-ATPase was developed to simulate these data and the results of the accompanying paper (Peluffo, R.D., J.M. Argüello, and J.R. Berlin. 2000. J. Gen. Physiol. 116:47-59). This model showed that alterations in the kinetics of extracellular ion-dependent reactions alone could explain the effects of Glu779Ala substitution on the Na,K-ATPase.

Inhibition of Mouse and Human CYP 1A- and 2E1-dependent Substrate Metabolism by the Isoflavonoids Genistein and Equol

The inhibitory effect of the isoflavonoids genistein and equol on cytochrome P450 activities has been investigated. Genistein and equol inhibited the high capacity component of p-nitrophenol (CYP2E1 substrate) metabolism in liver microsomes from acetone-induced mice with IC 50 values of approximately 10 m m and 560 μ m, respectively (cf. diethyldithiocarbamate, IC 50, 69 μ m). Using human CYP2E1 from a specific expression system (which overcame multienzyme involvement in the rodent system), non-competitive inhibition was also seen with both isoflavonoids. Genistein and equol also inhibited the high capacity component of ethoxyresorufin (CYP1A substrate) metabolism in liver microsomes from β-naphthoflavone-induced mice with IC 50 values of 5.6 m m and 1.7 m m, respectively (cf. α-naphthoflavone, IC 50 0.8 μ m). Using human CYP1A2 from a specific expression system, non-competitive inhibition was seen with both isoflavonoids. CYP1A1 inhibition offers a possible explanation for the chemopreventative effect of genistein against, for example, dimethylbenz[ a]anthracene genotoxicity reported in animals but the IC 50 values negate the relevance of this specific chemopreventative action at the levels likely to be achieved from the human diet.

Therlt11 andraec1 mutants ofArabidopsis thaliana lack the activity of a basic-amino-acid transporter

The concentration dependence of the influx ofl-lysine in excised roots ofArabidopsis thaliana seedlings was analyzed for the wild-type (WT) and two mutants,rlt11 andraec1, which had been selected as resistant to lysine plus threonine, and to S-2-aminoethyl-l-cysteine, respectively. In the WT three components were resolved: (i) a high-affinity, low-capacity component [K m = 2.2 μM;V max = 23 nmol·(g FW)−1·h−1]; (ii) a low-affinity, high-capacity component [K m = 159 μM;V max = 742 nmol·(g FW)−1·h−1]; (iii) a component which is proportional to the external concentration, with a constant of proportionalityk = 104 nmol·(g FW)−1 h−1];·mM−1. The influx ofl-lysine in the mutants was lower than in the WT, notably in the concentration range 0.1–0.4 mM, where it was only 7% of that in the WT. In both mutants the reduced influx could be fully attributed to the absence of the low-affinity (high-K m ) component. This component most likely represents the activity of a specific basic-amino-acid transporter, since it was inhibited by several other basic amino acids (arginine, ornithine, hydroxylysine, aminoethylcysteine) but not byl-valine. The high-affinity uptake ofl-lysine may be due to the activity of at least two general amino acid transporters, as it was inhibitable byl-valine, and could be further dissected into two components with a high affinity (K i = 1–5 μM; and a low affinity (K i = 0.5–1mM) forl-valine, respectively. Therlt11 andraecl mutant have the same phenotype and the corresponding loci were mapped on chromosome 1, but it is not yet clear whether they are allelic.

Possible functional interactions of apolipoprotein B-100 segments that associate with cell proteoglycans and the ApoB/E receptor.

The interaction of apoE lipoproteins with cells appears to be mediated by an association with basic sequences of proteoglycans and the apoB/E receptor. ApoB-100 has basic sequences, homologous with those of apoE, that form part of the apoB/E receptor-binding domain. These sequences of apoB-100 also interact with proteoglycans. We investigated whether such segments, in analogy with apoE, could act cooperatively on LDL interactions with proteoglycans and the receptor. As a model we used the two most basic regions of apoB-100, 3147 through 3157 and 3359 through 3367, connected by three glycines (3145-3157-GGG-3359-3367). Such segments may be proximal in LDL by the presence of a disulfide bridge between Cys(3167) and Cys(3297). The apoB heterodimer but not the separated monomers inhibited 125I-LDL degradation in fibroblasts and THP-1 cells by 50% at approximately 11 mumol/L. The heterodimer affinity with arterial proteoglycans was closer to that of LDL and higher than that of the individual peptides. The heterodimer appears to bind specifically to THP-1 cells, with a Kd of 6.2 x 10(-8) mol/L and a Bmax of 1.3 x 10(6) molecules/cell. Monoclonal antibody C-7, which recognizes the apoB receptor, inhibited the binding to cells. Treatment of fibroblasts with chondroitinase ABC or chlorate decreased 125I-LDL degradation markedly. Hydrolysis of pericellular proteoglycans of fibroblasts by chondroitinases reduced mostly the low-affinity, high-capacity component of LDL binding. This compartment appears to hold 70% of the cell-associated LDL when internalization is inhibited at 4 degrees C. Therefore, cell-surface chondroitin sulfate/dermatan sulfate proteoglycans appear to modulate binding and receptor-mediated internalization of LDL. This may be caused, at least in part, by the association of proteoglycans with the apoB-100 segments 3145 through 3157 and 3359 through 3367.

The raz1 mutant of Arabidopsis thaliana lacks the activity of a high-affinity amino acid transporter

The raz1 mutant of Arabidopsis thaliana (L.) Heynh. has been selected as resistant to the toxic proline analogue, azetidine-2-carboxylic acid (2AZ). Seedlings of the mutant tolerated fivefold higher concentrations of 2AZ (ED50 = 0.25 mM) than the wild-type seedlings (EC50 = 0.05 mM). The mutant gene was found to be semi-dominant and the corresponding RAZ1 locus was mapped on chromosome 5 at 69.6 +/- 1.8 cM. The resistance to 2AZ could be fully and exclusively accounted for by the lower uptake rate of the proline analogue in the mutant. The influx of L-proline in roots of wild-type seedlings could be dissected into two components: (i) a component with a high affinity and a low capacity for L-proline (Km) approximately 20 microM, Vmax approximately 60 nmol.(g FW)-1.h-1) and also a high affinity for L-2AZ (Ki approximately 40 microM) and (ii) a low-affinity, high-capacity component (Km) approximately 5 mM: Vmax = 1300 nmol.(g FW)-1.h-1). Clearly, the raz1 mutation affects the activity of a high-affinity transporter, because the high-affinity uptake of proline in the mutant was at least fivefold lower than in the wild-type, whereas the low-affinity uptake was unchanged.

Tumour growth results in changes in placental amino acid transport in the rat: a tumour necrosis factor α-mediated effect

The implantation of a fast growing tumour (Yoshida AH-130 ascites hepatoma) to late pregnant rats resulted in no changes in fetal growth, this possibly being associated with an important increase in the fetal uptake of maternal-derived amino acids [Carbó, López-Soriano and Argilés (1995) Endocrinology 136, 3579-3584]. The present investigation was undertaken to see whether the presence of the tumour induced changes in placental transport systems. For alanine transport, although no changes in affinity (Km) were observed, tumour growth resulted in a 192% increase in Vmax in the Na(+)-independent component. Kinetic analysis of the Na(+)-dependent component resulted in two clearly different components: while the low-affinity and high-capacity component was unaffected by tumour growth, the high-affinity, low-capacity component of the tumour-bearing rats showed an important increase in Vmax. (78%). With regard to leucine transport, tumour burden induced important increases in the Na(+)-independent component, not only in Km (262%) but also in Vmax. (189%). Since elevated tumour necrosis factor-alpha (TNF) concentrations have been reported in this kind of tumour model, we performed the same type of transport experiments in rats chronically treated with TNF, the results obtained showing great similarities with those observed with tumour growth. The Vmax. of Na(+)-independent alanine transport was also increased by the cytokine (104%) while no changes were observed in affinity. TNF treatment also induced an increase in the Vmax. (67%) of the Na(+)-dependent (high-affinity, low-capacity) component while no changes in affinity were observed. Concerning leucine kinetics, TNF treatment, as in the case of tumour growth, also increased Km (155%) and Vmax. (72%) associated with Na(+)-independent transport. Interestingly, treatment with the cytokine increased both the Km (43%) and Vmax. (64%) of the Na(+)-dependent component. The inhibition patterns suggest the existence of more that one Na(+)-dependent transport for alanine although the majority of the amino acid is transported through the A system. The results presented suggest that, during gestation, the mother is able to adapt her placental amino acid transport systems to compensate for the nitrogen drainage associated with tumour growth and thus provide the fetus with enough amino acids to allow its normal growth, and that TNF could be responsible for the triggering of this compensatory mechanism.

Cerebellar and striatal dopamine receptors: Effects of reeler and weaver murine mutations

The presence and the binding characteristics of D1 and D2 receptors were investigated in normal-reeler and normal-weaver mutant mice utilizing [3H]spiperone (D2 antagonist), [3H]SKF 38393 (D1 agonist), and [3H]DA as ligands. Analysis of the binding data showed that in the cerebellum there are two binding components for all [3H]ligands. Comparison of the binding constants from cerebellum and striatum showed that in cerebellum the high affinity-low capacity component has similar affinity with that of striatum. The reeler and weaver mutations affected the binding of all ligands: In reeler, total cerebellar specific binding sites for [3H]spiperone and [3H]SKF 38393 decrease significantly (approximately 50% and approximately 70%, respectively), while those for [3H]DA show a small (approximately 10-15%) but not significant decrease. In weaver, total cerebellar specific binding sites for [3H]spiperone, [3H]SKF 38393, and [3H]DA also decrease significantly (approximately 60%, approximately 70%, and approximately 50%, respectively). In reeler striatum [3H]SKF 38393 binding (Bmax) is significantly decreased (approximately 24%), while [3H]spiperone and [3H]DA binding (Bmax) is not affected. In weaver striatum, [3H]SKF 38393 binding is significantly increased (approximately 40%), while [3H]DA binding (Bmax) decreases significantly (approximately 70%). On the basis of the cytoarchitectural aberrations that characterize the cerebellum of these mutants and some well-established information regarding the dopaminergic system of the cerebellum, the above results indicate that in this region a) D1 receptors are mainly localized on granule cells and b) D2 receptors are localized postsynaptically on granule cells and presynaptically on the DA fibers innervating the cerebellum.

Inhibition kinetics of hepatic microsomal long chain fatty acid-CoA ligase by 2-arylpropionic acid non-steroidal anti-inflammatory drugs

Microsomal long chain fatty acid CoA ligase (EC 6.2.1.3) has been implicated in the formation of CoA thioesters of xenobiotics containing a carboxylic acid moiety. In this study we have demonstrated that the microsomal enzyme from rat liver exhibits biphasic kinetics for the formation of palmitoyl-CoA, i.e. there are high affinity low capacity K m high , 1.6 μM, V max high , 12.9 nmol/ mg/ min) and low affinity high capacity ( K m low , 506 μM, V max low , 58.3 nmol/ mg/ min) components. Inhibition of the high affinity isoform was studied using the R and S enantiomers of ibuprofen, fenoprofen, ketoprofen and naproxen. The high affinity component of palmitoyl-CoA formation was competitively inhibited by R-fenoprofen( K i 15.4 μM) while R-ibuprofen exhibited mixed inhibition kinetics. In contrast the R and S enantiomers of ketoprofen and naproxen were non-competitive inhibitors. This diversity of inhibition kinetics observed argues in favour of a binding site in addition to the catalytic site. A competitive interaction with the high affinity form correlated with literature evidence of enantiospecific chiral inversion and “hybrid” triglyceride formation for the R enantiomers of fenoprofen and ibuprofen. Paradoxically, R-ketoprofen which is extensively inverted in rats was a non-competitive inhibitor of palmitoyl-CoA formation by the high affinity isoform suggesting that it may not act as an alternate substrate. The results of this study clearly indicate that formation of R-2-arylpropionate-CoAs is not fully explained by interaction with the high affinity isoform of a microsomal long chain (palmitoyl) CoA ligase and therefore the involvement of other isofonns cannot be discounted.

In vitro evidence for the involvement of at least two forms of human liver UDP-glucuronosyltransferase in morphine 3-glucuronidation

Morphine 3-glucuronidation kinetics and the inhibitory effects of a number of xenobiotics on morphine glucuronidation in human liver microsomes have been investigated. In both native and detergent-activated microsomes morphine glucuronidation exhibited biphasic kinetics, with a high affinity, low capacity component and a low affinity, high capacity component. These data suggest the involvement of at least two forms of human liver UDP-glucuronosyltransferase (UDPGT) in morphine glucuronidation. The high affinity morphine-UDPGT activity is likely to be of most importance in morphine glucuronidation in vivo. Chloramphenicol, 4-hydroxybiphenyl, 4-methylumbelliferone, 1-naphthol and 4-nitrophenol were all shown to inhibit the low affinity morphine-UDPGT activity, but only chloramphenicol and 1-naphthol were competitive inhibitors. Each of these xenobiotics were shown to be a non-inhibitor of the high affinity morphine-UDPGT activity, or at least to have considerably lower affinity for this enzyme form(s) than morphine itself. Overall the results provide further evidence for the heterogeneity of human liver UDPGT and, in conjunction with other recent studies (Miners JO et al., Kinetic and inhibitor studies of 4-methylumbelliferone and 1-naphthol glucuronidation in human liver microsomes, Biochem Pharmacol 37: 665–671, 1988) of the kinetics of human liver glucuronidation reactions, indicate that xenobiotic substrates such as morphine, 4-methylumbelliferone and 1-naphthol may be used to differentiate UDPGT isozyme activities in human liver microsomes.

The chronic effects of desipramine and sertraline on platelet and synaptosomal 5HT uptake in olfactory bulbectomised rats

1. 1. Depressed patients show a characteristic decrease in the rate of uptake of serotonin into their platelets, which is normalised only by clinically effective antidepressant treatment. 2. 2. We also find a decrease in platelet 5HT uptake rates in the olfactory bulbectomised (OB) rat model of depression, which return to normal following three weeks of treatment with desipramine or sertraline. 3. 3. Synaptosomal 5HT uptake appears to consist of a low affinity, high capacity component and a high affinity, low capacity component, both of which are increased in the OB rat, compared to its sham operated control, and normalised by chronic antidepressant treatment. 4. 4. The low affinity uptake of serotonin is not inhibited by in vitro incubation with sertraline, which suggests that the low affinity system may be associated with a non-specific uptake of 5HT into noradrenergic or dopaminergic nerve endings.

Two populations of neurotensin binding sites in murine brain: discrimination by the antihistamine levocabastine reveals markedly different radioautographic distribution

Monoiodo-[ 125I-Tyr 3]neurotensin (NT) bound to a high affinity, low capacity binding component and a lower affinity, high capacity component in rat brain synaptic membranes. The antihistamine H 1 agent levocabastine, which bears no structural relationship to NT, selectively and totally inhibited NT binding to its low affinity binding sites. The IC 50 for levocabastine was 7 nM. Lowering the temperature of the binding assay from 25 to 4°C markedly reduced the affinity of the high affinity NT binding site but did not affect the ability of levocabastine to discriminate between high and low affinity NT binding sites in rat brain membranes and tissue sections. Radioautographic studies of [ 125I-Tyr 3]NT binding to rat brain tissue sections in the absence and presence of levocabastine revealed markedly different regional distributions of the two NT binding components. The levocabastine-sensitive NT binding site was present in membranes from rat and mouse brain but absent from rabbit brain membranes and from human brain tissue sections. It was also absent from mouse neuroblastoma N1E115 and human colonic adenocarcinoma HT29 cell membranes, two cell lines which have previously been shown to possess NT receptors functionally coupled to intracellular second messenger-generating systems. These findings are discussed in the light of the known properties of the high and low affinity NT binding sites in rat brain.

Thermal contacts through mechanical moving parts in low thermal budget optical cryogenic assemblies

Ball bearings or mechanical reductors constitute thermal impedances that can reach the known poor level of thermal radiative exchange at low temperatures, 6 × 10 4 Km −2 W −1. This can induce unacceptable hoop stresses when cooling down high heat capacity components or create thermal heterogeneities on scientific experiments and superconducting devices which are supposed to be cold and isothermic. Soft metallic contacts afford good thermal contacts but cause higher mechanical torque and then increase the heat flux through the contact line. The developments described here were made on one of the four Infrared Space Observatory experiments.