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PubMed2005

The diffusion of health economics knowledge in Europe : The EURONHEED (European Network of Health Economics Evaluation Database) project.

This paper overviews the EURONHEED (EUROpean Network of Health Economics Evaluation Databases) project. Launched in 2003, this project is funded by the EU. Its aim is to create a network of national and international databases dedicated to health economic evaluation of health services and innovations. Seven centres (France, Germany, Italy, The Netherlands, Spain, Sweden and the UK) are involved covering 17 countries. The network is based on two existing databases, the French CODECS (COnnaissance et Decision en EConomie de la Sante) database, created in 2000 by the French Health Economists Association (College des Economistes de la Sante), and the UK NHS-EED (NHS Economic Electronic Database), run by the Centre for Reviews and Dissemination, University of York, York, England. The network will provide bibliographic records of published full health economic evaluation studies (cost-benefit, cost-utility and cost-effectiveness studies) as well as cost studies, methodological articles and review papers. Moreover, a structured abstract of full evaluation studies will be provided to users, allowing them access to a detailed description of each study and to a commentary stressing the implications and limits, for decision making, of the study. Access will be free of charge. The database features and its ease of access (via the internet: http://www.euronheed.org) should facilitate the diffusion of existing economic evidence on health services and the generalisation of common standards in the field at the European level, thereby improving the quality, generalisability and transferability of results across countries.

Databases as Topic↗
PubMed2001

Nitric oxide is required for the induction and heterosynaptic spread of long-term potentiation in rat cerebellar slices.

1. In the cerebellar cortex, brief, 8 Hz activation of parallel fibres (PFs) induces a cyclic adenosine 3'5'-monophosphate (cAMP) and protein kinase A (PKA)-dependent form of long-term potentiation between PFs and Purkinje cells. 2. With 10 mM BAPTA in the recording pipette, potentiation evoked by raised frequency stimulation (RFS) to one of two, synaptically independent PF inputs to the same Purkinje cell did not remain input specific but consistently spread to synapses that did not receive RFS, up to the maximum distance tested of 168 microm. 3. LTP at activated and non-activated sites was accompanied by a decrease in paired pulse facilitation (PPF). The PKA inhibitor H-89 blocked both of these effects. Inhibition of nitric oxide synthase (NOS), either by 7-nitro-indazole (7-NI) or N (G)-nitro-L-arginine methyl ester (L-NAME), completely prevented heterosynaptic potentiation and associated reduction in PPF. LTP at distant synapses was selectively prevented by the nitric oxide scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). Inhibition of soluble guanylate cyclase or protein kinase G had no effect on either pathway. 4. Synaptic potentiation at PF-PC synapses, induced by the adenylate cyclase activator forskolin, was also prevented by inhibition of NOS. Forskolin-induced increases in mEPSC frequency were similarly prevented by NOS inhibition and mimicked by the NO donor spermine NONOate. 5. These results are consistent with the notion that heterosynaptic potentiation is of pre-synaptic origin and dependent upon activation of cAMP/PKA and NO. Moreover, they suggest that cAMP/PKA activation stimulates NO production and this diffusible messenger facilitates pre-synaptic transmitter release at synapses within a radius of upwards of 150 microm, through a mechanism that does not involve cGMP.

Algorithms↗
PubMed1998

Effect of modifying O2 diffusivity and delivery on glomerular and tubular function in hypoxic perfused kidney.

Is O2 diffusivity within renal capillaries rate limiting for O2 delivery to hypoxic renal tubules? Equations based on diffusion theory and developed here predict that soluble hemoglobin (Hb) increases O2 diffusivity by a factor of 1 + [442 Hb%/(P50 + PO2)], where P50 is the partial pressure of O2 at which the Hb is half saturated. To examine the effect of P50 and Hb concentrations on renal function, we perfused isolated rat kidneys with Hb-P35 (P50 = 35 mmHg) and Hb-P11 (P50 = 11 mmHg). Venous PO2 was lower with Hb-P11 (10 +/- 1 vs 16 +/- 1 mmHg with arterial PO2 = 35 mmHg and 28 +/- 2 vs. 40 +/- 2 mmHg with arterial PO2 = 140 mmHg; P < 0.001). Perfusate P50 did not influence vascular resistance, glomerular filtration rate, O2 consumption, Na reabsorption, protein excretion, or free water clearance. Percent glucose and phosphate excretion were lower with Hb-P11 than with Hb-P35 (P < 0.001). Urine glucose was 0.17 mmol/l with Hb-P11 and 0.77 mmol/l with Hb-P35 (P < 0.001). Hb-P35 (2%) doubled O2 delivery and lowered glucose and phosphate excretion to the level obtained with 1% Hb-P11. Thus Hb-P11 delivered O2 twice as effectively as Hb-P35 to high-affinity sodium glucose and phosphate cotransporters in the late proximal tubule (S3 segment). Hb-P11 may also have shunted O2 from the outer cortex to the outer medulla and facilitated O2 diffusion where PO2 was low. We conclude that diffusivity is a limiting factor in delivery of O2 to hypoxic tubules.

Animals↗
PubMed2006

Functional implications of calcium permeability of the channel formed by pannexin 1.

Although human pannexins (PanX) are homologous to gap junction molecules, their physiological function in vertebrates remains poorly understood. Our results demonstrate that overexpression of PanX1 results in the formation of Ca(2+)-permeable gap junction channels between adjacent cells, thus, allowing direct intercellular Ca(2+) diffusion and facilitating intercellular Ca(2+) wave propagation. More intriguingly, our results strongly suggest that PanX1 may also form Ca(2+)-permeable channels in the endoplasmic reticulum (ER). These channels contribute to the ER Ca(2+) leak and thereby affect the ER Ca(2+) load. Because leakage remains the most enigmatic of those processes involved in intracellular calcium homeostasis, and the molecular nature of the leak channels is as yet unknown, the results of this work provide new insight into calcium signaling mechanisms. These results imply that for vertebrates, a new protein family, referred to as pannexins, may not simply duplicate the connexin function but may also provide additional pathways for intra- and intercellular calcium signaling and homeostasis.

Calcium↗
PubMed2004

Analysis of size distribution and areal cell density of ammonia-oxidizing bacterial microcolonies in relation to substrate microprofiles in biofilms.

A fine-scale in situ spatial organization of ammonia-oxidizing bacteria (AOB) in biofilms was investigated by combining molecular techniques (i.e., fluorescence in situ hybridization (FISH) and 16S rDNA-cloning analysis) and microelectrode measurements. Important parameters of AOB microcolonies such as size distribution and areal cell density of the microcolonies were determined and correlated with substrate microprofiles in the biofilms. In situ hybridization with a nested 16S rRNA-targeted oligonucleotide probe set revealed two different populations of AOB, Nitrosomonas europaea-lineage and Nitrosospira multiformis-lineage, coexisting in an autotrophic nitrifying biofilm. Nitrosospira formed looser microcolonies, with an areal cell density of 0.51 cells microm(-2), which was half of the cell density of Nitrosomonas (1.12 cells microm(-2)). It is speculated that the formation of looser microcolonies facilitates substrate diffusion into the microcolonies, which might be a survival strategy to low O(2) and NH(4) (+) conditions in the biofilm. A long-term experiment (4-week cultivation at different substrate C/N ratios) revealed that the size distribution of AOB microcolonies was strongly affected by better substrate supply due to shorter distance from the surface and the presence of organic carbon. The microcolony size was relatively constant throughout the autotrophic nitrifying biofilm, while the size increased by approximately 80% toward the depth of the biofilm cultured at the substrate C/N = 1. A short-term ( approximately 3 h) organic carbon addition experiment showed that the addition of organic carbon created interspecies competition for O(2) between AOB and heterotrophic bacteria, which dramatically decreased the in situ NH(4) (+)-uptake activity of AOB in the surface of the biofilms. This result might explain the spatial distribution of AOB microcolony size in the biofilms cultured at the substrate C/N = 1. These experimental results suggest O(2) and organic carbon were the main factors controlling the spatial organization and activity of AOB in biofilms. These findings are significantly important to further improve mathematical models used to describe how the slow-growing AOB develop their niches in biofilms and how that configuration affects nitrification performance in the biofilm.

Ammonia↗
PubMed1976

Cell envelope proteins involved in the transport of maltose and sn-glycerol-3-phosphate in Escherichia coli.

Two types of proteins are discussed in their role of facilitating the transport of maltose and sn-glycerol-3-phosphate in E. coli. The first protein is the receptor for phage lambda, known to be an outer membrane protein. By facilitating the diffusion of maltose and the higher maltodextrins through the outer membrane the effect of the lambda receptor is to decrease the Km of the transport system without influencing the Vmax of substrate flux. The second protein is a periplasmic protein that is induced by growth on glycerol and is essential for transport of sn-glycerol-3-phosphate in whole cells but not in membrane vesicles. This protein has solely been identified by the use of a two-dimensional polyacrylamide gel electrophoresis of periplasmic proteins in wild-type and mutants defective in sn-glycerol-3-phosphate transport.

Bacterial Proteins↗
PubMed2004

Visualization of vesicle transport along and between distinct pathways in neurites of living cells.

Trafficking of secretory vesicles along neurites of PC12 cells was visualized by 2D and 3D real-time imaging using fluorescence microscopy. Vesicle motion along distinct pathways was directly seen. From an overlay of individual pathways, the underlying cytoskeletal filament could be imaged at a subwavelength resolution. Continuous vesicle transport was interrupted by periods of diffusive motion with concomitant pathway changes. Statistical analysis shows that such interruptions were distributed stochastically along the filament, indicating a limited processivity of motor proteins also in a cellular context. Periods of diffusive motion facilitated the interaction with actively transported vesicles. Frequent associations and dissociations of vesicles have been observed consistently, pointing to a functional relevance of vesicle cotransport.

Animals↗
PubMed2002

Release and uptake of catecholamines in the bed nucleus of the stria terminalis measured in the mouse brain slice.

The release and clearance of electrically evoked catecholamine (CA) in the ventral portion of the bed nucleus of the stria terminalis (BSTV) in mouse brain slices was evaluated with fast-scan cyclic voltammetry at carbon-fiber microelectrodes (CFME). Uptake in this region was observed to be markedly slower than in the caudate putamen (CPu). Clearance rates were reduced in the BSTV in both norepinephrine transporter knockout (NET KO) and dopamine transporter knockout (DAT KO) mice when compared to results in wild-type (WT) mice. However, uptake was faster in the BSTV in both the DAT and NET KO mice than in the CPu of DAT KO mice. This indicates that both transporters play a role in CA clearance in the BSTV. The transporters restrict extracellular CA to the general area of the BSTV, as revealed by the diminished signal as the CFME is moved sequentially further and further from the site where CA release is evoked. However, in slices from the DAT KOs and NET KOs, CA release could be observed outside of the BSTV region during such experiments. These results show that the low rate uptake in the BSTV facilitates extrasynaptic diffusion of catecholamine, but that uptake still regulates and limits the range of the transmitter to the region. Slower clearance from the extracellular fluid allows the released CA to act as a volume transmitter and diffuse to distant sites within the region to exert its neurochemical action.

Alkaline Phosphatase↗
PubMed1983

In vitro studies on methyl mercury distribution in human blood.

Studies comparing the methyl mercury (mHg) content of maternal and newborn blood have shown increased levels in the newborn. This has been attributed to facilitated transplacental diffusion because of high fetal hematocrit (Hct). This study shows the converse, that the diffusion of mHg diminishes progressively with increasing Hct. The diffusion of m203Hg across a Millipore membrane (0.45 microns) separating compartments A and B of a diffusion cell was studied. When both compartments contained saline or plasma alone, equilibration from A to B occurred in 5 h. Introduction of human red blood cells (RBC) in saline (Hct 20%) into B resulted in a twofold increase in diffusion of mHg when compared to saline alone. Increasing Hct in saline in compartment B resulted in a progressive decrease in diffusion (r = -0.95, P less than 0.001). The presence of RBC in plasma (Hct 20%) in B resulted in a 70% decrease in diffusion; with increasing Hct, diffusion was further reduced (r = -0.95, P less than 0.001). Direct addition of mHg to RBC in saline resulted in 98% RBC uptake. Increasing concentrations of plasma (at a constant Hct) resulted in a progressive decrease in RBC uptake. In undiluted plasma at Hct 14%, RBC uptake of mHg was 35%. Plasma electrophoresis showed that much of the mHg was associated with a high-molecular-weight lipoprotein fraction. Plasma components appear to be important in the distribution of mHg in blood, and may be a factor in the relatively higher blood levels in the fetus.

Blood Proteins↗
PubMed1994

Electrostatic properties of two porin channels from Escherichia coli.

The electrostatic interactions in the channels of OmpF and PhoE porins from Escherichia coli were analysed on the basis of a macroscopic multi-dielectric model of the protein-membrane complex derived from the respective porin X-ray structures. The membrane was represented as layers of distinct dielectric constants corresponding to the aliphatic core and the polar head groups of the lipids. The pKa values of the titratable groups and the electrostatic field in the region of the channel were calculated by the finite difference technique. In spite of the differences in sequences and charge constellations, the calculated electrostatic properties of the two porins are similar in several aspects: (1) unusual titration behaviour (pKa below 7) was found for some groups of the cluster of basic residues at the constriction of the pore; (2) a number of acidic groups buried between the internal loop and the barrel wall are stabilized in their protonated forms at neutral pH; (3) there is a strong transverse electrostatic field in the channel characterized by a screw-like form. The strength of the field is greatest at the region of the constriction zone. This would facilitate the diffusion of solutes with a large dipole moment such as free amino acids. Differences between the electrostatic fields of OmpF and PhoE are mainly confined to that end of the pore that faces the cell exterior in vivo. In OmpF the electrostatic potential is close to zero in this region of the channel, whereas a positive potential was found in PhoE. It was shown that the experimentally observed difference in ion selectivity of the two porins can largely be attributed to this distinct electrostatic property.

Amino Acid Sequence↗
PubMed1997

Channel specificity: structural basis for sugar discrimination and differential flux rates in maltoporin.

Maltoporin (LamB) facilitates the diffusion of maltodextrins across the outer membrane of E. coli. The structural basis for the specificity of the channel is investigated by X-ray structure analysis of maltoporin in complex with the disaccharides sucrose, trehalose, and melibiose. The sucrose complex, determined to 2.4 A resolution, shows that the glucosyl moiety is partly inserted into the channel constriction, while the bulky fructosyl residue appears to be hindered to enter the constriction, thus interfering with its further translocation. One of the glucosyl moieties of trehalose is found in a similar position as the glucosyl moiety of sucrose, whereas melibiose appears disordered when bound to maltoporin. A comparison with the previously reported maltoporin-maltose complex sheds light on the basis for sugar discrimination, and explains the different permeation rates observed for the saccharides.

Bacterial Outer Membrane Proteins↗
PubMed1987

The mechanism of the 3H-noradrenaline releasing effect of various substrates of uptake1: multifactorial induction of outward transport.

The mechanism of action of indirectly acting sympathomimetic amines was studied in the rat vas deferens, after inhibition of vesicular uptake (by reserpine), of MAO (by pargyline) and of COMT (by U-0521). 1. Km-values for the neuronal uptake of 12 substrates were determined as the IC50 of the unlabelled substrate inhibiting the initial rate of neuronal uptake of 0.2 mumol/l 3H-(-)-noradrenaline. The IC50 ranged from 0.35 mumol/l (for(+)-amphetamine) to 44.3 mumol/l (for 5-HT). The Vmax (determined for 8 substrates) was substrate-dependent. 2. Tissues were loaded with 0.2 mumol/l 3H-(-)-noradrenaline and then washed out with amine-free solution. All 12 substrates of uptake1 induced an outward transport of 3H-noradrenaline, and equieffective concentrations were positively correlated with Km. Moreover, the EC50 for release greatly exceeded Km. It is proposed that this discrepancy between EC50 and Km is indicative of the fact that at least four factors (each one in strict dependence on Km) contribute to the initiation of outward transport of 3H-noradreanline: a) the appearance of the carrier on the inside of the axonal membrane (facilitated exchange diffusion), b) the co-transport of Na+, c) the co-transport of Cl- (both lowering the Km for 3H-noradrenaline at the inside carrier), and d) inhibition of the re-uptake of released 3H-noradrenaline (through competition for the outside carrier). 3. At least for amezinium, Vmax appears to limit the maximum rate of outward transport. 4. For some substrates (especially for the highly lipophilic ones) bell-shaped concentration-release curves were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1977

Effect of the rate of oxygen consumption on muscle respiration.

An important role of myoglobin in red muscle is to facilitate the diffusion of oxygen for metabolism. We consider a model for muscle respiration in which the oxygen consumption is of a Michaelis-Menten form. The resulting mathematical model is solved in two different ways with two different boundary conditions. The first uses the singular perturbation method of Murray (1974), while the second, which gives another justication of the simpler procedure, is a direct numerical computation of the full problem. The oxygen tension and saturation are often small. For realistic values of the Michaelis-MENTEN CONSTANT the oxygen tension, the saturation and the radius of the region in which the oxygen tension is negligibly small can be calculated using the constant consumption model of Murray (1974), with corrected boundary conditions (those for a Stefan problem), which in certain circumstances mardedly affect the solution.

Diffusion↗
PubMed1988

Identification and immunocytochemical localization of two different carbonic anhydrase isoenzymes in teleostean fish erythrocytes and gill epithelia.

Carbonic anhydrase was purified from the gills (CAB) of the rainbow trout Salmo gairdneri and from erythrocytes (CAE) of the fresh water carp Cyprinus carpio. The purification of the isozymes was confirmed by SDS acrylamide gel electrophoresis. Antibodies against the purified CAB and CAE were then raised in rabbits. Specificity was verified by immunoblotting. No cross-reaction was found between them, using the immunodot technique. CAB antiserum was used to specifically localize gill CA in the trout. Immunoperoxidase labelling revealed a concentration of enzyme on the apical region of the outer layer of the gill epithelial cells. The inner layer of the epithelium was only weakly positive. Results obtained using the immuno-gold technique confirmed the immunoperoxidase labelling: there was a concentration of label in the apical regions of chloride cells. In mucous cells, only the mucous granules were labelled. In the lamellae, the label was distributed in the apical part of the pavement cells. The villi and microplicae were strongly positive. CAE antiserum stained the red blood cells. The discrepancy between histochemical localization in the gill or in the opercular skin of killifish and our present immunolocalization was discussed. It was concluded that the most typical localization of CA is on the apical surface of the lamellar epithelium lying in contact with the environment. The result suggests that one of the main roles of gill CA may be to facilitate the diffusion of CO2 from blood to water.

Animals↗
PubMed1989

Changes of amino acid gradients in brain tissues induced by microwave irradiation and other means.

Focused microwave irradiation to the head (FMI) has been used extensively by neurochemists for rapid inactivation of enzymatic activity in brain tissues and the preservation, for in vitro analysis, of in vivo substrate concentrations. Periodically the suitability of this technique for regional studies has been questioned. Evidence has now been obtained, on the basis of altered concentration gradients for GABA and taurine from the Substantia Nigra (SN) to an Adjacent Dorsal Area (ADJ), that FMI not only inactivates enzymes, but also facilitates rapid diffusion of small molecules from areas of high concentrations to adjacent areas of lower concentration. To a lesser extent, the implantation of plastic injection cannulas also decreased these concentration gradients. These results offer clear evidence that FMI is ill suited and unreliable for studies designed to map and compare the "in vivo" regional concentrations of diffusible organic molecules (such as amino acids) in brain tissues. Any invasive technique that compromises membrane barriers is likely to produce smaller similar effects.

Amino Acids↗
PubMed2005

Anatomical consequences of "open-book" pelvic ring disruption: a cadaver experimental study.

UNLABELLED: "Open-book" pelvic fractures associate a diastasis and/or a fracture of the pubic rami with a posterior pelvic disruption of the sacro-iliac joint. These uni or bilateral lesions are potentially lethal mainly due to associated injuries and massive pelvic hemorrhage. The most frequently injured arteries are parietal branch of the commune, internal or external arteries because of their proximity to the bone, the sacro-iliac joint and the inferior ligaments of the pelvis. The pelvic bone dislocation and the increase of pelvic volume facilitate blood effusion. The aim of this study was to determine, on a cadaver fracture model, the direct anatomical consequences of "open-book" pelvic fracture on the ilio-lumbar pedicle and the pelvic cavity volume. MATERIALS AND METHODS: Bilateral open-book pelvic ring injuries were created in ten non-embalmed cadaver specimens by directly disrupting the pubic symphysis, the right and the left sacro-iliac joints. Pelvic volume was determined after total pelvic exenteration. Consequences of this fracture on vascular parietal network, nervous pelvic trunk and pelvic cavity volume were studied. RESULTS: The mean volume of the pelvic cavity after complete visceral exenteration was 872.5 cm(3) (extremes 580-756 cm(3)). The average increase of pelvic volume was 20.8% after 5 cm of pubic diastasis. In all cases, because of a transversal disposition of the ilio-lumbar pedicle with regard to the sacro-iliac joint, reproduction of the open-book fracture caused a venous dilaceration of the ilio-lumbar vein in 12 cases after 5 cm of pubic diastasis (12/20=60%). No arterial dilaceration was observed on the ilio-lumbar artery, but this artery was put in tension. CONCLUSION: Open-book fractures create an increase of pelvic volume that facilitates blood diffusion from parietal pelvic vascular network. Ilio-lumbar pedicle seems to be very vulnerable in this type of fracture because of its relations to the sacro-iliac joint and its transversal disposition with regard to this joint.

Aged↗
PubMed2005

The effect of neuronal morphology and membrane-permeant weak acid and base on the dissipation of depolarization-induced pH gradients in snail neurons.

Neuronal depolarization causes larger intracellular pH (pH(i)) shifts in axonal and dendritic regions than in the cell body. In this paper, we present evidence relating the time for collapse of these gradients to neuronal morphology. We have used ratiometric pH(i) measurements using 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) in whole-cell patch-clamped snail neurons to study the collapse of longitudinal pH gradients. Using depolarization to open voltage-gated proton channels, we produced alkaline pH(i) microdomains. In the absence of added mobile buffers, facilitated H(+) diffusion down the length of the axon plays a critical role in determining pH(i) microdomain lifetime, with axons of approximately 100 microm allowing pH differences to be maintained for >60 s. An application of mobile, membrane-permeant pH buffers accelerated the collapse of the alkaline-pH gradients but, even at 30 mM, was unable to abolish them. Modeling of the pH(i) dynamics showed that both the relatively weak effect of the weak acid/base on the peak size of the pH gradient and the accelerated collapse of the pH gradient could be due to the time taken for equilibration of the weak acid and base across the cell. We propose that appropriate weak acid/base mixes may provide a simple method for studying the role of local pH(i) signals without perturbing steady-state pH(i). Furthermore, an extrapolation of our in vitro data to longer and thinner neuronal structures found in the mammalian nervous system suggests that dendritic and axonal pH(i) are likely to be dominated by local pH(i)-regulating mechanisms rather than simply following the soma pH(i).

Acids↗
PubMed2001

Characterisation of programmed cell death during aerenchyma formation induced by ethylene or hypoxia in roots of maize (Zea mays L.).

Aerenchyma is a tissue type characterised by prominent intercellular spaces which enhance flooding tolerance in some plant species by facilitating gas diffusion between roots and the aerial environment. Aerenchyma in maize roots forms by collapse and death of some of the cortical cells in a process that can be promoted by imposing oxygen shortage or by ethylene treatment. Maize roots grown hydroponically in 3% oxygen, 1 microl x l(-1) ethylene or 21% oxygen (control) were analysed by a combination of light and electron microscopy. Use of in-situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) suggested internucleosomal cleavage of DNA. However, chromatin condensation detectable by electron microscopy was preceded by cytoplasmic changes including plasma membrane invagination and the formation of vesicles, in contrast to mammalian apoptosis in which chromatin condensation is the first detectable event. Later, cellular condensation, condensation of chromatin and the presence of intact organelles surrounded by membrane resembling apoptotic bodies were observed. All these events were complete before cell wall degradation was apparent. Therefore, aerenchyma formation initiated by hypoxia or ethylene appears to be a form of programmed cell death that shows characteristics in part resembling both apoptosis and cytoplasmic cell death in animal cells.

Apoptosis↗