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Developmental changes in plasma membrane fluidity in chick embryo heart.

1. Decreases in the rate of transport of sugars (facilitated transport), amino acids (active transport), and urea (simple diffusion) occur in chick embryo heart during development. This work considers the possibility that changes in the plasma membrane fluidity during development contribute to the observed changes in transport activities. 2. Technics were developed for subcellar fractionation of chick embryos and adult chickens. 3. The depolarization of the fluorescence of 1,6-diphenylhexatriene was used to estimate the fluidity of the lipid portion of plasma membrane enriched fractions of hearts from chick embryos at various stages of development and from adult hearts. 4. There is a pattern of decreasing membrane viscosity as development proceeds. Between 5-6 days and 10 days of embryonic life a 20% decrease in viscosity of the plasma membrane-enriched fraction occurs. Between 10 and 20 days of embryonic life there is no significant change in viscosity. Between 20 days of development (1 day before hatching) and adulthood there is a further 55% decrease in plasma membrane viscosity. 5. It is proposed that the changes in membrane fluidity observed may contribute to developmental changes in membrane transport activities, but other factors must also be involved.

Amino Acids↗

Phospholipid packing and conformation in small vesicles revealed by two-dimensional 1H nuclear magnetic resonance cross-relaxation spectroscopy.

Two-dimensional 1H-NMR spectroscopy has been used to examine cross-relaxation in sonicated phospholipid vesicle systems. The observed pattern of proton cross-relaxation reveals several important features of these vesicle systems. For example, cross-relaxation rates on each monolayer of the vesicle system can be resolved and reflect the expected geometric packing constraints of the vesicle system. Small but significant magnetization-exchange is also seen to develop between the headgroup N-methyl resonance and the terminal methyl resonance. Spectra taken with deuterated lipids indicate that this exchange is not mediated by spin-diffusion down the length of the alkyl chains. Since spin-diffusion is the only process that is expected to facilitate magnetization-exchange over distances of 15-20 A, a close proximity of headgroup and terminal methyl protons in a fraction of the membrane lipid is indicated by these results. This could occur by events such as lipid interdigitation or alkyl chain bends that terminate lipid alkyl chain ends near the membrane surface.

Liposomes↗

Treatment of ampicillin-resistant Haemophilus influenzae in soft tissue infections with high doses of ampicillin.

Six soft tissue infections (three epiglottitis, one cellulitis, one pneumonia, and one arthritis) with ampicillin-resistant Haemophilus influenzae were treated initially with high doses of ampicillin (200 to 400 mg/kg/day intravenously) alone and had good clinical responses. All had documented bacteremia with H. influenzae. One child was treated only with ampicillin; treatment in the remainder was changed to oral therapy with other antibiotics to facilitate discharge. There was no recurrence of disease. Disc diffusion studies done on clinical isolates of both resistant and sensitive organisms indicate a break point at which the resistant organism shows progressive sensitivity to increasingly higher concentrations of ampicillin.

Ampicillin↗

Biomimetic nucleation and growth of CaCO3 in hydrogels incorporating carboxylate groups.

Poly-acrylamide hydrogels were modified by copolymerization with acrylic acid and used as growth medium for CaCO3 in a double-diffusion arrangement. The carboxylate functionalities in the gel network facilitate the nucleation of a multitude of small crystallites of vaterite and calcite, which are temporarily stabilized even while supersaturation is increasing within the hydrogel. After an extended induction period the rapid spherulitic growth of calcite crystals along their c-axis is observed yielding spheres with diameters exceeding 300 microm. In the center of those aggregates disordered, porous regions can be identified as starting point of this rapid crystallization. The results are compared to previous studies on native poly-acrylamide hydrogels and networks modified with -SO(3)H functional groups. The mineralization mechanism is significantly altered by specific interactions between the -COOH functionalized network and the evolving mineral phase.

Calcium Carbonate↗

The effect of trigeminal nociceptive stimulation on blink reflexes and pain evoked by stimulation of the supraorbital nerve.

The aim of this study was to investigate the effect of painful conditioning stimuli on pain and blink reflexes to supraorbital nerve stimulation. Electromyograph activity was recorded bilaterally from the orbicularis oculi muscles in 13 normal participants in response to low (2.3 mA) and high-intensity (18.6 mA) electrical stimulation of the left supraorbital nerve before, during and after the application of ice to the left or right temple or immersion of the left hand in ice-water for 60 s. The pain evoked by the high-intensity electrical stimulus was greater during painful conditioning stimulation of the ipsilateral temple than during the recovery period afterwards, and was greater than during painful conditioning stimulation of the contralateral temple. These findings imply that spatial summation of nociceptive signals across different divisions of the trigeminal nerve can heighten pain. However, painful conditioning stimulation, particularly to the right temple, strongly suppressed the R2 component of the blink reflex to the low-intensity stimulus, and also suppressed R2 to the high-intensity stimulus. Thus, an inhibitory influence (e.g. diffuse noxious inhibitory controls) appeared to mask ipsilateral segmental facilitation of R2 during ice-induced headache. This finding contrasts with recent electrophysiological evidence of trigeminal sensitization in migraine.

Adult↗

Expression, purification, crystallization and preliminary X-ray analysis of phosphotransacetylase from Methanosarcina thermophila.

Phosphotransacetylase (Pta) from the anaerobic archaeon Methanosarcina thermophila has been heterologously expressed in a soluble form which facilitated crystallization using the hanging-drop vapor-diffusion method with ammonium sulfate as a precipitant. This is the first report of the crystallization of any Pta. While the M. thermophila Pta has high sequence identity to Ptas from other organisms, it has no homology to any previously crystallized proteins. The protein crystallized in space group I4(1), with unit-cell parameters a = b = 114.8, c = 127.8 A, alpha = beta = gamma = 90 degrees. The crystals diffracted to 2.5 A resolution using Cu Kalpha radiation. The enzyme had previously been reported to exist as a monomer; however, the self-rotation function showed the presence of a non-crystallographic symmetry axis at psi = 90, phi = 90, kappa = 180 degrees, suggesting oligomerization. Dynamic light-scattering analysis supported a dimeric state for Pta in solution.

Crystallization↗

Epithelial carbonic anhydrases facilitate PCO2 and pH regulation in rat duodenal mucosa.

The duodenum is the site of mixing of massive amounts of gastric H+ with secreted HCO3-, generating CO2 and H2O accompanied by the neutralization of H+. We examined the role of membrane-bound and soluble carbonic anhydrases (CA) by which H+ is neutralized, CO2 is absorbed, and HCO3- is secreted. Rat duodena were perfused with solutions of different pH and PCO2 with or without a cell-permeant CA inhibitor methazolamide (MTZ) or impermeant CA inhibitors. Flow-through pH and PCO2 electrodes simultaneously measured perfusate and effluent pH and PCO2. High CO2 (34.7 kPa) perfusion increased net CO2 loss from the perfusate compared with controls (pH 6.4 saline, PCO2 approximately 0) accompanied by portal venous (PV) acidification and PCO2 increase. Impermeant CA inhibitors abolished net perfusate CO2 loss and increased net HCO3- gain, whereas all CA inhibitors inhibited PV acidification and PCO2 increase. The changes in luminal and PV pH and [CO2] were also inhibited by the Na+-H+ exchanger-1 (NHE1) inhibitor dimethylamiloride, but not by the NHE3 inhibitor S3226. Luminal acid decreased total CO2 output and increased H+ loss with PV acidification and PCO2 increase, all inhibited by all CA inhibitors. During perfusion of a 30% CO2 buffer, loss of CO2 from the lumen was CA dependent as was transepithelial transport of perfused 13CO2. H+ and CO2 loss from the perfusate were accompanied by increases of PV H+ and tracer CO2, but unchanged PV total CO2, consistent with CA-dependent transmucosal H+ and CO2 movement. Inhibition of membrane-bound CAs augments the apparent rate of net basal HCO3- secretion. Luminal H+ traverses the apical membrane as CO2, is converted back to cytosolic H+, which is extruded via NHE1. Membrane-bound and cytosolic CAs cooperatively facilitate secretion of HCO3- into the lumen and CO2 diffusion into duodenal mucosa, serving as important acid-base regulators.

Acid-Base Equilibrium↗

Oleate uptake by isolated hepatocytes and the perfused rat liver is competitively inhibited by palmitate.

Competition for uptake between long-chain free fatty acids has been difficult to document, because there has been no algorithm for computing unbound concentrations of two fatty acids simultaneously in solution with albumin. We modified an iterative procedure to permit this computation and studied initial [3H]oleate uptake by isolated hepatocytes and steady-state uptake by the single-pass perfused rat liver from 600 microM bovine serum albumin solutions containing various concentrations of oleate in the presence and absence of palmitate. In both systems, the Michaelis-Menten constant was significantly higher in the presence of palmitate than in its absence, whereas the maximal reaction velocity was unaltered, indicating competitive inhibition. In additional experiments employing the multiple transhepatic indicator-dilution technique, the influx rate constant and permeability-surface area product for oleate influx were significantly reduced by palmitate, confirming that the competition observed in the conventional perfused liver studies was at the influx step. Long-chain fatty acid uptake has now been shown to exhibit all the kinetic properties of facilitated transport and cannot be attributed solely to passive diffusion.

Animals↗

Inhibition of urea transport in inner medullary collecting duct by phloretin and urea analogues.

Arginine vasopressin (AVP) increases the urea permeability of the rat terminal inner medullary collecting duct (IMCD) to levels much greater than can be explained by lipid-phase permeation or paracellular diffusion, suggesting the presence of an AVP-stimulated facilitated transport pathway. We tested whether inhibitors of facilitated urea transport in erythrocytes and toad bladder also inhibit urea transport in the isolated perfused IMCD. Apparent urea permeability (Purea) was determined by measuring the flux due to an imposed 5 mM concentration gradient. Phloretin (0.25 mM in lumen or bath) reversibly inhibited Purea. Phloretin, however, did not alter the osmotic water permeability. Urea analogues (200 mM) in the bath inhibited Purea (thiourea, 74% inhibition; methylurea 65%; acetamide 35%). Urea analogues in the lumen decreased Purea with the same order of potency. The inhibitory K1/2 for thiourea in the lumen was 27 +/- 2 mM and did not change with 10(-10) M AVP (28 +/- 3), despite a fourfold increase in Purea. We conclude the following. 1) Inhibitor actions on urea transport in the IMCD are similar to those in red blood cells and toad bladder, suggesting that the urea transporter could be a membrane protein similar to that in the other tissues. 2) Inhibition of Purea by phloretin without an effect on vasopressin-stimulated water permeability supports the view that the urea pathway is not the vasopressin-stimulated water channel. 3) The ability of AVP to increase Purea without an effect on the inhibitory K1/2 for thiourea indicates that AVP probably does not act by altering the binding affinity of individual transporters for urea.

Amiloride↗

Effect of hypoxia and CO on a cytochrome P-450-mediated reaction in rabbit lungs.

Evidence indicates that the diffusion of O2 and CO in tissue may be facilitated by a carrier molecule having a P50 that approximates tissue O2 partial pressure (PO2; 1-15 Torr) and a much higher affinity for CO than for O2. To determine whether cytochrome P-450 in lung satisfies these criteria, we measured the effect of hypoxia and of CO on the rate of metabolism of the cytochrome P-450 mediated O-demethylation of p-nitroanisole in isolated perfused rabbit lungs. Metabolism was inhibited by 50% of a control at an estimated tissue PO2 fo 4 Torr (5.5 microM). When inspired CO2 was kept at 200 Torr and inspired CO partial pressure (PCO) varied an estimated tissue PCO/PO2 ratio of 0.025 reduced the reaction rate by 50% of control, but some metabolism persisted at PCO/PO2 ratios larger than one. The relationship between reaction rate and PCO/PO2 ratio could not be fit by a single value for Haldane constant for M (CO affinity/O2 affinity) but could be described with a two-component model in which metabolism was equally divided between a high-affinity cytochrome (M = 200) and a low-affinity cytochrome (M = 2). These findings suggest that cytochrome P-450 could act as a carrier for O2 and CO in tissue with low PO2's.

Animals↗

Managing telemedicine: from noble ideas to action.

The aim of the present study was to elucidate how telemedicine can be used in an integrated and comprehensive manner. Two Swedish telemedicine projects were studied. The technical platform was an ISDN videoconferencing system which could be connected to various items of medical equipment. The first project, general telemedicine, concerned communication between two primary care centres, one county hospital and one university hospital. The specialties involved were dermatology, orthopaedics and otolaryngology. The second project, telepathology, included pathology and cytology at the university hospital, and surgery and gynaecology at a county hospital. The first round of interviews was conducted to reveal the expectations of the physicians regarding the potential benefits and applications of the technology and potential organizational obstacles. Subsequent interview rounds were carried out to reveal what had happened since the previous interview. In total 62 interviews were carried out with 32 respondents. The main conclusions were that the technology's generic features, namely the transmission of pictures and sound, had been translated into appropriate fields of application, which had been diffused and routinized in organizational activities. In order to facilitate this process, there were two crucial issues for managers. First, due to the 'openness' of the technology, actors who had the will to test the limits of the technology had to be identified and engaged. Second, while the use of the new technologies implied that new patterns of action were established, it was necessary to discover and develop routines that could be used as a facilitator for the further use of telemedicine.

Attitude of Health Personnel↗

Using knowledge management practices to develop a state-of-the-art digital library.

Diffusing knowledge management practices within an organization encourages and facilitates reuse of the institution's knowledge commodity. Following knowledge management practices, the Eskind Biomedical Library (EBL) has created a Digital Library that uses a holistic approach for integration of information and skills to best represent both explicit and tacit knowledge inherent in libraries. EBL's Digital Library exemplifies a clear attempt to organize institutional knowledge in the field of librarianship, in an effort to positively impact clinical, research, and educational processes in the medical center.

Academic Medical Centers↗

[Mesentery capillary barrier in rats injected intravascularly with ascitic Zajdela hepatoma. III. Effect of serotonin and histamine on the extravasation of the tumor].

The addition of serotonin or of histamin with tumoral cells of ascitic Zajdela's hepatoma and their injection in aorta induce plain hemodynamic changes and increase the tumoral extravasation. So only cells blocked in thrombi are observed in blood vessels. Therefore, serotonin and histamin do facilitate tumoral cells extravasation, allowing so a better metastatic diffusion in this experimental pattern.

Animals↗

[Effect of early deprivation of visual evoked potentials of rabbit cerebral cortex under conditions of dark and light adaptation].

Rabbits raised in the dark revealed a significant decrease in amplitude and an increase in temporal parameters of the main components of evoked potentials (EP) to diffuse flashes under dark adaptation, as well as a facilitation of the postprimary components and intensification of the sensory after-discharge. In contradistinction to normal, the deprived animals exhibited no augmentation of the amplitude of the EP primary positive phase at higher intensity of the flahses or any significant decrease in the EP amplitude under light adaptation conditions. It is suggested that early deprivation brings about a decrease in the number of elements reacting to a specific stimulation, especially of elements working in photopic conditions; the decrease in the number of activated afferent inputs in the visual cortex due to deprivation reduces the effectiveness of the processes of successive inhibition; at the same time there is an increase of synchronic influences of the thalamic inhibitory mechanisms of the cortex.

Animals↗

Diffusion and physiological responses to the influenza pandemic of 1918-19 in Nigeria.

Although virologists are not in agreement on the origins of the 1918-19 influenza pandemic, it has long been associated with the virulent type A virus. At least 21 million people died from the disease over a 12-month period, becoming one of the world's worst short-term demographic disasters. The disease was introduced into Nigeria by passengers and crews who arrived via ship from overseas. Thus, coastal ports were the primary focus of the diffusion of the disease. Its spread to the hinterland was facilitated by improvements in transportation technology. Neither maritime quarantine, nor the isolation of patients checked the spread of the disease. About 500,000 Nigerians, out of a population of 18 million, died in less than 6 months, and between 50 and 80% of the population was stricken. The over-crowded urban centers were the hardest hit and, even though pandemic declined almost as suddenly as it began, morbidity, mortality, and panic adversely affected the productive capacity of the country. Since the 1930s, virologists have gained much knowledge about the agents responsible for influenza diffusion, but the disease remains one of the few plagues to be eradicated. This is partly because of the exceptional adaptability of influenza viruses, and partly because artificially and naturally-acquired immunity to influenza are temporary in duration, making reinfection possible even by the same type or subtype of influenza.

Disease Outbreaks↗

Water permeability and fluidity of renal basolateral membranes.

Water and nonelectrolyte permeability in basolateral membrane vesicles (BLMV) isolated from rat and rabbit renal cortex were characterized. Osmotic water (Pf) and solute (Ps) permeabilities were determined from the time course of scattered light intensity in response to osmotic gradients. In rabbit BLMV, Pf = 2.5 X 10(-2) cm/s, Purea = 1.2 X 10(-6) cm/s, and sigma urea = 0.95 (23 degrees C). Relative solute permeabilities were urea, 1; thiourea, 0.83; ethylene glycol, 9.7; glycerol, 4.6; formamide, 20; and acetamide, 12. Pf and Purea were not altered by organic mercurials, phloretin, urea, and high-affinity urea analogues. delta H (12-50 degrees C) was 10.7 and 2.5 kcal/mol for Purea and Pf, respectively; in contrast, reported delta H for Pf in rabbit brush-border membrane vesicles (BBMV) was 2 kcal/mol (T less than 33 degrees C) and 14 kcal/mol (T greater than 33 degrees C). To examine whether membrane fluidity changes were associated with this difference, fluorescence anisotropy decay was measured using 1,6-diphenyl-1,3,5-hexatriene (DPH). In both BLMV and BBMV, DPH rotation was hindered at all temperatures (5-53 degrees C). Changes in steady-state anisotropy were attributable to changes in DPH rotational freedom rather than to changes in DPH rotational rate without evidence for a definitive membrane thermotropic phase transition. These results suggest that BLMV urea transport occurs by lipid diffusion and that osmotic water transport is rapid and may be facilitated. A comparison of transepithelial Pf with BLMV and BBMV Pf is consistent with transcellular osmotic water flow in the proximal tubule.

Animals↗

Self-diffusion of supercooled o-terphenyl near the glass transition temperature.

Self-diffusion coefficients for the low molecular weight glass former o-terphenyl have been measured near Tg by isothermally desorbing thin film bilayers of deuterio and protio o-terphenyl in a vacuum chamber. We observe translational diffusion that is about 100 times faster at Tg + 3 K than the Stokes-Einstein prediction. Predictions from random first order transition theory and a dynamic facilitation approach are in reasonable agreement with our results; in these approaches, enhanced translational diffusion is associated with spatially heterogeneous dynamics. Self-diffusion controls crystallization in o-terphenyl for most of the supercooled liquid regime, but at temperatures below Tg + 10 K, the reported crystallization rate increases suddenly while the self-diffusion coefficient does not. This work and previous work on trisnaphthylbenzene both find a self-diffusion-controlled crystal growth regime and an enhancement in self-diffusion near Tg, suggesting that these phenomena are general characteristics of fragile low molecular weight glass formers. We discuss the width of the relaxation time distributions of o-terphenyl and trisnaphthylbenzene as they relate to the observation of enhanced translational diffusion.

Journal Article↗

Diffusion of innovation theory for clinical change.

Maximising the adoption of evidence-based practice has been argued to be a major factor in determining healthcare outcomes. However, there are gaps between evidence-based recommendations and current care. Bridging the evidence gap will not be achieved simply by informing clinicians about the evidence. One theoretical approach to understanding how change may be achieved is Rogers' diffusion model. He argues that certain characteristics of the innovation itself may facilitate its adoption. Other factors influencing acceptance include promotion by influential role models, the degree of complexity of the change, compatibility with existing values and needs, and the ability to test and modify the new procedure before adopting it. The diffusion model may provide valuable insights into why some practices change and others do not, as well as guiding those who try to effect adoption of best-evidence practice.

Communication↗