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PubMed1975

[Oxygen transport by the fetal blood].

In the mammalian foetus, the blood oxygen tension is low (PaO2 congruent to 25 Torr). The factors limiting the oxygen transfer from maternal into foetal blood are mainly the vascular arrangement and the distribution of blood flow within the placenta. The oxygen diffusion across the placenta in facilitated by a higher oxygen affinity in foetal than in maternal blood. During placental gas exchange the Bohr Effect acts in both the maternal and foetal blood to shift their oxyhaemoglobin dissociation curve so that the mean oxygen pressure gradient across the placental membrane is increased. The two main characteristics of foetal blood, a high oxygen capacity and a high oxygen affinity are well adapted to hypoxaemia since, together with a high cardiac output, they ensure an adequate oxygen supply to the foetal tissues. These characteristics of foetal blood disappear during the postnatal period in all the species thus far investigated. The change in the blood oxygen affinity which occurs in the foetus and the newborn have been attributed in some species to the presence of a foetal haemoglobin (HbF) which differs from the adult haemoglobin (HbA) either by an intrinsically higher oxygen affinity, independant of any intracellular cofactor, or by an impaired reactivity towards cofactors which alter haemoglobin oxygen affinity by directly interacting with the haemoglobin molecule (2,3 DPG, CO2). In those species in which HbF has not been shown to be structurally and functionally different from HbA, change in 2,3 DPG concentration can explain change in oxygen affinity.

Animals↗
PubMed2003

[Cardiocirculatory effects of insulin in patients with heart failure].

Insulin is a hormone that possesses several therapeutic properties, some of which are only partially known and not definitely appreciated. Insulin appears to be an attractive therapeutic tool in several cardiovascular diseases and particularly in chronic heart failure (CHF). Insulin, in fact, exerts a direct effect on biological properties of myocytes by increasing the transmembrane glucose transport through glucose-specific insulin-regulated receptors, whose gene expression is down-regulated since the initial stages of myocyte hypertrophy. In addition, a hormonal antiapoptotic molecular effect has also been reported. These effects explain, at least in part, the observed improvement in ejection fraction and cardiac output in CHF patients when given insulin. Vasodilation is the most remarkable peripheral effect of insulin that seems to be due to a direct activity on vascular smooth muscle cells and, more remarkably, on an increased release of endothelium-derived relaxing factors, such as nitric oxide and vasodilator prostaglandins. In accordance with most recent clinical observations, this endothelial modulatory activity is not limited to the systemic circulation but involves also the pulmonary one and the alveolar-capillary interface, resulting in a facilitation of the alveolar gas diffusion. Such an effect on alveolar gas diffusion appears to play a major role in CHF patients. The present review focuses on the pathophysiological mechanisms underlying the insulin benefits, and emphasizes the hormone therapeutic applicability in a CHF setting.

Endothelium, Vascular↗
PubMedDate not supplied

Rotation-induced Taylor vortex enhances filtrate flux in plasma separation.

Techniques of plasma filtration with rotating flat membranes are capable of producing a Taylor vortex and concomitantly reducing concentration polarization by formed elements. The present study describes filtration characteristics of a small-sized rotating filter that is superior to a capillary filter in terms of filtrate flux. The rotating filter with a surface area of 60 cm2 was composed of two concentric cylinders, with the inner cylinder mobile, with a flat polycarbonate membrane (pore diameter: 0.8 micron), and the outer cylinder fixed. Filtration experiments were performed using bovine blood to determine filtrate flux at rotational speeds from 600 to 4,500 rpm. Photographic observations using aluminum powder revealed that many Taylor vortices were present in the radial gap (0.6 mm). Filtrate flux increased with transmembrane pressure until a maximum filtrate flux of 0.02 cm/min at 600 rpm, 0.42 cm/min at 1,800 rpm, 0.60 cm/min at 3,600 rpm, and 0.69 cm/min at 4,500 rpm were reached at a blood flow rate of 100 ml/min. Based on the filtration resistance model, values for fractional filtration resistance of the red blood cell polarization layer ranged from 0.25 to 0.80 at a rotational speed of 3,600 rpm, whereas those of a capillary filter range from 0.80 to 0.90. This indicates that Taylor vortices promote back diffusion of red blood cells accumulated on membrane surfaces. Thus, the filtrate flux of a rotating filter is two orders of magnitude higher than that of a capillary filter because of the back diffusion of red blood cells facilitated by Taylor vortices.

Animals↗
PubMed1993

Influence of connective tissues on the in vitro growth and differentiation of murine epidermis.

Various experiments indicate that normal growth and differentiation of murine epithelia in vivo are dependent on dermal influences, and the growth-enhancing effects of various connective tissue elements have also been demonstrated in vitro. Such effects were examined by the in vitro growth of murine epidermis on various substrata (collagen, lens capsule) at the air/medium interface with various connective tissue elements or cells apposed to the undersurface of the supporting matrix. Patterns of epithelial growth, morphology and differentiation were examined by histology, electron microscopy, gel electrophoresis and antibody staining. Growth and differentiation varied with differing substrata but good patterns of growth and morphology, and appropriate expression of cytoplasmic and cell surface differentiation markers, were found only in specimens grown in association with dermal elements. It is concluded that diffusible factors of dermal origin facilitate epithelial growth and differentiation.

3T3 Cells↗
PubMed1994

Recent studies of the cellular uptake of long chain free fatty acids.

Over the last 12 years, we and others have demonstrated that fatty acid uptake is not simply a passive, diffusive process, but an interesting, facilitated mechanism the regulation of which has specific implications for disease. This work also tells another tale. Our earliest experiments were called "squirt studies" by our technician because they involved "squirting" a bolus of labelled metabolite intravenously into one limb of the subject and drawing blood samples from another. These studies were conducted in patients, and later in intact animals. From these we moved progressively to investigations in isolated perfused organs, isolated cells, and sub-cellular organelles and membrane vesicles; to the chemistry of membrane proteins, and most recently, to studies combining recombinant DNA technology with cellular biologic studies of controlled differentiation in tissue culture (Figure 5). The work has been not only a continuing process of scientific investigation but, for the investigators, an on-going process of self-education.

Animals↗
PubMed1997

[Incidence of the standardization of scientific journals in the transfer and evaluation of scientific information].

INTRODUCTION AND OBJECTIVE: I analyze the repercussions of standardization of scientific publications in general, and of journals in particular, on the processes of scientific information transfer, diffusion and evaluation. DEVELOPMENT: Standardization facilitates the work of all agents in the primary (authors, publishers and readers) and secondary communication systems (librarians, information scientifics). Compliance with standards influences the presence of journal in bibliographic databases and de quality of bibliometric studies. Standardization thus has repercussions in the evaluation of science.

Documentation↗
PubMed2001

Cellular cholesterol efflux.

Efflux of free cholesterol (FC) continues even when cellular FC mass is unchanged. This reflects a recirculation of preformed FC between cells and extracellular fluids which has multiple functions in cell biology including receptor recycling and signaling as well as cellular FC homeostasis. Total FC efflux is heterogeneous. Simple diffusion to mature high density lipoprotein (HDL), mainly via albumin as intermediate, initiates FC net transport driven by plasma lecithin:cholesterol acyltransferase activity. A second major efflux component reflects protein-facilitated transport from cell surface domains (caveolae, rafts) driven by FC binding to lipid-poor, pre-beta-migrating HDL (pre-beta-HDL). Facilitated efflux from caveolae, unlike simple diffusion, is highly regulated. Neither ABC1 (the protein defective in Tangier disease) nor other ATP-dependent transporters now appear likely to contribute directly to FC efflux. Their role is limited to the initial formation of a particle precursor to circulating pre-beta-HDL, which recycles without further lipid input from ATP-dependent transporter proteins. Lipid-free apolipoprotein A-I, previously considered a surrogate for pre-beta-HDL, has a reactivity much lower than that of native lipoprotein FC acceptors.

ATP Binding Cassette Transporter 1↗
PubMed1993

Spatial facilitation and depression within one motor nerve terminal of frogs.

1. Perfused macropatch electrodes were used to stimulate and simultaneously measure release from two sites on the same terminal of the frog cutaneous pectoris muscle. 2. It was found that release occurring at one site often affected release at an adjacent site 50 microns away, either enhancing it ('spatial facilitation') or depressing it ('spatial depression'). Spatial facilitation (or depression) was defined as the release produced by a test pulse at the second site (test electrode) when preceded by a pulse at the first site (prepulse electrode) divided by the release produced by the test pulse alone. 3. Spatial facilitation varied with the time interval between the prepulse and the test pulse. Peak spatial facilitation, which on the average was 2.14, occurred with an interval of 1-3 ms. With longer intervals spatial facilitation decayed with a time constant between 3-6 ms. When the time interval between the prepulse and the test pulse was zero (no delay), the release after the test pulse was always depressed. 4. When Ca2+ was omitted from the perfusate of the prepulse electrode, spatial facilitation was abolished. When a brief hyperpolarizing pulse followed the depolarizing prepulse with zero delay spatial facilitation was also abolished. 5. Electrotonic spread or Ca2+ diffusion within the axon terminal are excluded as coupling agents for spatial facilitation. It is suggested that the coupling agent may possibly be related to a hypothetical release-promoting factor.

Animals↗
PubMed2003

Influence of aeration on hydrophobic organic contaminant distribution and diffusive flux in estuarine sediments.

Dredging operations, resuspension events during storms, and bioturbation alter the oxic state of estuarine sediments and induce changes in the composition of dissolved and particle-associated natural organic matter. These changes may alter the distribution of hydrophobic organic chemicals (HOCs) in sediments and their diffusive flux across the sediment-water interface. In this study, the impact of aerating anoxic sediments on the distribution and diffusive flux of a model HOC, 2,2',4,4'-tetrachlorobiphenyl (TeCB), was investigated. Anoxic estuarine sediments collected from three sites along a salinity gradient were used to determine site-specific apparent sorption coefficients for porewater dissolved organic carbon (Kpwdoc) and sediment organic carbon (Koc) under anoxic and oxic conditions. A two-compartment sediment flux model was employed to examine the diffusive flux of TeCB under both oxic states. Aeration of anoxic porewaters resulted in significant decreases in porewater dissolved organic matter (DOMpw) aromaticity as indicated by declines in molar absorptivity at 254 nm (p < 0.005). Aeration also resulted in a 9-13% decrease in DOMpw concentration (p < 0.005) at the two sites exhibiting lower ionic strengths; the high ionic strength site did not exhibit a significant change in DOMpw concentration (p > 0.10). The impact of aeration on TeCB distribution and diffusive flux appeared to be site-specific. Aeration of anoxic sediments induced a significant 1.4 log unit reduction in Kpwdoc at the lowest ionic strength site (p < 0.0005), while sediments from the intermediate ionic strength site exhibited a significant 0.6 log unit increase (p < 0.005). No significant change in sorption to DOMpw was observed for the high ionic strength site (p > 0.10). The sediment displaying the drop in Kpwdoc also exhibited a significant 0.4 log unit drop in Koc (p < 0.01), while the other two sites did not exhibit significant aeration-induced changes in sorption to particle-associated organic matter (p > 0.10). No significant change in diffusive flux was observed for two sites (p > 0.10), while a significant 89-110 mg m(-2) yr(-1) increase in diffusive flux was observed at the low ionic strength site (p < 0.10). This latter result represented approximately a doubling in diffusive flux. In the systems studied, facilitation of TeCB transport across the sediment-water interface by organic colloids did not appear important.

Diffusion↗
PubMed2006

Rationale for the combination of nuclear medicine with magnetic resonance for pre-clinical imaging.

Multi-modality combinations of SPECT/CT and PET/CT have proven to be highly successful in the clinic and small animal SPECT/CT and PET/CT are becoming the norm in the research and drug development setting. However, the use of ionizing radiation from a high-resolution CT scanner is undesirable in any setting and particularly in small animal imaging (SAI), in laboratory experiments where it can result in radiation doses of sufficient magnitude that the experimental results can be influenced by the organism's response to radiation. The alternative use of magnetic resonance (MR) would offer a high-resolution, non-ionizing method for anatomical imaging of laboratory animals. MR brings considerably more than its 3D anatomical capability, especially regarding the imaging of laboratory animals. Dynamic MR imaging techniques can facilitate studies of perfusion, oxygenation, and diffusion amongst others. Further, MR spectroscopy can provide images that can be related to the concentration of endogenous molecules in vivo. MR imaging of injected contrast agents extends MR into the domain of molecular imaging. In combination with nuclear medicine (NM) SPECT and PET modalities in small animal imaging, MR would facilitate studies of dynamic processes such as biodistribution, pharmacokinetics, and pharmacodynamics. However, the detectors for nearly all PET and SPECT systems are still based on vacuum tube technology, namely: photomultiplier tubes (PMT's) in which the signal is generated by transporting electrons over a substantial distance within an evacuated glass tube, making them inoperable in even small magnetic fields. Thus the combination of SPECT or PET with MR has not been practical until the recent availability of semiconductor detectors such as silicon avalanche photodiodes (APD's) for PET and CdZnTe (CZT) detectors for SPECT coupled with the availability of high-density low noise ASIC electronics to read out the semiconductor detectors. The strong advantage of these technologies over PMT's is their insensitivity to magnetic fields which makes their use in co-axial multi-modality nuclear medicine/magnetic resonance instrumentation possible.

Animals↗
PubMed1990

Diffusion-weighted MR imaging and T2-weighted MR imaging in acute cerebral ischaemia: comparison and correlation with histopathology.

Diffusion-weighted MR imaging is a new technique which measures the microscopic motion of water protons. Signal hyperintensity on diffusion-weighted images correlates closely with evidence of ischaemic damage on histopathologic sections. Following occlusion of the middle cerebral artery (MCA), diffusion-weighted images indicate the presence of early pathophysiologic changes occurring first in the basal ganglia and, subsequently, in cortical gray matter within the MCA vascular territory. Diffusion-weighted images also better define the anatomic locus of ischaemic tissue injury than T2-weighted images. Diffusion-weighted imaging thus appears to facilitate early detection and thereby possible therapeutic intervention in patients with acute stroke.

Acute Disease↗
PubMed2003

[Individual and collective facilitators of and barriers to the use of clinical practice guidelines by physicians: a literature review].

BACKGROUND: The effectiveness of Clinical Practice Guidelines (CPG) diffusion to physicians depends on local barriers or facilitators related to the CPG, to the individual clinician and the professional context. Our project aimed to retrieve, by a literature review, all the facilitators of and barriers to physician's adherence to CPG and propose a classification of these barriers and facilitators. METHOD: A comprehensive review of the literature. We searched in Medline, Healthstar, Current contents, Cochrane library databases, consulted experts in the domain of CPG implementation and reviewed study bibliography to retrieve all original reports studying facilitators of and barriers to physician's adherence to CPG (inclusion criteria). The article selection followed a two stepped procedure: first, quick reading of the retrieved articles, then reading in depth of the potentially appropriate articles. RESULTS: Fifty nine studies published between 1986 and 2001 were eligible. The majority (29 studies) used a quantitative design, having studied the statistical association between some a priori defined barriers or facilitators (collected by questionnaires or by record audits) and CPG use. The others have used a qualitative design (barriers and facilitators collected through qualitative methods or open-ended questions in questionnaires) (21 studies) or a mixed design (qualitative and quantitative) (8 studies). Study samples sizes ranked between 10 and 1878 physicians. The CPG were mostly about prevention or curative care. The retrieved barriers or facilitators were classified into three categories: 1) the CPG characteristics (form, compatibility, trialability, scientific basis, observability, adaptability, legal implications) (27 articles), 2) the physician characteristics (knowledge about CPG, attitude and agreement to CPG, psychological and socio-demographic and economic characteristics, job satisfaction, training) (38 articles), 3) the physician environment (divided into 3a the physician human environment--the patient influence and the pairs influence (16 articles)--and 3b the physician organizational environment--the internal environment and the external environment (33 articles). CONCLUSION: The interpretation of the results is hampered by the absence of previous conceptual framework of the barriers or facilitators and by the absence of multifactorial analysis.

Clinical Competence↗
PubMedDate not supplied

Evidence-based practice: how nurse leaders can facilitate innovation.

Evidence-based nursing practice (EBNP) is the wave of the future. Increasingly, EBNP is being identified as a key to quality and excellence in nursing services. Incorporating evidence into practice is necessary to deliver scientifically sound patient care. In addition, understanding the importance of evidence is crucial for meeting the excellence requirements of Magnet designation. Despite the growing popularity of EBNP and its documented significant benefits, the literature demonstrates that only 15% of the nursing workforce consistently practices within an EBNP framework. If EBNP adoption is to increase in the profession, it will require the active efforts of nurse leaders to pursue an aggressive innovation diffusion strategy. The purpose of this article is to discuss the nurse leader's role in facilitating EBNP in nursing using a theoretical framework grounded in innovation diffusion theory. The article develops 4 areas of focus. First, the components of innovation diffusion theory are discussed. Second, a pertinent empirical review of the EBNP adoption literature is presented. Third, strategies for applying innovation diffusion theory to facilitate EBNP adoption are proposed. Lastly, the article ends with a leadership call to action.

Attitude of Health Personnel↗
PubMed2003

Facilitation of iontophoretic drug delivery through intact and caries-affected dentine.

AIM: To investigate the facilitative role of iontophoresis in drug delivery through intact and caries-affected dentine into the pulp. METHODOLOGY: Forty-eight intact dentine or caries-affected dentine discs were prepared from freshly extracted human third molars. The hydraulic conductance was measured before and after the experiments. Drug diffusion with and without iontophoresis (0.05 mA, 10 min) was evaluated using a split-chamber device. The enamel side chamber was filled with metronidazole (MN), sodium salicylate (SS) or naproxen sodium (NA), while the pulpal side was circulated with phosphate buffered saline (PBS) and pressurized (15 cmH2O). Samples were collected after 1 h. Drug concentrations of the pulpal side solution were determined using a spectrophotometer. Then, electrical impedance of each dentine disc was measured. Finally, the dentine disc surfaces were observed by scanning electron microscopy. RESULTS: Drug diffusion was significantly influenced by iontophoresis, caries-induced changes in dentine and the drugs used (three-way anova, P < 0.05). The diffusion of all the drugs through caries-affected dentine was significantly less than that through intact dentine (independent t-test, P < 0.05). Also, iontophoresis facilitated the diffusion of all the drugs through intact and caries-affected dentine. The drug diffusion of SS was significantly higher than MN and NA (one-way anova, P < 0.05), independent of iontophoresis. CONCLUSIONS: Presence of dental caries may inhibit drug diffusion through dentine into the pulp. However, iontophoresis could enhance the delivery of ionized drugs through both intact and caries-affected dentine.

Adult↗
PubMed1970

Nonequilibrium facilitated oxygen transport in hemoglobin solution.

We have used the quasi-linearization method to obtain numerical solutions to the equations which describe steady-state diffusion of oxygen through layers of hemoglobin solution. The numerical solutions show how the facilitated flux of oxygen depends upon the layer thickness, reaction-rate coefficients, and other parameters of the system. The results indicate that steady-state oxygen diffusion in layers of hemoglobin solution, similar to those studied by Scholander, should be adequately described by the models which assume chemical equilibrium exists throughout the layer, but for layers of concentrated hemoglobin solution about the thickness of a human erythrocyte, the facilitation of oxygen diffusion should be much less than the equilibrium models predict.

Biological Transport↗
PubMed1999

Regulation of the bacteriorhodopsin photocycle and proton pumping in whole cells of Halobacterium salinarium.

Single-turnover kinetics of the bacteriorhodopsin photocycle and proton-pumping capabilities of whole cells were studied. It was found that the Delta mu (tilde)H+ of the cell had a profound influence on the kinetics and components of the cycle. For example, comparing the photocycle in whole cells to that seen in PM preparations, we found that (1) the single-turnover time of the cycle was increased approximately 10-fold, (2) the mole fraction of M-fast (at high actinic light) decreased from 50 to 20%, and (3) the time constant for M-slow increased significantly. The level of Delta mu(tilde)H+ was dependent on respiration, ATP formation and breakdown, and the magnitude of a pre-existing K+ diffusion gradient. The size of the Delta mu(tilde)H+ could be manipulated by additions of HCN, nigericin, and DCCD (N,N'-dicyclohexylcarbodamide). At higher levels of Delta mu(tilde)H+, further changes in the photocycle were seen. (4) Two slower components of M-decay appeared as major components. (5) The apparent conversion of the M-fast to the O intermediate disappeared. (6) A partial reversal of an early photocycle step occurred. The photocycle of intact cells could be changed to that seen in purple membrane suspensions by the energy-uncoupler CCCP or by lysis of the cells. In fresh whole cells, light-induced proton pumping was not seen until the K+ diffusion potential was dissipated and proton accumulation facilitated by use of a K+-H+ exchanger (nigericin), respiration was inhibited by HCN, and ATP synthesis and breakdown were inhibited by DCCD. In stored cells, the pre-existing K+ diffusion gradient was diminished through slow diffusion, and only DCCD and HCN were required to elicit proton extrusion.

Bacteriorhodopsins↗
PubMed2005

Kokua Mau: a statewide effort to improve end-of-life care.

BACKGROUND: Many Americans die in pain, without hospice, and without regard to advance directives, suggesting a need to improve end-of-life (EOL) awareness and services. OBJECTIVE: This paper describes Kokua Mau, a community-state partnership to improve EOL in Hawaii funded by The Robert Wood Johnson Foundation (RWJF). Coalition activities were guided by innovation-diffusion theory, targeting "innovators" and "change agents" within communities and organizations willing to learn about and facilitate improvements to EOL care. DESIGN: Evaluation of a community-wide intervention to improve EOL care. SETTING/SUBJECTS: Honolulu, Hawaii. MEASUREMENTS: We tracked dissemination of campaign messages by counting numbers of coalition members (including innovators and change agents to carry on the work), individuals reached through awareness and educational offerings, and new EOL projects initiated during and after the initial 3-year RWJF funding. To measure change, we counted the number of legislative policies that were modified by the coalition as well as indicators of hospice utilization, advance directive (AD) completion, support for physician-assisted death, and place of death. RESULTS: In the first 3 years of the project: coalition membership grew to 350 members; EOL care curricula were developed and offered to various target audiences; 17,000 individuals attended educational events; policy changes were facilitated; decreases were seen in proportions of residents supporting physician-assisted suicide; and increases were seen in advance directive completion rates and hospice utilization. Most importantly, after the grant period, coalition members went on to develop and implement new programs to improve care to the dying. CONCLUSIONS: Although it will take several years to effect comprehensive and sustained changes in the way death is perceived and the dying process is facilitated, findings suggest that programs based on innovation-diffusion theory can increase EOL awareness and help develop the change agents and role models needed to affect community-wide change over the long term.

Adolescent↗
PubMed1985

Effect of cortical-medullary gradient for ammonia on urinary excretion of ammonia.

Previous studies suggested that a portion of ammonia secreted into the proximal tubule may diffuse directly from Henle's loop into the medullary collecting duct. Since water is absorbed along the course of the descending portion of the loop, it was proposed that the concentration of ammonia increased in loop fluid, and that rapid diffusibility of the free base would facilitate the delivery of ammonia into medullary interstitium where a high level could be maintained by the countercurrent exchange process. In this schema it was proposed that there was an ammonia concentration gradient between medullary structures and cortex, and recovery of ammonia by the medullary collecting duct due to the low pH in tubule fluid at that site. The present study was designed to evaluate this hypothesis by estimating ammonia concentrations in medullary and cortical tissue, and by correlating medullary levels with secretion rate into the inner medullary collecting duct. In control animals the concentration of total ammonia (NH4+ + NH3+) in inner medullary vasa recta was 9.2 +/- 1.5 mumoles/ml, a level 100-fold higher than the cortical level of 0.10 +/- 0.01. During acute acidosis the medullary level rose to 22.5 +/- 2.7 mumoles/ml, but in acute acidosis during mannitol infusion the level fell to 8.0 +/- 1.2. The rate of ammonia secretion into inner medullary collecting duct fluid correlated directly with medullary vasa recta ammonia concentration. These data provide evidence for a steep ammonia concentration gradient between the medulla and cortex, and suggest that the diffusion gradient across collecting duct epithelium governs the rate of the addition of ammonia to collecting duct fluid.

Acidosis↗