Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 385
Filter
1.
Anaesthesia ; 77(12): 1439-1444, 2022 12.
Article in English | MEDLINE | ID: mdl-35727950
2.
J Coat Technol Res ; 17(1): 255-269, 2020 Jan.
Article in English | MEDLINE | ID: mdl-32454951

ABSTRACT

Graphene oxide (GO) is a good nanofiller candidate for waterborne coatings because of its outstanding physical and mechanical properties, good dispersibility in water, and low cost relative to graphene. Here, we report on the performance of a one-part, waterborne polyurethane (WPU) nanocoating formulated with four different GO loadings ([0.4% to 2.0%] by mass). The degree of GO dispersion/adhesion was evaluated using scanning electron microscopy, laser scanning confocal microscopy, and Raman microscopy. Nanocoating performance was evaluated using a dynamic mechanical thermal analyzer for mechanical properties, a customized coulometric permeation apparatus for oxygen barrier properties, a combustion microcalorimeter for flammability, a hot disk analyzer for thermal conductivity, thermogravimetric analysis for thermal stability, and a moisture sorption analyzer for water uptake. The results show that GO sheets were well dispersed in, and have good adhesion to, WPU. At the higher mass loadings ([1.2% or 2%] by mass), GO increased the modulus and yield strength of WPU by 300% and 200%, respectively, increased the thermal conductivity by 38%, reduced the burning heat release rate (flammability) by 43%, and reduced the oxygen permeability by up to sevenfold. The presence of GO, however, increased water vapor uptake at high humidity; the moisture content of 2% mass loading GO/WPU nanocoatings at 90% RH was almost twice that of the moisture content for unfilled WPU. Overall, with the exception of water uptake at very high humidity (> 70% RH), the observed improvements in physical and mechanical properties combined with the ease of processing suggest that GO is a viable nanofiller for WPU coatings.

3.
Sci Total Environ ; 674: 439-450, 2019 Jul 15.
Article in English | MEDLINE | ID: mdl-31005845

ABSTRACT

Non-potable recycled water schemes can benefit sustainable urban water management through reducing demand for drinking water and mitigating environmental loadings through the provision of advanced wastewater treatment. However, scheme feasibility can be diminished by high capital and operating costs which can be elevated by perceptions of health risks and subsequently overly cautious risk reduction measures. Conversely, a failure to anticipate the risk management expectations of stakeholders can undermine scheme feasibility through insufficient demand for recycled water. The aim of this study was to explore how stakeholders' perceptions and preferences for risk management and recycled water end-uses might influence scheme design. Using a case study scheme in London, four risk management intervention scenarios and six alternative end uses were evaluated using a stochastic PROMETHEE-based method that incorporated quantitative microbial risk assessment and stakeholder criteria weights together with an attitudinal survey of stakeholders' risk perceptions. Through pair-wise criteria judgements, results showed that stakeholders prioritised health risk reductions which led to the more conservative management intervention of adding water treatment processes being ranked the highest. In contrast, responses to the attitudinal survey indicated that the stakeholders favoured maintaining the case study's existing levels of risk control but with more stakeholder engagement. The findings highlighted potential benefits of understanding risk perceptions associated with different design options and contrasting these with multi-criteria model results. Extrapolating from these findings, future research could explore potential challenges and benefits of providing flexibility in scheme designs to appeal to a wider range of stakeholder needs as well as being more adaptable to future social, environmental or economic challenges. The study concludes that contemporary risk management guidance would benefit from more explicitly outlining constructive ways to engage stakeholders in scheme evaluation.

4.
Water Res ; 145: 125-135, 2018 11 15.
Article in English | MEDLINE | ID: mdl-30125815

ABSTRACT

Water reuse is of increasing relevance for water-stressed regions but is often considered a contentious option. Research has shown that providing the public with information about reuse options can impact positively on its acceptability, although such impacts can be confined to specific groups. In this context, there is growing interest in understanding the impact of different forms and mechanisms of communication with the public around reuse. This contribution has investigated the use of video animations to communicate the safety of non-potable recycled water schemes. The aim of this study was to evaluate how different ways of framing messages about the safety of recycled water might impact on public attitudes. Participants were recruited in London (n = 689), UK, and randomly allocated to test and control groups, with the former being exposed to one of four video animations that used different frames to convey messages about recycled water safety. Surveys collected pre- and post-video message responses for dependent variables including the general acceptance of diverse non-potable recycled water uses, risk perceptions and trust. The findings complement existing knowledge on the impacts of different types of messaging on public attitudes to reuse schemes with important evidence for the positive impact of water safety communications framed in terms of compliance with water quality requirements. Contrarily, a positive attitudinal impact was not evident for safety message framed in terms of the selection of water treatment technology to remove contaminants nor in terms of non-potable water risks relative to other every-day risks. The results are of value to water resource planners looking to develop communication resources, as part of more comprehensive public engagement strategies, for improving perceptions of water reuse. Importantly, the findings help isolate the effects of specific message frames, and inform the debate on whether an increased understanding of risk positively or negatively influences willingness to support water reuse schemes.


Subject(s)
Public Opinion , Water Purification , Attitude , London , Recycling
5.
Br J Anaesth ; 120(5): 1132-1133, 2018 05.
Article in English | MEDLINE | ID: mdl-29661393
6.
Int J Pharm ; 514(2): 428-444, 2016 Dec 05.
Article in English | MEDLINE | ID: mdl-27693736

ABSTRACT

The ability of a range of hydrophilic nonionic cellulose ethers (CEs) (namely methylhydroxethylcellulose, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose) to prepare stable nabumetone nanoparticles (<1000nm, as measured by laser diffraction) using wet-bead milling has been investigated. Due to the limited range of CE molecular weights commercially available, the CEs were degraded using ultrasonication for varying lengths of time to yield CEs of lower molecular weight. Of the CEs tested, only hydroxyethylcellulose was found not to stabilise the production of nabumetone nanoparticles at any of the molecular weights tested, namely viscosity average molecular weights (Mv) in the range of 236-33kg/mol. All other CEs successfully stabilised nabumetone nanoparticles, with the lower molecular weight/viscosity polymers within a series being more likely to result in nanoparticle production than their higher molecular weight counterparts. Unfortunately due to the nature of the ultrasonication process, it was not possible to compare the size of nabumetone particles produced using polymers of identical Mv. There was, however, enough similarity in the Mv of the various polymers to draw the general conclusion that there was no strong correlation between the Mv of the various polymers and their ability to produce nanoparticles. For example hydroxypropylcellulose of 112.2kg/mol or less successfully produced nanoparticles while only ethylhydroxyethylcellulose and hydroxypropylmethyl polymers of 52 and 38.8kg/mol or less produced nanoparticles. These results suggest that polymer molecular weight is not the only determinant of nanoparticle production and that structure of the polymer is at least as important as its molecular weight. In particular the hydrophobic nature of the CE was thought to be an important factor in the production of nabumetone nanoparticles: the more hydrophobic the polymer, the stronger its interaction with nabumetone and the greater its ability to produce nanoparticles. In this context HPC was the most hydrophobic polymer and HEC the least hydrophobic.


Subject(s)
Butanones/chemistry , Cellulose/analogs & derivatives , Cellulose/chemistry , Molecular Weight , Nanoparticles/chemistry , Viscosity , Drug Stability , Nabumetone , Nanoparticles/ultrastructure , Particle Size , Polymers/chemistry , Ultrasonics
7.
J Chem Phys ; 144(20): 204107, 2016 May 28.
Article in English | MEDLINE | ID: mdl-27250279

ABSTRACT

Quadratic convergence throughout the active space is achieved for the gradient ascent pulse engineering (GRAPE) family of quantum optimal control algorithms. We demonstrate in this communication that the Hessian of the GRAPE fidelity functional is unusually cheap, having the same asymptotic complexity scaling as the functional itself. This leads to the possibility of using very efficient numerical optimization techniques. In particular, the Newton-Raphson method with a rational function optimization (RFO) regularized Hessian is shown in this work to require fewer system trajectory evaluations than any other algorithm in the GRAPE family. This communication describes algebraic and numerical implementation aspects (matrix exponential recycling, Hessian regularization, etc.) for the RFO Newton-Raphson version of GRAPE and reports benchmarks for common spin state control problems in magnetic resonance spectroscopy.

8.
J Chem Phys ; 143(8): 084113, 2015 Aug 28.
Article in English | MEDLINE | ID: mdl-26328824

ABSTRACT

Auxiliary matrix exponential method is used to derive simple and numerically efficient general expressions for the following, historically rather cumbersome, and hard to compute, theoretical methods: (1) average Hamiltonian theory following interaction representation transformations; (2) Bloch-Redfield-Wangsness theory of nuclear and electron relaxation; (3) gradient ascent pulse engineering version of quantum optimal control theory. In the context of spin dynamics, the auxiliary matrix exponential method is more efficient than methods based on matrix factorizations and also exhibits more favourable complexity scaling with the dimension of the Hamiltonian matrix.

9.
Equine Vet J ; 47(5): 603-8, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25256848

ABSTRACT

REASONS FOR PERFORMING STUDY: The pathogenesis of bilateral dynamic laryngeal collapse associated with poll flexion (DLC) of horses is unknown but might be associated with intrinsic laryngeal muscle weakness. OBJECTIVES: To investigate histopathological characteristics of the cricoarytenoideus dorsalis, the cricothyroid (CT) and the cricoarytenoideus lateralis muscles in DLC-affected horses and compare these with unaffected controls. Our hypotheses were that evidence of neurogenic atrophy of the CT or cricoarytenoideus dorsalis muscles would be found in DLC-affected horses and that observed changes would be symmetrically (left/right) distributed, or that muscle fibre diameter would be significantly reduced in DLC-affected horses compared to unaffected controls, reflecting an underlying paresis. STUDY DESIGN: Case-control study. METHODS: Five DLC horses and 8 controls were included. Muscle samples were harvested immediately following euthanasia. Fibre type proportions and size were evaluated by multiple immunofluorescence labelling of cryosections, and compared between sides (left/right) and groups (DLC-affected cases/ unaffected controls). Subjective and objective assessments of fibre type grouping were compared between sides and groups. RESULTS: Fibre type proportions, fibre size and the subjective assessment of fibre type grouping did not reveal any statistically significant differences between the groups. Objective assessment of fibre type grouping revealed significantly more large clusters of T1 fibres within the left cricoarytenoideus lateralis muscle of DLC-affected cases versus controls, and within the right CT muscle of control horses compared to the DLC-cases. CONCLUSIONS: The absence of bilateral symmetric fibre type grouping, fibre type loss and fibre atrophy in the DLC-affected cases do not support a neuromuscular component within the pathogenesis of DLC. The objective assessment of fibre type grouping revealed some statistical differences between the DLC-affected cases and the unaffected controls; however, these findings were inconsistent with regard to DLC. An alternative aetiology of DLC seems likely.


Subject(s)
Horse Diseases/pathology , Laryngeal Diseases/veterinary , Larynx/pathology , Animals , Case-Control Studies , Collagen/metabolism , Female , Gene Expression Regulation , Horses , Laryngeal Diseases/pathology , Laryngeal Nerves , Larynx/anatomy & histology , Larynx/physiology , Male , Muscles/pathology
10.
J Comput Neurosci ; 36(3): 499-514, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24150916

ABSTRACT

We use neural field theory and spike-timing dependent plasticity to make a simple but biophysically reasonable model of long-term plasticity changes in the cortex due to transcranial magnetic stimulation (TMS). We show how common TMS protocols can be captured and studied within existing neural field theory. Specifically, we look at repetitive TMS protocols such as theta burst stimulation and paired-pulse protocols. Continuous repetitive protocols result mostly in depression, but intermittent repetitive protocols in potentiation. A paired pulse protocol results in depression at short ( < ∼ 10 ms) and long ( > ∼ 100 ms) interstimulus intervals, but potentiation for mid-range intervals. The model is sensitive to the choice of neural populations that are driven by the TMS pulses, and to the parameters that describe plasticity, which may aid interpretation of the high variability in existing experimental results. Driving excitatory populations results in greater plasticity changes than driving inhibitory populations. Modelling also shows the merit in optimizing a TMS protocol based on an individual's electroencephalogram. Moreover, the model can be used to make predictions about protocols that may lead to improvements in repetitive TMS outcomes.


Subject(s)
Evoked Potentials, Motor/physiology , Models, Neurological , Motor Cortex/physiology , Neuronal Plasticity/physiology , Transcranial Magnetic Stimulation , Action Potentials/physiology , Humans , Neural Inhibition/physiology
11.
Curr Med Chem ; 19(26): 4451-61, 2012.
Article in English | MEDLINE | ID: mdl-22830348

ABSTRACT

The development of techniques for efficient peptide production renewed interest in peptides as therapeutics. Numerous modifications for improving stability, transport and affinity profiles now exist. Several new adjuvant and carrier systems have also been developed, enhancing the immunogenicity of peptides thus allowing their development as vaccines. This review describes the established and experimental approaches for manufacturing peptide drugs and highlights the techniques currently used for improving their drug like properties.


Subject(s)
Peptides/chemistry , Peptides/pharmacology , Amino Acid Sequence , Animals , Humans , Peptides/chemical synthesis , Peptides/therapeutic use , Vaccines, Subunit/chemical synthesis , Vaccines, Subunit/chemistry , Vaccines, Subunit/pharmacology , Vaccines, Subunit/therapeutic use
12.
Spinal Cord ; 49(11): 1088-96, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21647164

ABSTRACT

OBJECTIVES: To systematically develop evidence-informed physical activity guidelines to improve physical fitness in people with spinal cord injury (SCI). SETTING: This study was conducted in Canada. METHODS: The Appraisal of Guidelines, Research and Evaluation II guideline development protocol was used to develop exercise guidelines to improve physical capacity and muscular strength. The evidence base for the guideline development process consisted of a systematic review and quality appraisal of research examining the effects of exercise on physical fitness among people with SCI. A multidisciplinary expert panel deliberated the evidence and generated the guidelines. Pilot testing led to refinement of the wording and presentation of the guidelines. RESULTS: The expert panel generated the following guidelines: for important fitness benefits, adults with a SCI should engage in (a) at least 20 min of moderate to vigorous intensity aerobic activity two times per week and (b) strength training exercises two times per week, consisting of three sets of 8-10 repetitions of each exercise for each major muscle group. CONCLUSION: People with SCI, clinicians, researchers and fitness programmers are encouraged to adopt these rigorously developed guidelines.


Subject(s)
Evidence-Based Medicine/standards , Motor Activity , Practice Guidelines as Topic/standards , Spinal Cord Injuries/rehabilitation , Adult , Humans , Spinal Cord Injuries/physiopathology
13.
Br J Anaesth ; 101(3): 332-7, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18556692

ABSTRACT

BACKGROUND: We aimed to describe how anaesthetists hand over information and professional responsibility to nurses in the operating theatre recovery room. METHODS: We carried out non-participant practice observation and in-depth interviews with practitioners working in the recovery room of an English hospital and used qualitative methods to analyse the resulting transcripts. RESULTS: We observed 45 handovers taking place between 17 anaesthetists and 15 nurses in the recovery room of the operating theatre suite. These took place in an environment that is event-driven, time-pressured, and prone to concurrent distractions. Anaesthetists and nurses often had differing expectations of the content and timing of information transfer. The point at which transfer of responsibility for the patient occurred during the handover process was variable and depended not only on the condition of the patient but also on the professional relationship between the nurse and doctor concerned. Handover also provided an 'audit point' in care where the patient's intraoperative progress was reviewed and plans were made for further management. Here, as in the transfer of responsibility, we found evidence that nurses play a greater role in defining the limits of anaesthetists' practice than might be expected. CONCLUSIONS: Patient handovers in the recovery room are largely informal, but nevertheless show many inherent tensions, both professional and organizational. Although formalized handover procedures are often advocated for the promotion of safety, we suggest that they are likely to work best when the informal elements, and the cultural factors underlying them, are acknowledged.


Subject(s)
Anesthesiology/organization & administration , Interprofessional Relations , Postanesthesia Nursing/organization & administration , Postoperative Care/nursing , Recovery Room , Anesthesia Recovery Period , Communication , Continuity of Patient Care/organization & administration , England , Humans , Interviews as Topic , Postoperative Care/psychology , Professional Practice , Safety Management/organization & administration
14.
J Hand Surg Eur Vol ; 32(5): 543-6, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17950218

ABSTRACT

Twelve month minimum follow-up was available for 19 Oriental Jewish patients who underwent surgery for Dupuytren's disease over a 10-year period. In this population, the disease is uncommon. The initial deformity, operative findings and results of surgery were similar to those described for North European Caucasian patients. Possible factors that may result in a low genetic predisposition to Dupuytren's disease amongst Jews are discussed.


Subject(s)
Asian People/genetics , Dupuytren Contracture/genetics , Jews/genetics , Aged , Aged, 80 and over , Cross-Cultural Comparison , Dupuytren Contracture/surgery , Europe , Fasciotomy , Female , Genetic Predisposition to Disease/genetics , Humans , Israel , Male , Middle Aged , Retrospective Studies , Risk Factors
15.
J Pharm Sci ; 96(10): 2655-66, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17696165

ABSTRACT

Stable, polymer-coated nanoparticles of two hydrophobic drugs, namely nabumetone and halofantrine, have been prepared by a wet-bead milling process performed in the presence of a stabilizing homopolymer, either hydroxypropylmethylcellulose (HPMC) or polyvinylpyrrolidone (PVP), of differing molecular weights and concentrations. Although nabumetone nanoparticles could only be produced when HPMC was used as stabilizing polymer, halofantrine nanoparticles could be prepared using either HPMC or PVP. Stable nanoparticles of nabumetone could be produced using a HPMC solution of viscosity average molecular weight, M(v), of 5 kg/mol over an approximate four fold polymer concentration range (0.63-2.5% w/w) when a drug loading of 20% w/w was used. Increasing the molecular weight of HPMC up to a limiting M(v) of 89 kg/mol did not result in the formation of nanoparticles at any of the polymer concentrations examined. The amount of polymer absorbed onto the nanoparticles was determined by measuring the depletion of polymer from solution based on either an ultra-violet (PVP) or optical rotatory dispersion (ORD) (HPMC) assay. The slightly lower concentration of HMPC found to be present on the surface of the halofantrine nanoparticles compared with the nabumetone nanoparticles suggested a differing affinity of the polymer for the surface of the two drugs.


Subject(s)
Drug Carriers , Excipients/chemistry , Methylcellulose/analogs & derivatives , Nanoparticles , Povidone/chemistry , Adsorption , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Antimalarials/chemistry , Butanones/chemistry , Chemistry, Pharmaceutical , Colloids , Drug Compounding , Hypromellose Derivatives , Methylcellulose/chemistry , Molecular Weight , Nabumetone , Particle Size , Phenanthrenes/chemistry , Solubility , Surface Properties , Technology, Pharmaceutical , Viscosity , Water/chemistry
16.
Vet Rec ; 160(16): 548-51, 2007 Apr 21.
Article in English | MEDLINE | ID: mdl-17449710

ABSTRACT

To investigate the choices of foraging location of horses, 10 to 12 horses were introduced for five minutes into each of two similar stables containing a single forage or six forages, in four replicated trials. The horses were then removed and released into the gangway between the stables, and allowed five minutes to choose between the stables. Their initial and final choices, mean duration in each stable and proportional frequency of change of location were compared. Most of the horses initially entered the closest stable on release (P<0.05); if the closest stable contained a single hay, most horses transferred to the stable containing multiple forages (P<0.001). The length of time spent by the horses in the two stables suggested that they preferred multiple forages in multiple locations (P<0.001). Eleven horses moved from one stable to the other on one or more occasions during trials when hay or a preferred forage was available in both stables, possibly indicating a motivation to move between foraging locations regardless of the palatability of the forages offered or the horses' preference for a forage.


Subject(s)
Animal Feed , Behavior, Animal , Horses/psychology , Animal Husbandry , Animals , Female , Male
17.
Br J Anaesth ; 97(3): 401-7, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16835256

ABSTRACT

BACKGROUND: Published work on knowledge in regional anaesthesia has focused on competence, for instance by identifying numbers of procedures required to achieve competence, or by defining criteria for successful performance of blocks. We aimed to define expertise in regional anaesthesia and examine how it is acquired. METHODS: We observed anaesthetists performing 15 regional anaesthetic blocks and analysed the resulting transcripts qualitatively and in detail. RESULTS: Expertise in regional anaesthesia encompasses technical fluency but also includes non-cognitive skills such as handling of the patient (communicating, anticipating and minimizing discomfort) and recognizing the limits of safe practice (particularly deciding when to stop trying to insert a block). Such elements may be underplayed by the experts who possess them. Focusing on a small number of regional anaesthetic procedures in detail (as is standard with such qualitative analytical approaches) has also allowed us to develop a model for the acquisition of expertise. In this model, trainees learn how to balance theoretical and practical knowledge by reflection on their clinical experiences, an iterative process which leads to the embedding of knowledge in the expert's personal repertoire of individual techniques. CONCLUSIONS: Expertise in regional anaesthesia extends beyond competence at technical performance; non-cognitive elements are also vital. Further work is needed to test our learning model, and the hypothesis that learning can be enhanced by deliberate promotion of the tacit elements of 'expertise' we have described.


Subject(s)
Anesthesia, Conduction/standards , Clinical Competence , Anesthesia, Conduction/methods , Anesthesiology/education , Education, Medical, Graduate/methods , England , Humans
18.
Br J Anaesth ; 96(6): 715-21, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16698867

ABSTRACT

BACKGROUND: This study aimed to explore how critical and acceptable practice are defined in anaesthesia and how this influences the discussion and reporting of adverse incidents. Method. We conducted workplace observations of, and interviews with, anaesthetists and anaesthetic staff. Transcripts were analysed qualitatively for recurrent themes and quantitatively for adverse events in anaesthetic process witnessed. We also observed departmental audit meetings and analysed meeting minutes and report forms. RESULTS: The educational value of discussing events was well-recognized; 28 events were discussed at departmental meetings, of which 5 (18%) were presented as 'critical incidents'. However, only one incident was reported formally. Our observations of anaesthetic practice revealed 103 minor events during the course of over 50 anaesthetic procedures, but none were acknowledged as offering the potential to improve safety, although some were direct violations of 'acceptable' practice. Formal reporting appears to be constrained by changing boundaries of what might be considered 'critical', by concerns of loss of control over formally reported incidents and by the perception that reporting schemes outside anaesthesia have purposes other than education. CONCLUSIONS: Despite clear official definitions of criticality in anaesthesia, there is ambiguity in how these are applied in practice. Many educationally useful events fall outside critical incident reporting schemes. Professional expertise in anaesthesia brings its own implicit safety culture but the reluctance to adopt a more explicit 'systems approach' to adverse events may impede further gains in patient safety in anaesthesia.


Subject(s)
Anesthesia , Attitude of Health Personnel , Risk Management/standards , Anesthesia/adverse effects , Anesthesia/standards , Anesthesiology/education , Anesthesiology/organization & administration , Education, Medical, Continuing/methods , England , Health Services Research/methods , Humans , Medical Audit , Medical Staff, Hospital/psychology , Qualitative Research , Risk Management/statistics & numerical data , Terminology as Topic
19.
Eur J Neurosci ; 21(8): 2127-35, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15869509

ABSTRACT

Excessive nitric oxide (NO) production from the inducible isoform of nitric oxide synthase (iNOS) has been invoked as a causative factor in many neurodegenerative disorders, including multiple sclerosis. This hypothesis has been supported by in vitro studies showing that glial iNOS expression results in toxic NO concentrations (near 1 microm). To investigate the relevance of such findings, experiments were carried out ex vivo on optic nerves from rats with exacerbated experimental allergic encephalomyelitis, a model of multiple sclerosis. The nerves displayed characteristic immunopathology and expression of iNOS in macrophages and/or microglia and there was overt axonal damage in localized regions of the optic chiasm. The resulting NO levels in the optic nerve were sufficient to cause activation of guanylyl cyclase-coupled NO receptors, resulting in marked cGMP accumulation in axons throughout the nerve. Nevertheless, calibration of cGMP levels against those evoked by exogenous NO indicated that the nerves were not compromised metabolically and that their ambient NO concentration was only approximately 1 nm. Consistent with this observation, electrophysiological tests indicated that there was no ongoing malfunctioning of the type that can be elicited by high exogenous NO concentrations. It is concluded that, with iNOS expressed in physiological locations and levels, the tissue levels of NO remain at concentrations far lower than those shown to have toxic effects, despite continuous NO synthesis. The fact that NO can rise to much higher levels in dispersed cultures in vitro may be attributable to a deficiency in NO inactivation in such preparations.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/enzymology , Encephalomyelitis, Autoimmune, Experimental/pathology , Macrophages/enzymology , Nitric Oxide Synthase/metabolism , Optic Nerve/pathology , Ornithine/analogs & derivatives , 1-Methyl-3-isobutylxanthine/pharmacology , Action Potentials/drug effects , Animals , Arginine/pharmacology , Biomarkers/metabolism , CD11b Antigen/metabolism , CD2 Antigens/metabolism , Cyclic GMP/metabolism , DEET/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Electric Stimulation/methods , Encephalomyelitis, Autoimmune, Experimental/chemically induced , Female , Guanylate Cyclase/metabolism , Guinea Pigs , Hydrazines/pharmacology , Immunohistochemistry/methods , Macrophages/pathology , Microscopy, Electron, Transmission/methods , Myelin Basic Protein/metabolism , Nitric Oxide/pharmacology , Nitric Oxide Synthase Type II , Optic Chiasm/pathology , Optic Chiasm/ultrastructure , Optic Nerve/drug effects , Optic Nerve/enzymology , Optic Nerve/ultrastructure , Ornithine/pharmacology , Phosphodiesterase Inhibitors/pharmacology , Rats , Rats, Inbred Lew , Time Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...