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101.
P van Ruitenbeek A Sambeth A Vermeeren SN Young WJ Riedel 《British journal of pharmacology》2009,157(1):92-103
Background and purpose:
Animal studies show that histamine plays a role in cognitive functioning and that histamine H3-receptor antagonists, which increase histaminergic function through presynaptic receptors, improve cognitive performance in models of clinical cognitive deficits. In order to test such new drugs in humans, a model for cognitive impairments induced by low histaminergic functions would be useful. Studies with histamine H1-receptor antagonists have shown limitations as a model. Here we evaluated whether depletion of L-histidine, the precursor of histamine, was effective in altering measures associated with histamine in humans and the behavioural and electrophysiological (event-related-potentials) effects.Experimental approach:
Seventeen healthy volunteers completed a three-way, double-blind, crossover study with L-histidine depletion, L-tyrosine/L-phenylalanine depletion (active control) and placebo as treatments. Interactions with task manipulations in a choice reaction time task were studied. Task demands were increased using visual stimulus degradation and increased response complexity. In addition, subjective and objective measures of sedation and critical tracking task performance were assessed.Key results:
Measures of sedation and critical tracking task performance were not affected by treatment. L-histidine depletion was effective and enlarged the effect of response complexity as measured with the response-locked lateralized readiness potential onset latency.Conclusions and implications:
L-histidine depletion affected response- but not stimulus-related processes, in contrast to the effects of H1-receptor antagonists which were previously found to affect primarily stimulus-related processes. L-histidine depletion is promising as a model for histamine-based cognitive impairment. However, these effects need to be confirmed by further studies. 相似文献102.
Z Luo Y Chen S Chen WJ Welch BT Andresen PA Jose CS Wilcox 《British journal of pharmacology》2009,157(6):935-943
Background and purpose:
We compared the dose-dependent reductions in cellular superoxide anion (O2−) by catalytic agents: superoxide dismutase (SOD), polyethylene glycol (PEG)-SOD and the nitroxide 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (tempol) with uncharacterized antioxidants: 5,10,15,20-tetrakis (4-sulphonatophenyl) porphyrinate iron (III)(Fe-TTPS), (-)-cis-3,3′,4′,5,7-pentahydroxyflavane (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol (-epicatechin), 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) and N-acetyl-L-cysteine (NAC) with the spin trap nitroblue tetrazolium (NBT) and with the vitamins or their analogues: ascorbate, α-tocopherol and 6-hydroxy-2,5,7,8-tetramethylkroman-2-carboxy acid (trolox).Experimental approach:
O2− was generated in primary cultures of angiotensin II-stimulated preglomerular vascular smooth muscle cells from spontaneously hypertensive rats and detected by lucigenin-enhanced chemiluminescence.Key results:
SOD, PEG-SOD, NAC and tempol produced a similar maximum inhibition of O2− of 80–90%. -Epicatechin, NBT, ebselen and Fe-TTPS were significantly (P < 0.0125) less effective (50–70%), whereas trolox, α-tocopherol and ascorbate had little action even over 24 h of incubation (<31%). Effectiveness in disrupted and intact cells was similar for the permeable agents, PEG-SOD and tempol, but was enhanced for SOD. Generation of O2− was increased by NAC and NBT at low concentrations but reduced at high concentrations.Conclusions and implications:
Maximum effectiveness against cellular production of O2− requires cell membrane permeability and catalytic action as exemplified by PEG-SOD or tempol. NAC and NBT have biphasic effects on O2− production. Vitamins C and E or analogues have low efficacy. 相似文献103.
INTRODUCTION
Diagnostic errors in orthopaedics are usually caused by missing a fracture or misreading radiographs. The aim of this study was to document the pick-up rate of the wrong diagnoses by reviewing X-rays and casualty notes in the next-day trauma meeting.PATIENTS AND METHODS
The casualty notes and radiographs of 503 patients were prospectively reviewed in the daily trauma meeting between August 2002 and December 2002 in a district general hospital. The relevant data were collected and analysed by a single assessor.RESULTS
The false positive rate for making an orthopaedic diagnosis was 12.6% (i.e.) diagnosing a fracture, when none existed). The false negative (missing) rate was 4%, while 2.4% incidental findings were missed, or at least not documented, after reading the X-rays. There were 7.8% wrong diagnoses made. The majority of the patients were seen by the senior house officers.CONCLUSIONS
The medicolegal significance of false negative diagnosis is obviously greater. In a busy emergency department, where a large number of patients are seen, there is a greater risk. This study shows the importance in a small-to-medium sized accident and emergency unit as well, where there is no senior cover available out-of-hours for final radiological interpretation. A morning trauma meeting which covers reviewing admitted patients as well as non-admission orthopaedic referrals has an effective risk management solution to early detection of missed and wrong diagnoses. 相似文献104.
本实验采用性腺摘除或经假摘除手术的两性SD大鼠,其中部分动物分别予以睾酮(T)或雌二醇(E_2),观察它们在急性饥饿或非饥饿状态下血清T_4、TSH与T浓度变化。结果提示急性饥饿可使雄鼠甲状腺合成或分泌T_4和性腺分泌睾酮减少,从而不完全地抑制了雄激素所介导的对垂体TSH分泌的兴奋作用。外源性T替代虽然可以使去势雄鼠血清T浓度恢复正常,但却无兴奋TSH分泌的作用;饥饿组去势雄鼠接受外源性T后血清TSH更为减少。提示外源性T可抑制此组雄鼠垂体TSH合成及(或)释放。 相似文献
105.
106.
Sjors FPJ Coppus Jose I Emparanza Julie Hadley Regina Kulier Susanne Weinbrenner Theodoros N Arvanitis Amanda Burls Juan B Cabello Tamas Decsi Andrea R Horvath Marcin Kaczor Gianni Zanrei Karin Pierer Katarzyna Stawiarz Regina Kunz Ben WJ Mol Khalid S Khan 《BMC medical education》2007,7(1):1-10
Background
Little research has been conducted to investigate role stress experienced by faculty members in medical schools in developing countries. This becomes even more important when the process of reform in medical education has already taken place, such as the case of Iran. The objectives of this study were to investigate and assess the level and source of role-related stress as well as dimensions of conflict among the faculty members of Iranian medical schools. Variables like the length of academic work, academic rank, employment position, and the departments of affiliation were also taken into consideration in order to determine potentially related factors.Methods
A survey was conducted at three different ranks of public medical schools. The validated Organizational Role Stress Scale was used to investigate the level of role stress and dimensions of role conflict among medical faculty members. The response rate was 66.5%.Results
The findings show that role stress was experienced in high level among almost all faculty members. All three studied medical schools with different ranks are threatened with relatively the same levels of role stress. Specific differences were found among faculty members from different disciplines, and academic ranks. Also having permanent position and the length of services had significant correlation with the level of role stress. The major role- related stress and forms of conflict among faculty members were role overload, role expectation conflict, inter-role distance, resource inadequacy, role stagnation, and role isolation.Conclusion
The most role-related stressors and forms of conflict among faculty members include too many tasks and everyday work load; conflicting demands from colleagues and superiors; incompatible demands from their different personal and organizational roles; inadequate resources for appropriate performance; insufficient competency to meet the demands of their role; inadequate autonomy to make decision on different tasks; and a feeling of underutilization. The findings of this study can assist administrators and policy makers to provide an attractive working climate in order to decrease side effects and consequences of role stress and to increase productivity of faculty members. Furthermore, understanding this situation can help to develop coping strategies in order to reduce role-related stress. 相似文献107.
Papadopoulos NG Xepapadaki P Mallia P Brusselle G Watelet JB Xatzipsalti M Foteinos G van Drunen CM Fokkens WJ D'Ambrosio C Bonini S Bossios A Lötvall J van Cauwenberge P Holgate ST Canonica GW Szczeklik A Rohde G Kimpen J Pitkäranta A Mäkelä M Chanez P Ring J Johnston SL 《Allergy》2007,62(5):457-470
Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti-inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research. 相似文献
108.
109.
110.
Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder, occurring predominantly in women. We studied by flow cytofluorimetry the T cell subsets in men and women with ITP and compared them with healthy sex-matched volunteers. In healthy controls, women were found to have higher proportions of T helper/inducer (Th/i) and lower T suppressor/cytotoxic (Ts/c) lymphocytes and consequently higher Th/i:Ts/c ratios than men. Accordingly, in clinical surveys, patients and controls should be matched for sex for proper comparisons. In patients with ITP in its active phase, an imbalance in T cell subsets was found in both sexes. The perturbation was more severe in women who had a marked decrease in number and proportion of Th/i lymphocytes and an increase in the proportion of Ts/c lymphocytes, whereas in men only, the proportion of Th/i lymphocytes was decreased. When patients with active disease were compared to those with ITP in remission, the decrease in Th/i subsets still persisted in both sexes but the Ts/c subset in women had returned to normal proportions. Therefore, the immune imbalance in ITP is more marked in women than men; imbalances in both Th/i and Ts/c are present in women while Ts/c appears not to be involved in men. 相似文献