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51.
52.
Do local anaesthetics interact with dihydropyridine binding sites on neuronal L-type Ca2+ channels? 总被引:1,自引:0,他引:1
Hirota K.; Browne T.; Appadu B. L.; Lambert D. G. 《British journal of anaesthesia》1997,78(2):185-188
We have examined the interaction of procaine, prilocaine, lignocaine,
bupivacaine, amylocaine and R(+) and S(-) ropivacaine with L-type
voltage-sensitive Ca2+ channels in rat cerebrocortical membranes. Membranes
were prepared in Tris HCl 50 mmol litre-1, pH 7.4, by homogenization and
centrifugation. Binding assays were performed in 1- ml volumes of Tris HCl
50 mmol litre-1, pH 7.4, for 90 min at room temperature using approximately
200 micrograms of protein. Non-specific binding was defined in the presence
of nifedipine 10(-5) mol litre-1, and bound and free radioactivity were
separated by vacuum filtration. The effects of local anaesthetics were
determined by displacement of [3H]PN200-110 (approximately 0.2 nmol
litre-1), a radiolabelled 1,4- dihydropyridine (DHP) L-channel antagonist.
The concentration of displacer producing 50% displacement was corrected for
the competing mass of [3H]PN200-110 to yield the affinity constant, K50.
All local anaesthetics displaced [3H]PN200-110 in a dose-dependent manner
with a rank order potency of (K50, mmol litre-1) bupivacaine (0.48),
amylocaine (0.74), lignocaine (1.09), prilocaine (2.06) and procaine
(2.09). Ropivacaine enantiomers did not show stereo-selective displacement,
with K50 values of 0.99 and 0.92 mmol litre-1 for R(+) and S(-)
ropivacaine, respectively. There was a significant correlation between pK50
and p (octanol:buffer partition coefficient) (r2 = 0.872, P = 0.020), pK50
and p (local anaesthetic potency) (r2 = 0.816, P = 0.036), pK50 and p
(relative conduction blocking potency) (r2 = 0.843, P = 0.028) and between
pK50 and p (IC50 for inhibition of cardiac output) (r2 = 0.897, P = 0.015).
These data suggest that DHP binding sites may be involved in both the
mechanism of local anaesthesia and the cardiotoxicity of these agents.
相似文献
53.
H Angus-Leppan GA Lambert J Michalicek 《Cephalalgia : an international journal of headache》1997,17(6):625-630
Co-existence of facial and occipital pain may occur in occipital neuralgia, migraine and cluster headache; suggesting convergence of trigeminal and cervical afferents. Such convergence has been shown in humans and other animals, but the site and extent of this are uncertain. In anaesthetized adult cats, the superior sagittal sinus and occipital nerve were stimulated electrically, and extracellular recordings made in the dorsolateral area of the upper cervical cord using glass-coated tungsten electrodes. Of 49 units in 10 cats, 33 (67%) had input from the superior sagittal sinus and the occipital nerve. Thirteen (27%) had superior sagittal sinus input and 3 (6%) had occipital nerve input. Convergent receptive fields were identified mechanically in 7 units. These experiments in cats show convergent input from occipital nerve and superior sagittal sinus on dorsolateral area units in two-thirds of cases studied. This experimental site of trigeminocervical convergence may relate to referral of pain in occipital neuralgia and other headaches. 相似文献
54.
55.
Michael J. Lambert Jason L. Whipple David A. Vermeersch David W. Smart Eric J. Hawkins Stevan Lars Nielsen Melissa Goates 《Clinical psychology & psychotherapy》2002,9(2):91-103
Several systems have been developed to monitor and feedback information about a client's responses to psychotherapy as a method of enhancing client outcome. The current study divided 1020 clients into four groups (two experimental and two control) to determine if feedback regarding client progress, when provided to a therapist, affected client outcome and number of sessions attended. Results showed that feedback increased the duration of treatment and improved outcome for clients identified as potential treatment failures thereby replicating an earlier study using nearly identical methodology. Nearly twice as many clients in the feedback group achieved clinically significant or reliable change and fewer were classified as deteriorated by the time treatment ended. For those clients who were predicted to have a positive response to treatment, feedback to therapists resulted in an equal number of treatment sessions and equivalent outcomes compared to the no feedback controls. The results are discussed in terms of quality management in routine clinical practice and the need to base treatment decisions on clients' response to treatment rather than arbitrary session limits. Suggestions for additional research aimed at enhancing the effects of feedback on client outcome are made. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
56.
Leonore C Dijkgraaf Gustavo Zardeneta Fabian W Cordewener Robert S b Liem John P Schmitz Lambert G m de Bont Stephen B Milam 《Journal of oral and maxillofacial surgery》2003,61(1):101-111
PURPOSE: Adhesion formation in osteoarthritis (OA) of the temporomandibular joint (TMJ) typically results in a sustained limitation of joint movement. We propose the hypothesis that free-radical-mediated crosslinking of proteins underlies this adhesion formation in affected joints. Free radicals may cause oxidative modification of proteins, creating an opportunity for the formation of intramolecular and intermolecular crosslinks via covalent bonds. This may stabilize protein aggregates, rendering them more resistant to degradation. In this study, the free-radical-mediated crosslinking of model proteins (fibrinogen and fibronectin) was investigated to test our hypothesis that free radicals contribute to adhesion formation via this mechanism in OA of the TMJ. MATERIALS AND METHODS: Physiological clot formation of fibrinogen by thrombin and free-radical-induced crosslinking of fibrinogen and of fibronectin were analyzed using spectrophotometric turbidity measurements, light-scattering techniques, polyacrylamide gel electrophoresis (PAGE), and rotary shadowing. RESULTS: Fibrinogen was shown to aggregate after free radical treatment, as detected using turbidity measurements and light-scattering techniques. Using PAGE, fibrinogen as well as fibronectin was shown to degrade under low oxidative stress. Under high oxidative stress, however, fragments from both proteins were found to be covalently crosslinked, resulting in high-molecular-weight protein aggregates. The aggregation was shown to be at random with rotary shadowing. CONCLUSION: The study shows that high oxidative stress contributes to the formation of crosslinked proteins that may serve as an initial scaffolding for the development of adhesions frequently seen in OA of the TMJ. 相似文献
57.
Topiramate is a neuromodulatory compound with stabilizing properties that was initially introduced for the management of partial seizures. Topiramate has been demonstrated to modify several receptor-gated and voltage-sensitive ion channels, including voltage-activated Na+ and Ca2+ channels and non-NMDA receptors. These receptors have been implicated in the pathophysiology of both epilepsy and migraine. The pharmacological mechanisms of action for topiramate that may explain its antiepileptic and migraine preventive activities will be discussed in this review. In addition, the potential relationship between the molecular activities of topiramate and its efficacy in epilepsy and migraine prevention will be emphasized. 相似文献
58.
Ke-Zhong Shen Steve W. Johnson 《皖南医学院学报》2003,22(Z1):30-31
Parkinson's disease is a neurodegenerative movement disorder that results from progressive loss of midbrain dopamine neurons, which consequently leads to hyperactivity of subthalamic neurons. 相似文献
59.
Molecular characterization of in vivo mutation at the human hypoxanthine phosphoribosyltransferase (hprt) locus has revealed a broad spectrum of mutation, both with regard to germ-line mutation in Lesch-Nyhan and gout patients, and somatic mutation in 6-thioguanine resistant T-lymphocytes from healthy individuals. The pattern of missense mutation shows a non-random distribution with a preferential location to codons for amino acids which are identical in human and the two parasites Schistosoma mansoni and Plasmodium falciparum. Although these 'evolutionary conserved' amino acids account for only 32% of the amino acids in the human hprt protein, they are involved in 76% of the missense mutations at the hprt locus in human T-lymphocytes, 67% in Lesch-Nyhan patients (with severe hprt-deficiency), but only 43% in gout patients (with partial hprt deficiency). This observation supports the notion that evolutionary conserved amino acids constitute functionally important sites in the hprt enzyme, and missense mutations affecting these amino acids will often lead to complete loss of enzyme activity. Substitutions of 'non-conserved' amino acids cause less severe hprt-deficiency (as seen in the gout patients), or may even escape clinical diagnosis. These considerations are important for the understanding of structure-activity relationships in the hprt protein, possible differences between hprt mutational spectra in germ-line and somatic cells, and the mutational spectra induced by specific exogeneous mutagens. 相似文献
60.
Rebecca Setliff Janet E Porter Michael Malison Steve Frederick Thomas R Balderson 《JPHMP》2003,9(2):91-102
To address the need for management development in public health, the Centers for Disease Control and Prevention (CDC) established three independent workforce development initiatives aimed primarily at strengthening management and leadership capacity: the Sustainable Management Development Program, the Management Academy for Public Health, and the CDC Leadership and Management Institute. Though independently designed and implemented, the programs share similar guiding principles in their approach to management development: interactive (adult) learning, management tools that reinforce evidence-based decision making, individual feedback, continuous improvement of the learning process, posttraining support for networking and life-long learning, and teamwork. This article will discuss important lessons learned regarding best practices in management and leadership development. 相似文献