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We previously reported that administration of (-)-linalool, the naturally occurring enantiomer in essential oils, induced a significant reduction in carrageenin-induced oedema and in acetic acid-induced writhing. The latter effect was completely antagonised by the muscarinic receptor antagonist atropine and by the opioid receptor antagonist naloxone. To further characterise the antinociceptive profile of (-)-linalool, we studied its effect in the hot plate and the formalin in tests. In addition, to determine the possible involvement of the cholinergic, opioidergic and dopaminergic systems, we tested the effects of atropine, pirenzepine, a muscarinic M1 receptor antagonist, naloxone, sulpiride, a dopamine D2 receptor antagonist and (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH-23390), a dopamine D1 receptor antagonist on (-)-linalool-induced antinociception. Moreover, since K(+) channels seem to play an important role in the mechanisms of pain modulation, we examined the effect of glibenclamide, an ATP-sensitive K(+) channel inhibitor on (-)-linalool-induced antinociception. The administration of (-)-linalool (100 and 150 mg/kg, s.c.) increased the reaction time in the hot-plate test. Moreover, (-)-linalool (50 and 100 mg/kg) produced a significant reduction in the early acute phase of the formalin model, but not in the late tonic phase. The highest dose (150 mg/kg) caused a significant antinociceptive effect on both phases. The antinociceptive effects of (-)-linalool were decreased by pre-treatment with atropine, naloxone, sulpiride and glibenclamide but not by pirenzepine and SCH-23390. These results are in agreement with the demonstrated pharmacological properties of linalool, mainly its cholinergic, local anaesthetic activity and its ability to block NMDA receptors. Furthermore, a key role seems to be played by K(+) channels, whose opening might be the consequence of a stimulation of muscarinic M2, opioid or dopamine D2 receptors.  相似文献   
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Background

Stopping antipsychotic treatment can interrupt improvement and exacerbate the illness. The reasons for discontinuing treatment during controlled clinical trials were analyzed to explore this phenomenon.

Methods

A post-hoc, pooled analysis was made of 4 randomized, double-blind clinical trials, 24–28 weeks in duration, involving 1627 patients with schizophrenia or a related disorder. Analyses combined all the atypical antipsychotic treatment groups in the studies.

Results

The majority of patients (53%) stopped their treatment at an early stage. Poor psychiatric response along with worsening symptoms was the most frequently given reason for discontinuing the course (36%), which was substantially more common than discontinuation due to poor tolerability of the medication (12%). This phenomenon was corroborated by less improvement in patients who discontinued treatment compared with those who completed, based on the PANSS total scores. Discontinuation due to poor response was, apparently, more predominantly linked to patient perception than to physicians' conclusions alone (80% vs. 20%). Discontinuation due to patient perception of poor response appeared to occur particularly early in the course of treatment. Patients who discontinued due to poor toleration of the medication responded in a more comparable manner with completers.

Conclusion

Discontinuing treatment may lead to exacerbation of symptoms, undermining therapeutic progress. In these studies, poor response to treatment and worsening of underlying psychiatric symptoms, and to a lesser extent, intolerability to medication were the primary contributors to treatment being discontinued. Our findings suggest that adherence may be enhanced by effective symptom control, as objectively measured and as subjectively perceived. Such strategies may improve patients' willingness to undertake long-term therapy and increase the likelihood of a better prognosis.  相似文献   
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FMRP is associated to the ribosomes via RNA   总被引:8,自引:8,他引:8  
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We describe a new pyeloureteral drainage catheter that can be used for both genitourinary tract stenting and drainage, as well as tamponade of bleeding from the renal parenchyma or subcutaneous tissue. Primary indications for the use of this catheter and recommendations on insertion techniques are presented. With the exception of one case of minor kinking of the catheter, we have had no complications or failures with this catheter. While insertion through an unprotected tissue track is somewhat difficult, we have had good success introducing the catheter through a 24-F or larger Teflon working sheath. The catheter has excellent patient retention properties. It can be converted from external to internal drainage or vice versa simply and quickly on the ward.  相似文献   
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1 OverviewoffemalemalignanciesinEuropeCancerincidenceandmortalityestimatesfor 1995werereportedrecentlyfor 38countriesinEurope[1] .Therewereestimated 2 .6millionnewcasesofcancerinEuropein 1995 ,representingoverone quarteroftheworldburdenofcancerwhileEurope’sinhabi…  相似文献   
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