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建立了超高效液相色谱-质谱联用法(UPLC-MS/MS)快速测定中药材熊胆粉中9种苯二氮?类药物残留的方法。样品以乙腈为提取溶剂,经萃取盐包除杂提取,采用分散式固相萃取管 (EMR-Lipid dSPE) 净化,ACQUITY BEH C18色谱柱(1.7 μm,2.1×100 mm)分离,多反应监测模式(MRM)采集数据,外标法定量。在优化的条件下,虽9种药物存在不同程度的基质效应,但不影响检测结果的准确性。方法学考察结果显示,9种苯二氮?类药物在对应的浓度范围内线性关系良好,决定系数(R2)≥0.9961,方法检出限(LOD,S/N =3)在0.06~0.71 μg/kg范围内,定量限(LOQ,S/N =10)在0.20~2.60 μg/kg范围内,3个加标水平的平均回收率在69.1%~108.0%范围内,日内RSD为1.8%~9.0%,日间RSD为2.6%~9.3%。该方法前处理操作简便、重现性好,准确度高,为熊胆粉中苯二氮?类药物残留的风险监控提供了一种有效的检测技术。  相似文献   
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ObjectiveThe present study describes the isolation of linalool from the essential oil of Lippia alba (Mill.) N. E. Brown, and its anesthetic effect in silver catfish (Rhamdia quelen) in comparison with essential oil. The potentiation of depressant effects of linalool with a benzodiazepine (BDZ) and the involvement of GABAergic system in its antagonism by flumazenil were also evaluated.Study designProspective experimental study.AnimalsJuvenile silver catfish unknown sex weighing mean 9.24 ± 2.83 g (n = 6 for each experimental group per experiment).MethodsColumn chromatography was used for the isolation of S-(+)-linalool. Fish (n = 6 for each concentration) were transferred to aquaria with linalool (30, 60, and 180 μL L?1) or EO of L. alba (50, 100, and 300 μL L?1) to determine the induction time for anesthesia. After induction, the animals were transferred to anesthetic-free aquaria to assess their recovery time. To observe the potentiation, fish were exposed to linalool (30, 60, and 180 μL L?1) in the presence or absence of BDZ (diazepam 150 μm). In another experiment, fish exposed to linalool (30 and 180 μL L?1) or BDZ were transferred to an anesthetic-free aquaria containing flumazenil (5 μm) or water to assess recovery time.ResultsLinalool had a similar sedation profile to the essential oil at a proportional concentration in silver catfish. However, the anesthesia profile was different. Potentiation of linalool effect occurred only when tested at low concentration. Fish exposed to BDZ showed faster anesthesia recovery in water with flumazenil, but the same did not occur with linalool.Conclusions and clinical relevanceThe use of linalool as a sedative and anesthetic for silver catfish was effective at 30 and 180 μL L?1, respectively. The mechanism of action seems not to involve the benzodiazepine site of the GABAergic system.  相似文献   
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ObjectiveTo evaluate the sedative effects of a combination of sufentanil and midazolam administered intramuscularly (IM) or intranasally (IN) prior to induction of anesthesia with propofol in New Zealand White rabbits.Study designProspective, randomized, crossover, experimental study.AnimalsA total of 11 adult New Zealand White rabbits.MethodsSufentanil (0.5 μg kg–1) and midazolam (2 mg kg–1) were administered to rabbits via IM or IN route. The righting reflex was assessed, and sedation was scored. Heart rate, respiratory rate (fR) and temperature were recorded prior to treatment administration and after loss of the righting reflex.ResultsMeasured variables remained within normal physiologic ranges for all rabbits. The only statistically significant change was for fR, which was significantly lower after sedation for both routes. The time to loss of righting reflex was 14.8 ± 6.5 and 12.5 ± 7.4 minutes and sedation scores were 6 (4–8) and 7 (6–8) for IM and IN routes, respectively, with no difference between treatments. No adverse effects were observed during the experimental period.Conclusions and clinical relevanceSufentanil combined with midazolam administered either IM or IN resulted in moderate to deep sedation in New Zealand White rabbits at the dose rates studied.  相似文献   
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Objective

To evaluate the dose-sparing effect of midazolam or diazepam on the dose of alfaxalone required to achieve endotracheal intubation in premedicated dogs.

Study design

Prospective, randomized, ‘blinded’, controlled clinical trial.

Animals

Ninety healthy dogs anaesthetized for elective surgery or diagnostic procedures.

Methods

Saline (0.1 mL kg–1), or midazolam or diazepam (0.2, 0.3, 0.4 or 0.5 mg kg–1) intravenously (IV) was randomly assigned; investigators were unaware of group designation. After premedication with IV acepromazine 0.01 mg kg–1 and methadone 0.2 mg kg–1, the degree of sedation was assessed. Alfaxalone (0.5 mg kg–1) was administered IV, followed by the assigned treatment. Further alfaxalone was administered until endotracheal intubation could be performed. Ease of endotracheal intubation, pulse rate and arterial blood pressure were assessed. General linear models were used to examine the effect of treatment drug and dose on induction dose of alfaxalone with Tukey’s post hoc tests. Incidence of adverse reactions was assessed with chi-square tests.

Results

There were no significant differences between groups with regard to demographic data or sedation. Median (range) induction dose of alfaxalone in the saline group was 0.74 (0.43–1.26) mg kg–1 compared with 0.5 (0.46–0.75) mg kg–1 and 0.5 (0.42–1.2) mg kg–1 for the midazolam and diazepam groups, respectively. Midazolam 0.3 and 0.5 mg kg–1 (p = 0.005 and 0.044, respectively) and diazepam 0.4 mg kg–1 (p = 0.032) reduced the alfaxalone dose compared with saline. Adverse effects were not significantly different between groups. Midazolam 0.2, 0.3, 0.4 and 0.5 mg kg–1 (p < 0.044, p = 0.001, p = 0.007, p = 0.044, respectively) and diazepam 0.2 and 0.5 mg kg–1 (p = 0.025 and p = 0.025) improved intubation score compared with saline.

Conclusion and clinical relevance

Midazolam 0.3 and 0.5 mg kg–1 and diazepam 0.4 mg kg–1 coadministered at anaesthetic induction allow alfaxalone dose reduction in healthy dogs. Use of benzodiazepines improved the ease of endotracheal intubation.  相似文献   
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AIM:To evaluate the changes of peripheral-type benzodiazepine receptors (PBRs) in platelet membrane in post-stroke depression (PSD) patients and to investigate the effects of PBRs on PSD. METHODS:Forty-three patients with PSD, fifty-nine patients with first-ever cerebral infarction and fifty-six healthy volunteers participated in this study. Platelet membrane in venous blood was prepared. Binding assay of the radioactive PBRs antagonist [3H]PK11195 to platelet membrane was performed. RESULTS:A significant difference of [3H]PK11195 binding was found among the 3 groups (P<0.01). Compared with the healthy volunteers [(298.2±25.1) pmol/(g protein)], a highly significant increase in [3H]PK11195 binding was observed in platelet membrane in the patients with first attack of cerebral infarction [(1 410.8±41.4) pmol/(g protein), P<0.01]. Compared with the patients with first attack of cerebral infarction, a significant reduction in [3H]PK11195 binding was detected in platelet membrane in the patients with PSD [(361.7±30.6) pmol/(g protein), P<0.01]. In the patients with PSD, no significant difference of [3H]PK11195 binding was found between men and women (P>0.05). [3H]PK11195 binding was related to the score of Hamilton depression rating scale (r=-0.44, P<0.01) but not to the duration of cerebral infarction (r=0.27,P>0.05). CONCLUSION:PBRs binding activity in platelet membrane decreases in the patients with PSD and affects the degree of depression.  相似文献   
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Objective

To evaluate dexmedetomidine, midazolam and dexmedetomidine–midazolam for sedation and antinociception in tegus.

Study design

Prospective, crossover, randomized, blinded study.

Animals

Six healthy tegus (Salvator merianae) weighing 1.6 ± 0.3 kg.

Methods

Tegus were administered intramuscularly saline (0.5 mL; CON), dexmedetomidine (0.2 mg kg?1; DX), midazolam (1 mg kg?1; MZ) and dexmedetomidine–midazolam (same doses; DM). Heart rate (HR) and respiratory frequency (fR) were recorded before treatment (baseline) and 15, 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after the treatments. Sedation scores were recorded according to resistance to manual restraint, posture and response to noxious stimulus, at baseline and 5, 10, 15, 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after the treatments. Antinociception was evaluated by measurement of latency of limb withdrawal reflex (LWR) to thermal stimulus, recorded at baseline and 15 minutes, 1, 2, 4, 8, 12 and 24 hours after the treatments.

Results

Lower HR (DX and DM) and fR (MZ, DX and DM) than CON were measured 15 minutes after the treatment and for up to 6 hours. Sedation was mild to moderate in MZ, deep in DM and absent in DX, although animals showed behavioral changes in DX, with increase in aggressiveness. Median (interquartile range) duration of sedation were 170 (50; 235) minutes in MZ and 230 (115; 235) minutes in DM. Recovery period was prolonged in both treatments, surpassing the duration of the experiment. Higher LWR than CON was detected from 15 minutes until 12 hours in DX and DM.

Conclusions and clinical relevance

Midazolam provided sedation without antinociception, and dexmedetomidine provided antinociception without sedation. Drug combination increased the duration of sedation but not antinociception. Due to increased duration of sedation, reversal of effects with flumazenil and atipamezole should be considered after conclusion of clinical procedures.  相似文献   
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