Objective To observe the effect of circadian rhythm on hypnotic median effective dose( ED50) of ketamine. Methods Sixty mice were randomly divided into 4 groups which had 15 mice in each group. They were intraperitoneally injected with ketamine at different times of 2 Am,8 Am,2 Pm and 8 Pm, respectively. Righting reflex was recorded and the value of ED50 was measured with sequential experimental method. Results The hypnotic ED50 of ketamine at 2 Am was(54.57?0.82) mg/kg, with 95% confidence limit of ED50 38.06-78.22 mg/kg;ED50 was(49. 27?0. 12) mg/kg at 8 Am, with 95% confidence limit of ED50 40. 21-60. 37 mg/kg;ED50 at 2 Pm was (42.28?0.21) mg/kg, with 95% confidence limit 37.35 - 47 83 mg/kg;and ED50 at 8 Pm was(57.42?0.14) mg/kg, with 95% confidence limit 37.51-73 72 mg/kg,respectively. The ED50 were significant different at 2 Pm and 8 Pm. However, there were no significant difference in ED50 value among other groups. Conclusion The hypnotic effect of ketamine has circadian rhythm - dependent.

Objective To observe the effects of diazepam on the percen-tage of δ -band power of quantitative pharmaco -electroencephalogram ( QPEEG ) in rabbits and the relation with benzodiazepine receptor.Methods Thirty-six healthy rabbits were randomly divided into 6 groups (each n=6),where rabbits in each group were intravenously injected with 1 mL· kg-1 0.9%NaCl (blank group), 0.12 mg· kg-1 , 0.25 mg· kg-1 or 0.50 mg· kg-1 diazepam groups, 0.1 mg· kg-1 flumazenil group and 0.1 mg· kg-1 flumazenil +0.5 mg· kg-1 diazepam ( combined group ).Then a digital EEG system was adopted to record the changes of QPEEG in eight encepha-lic regions before and after injection at each time point.Results The per-centage of δband power in eight encephalic regions of 0.25, 0.50 mg· kg-1 diazepam groups are noted increase within 0.5 to 30 min.The change of the percentage of δ band power has a positive correlation with diazepam dose.Compared with the 0.5 mg· kg-1 diazepam group,the percentage of δ-band power in combined group was lower at same time point.Conclusion Diazepam increases the percentage ofδ-band power of QPEEG in the way of dose dependence in rabbits.It indicates that benzodiazepine receptor mediates the effect of diazepam and the percentage of δ-band power may become an index that reflects the degree of sedation and hypnosis.

Objective To observe the clinical efficacy and safety of flupentixol and melitracen tablets combined with psychological intervention in the treatment of cerebral infarction with anxiety disorder.Methods Eighty patients with cerebral infarction and anxiety disorders were randomly divided into control group and treatment group with 40 cases per group.Control group was treated with antiplatelet aggregation,activating blood stasis and brain protectant and so on.Treatment group was treated with flupentixol and melitracen tablet 10 mg per group,bid,orally,and psychological intervention once every 3-5 days,on the basis of control group.Two groups were treated for 6 weeks.The self rating scale (SAS)scores,depression self rating scale (SDS) scores,the United States national institutes of health stroke scale (NIHSS) scores and adverse drug reactions were compared between two groups.Results After treatment,the main indexes in treatment and control groups were compared:SAS scores were (40.07 ± 3.02) and (52.07 ± 6.94) points,SDS scores were (40.03 ±3.38) and (51.48 ± 7.22) points,NIHSS scores were (6.04 ± 1.51) and (8.92 ± 4.12) points,the differences were statistically significant (all P ＜ 0.05).No adverse drug reactions in two groups occurred during the treatment.Conclusion Flupentixol and melitracen tablets combined with psychological intervention have a definitive clinical efficacy and safety in the treatment of cerebral infarction with anxiety disorder,which can significantly reduce the NIHSS scores and improve prognosis.

This study is to investigate the effect of gamma-hydroxybutyric acid receptor (GHBR) on focal cerebral ischemia-reperfusion injury in rats and its mechanism. NCS-356 (the agonist of GHBR) and NCS-382 (the antagonist of GHBR) were adopted as the tool medicine. The ripe male Sprague-Dawley rats weighing 240 - 280 g were randomly divided into seven groups: sham operation group (sham), ischemia-reperfusion group (Isc/R), NCS-356 160 microg x kg(-1) group (N1), NCS-356 320 microg x kg(-1) group (N2), NCS-356 640 microg x kg(-1) group (N3), NCS-382 640 microg x kg(-1) + NCS-356 640 microg x kg(-1) group (NCS-382 + N3), and nimodipine (Nim) 600 microg x kg(-1) group. The middle cerebral artery occlusion (MCAO) model referring to Longa's method with modifications was adopted. The effect of GHBR on behavioral consequence of MCAO rats was studied after 2 h of ischemia-reperfusion. After 24 h of ischemia-reperfusion, part of animals were used to measure the cerebral infarction volume by TTC staining; ischemic cortex of another part of animals were used to measure the content of intracellular free calcium by flow cytometry, the tNOS, iNOS activity and the content of NO by spectrophotometric method, the content of cGMP by radioimmunoassay. The neurological function score and infarction volume rate in Isc/R group rats increased significantly than that in sham group; The content of intracellular calcium ([Ca2+]) of cortex neuron and cGMP, the activities of tNOS and iNOS, and the content of NO in Isc/R group were higher than that in sham group obviously (P < 0.01); These consequence we mentioned of N1, N2, N3 and Nim group were lower than that of Isc/R. NCS-382 + N3 group could significantly antagonize the above effect of N3. Thus, NCS-356 has protective effects against ischemia-reperfusion brain injury by activating GHBR. The neuroprotective effect of GHBR is related with decreasing the content of [Ca2+]i, NO, cGMP and tNOS, iNOS activity in MCAO rats.
Animals ; Benzocycloheptenes ; pharmacology ; Calcium ; metabolism ; Cerebral Cortex ; metabolism ; Cerebral Infarction ; pathology ; Cyclic GMP ; metabolism ; Infarction, Middle Cerebral Artery ; complications ; Male ; Neuroprotective Agents ; pharmacology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; agonists ; antagonists & inhibitors ; metabolism ; Reperfusion Injury ; etiology ; metabolism ; pathology

AIMTo investigate the effects of melatonin (MT) on histology and behavioral tests during global cerebral ischemia-reperfusion in gerbils.

METHODSGlobal cerebral ischemia was induced by occluding the bilateral common carotid arteries for 10 min in gerbils. Three doses of MT were administrated intraperitoneally 30 min prior to the onset of ischemia. Locomotor activity was measured by using the open field method 3 and 7 days after the ischemic episode. T maze test was carried out 4, 5 and 6 days after ischemia to assess the working memory of gerbils. Neuronal damage was assessed in CA1 pyramidal layer of gerbil hippocampus and evaluated 7 days after ischemia.

RESULTSMT significantly reversed the locomotor activity increases, ameliorated learning and working memory deficit, and reduced the extent of CA1 hippocampal pyramidal cells injury after transient global cerebral ischemia in the Mongolian gerbil.

CONCLUSIONMT provides significantly protective effect against both histological and behavioral consequences of global cerebral ischemia-reperfusion injury in gerbils.

Animals ; Brain Ischemia ; complications ; Female ; Gerbillinae ; Hippocampus ; drug effects ; pathology ; Learning ; drug effects ; Male ; Melatonin ; pharmacology ; therapeutic use ; Memory ; drug effects ; Motor Activity ; drug effects ; Neurons ; pathology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Random Allocation ; Reperfusion Injury ; etiology ; physiopathology ; prevention & control

Objective To make a quantitative analysis on the existence of the second gas effect.Methods Under the guidance of the macro-scopic theories in thermodynamics and quantitative analysis in mathematics, the second gas effect was discussed at three aspects: the conditions for the existence of the second gas effect , those for the non-existence of the second gas effect and those for the existence of the re-verse second gas effect.Results When the uptake rate of the second gas was equal to the average uptake rate of other gas mixtures , the second gas effect did not exist .When the former was less than the latter , the second gas effect existed .When the former was greater than the latter , the reverse second gas effect existed.Conclusion The existence of the second gas effect is not absolute but conditional.The key factor is the relative size of the uptake rate of the second gas and the average uptake rate of other gas mixtures in alveolar.

Objective To explore the effects of sulfentanil on the per-centage of β1 -band power of quantitative pharmaco-electroencephalo-graphy ( QPEEG ) in rabbits, and its relationship with opioid recep-tor.Methods Thirty-six healthy rabbits were divided randomly into six groups(n=6):normal group (0.9%NaCl 1 mL? kg-1), low, medium, high doses sulfentanil groups ( 1.5 , 3 , 6 μg? kg -1 ) , naloxone group (400 μg? kg-1 ) and naloxone and sulfentanil group ( naloxone 400μg? kg -1 and sulfentanil 3 μg? kg-1 ) .The percentage of each band power was respectively noted down 30 s before administration and 1, 3, 5, 10, 20, 25 min after administration.Results Compared with the baseline, the percentage ofβ1 -band power was decreased in the groups of medium, high doses sulfentanil ( P <0.05 ) , which had a negative correlation with sulfentanil dose ( P <0.05 ) . There was no obvious change in the percentage of β1 -band power in the group of naloxone compared with the baseline ( P >0.05 ) .Conclusion Sulfentanil de-creases the percentage ofβ1 -band power in a dose-dependent manner, and this effect is mediated by the opioid receptor.

In formalin pain model, the effect of propofol on Fos expression in the spinal cord was examined by means of c -fos oncogene immunohistochemistry and NADPH-d histochemistry. Fos-like immunoreactive (FLI) neurons were mainly found in the ipsilateral dorsal horn after injection of formalin, some of which were FLI/NOS double-labeled neurons. Most of the FLI or FLI/NOS double-labeled neurons were observed in the medial part of lamina and the outer lamina . Before or after injection of formain, i.p. injection of propofol significantly decreased the number of FLI and FLI/NOS double-labeled neurons in all laminae (P<0.05 or P<0.01). By single i.p. injection of propofol or normal saline, few FLI neurons were found in the spinal cord. The results suggest that the antinociceptive function of propofol is possibly involved in the depression of the NOS neurons in the spinal cord.
Animals ; Female ; Formaldehyde ; Male ; Neurons ; metabolism ; Nitric Oxide Synthase ; metabolism ; Pain ; chemically induced ; metabolism ; Propofol ; pharmacology ; Proto-Oncogene Proteins c-fos ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; metabolism

Objective To investigate the effects of flurbiprofen axetil on percentage of each band power of quantitative pharmaco -electroence-hphalography ( QPEEG ) in rabbits.Methods Twenty -four healthy rabbits were randomly divided into four groups ( n =6 ): 0.9%NaCl 1 mL· kg -1 group, flurbiprofen axetil 5, 10, and 20 mg · kg -1 groups.The QPEEG and power spectral analysis were adopted to analyze the changes of brain electrical activities before and after the intravenous in-jection of flurbiprofen axetil.Results Compared with the baseline , the percentages of each encephalic region and band power had no significant differences in these four groups ( P>0.05 ).Conclusion Flurbiprofen axetil has no obvious effect on percentage of each band power of quantita-tive pharmaco-electroencephalography in rabbits , suggesting that its site of action is not in the cerebral cortex.It is quite different from the opioid analgesics.

Objective To compare the antiarrhythmic effects and safety of landiolol and esmolol .Methods The sequential method was used to detect the median lethal dose ( LD50 ) and 50%effective dose ( ED50 ) of the two drugs.Treatment index were calculated by LD 50/ED50 .Several of arrhythmia models were used to study the antiarrhythmic effects of landio-lol and esmolol in the equivalent dose .Results ED50 and LD50 of landio-lol and esmolol were 14.4 , 17.3 mg? kg -1 and 347 , 100 mg? kg -1 re-spectively , TI were 24.1 and 5.8.The ratio of equivalent dose between landiolol and esmolol on anti -chloroform induced arrhythmia was 0.83∶1.Landiolol and esmolol have similar anti -arrythmia effect on va-rious arrhythmia models.Esmolol has a stronger inhibition function on the heart rate than that of landiolol .Conclusion Compared with esmolol , landiolol has similar antiarrhythmic effect , gentle and slow effect on heart rate, higher treatment index and safety in equivalent dose .