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Objective To investigate the effect of preconditioning with cannabinoid CB2 receptor agonist AM1241 on microglial activation and injury induced by lipopolysaccharide ( LPS) and interferon-γ (IFN-γ). Methods The microglial cells were chosen and assigned to control group,AM1241 treatment group, LPS/IFN-γ inducement group and AM1241+LPS/IFN-γ treatment group. Cells of control group were cultured in normal medium;cells of AM1241 treatment group were preconditioned with AM 1241 for 2 h, and then the medium was changed with normal medium;cells of LPS/IFN-γ inducement group were exposed to the medium containing 1 μg/mL LPS plus 50 U/mL IFN-γ for 24 h;cells of AM1241+LPS/IFN-γ treatment group were preconditioned with AM1241, then the medium were changed with normal medium for 2 h, and at last, cells of this group were exposed to 1 μg/mL LPS plus 50 U/mL IFN-γ for 24 h. Microglial metabolism was assessed by MTT assay;NO release was measured by Reagent Kit;microglial shapes were observed through microscope. Results CB2 receptor agonist preconditioning can up-regulate the microglial CB2 receptor expression markedly;cell metabolism of AM1241+LPS/IFN-γ treatment group (92.55 ±8.37%) was obviously higher than that of LPS/IFN-γ inducement group (75.04±3.01%, P<0.05);AM1241+LPS/IFN-γ treatment group (43.44±5.52 μmol/L) released significantly less NO than LPS/IFN-γ inducement group (90.87±4.28 (μmol/L, P<0.05). Cells of the LPS/IFN-γ inducement group were destroyed seriously with enlarged soma and thickened and shortened pseudopodium;cells of the AM1241+LPS/IFN-γ treatment group were destroyed slightly with slightly enlarged soma and thickened and shortened pseudopodium. Conclusion Preconditioning with cannabinoid CB2 receptor agonist AM1241 reduces microglial activation and injury induced by LPS plus IFN-γ.
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<p><b>OBJECTIVE</b>To observe the relationship between protein sythesis and cardiomyocyte viability in neonatal rats.</p><p><b>METHODS</b>The protein sythesis in neonatal rat cardiomyocytes was measured according to Brandford's method, the absorbance at 490 nm (A(490 nm)) of the cells was measured with MTT assay and the cell viability evaluated by the ratio of A(490 nm) to the total cell number.</p><p><b>RESULTS</b>ET-1 increased cardiomyocyte protein synthesis dose-dependently, and this effect was attenuated by the application of lacidipine and tetramethylpyrazines Higher doses of ET-1 resulted in lower A(490 nm)/total cell number ratio, which was further lowered by larcidipine and tetramethylpyrazine.</p><p><b>CONCLUSION</b>The status of protein synthesis is not associated with the viability of neonatal rat cardiomyocytes.</p>
Subject(s)
Animals , Rats , Animals, Newborn , Calcium Channel Blockers , Pharmacology , Cell Survival , Cells, Cultured , Dihydropyridines , Pharmacology , Dose-Response Relationship, Drug , Endothelin-1 , Pharmacology , Myocytes, Cardiac , Cell Biology , Metabolism , Protein Biosynthesis , Pyrazines , Pharmacology , Rats, Sprague-DawleyABSTRACT
<p><b>BACKGROUND</b>Vasoactive drugs are often necessary for reversing hypotension in patients with severe infection. The standard for evaluating effects of vasoactive drugs should not only be based on the increase of arterial blood pressure, but also on the blood flow perfusion of internal organs. The effects of dopamine and metaraminol on the renal function of the patients with septic shock were investigated retrospectively in this study.</p><p><b>METHODS</b>Ninety-eight patients with septic shock were divided into three groups according to the highest infusing rate of metaraminol, with the lightest infusing rate of (0.1 - 0.5, 0.6 - 1.0, > 1.0) microgxkg(-1)xmin(-1) in group A, B and C respectively. Urine output, mean arterial blood pressure (MAP), heart rate (HR), urine output, blood urea nitrogen (BUN), creatinine (CRE), urine albumin (U-ALB), urine beta(2)-microglubulin (Ubeta(2)-MG) and Apache III scores were recorded.</p><p><b>RESULTS</b>Before antishock therapy, hypotension, tachycardia and oliguria occurred to all the 98 patients with septic shock and CRE, BUN, U-ALB, Ubeta(2)-MG and Apache III scoring were abnormal in most cases. With the antishock therapy, MAP, HR, urine output, BUN and CRE in all patients returned gradually to normal (P < 0.05 or < 0.01 compared to those before antishock therapy). U-ALB, Ubeta(2)-MG output and Apache III scoring also reverted but remained abnormal (P < 0.01 compared to those before antishock therapy). No statistically significant differences in the changes of these indices with the time existed among the three groups (P > 0.05).</p><p><b>CONCLUSION</b>Dopamine and metaraminol when applied to the patients with septic shock could effectively maintain the circulatory stability and promote restoration of renal function.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , APACHE , Blood Pressure , Blood Urea Nitrogen , Dopamine , Therapeutic Uses , Heart Rate , Kidney , Kidney Function Tests , Metaraminol , Therapeutic Uses , Retrospective Studies , Shock, Septic , Drug Therapy , Vasoconstrictor Agents , Therapeutic Uses , beta 2-Microglobulin , UrineABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of dopamine and norepinephrine on the renal function in the patients with septic shock.</p><p><b>METHODS</b>Eighty-seven patients with septic shock were divided into three groups (group A, B, C) according to the biggest infusing rate of norepinephrine, with the infusing rate of 0.5 - 0.9, 1.0 - 1.5, 1.6 - 2.0 microg x kg(-1) x min(-1), respectively. Mean arterial blood pressure (MAP), heart rate (HR), urine output, blood urea nitrogen (BUN), creatinine (CRE), urine albumin (U-ALB) and urine beta(2)-microglobulin (Ubeta(2)-MG) as well as APACHE III score in all the patients were detected.</p><p><b>RESULTS</b>Before anti-shock therapy was given, hypotension, tachycardia and oliguria occurred in all the 87 patients, and CRE, BUN, U-ALB, Ubeta(2)-MG and APACHE III score were abnormal in most cases. With the anti-shock therapy, MAP, HR, urine output and BUN, CRE in all patients returned to normal levels gradually, and U-ALB, Ubeta(2)-MG levels and APACHE III score also restored but still remained abnormal.</p><p><b>CONCLUSIONS</b>The first aim of treating septic shock should be restoring the organ blood supply, and based on volume resuscitation, dopamine, noradrenaline and other vasoactive drugs could be combined to maintain circulatory stability.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , APACHE , Blood Transfusion , Cardiotonic Agents , Combined Modality Therapy , Dopamine , Drug Therapy, Combination , Kidney , Norepinephrine , Retrospective Studies , Shock, Septic , Therapeutics , Vasoconstrictor AgentsABSTRACT
Simulation teaching is helpful to learn general principles of solving complex problems,making decisions,resource management and teamwork behaviors during clinical treatment in order to prevent,ameliorate and resolve critical incidents and crisis situations.The medical staff will improve their medical,cognitive and social skills in the recognition and treatment of realistic and complex medical situation.
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<p><b>OBJECTIVE</b>To evaluate the neuroprotective effect of tetramethylpyrazine (TMP) against focal cerebral ischemic injury in rats with diffusion-weighted magnetic resonance imaging (DWMRI).</p><p><b>METHODS</b>Rat models of focal cerebral ischemic injury were established in 16 male SD rats. They were randomly divided into the TMP group and the control group, eight in each group, and pretreated with TMP and normal saline respectively before modeling. Change of infarcted cerebral focus was observed with DWMRI at 1, 2, 6, 12 and 24 hrs after infarction, and the infarction volume (IV) at 24 hrs after modeling was estimated by triphenyltetrazolium chloride (TTC) stain.</p><p><b>RESULTS</b>The IV in all time points observed in the TMP group with DWMRI was significantly smaller than that in the control group (P<0.01). Compared with that at 1 hr after infarction, in the control group at 2, 6, 12 and 24 hrs after modeling, the IV enlarged by 13.3%, 29.7%, 50.3% and 57.3% respectively, while that in the TMP group 9.9%, 21.3%, 37.1% and 40.5% respectively. The cerebral IV estimated by TTC stain 24 hrs after modeling was larger than that estimated by DWMRI.</p><p><b>CONCLUSION</b>TMP pretreatment before modeling was effective in protecting brain against cerebral ischemic damage in rats. DWMRI dynamic scanning observation has important significance in observing the cerebral ischemic developing process and evaluating the effectiveness of brain protective measures.</p>
Subject(s)
Animals , Male , Rats , Diffusion Magnetic Resonance Imaging , Infarction, Middle Cerebral Artery , Drug Therapy , Pathology , Neuroprotective Agents , Pharmacology , Therapeutic Uses , Phytotherapy , Pyrazines , Pharmacology , Therapeutic Uses , Random Allocation , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of sodium ferulate (SF), an intravenous drug made from traditional Chinese herbs, on activation of postsynaptic density-95 (PSD-95) and neuroprotection after transient cerebral artery occlusion in rats.</p><p><b>METHODS</b>Forty-six male Sprague-Dawley rats were randomized into 2 groups (n=23 in each group): the control group and the SF group. After anesthesia, the middle cerebral artery occlusion (MCAO) was conducted with the intraluminal filament technique. The neurological deficit was assessed with the method devised by Bederson et al. The 2,3,4-triphenyltetrazolium chloride staining was used to assess the infarct volume. We adopted a modified six-point scale to conduct neurobehavioral evaluation. Immediately the activation of postsynaptic density-95 (PSD-95) was studied with Western blot analysis system in the cortex and striatum of rat brain.</p><p><b>RESULTS</b>The neurologic deficit score of the SF group decreased substantially compared with that of the control group (P<0.05). The infarct volume of the control group (168.1 mm3 +/- 42.2 mm3) was significantly larger than that of the SF group (61.5 mm3 +/- 28.7 mm3) at 24 hours after reperfusion (P<0.01). And the rats showed some neurological deficit. The activity of PSD-95 in the SF group at most timepoints was less than that in the control group. No upregulation of PSD-95 protein could be detected in the contralateral cortex.</p><p><b>CONCLUSIONS</b>Sodium ferulate can induce a neuroprotective effect against the transient focal cerebral ischemic injury and weaken the activation of PSD-95 in ischemic area after MCAO.</p>
Subject(s)
Animals , Male , Rats , Blotting, Western , Brain Infarction , Drug Therapy , Coumaric Acids , Therapeutic Uses , Disks Large Homolog 4 Protein , Intracellular Signaling Peptides and Proteins , Metabolism , Ischemic Attack, Transient , Drug Therapy , Metabolism , Membrane Proteins , Metabolism , Neuroprotective Agents , Therapeutic Uses , Random Allocation , Rats, Sprague-Dawley , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To study the activation of extracellular signal regulated kinase (ERK) after focal cerebral ischemia/reperfusion in rats and the effect of sodium ferulate (SF) on it.</p><p><b>METHODS</b>Forty-five male adult SD rats were randomly divided into 3 groups, the sham-operated group, the control group and the SF group. The model of middle cerebral artery occlusion (MCAO) was established by thread ligation method, and in the ischemic phase, to rats in the sham-operated and the control group 4 ml of normal saline was intraperitoneally injected, and to rats in the SF group, 100 mg/kg of SF dissolved in 4 ml of normal saline was injected. The rats were decapitated at 2 hrs, 6 hrs, 12 hrs, 24 hrs and 72 hrs after reperfusion, 3 rats of every group at each time point, and rats brains were taken for immunohistochemistry and histopathological examination.</p><p><b>RESULTS</b>Histopathological examination showed that the cerebral ischemic damage in the SF group was significantly milder than that in the control group at 2 hrs after reperfusion. The cerebral ischemia induced ERK activation reached the peak at 6 hrs and maintained to 72 hrs after reperfusion. As compared with the control group, the ERK activation in the SF group was significantly enhanced with increased positive immune reacted cells (P < 0.01).</p><p><b>CONCLUSION</b>Cerebral ischemia/reperfusion could induce the activation of ERK in the ischemic brain cells, intervention of SF could enhance the activation and alleviate the ischemic injury in cerebral cortex.</p>
Subject(s)
Animals , Male , Rats , Brain Ischemia , Pathology , Coumaric Acids , Pharmacology , Infarction, Middle Cerebral Artery , Pathology , Mitogen-Activated Protein Kinases , Metabolism , Neurons , Pathology , Random Allocation , Rats, Sprague-Dawley , Reperfusion Injury , PathologyABSTRACT
Objective To determine if pregnancy affects the toxicity of bupivacaine and to investigate the effect of Shenfu injectio,a preparation of Chinese herbal medicine,on central nervous system and cardiac toxicity of bupivacaine in pregnant rats.Methods Twenty-four SD rats weighing 320-360 g were assigned to 3 groups(n =8 each):Ⅰ non-pregnant control group,Ⅱ pregnant control group and Ⅲ Shenfu injectio pretreatment group. The animals were anesthetized with isoflorane(2%-4%)-O_2 inhalation which was stopped before bupivacaine infusion was started.Femoral artery was canunlated for MAP monitoring and blood sampling and femoral vein was cannulated for bupivacaine infusion.MAP,HR and ECG were continuously monitored.All animals in the 3 groups received continuous infusion of 5% bupivacaine at 2 mg?kg~(-1).min~(-1).In group Ⅲ Shenfu injectio 10 ml?kg~(-1) was injected intraperitoneally(IP)30 min before bupivacaine infusion whereas in the two control groups(group Ⅰ and Ⅱ)equal volume of normal saline was injected IP instead of Shenfu injectio.The duration between the beginning of bupivacaine infusion and onset of convulsion/arrhythmia(QRS≥90 ms)/asystol was recorded and the amount of bupivacaine infused was calculated.Results There was no significant difference in the amount of bupivacaine causing convulsion and asystol between group Ⅰ and Ⅱ but the amount of bupivacaine causing arrhythmia was significantly larger in group Ⅰ(non-pregnant) than in group Ⅱ(pregnant control group)(P<0.05).The amount of bupivacaine causing convulsion,arrhythmia and asystole was significantly larger in Shenfu injectio pretreatment group(group Ⅲ)than in pregnant control group(group Ⅱ)(P<0.05 or 0.01).Conclusion Bupivacaine- induced cardiotoxicity is increased in pregnant rats and Shenfu injectio pretreatment can reduce the systemic toxicity of bupivacaine in pregnant rats.