ObjectiveTo observe the inhibitory effect of sinomenine on human glioblastoma and its pharmacokinetic characteristics in glioblastoma. MethodA human glioblastoma U87 cell line stably expressing luciferase was constructed， and a mouse glioma model was established for use in both pharmacodynamic and pharmacokinetic studies. Pharmacodynamics： Model mice were randomly divided into model group and sinomenine low-， medium-， and high-dose groups （50， 100， 150 mg·kg^-1）. Sinomenine was administered intraperitoneally for 14 days. The fluorescence value of brain tumors was observed to analyze its inhibitory effect on glioblastoma proliferation. Brain tumors and the surrounding brain tissue were collected， and the expression levels of vascular endothelial growth factor A （VEGFA）， P-glycoprotein （P-gp）， breast cancer resistance protein （BCRP）， and Occludin were detected by Western blot. Pharmacokinetics： Mice were divided into a normal group （50 mg·kg^-1） and model groups （50， 100， 150 mg·kg^-1）. After a single intraperitoneal injection of sinomenine， extracellular fluid from brain tumors was collected in vivo by microdialysis every 15 min for 6 h. Sinomenine concentrations in the dialysate were detected by HPLC-MS/MS， and pharmacokinetic parameters were calculated to analyze pharmacokinetic characteristics of sinomenine in the brain and glioblastoma. ResultCompared with model group， after 14 days of sinomenine administration， the fluorescence value of brain tumors significantly decreased （P<0.05） in a dose-dependent manner. Sinomenine inhibited the increase in VEGF and the degradation of Occludin in the tissue surrounding the tumor and inhibited the expression of VEGF， P-gp， and BCRP in glioblastoma. After a single administration， sinomenine was detected in brain and tumor tissues within 7.5 min. Compared with normal group， the C_max and AUC in the tumor significantly increased， T_max shortened （from 1.63 h to 0.71 h）， and CLz/F decreased. In the dose range of 50-150 mg·kg^-1， sinomenine exhibited a linear pharmacokinetic process in glioblastoma. ConclusionSinomenine has a significant inhibitory effect on glioblastoma， which can inhibit VEGF elevation and drug transporter efflux， reduce tumor invasion， and maintain the integrity of the blood-brain barrier. Sinomenine can rapidly cross the blood-tumor barrier， reach peak concentration， and exhibit linear pharmacokinetic characteristics in the tumor.

Objective To explore the effect of intensive upper limb therapy assisted by a hand robot on motor function after stroke and performance in the activities of daily living.Methods Thirty-two hemiplegic stroke survivors were randomly divided into a conventional rehabilitation group (group A,n =10),a robot-assisted therapy group (group B,n=10),and a robot-assisted intensive therapy group (group C,n=12).The three groups all received routine drug therapy and daily 40 min sessions of conventional rehabilitation training 5 days a week for 4 weeks.Those in groups B and C were additionally provided with 20 min of robot-assisted therapy or 40 min of more intensive robot-assisted intensive therapy respectively.Before and after the intervention,the 3 groups were assessed using the Fugl-Meyer assessment for the upper extremities (FMA-UE),the action research arm test (ARAT) and the modified Barthel Index (MBI).Results No significant differences were observed among the 3 groups in any of the measurements before the treatment.In each group the average FMA-UE,MBI and ARAT scores had increased significantly after four weeks of treatment.The improvements in the average FMA-UE and ARAT scores were more significant in group B than in group A,while the FMA,MBI and ARAT scores suggested a significantly greater improvement in group C than in group B.Conclusion Robot assistance can help to improve upper extremity motor function after a stroke.It also has an obvious effect on improving performance in the activities of daily living.

Objective To observe the effect of exercise combined with fluoxetine medication on depression and the expression of BDNF and TrkB protein in the hippocampus and to explore possible mechanisms.Metbods Forty-eight male Wister rats were randomly divided into a sham operation group,a model group,a fluoxetine group and a combined treatment group,each of 10.A model of post-stroke depression was induced in all except the rats in the sham operation group through occlusion of the middle cerebral artery using the intraluminal tread method followed by imposing chronic but unpredictable stress.The model and sham operation groups were not given any training or medication.The fluoxetine group was treated with fluoxetine,while the combined treatment group received exercise training and the fluoxetine treatment at the same time for 28 days.After one,14 and 28 days the four groups were given the sucrose preference test,a forced swimming test and were weighed.Brain tissue was resected to detect the expression of BDNF and TrkB in the left hippocampus using western blotting.Results There were significant differences between the model group and the sham operation group in all measurements.After both 14 days and 28 days of treatment,the average immobility times in the fluoxetine and combined treatment groups was significantly shorter than that in the model group,while their sucrose preference,average body weight and the expression of BDNF and TrkB in the left hippocampus were all significantly higher.The same differences were observed between the combined group and the fluoxetine group.Conclusion Exercise combined with fluoxetine medication can relieve depression,at least in rats.

[Objective]To explore the relationship between peripheral arterial disease(PAD)and diabetic retinopathy(DR)in type 2 diabetes patients.[Methods]A total of 99 patients diagnosed with PAD were classified into grade 1-3 by their total scores of peripheral arterial stenosis assessed by color doppler ultrasound examinations,where the degree of stenosis 30% ~ 49% scored 0, 50%~99%scored 1,lumen occlusion(i.e. degree of stenosis 100%)scored 2,and therefore the total score 0-2 was categorized into Grade 1 ,3~4 into Grade 2 ,5~12 into Grade 3. The bilateral anterior tibial artery ,posterior tibial artery and dorsalis pedis artery of these patients were analyzed. The presence of diabetic retinopathy(DR)was graded from retinal photographs using a standard protocol.[Results]Among 99 cases of type 2 diabetic patients with peripheral arterial disease ,58.6%of them were male with average age of 67.3 ± 7.9 years old. Patients of Grade 1,Grade2,Grade 3 lesion accounted for 45.4%,30.3%,24.2%,respectively. Age, gender,smoking history,SBP,DBP,BMI,FBG,TC,TG,LDL-C,HDL-C,HbA1C among 3 groups were not statistically signifi-cant. The associations of DM duration and HbA1C value were significantly larger in DR than in PAD. The proportion of DR patients increased with the severity degree of PAD(p for trend=0.004). Degree of stenosis Grade 2 and Grade 3 could be predictive for DR.[Conclusions]DR is associated with the severity degree of PAD in type 2 diabetes patients as evaluated by duplex ultrasonography.Degree of stenosis Grade 2 and 3 could be used for screening or finding DR. Strategies for optimum treatment and early prevention are needed.

Ligustrazine which has extensive pharmacological effects has been clinically used in the treatment of cardiovascular and cerebrovascular diseases,respiratory diseases,urinary diseases,cirrhosis,cancer,etc.Research of protective effects of Ligustrazine on spinal cord injury has recently increased year by year.Numerous clinical trials and animal experiments suggest that Ligustrazine can play a role on ischemic cerebrovascular disease, degenerative brain disease,epilepsy,spinal cord injury and so on,whose main mechanisms include inhibiting of apoptosis and inflammation,enhancing the body’s antioxidant level,improving hemorheology,increasing expression of neurofilament protein and neurotrophic factors,and regulating balance of the ion intracellular and extracellular.Through consulting the relevant literature since 2003,this article reviews the protective roles and mechanisms of Ligustrazine on cerebra and spinal cord injury for the past 10 years.

Aim To investigate the behavioral changes of the pain related neuromodulation and neurotransmission in peripheral and central nervous systems in rats with trigeminal neuralgia (TN)and provide a disease relevant animal model for mecha-nism study of TN.Methods The male SD rats were randomly divided into sham operation group and TN surgical group.The latter group was further divided into model group and gabapentin group (100 mg · kg-1 ). TN was induced by intravenous erythrosine B injection and laser irradiation.The pain behavior of rats was evaluated using mechanical pain threshold measured with Von Frey hairs.Fluorescence quantitative PCR technique was deployed to study the change of Tac1 mRNA expressions in trigeminal ganglia.Utilizing microdialysis technique followed by high performance liquid chromatography fluorescence detection (HPLC-FLD),the extracellular striatum fluid was collected and glutamate(Glu)concentration was determined.Results In the model group,the average mechanical pain threshold in facial ar-ea innervated by the trigeminal nerve remained below 4g after 7 days post surgery.The mechanical threshold of the model group (1.63 ±1.27)g was significantly lower (P<0.01)than the control group (24.17 ±4.49)g on day10 post surgery.In gen-eral,the mechanical withdraw threshold was decreased from the preoperative value of 26g to the postoperative value of (1.60 ± 1.74)g (P<0.01),and maintained stable at (0.71 ±1.24) g during the whole dynamic monitoring period from day7 to day60.The successful rate of this model was 63%.After sur-gery,Tac1 mRNA expression in trigeminal ganglia and extracel-lular Glu levels in striatum were significantly up-regulated (P<0.05 ) in the model group. Animals receiving Gabapentin showed significant improvement in pain symptoms,as well as re-ductions of Tac1 mRNA expression in trigeminal ganglia and ex-tracellular Glu concentration in striatum (P<0.05 ).Conclu-sions The above described photochemically induced TN rat model can partially mimic the clinical TN symptoms and its pathophysiology.Considering its overall high stability,it is very likely that this model could be used in preclinical mechanism study or drug screening of TN.

OBJECTIVETo observe the allergenicity of chlorogenic acid (CA) in Qingkailing injection.

METHODCA was administrated to Beagle dogs through intravenous injection, and on experimental allergic sensitization of guinea pigs, it was through intraperitoneal and intravenous injection. The behavioral changes of Beagle dogs and guinea pigs were observed, and changes of the content of histamine, IgE, IgG, IgM, ECP and IL-4 in blood were detected. Then the allergenicity of CA was determined by experimental anaphylactoid and allergic methods.

RESULTThere were no typical behavioral changes and increasement of the content of histamine, IgE, IgG, IgM, ECP and IL-4 in blood.

CONCLUSIONCA can not provoke anaphylactoid and allergic reactions.

Allergens ; adverse effects ; Animals ; Behavior, Animal ; drug effects ; Chlorogenic Acid ; adverse effects ; Dogs ; Drug Hypersensitivity ; blood ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Female ; Guinea Pigs ; Injections ; Male

OBJECTIVETo establish a new, real time, dynamic and direct optical detection method for mast cell degranulation caused by anaphylactoid reaction.

METHODA CD63-GFP plasmid was constructed and introduced steadily into rat basophilic leukemia (RBL-2H3) cells. The movements of CD63-GFP, which was located on both the granule membranes and the plasma membranes of RBL cells stimulated by Compound 48/80, were studied by confocal laser scanning microscope (CLSM) and total internal reflection fluorescence microscope (TIRFM) both inside and on the surface of living RBL-2H3 cells.

RESULTBefore antigen stimulation, most granules with CD63-GFP hardly moved in RBL cells. However, after antigen stimulation, the granules moved dramatically. They reached the plasma membranes in a few minutes and fused with them instantaneously. The velocity of the granule movement toward the plasma membranes on antigen stimulation was calculated to be 0.05 micron x s(-1).

CONCLUSIONAnalysis of the movement of each granule provided a new insight into the elementary process of degranulation. The method is rapid, sensitive and reliable, which could be used as a new detection method for anaphylactoid reaction in vitro.

Anaphylaxis ; diagnosis ; immunology ; metabolism ; Animals ; Antigens, CD ; genetics ; Cell Degranulation ; Cell Line, Tumor ; Cell Movement ; Mast Cells ; cytology ; immunology ; Microscopy, Confocal ; Microscopy, Fluorescence ; Platelet Membrane Glycoproteins ; genetics ; Rats ; Tetraspanin 30 ; Time Factors

OBJECTIVETo establish animal model of histamine-induced anaphylactoid reactions on Beagle dogs through intravenous injection of histamine phosphate injection.

METHODAnaphylactoid reactions was determined according to the changes of praxiology and blood pressure of Beagle dogs after one intravenous injection of histamine phosphate injection.

RESULTIt showed that typical anaphylactoid reactions be caused by histamine phosphate injection on Beagle dogs, and the response of the high-dose group was more obvious than that of the low-dose group.

CONCLUSIONIntravenous injection of histamine phosphate injection could simulate Beagle dogs to bring typical clinical anaphylactoid reaction, that could be used as a sensitive animal model to evaluate anaphylactoid reaction of traditional Chinese medicine injections (TCMIs) in the pre-clinical experiments of both TCMIs and their composition.

Anaphylaxis ; chemically induced ; Animals ; Disease Models, Animal ; Dogs ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; adverse effects ; Female ; Histamine ; administration & dosage ; adverse effects ; analogs & derivatives ; Injections, Intravenous ; Male

Microdialysis (MD), as a living bio-sampling technique, can be utilizable in different tissues,organs or different parts of the same organs, in order to clarify the drug's pharmacokinetics, mechanism, and provide a basis for targeting. This article describes a number of points in recent years, the microdialysis technique in pharmacokinetic studies in the field of application of the status and significant progress.
Animals ; Humans ; Microdialysis ; Pharmaceutical Preparations ; analysis ; Pharmacokinetics ; Tissue Distribution