Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) μg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.
Administration, Intravenous ; Animals ; Caffeic Acids ; pharmacokinetics ; Chromatography, Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; Lactates ; pharmacokinetics ; Macaca mulatta ; Mass Spectrometry ; Plant Roots ; chemistry ; Salvia miltiorrhiza ; chemistry

Aspirin (AS) has been widely used globally for preventing incidence of cardio-cerebral ischemic disease for nearly 100 years.The people who takes AS for long term may reach several hun-dred million,but many persons were died from interned bleeding.We found salvianolic acids (salvianolic acid B 57％,salvianolic acid A 1％,rosmarinic acid,35％,SA)was much better than AS in preventing in-cidence of cardio-cerebral ischemic disease,and may avoid hemorrhage risk in clinical application.The research are summary briefly as follows: (1) both AS and AS have same anti-platelet aggregation ef-fect,but their mechanism is different.AS inhibited both TXA2 and PGI2,SA inhibited TXA2only;(2)For established thrombosis,SA could dissolved it, AS showed no effect. The thrombolytic mechanism of SA has been elucidated. (3) In SHRSP rats, the incidence of stroke and death rate in SA group was distinct less that of AS group;(4)In MCAO rats,SA and Sal B decreased stroke index and neural im-pairment. AS showed no such ability; (5) There is microcirculatory disturbance in cardio-cerebral isch-emic disease. SA could improve circulatory disturbance induced by LPS, adrenaline, ROS and I/r. there is no any paper reported AS could have beneficial effect on above mentioned microcirculatory dis-turbance models;(6)Hyperlipidemia is an independent risk factor for cardio-cerebral vascular disease. SA could significant hypolipidemic effect which is similar to that of statins(atovastin and simvastin)and ten times stronger than omega-3.AS has no inhibitory effect on hyperlipidemia.(7)Thereis overproduc-tion of ROS induced by ischemic/reperfusion in cardio-cererbal vascular disease.SA showed more ro-bust,anti-oxidant capacity than VitC,Vit E,melatonin,edalavone and resveratrol,etc.SA is one of the most powerful anti-oxidant in the world so far.(8)According to literatures,1/3 patients who take AS for long time will have hemorrhage, we found in normal rats and mice (coagulating and hemodynamics) SA had no apparent effect on coagulation system and this property of SA was confirmed in clinic trial with hundred thousand cases; (9) As well known, neurodegenerative disease are divided into acute and chronic neurodegenerative disease,and both have similar pathogenesis.We proved that SA could inhibit Aβ aggregation and fiber formation, inhibit tau hyperphosphorylation induced by OA and p25/CDK5,as well as increase neurogenesis and angiogenesis.More importantly,SA showed not only pre-ventive effect on cardio-cerebral vascular diseases. SA has been finished clinical trial phase I-IV for treatment of stroke.The therapeutic effect of SA is characterized by inducing multi-target effect and in-hibit pathogenesis of early,middle and late stage of stroke.SA as anti-stroke new drug was approved by the state food and drug administration of China in 2011.

Objective To investigate the effect of swimming exercise on insulin sensitivity and interleukin-1 beta(IL-1β)mRNA expression in muscle tissue of insulin-resistant (IR) rats induced by high-fat diet.Methods The IR rat model was induced by high-fat diet feeding for 10 weeks and assessed by hyperinsulinemic-euglycemic clamp technique (HEC). The rats were divided into the fllowing three groups: normal group without exercise, IR groups with and without swimming exercise. After 4 weeks swimming excersie, insulin sensitivity and serum IL-1β levels were measured.Results Glucose infusion rate (GIR) of the IR rats was significantly elevated than that of non-exercise IR rats (P<0.01). Moreover, serum IL-1β levels were reduced markedly in IR rats (P<0.01). Conclusion High-fat diet feeding can partly reverse IR of rats to normal value. Swimming exercise improves insulin sensitivity and reduces the levels of IL-1β in IR rats induced by high-fat diet.

Objective To investigate the F-wave and nerve conduction in patients with amyotrophic lateral sclerosis (ALS) and explore the correlation between these parameters and muscle strength, disease duration and onset site.Methods The data of outpatients and inpatients diagnosed with ALS were collected in Peking Union Medical College Hospital from January 1997 to May 2008.Standard sensory and motor nerve conduction study of the median nerve, ulnar nerve and tibial nerve was performed in 205 patients with ALS.F-wave velocity and frequency was measured in median nerve.Parameters for analyses included sensory conduction velocity and amplitude, distal motor latency (DML), and compound muscle action potential (CMAP) amplitude.Correlation between muscle strength and DML, CMAP amplitude or F-wave frequency were also explored.Results Delayed DML of the median nerve, ulnar nerve and tibial nerve were found in 24.9% (48/193), 15.3% (25/163), 21.2% (7/33) of patients respectively.Decreased CMAP amplitudes were found in 57.0% (110/193), 49.7% (81/163), 39.4% (13/33) of patients respectively.Decreased F-wave frequency of the median nerve was found in 68.9% (122/177) of patients.The abnormality of DML,CMAP amplitude and F-wave frequency of median nerve were increased in weaker muscles.Decreased median nerve CMAP amplitude (81.5% (53/65)) and F-wave abnormality (decreased persistence 70.9%(44/62), absent responses 45.1% (28/62)) in spinal onset groups were significantly higher than those in bulbar onset groups (CMAP 32.4% (11/34); F-wave: decreased persistence 38.2% (13/34), absent responses 14.7% (5/34); x2 = 23.629, 9.753, 9.029,all P <0.01).Compared with the bulbar onset group,the abnormality of DML in spinal onset group was higher, but not reach statistical significance.Logistic regression revealed a strong direct association between decreased CMAP amplitudes and upperextremity muscles strength, disease duration and onset symptom.Abnormality of F-wave frequency was associated with upper-extremity muscles strength and onset symptom.Conclusions Delayed DML and decreased amplitude of CMAP are found in ALS patients.CMAP amplitude is a sensitive parameter related to the severity of ALS.F-wave velocity is relatively normal while F-wave frequency of the median nerve is correlated with muscle strength.Decreasing CMAP amplitude and F-wave frequency are correlated strongly with muscle weakening,disease duration and symptom onset over limbs.

Objective to assess the utility of segmental motor nerve conduction study in differential diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy(CIDP)and Charcot-Marie-Tooth type 1(CMT1).Methods A segmental motor nerve conduction study was performed on 16 patients with CIDP and 13 patients with CMT1.Distal motor latency,motor nerve conduction velocity,the changes of amplitude,area and duration of compound motor action potential over conventional segment were compared between the groups.ResultsDistal motor latency was (5.6±3.4) ms in CIDP and (9.3±2.1) ms in CMT1(t=5.347 P=0.000),motor nerve conduction velocity was (31.1±14.3) m/s in CIDP and(22.2±5.8)m/s(t=6.369,P=0.000),M50 of the decrease in amplitude over conventional segment was 29.7% in CIDP and 4.9% in CMT1 (Z=7.141,P=0.000).Distal motor latency was normal in 40.3% (25/62) nerves and motor nerve conduction velocity was normal in 18.1% (26/44)of segments in CIDP,while distal motor latency and motor nerve conduction velocity were abnormal in all nerves in CMT1.Motor nerve conduction block or abnormal temporal dispersion was detected in 29.2% segments in CIDP and 3.0% in CMT1 (x2=20.829,P=0.000).Conclusions The segmental motor nerve conduction study can help separate CIDP and CMT1.When motor nerve conduction block or abnormal temporal dispersion is detected,the motor nerve conduction velocity is distinctly various in different segments,the diagnosis of CIDP but not CMT1 should be considered.

Objective To evaluate the damage caused by high intensity ultrasound(HIU)on tumor micro- vessels.Methods Rabbit models of the VX_2 tumor were set up.The target hepatic carcinomas were treated with HIU,and the results were observed using hematoxylin-eosin(HE)staining,vascular endothelial cell biotinylated-ulex europaeus agglutininiⅠ(UEAI)immunohistochemical staining,tumor micro-vessel counts,and electron microscopy. Results Histological examination through HE staining indicated that HIU induced carcinoma vascularities with whole tumor tissue coagulative necrosis.The UEAI immunohistochemical staining of the target lesions treated by HIU was ne- gative,and complete tumor micro-vessel uhrastructure damage was observed under the electron microscope.Conclu- sion HIU can damage tumor micro-vessels thoroughly,in such way that it may inhibit tumor growth and metastasis.

The chemical structures of P1 A was identified by complete acid hydrolysis, partial acid hydrolysis, periodate oxidation-Smith degradation, methylation analysis, IR and NMR. The results showed that P1 A had a backbone consisting rhamnose, mannose, glucose and galactose. The side chain possessed arabinose and xylose. 1-->, 1-->6 and non-reducing terminal linkages existed in polysaccharide P1A, but there are doubling amount of 1-->2 and 1-->4 linkages. Oxidable linkage of P1 A accounted for 45%, and inoxidable linkage of P1A accounted for 55%. Mannose, glucose and galactose were mainly linked by 1-->2 linkage. Rhamnose, arabinose and xylose were mainly linked by 1-->2 and 1-->4 linkages. PlA contained beta-Glc(1,6)-,beta-Gal(1,3)-,beta-Man(1,4)-beta-Rha,-Glc(1,4)-, Glc(1)-,-Gal(1,4)- and Man(1)-.
Acanthaceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Molecular Weight ; Polysaccharides ; chemistry

Objective To screen down regulated genes and find down regulated novel genes in gastric cancer. Methods Genes mRNA expression were detected between gastric cancer and normal gastric mucous membrane of five patients using cDNA microarray. Genes mRNA expression signals on hybridization membranes were analysized with computer software. Down regulated genes in gastric cancer were screened. cDNA suppression subtraction library was established by counterpart normal gastric mucous membrane mRNA(Tester) subtracting gastric cancer tissues mRNA(Driver) of five patients. After identification of the subtraction library, positive clones choosen randomly were sequenced , and down regulated novel genes in gastric cancer were screened. Some of the genes were identified by RT PCR.Results Down regulated genes in gastric cancer consist of 60 genes including tumor suppressing genes, apoptosis related genes, DNA replication and transcript or translate related genes, cell cycle related genes, cell migration related genes, etc. Two unknown gene fragments in gastric cancer were cloned. Conclusions Sixty down regulated genes in gastric cancer are confirmed. They are involved in gastric tumorigenicity and metastasis. cDNA subtraction library of gastric cancer was constructed successfully. Two down regulated novel gene fragments in gastric cancer was found.

OBJECTIVETo investigate the clinical curative effect of the combination between medicine and acupoint flow on SOD, NO in patients with ulcerative colitis.

METHODTwo hundred sixty two patients with ulcerative colitis were randomly divided into four groups: the patients in traditional Chinese medicine group were fed with changpikang, the patients in ear acupoint group were pasted and pressed spleen, large intestine, sympathesis, subcortex; the patients in medicine and acupoint group were taken with Changpikang and ear acupoint; the patients in treatment group were treated by taking sulfasalazine, with a treatment course of four weeks. The changes of SOD, NO before and after treatments were recored.

RESULTThere was a significant difference between four groups before and after treatment (P < 0.05), medicine and acupoint group was superior to that others (P < 0.05).

CONCLUSIONThe method of combination between medicine and acupoint could increase the contents of SOD, decrease the level of NO, elevate the potential of organism to resist oxygen free radical and promote intestinal tract ulcer concrescence.

Acupuncture, Ear ; methods ; Adult ; Aged ; Colitis, Ulcerative ; drug therapy ; metabolism ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Nitric Oxide ; metabolism ; Sulfasalazine ; therapeutic use ; Superoxide Dismutase ; metabolism ; Treatment Outcome ; Young Adult

Objective To investigate the correlation between NRAMP1 gene polymorphisms and susceptibility to tuberculosis ( TB) in Tibetan people in Qinghai. Methods A case-control study was con-ducted in this study, involving 99 Tibetan patients with TB and 89 healthy Tibetans. The single nucleotide polymorphisms of NRAMP1 gene at rs17235409 and rs3731865 sites were detected by using TaqMan probe method. Gene cloning and sequencing typing were performed to analyze the single nucleotide polymorphisms of NRAMP1 gene at the rs17235416 site. SPASS20. 0 software was used to statistically analyze the correla-tion between NRAMP1 gene polymorphisms and susceptibility to TB in Tibetan people. Results No signifi-cant difference in the genotype frequencies of rs3731865 and rs17235409 was found between the two groups (χ2=0. 852, P=0. 356;χ2=0. 279, P=0. 597). The genotype frequencies of TGTG/TGTG and TGTG/del+del/del at the rs17235416 site were 70. 7% ( 70/99 ) and 29. 3% ( 29/99 ) in patients with TB and 86. 5% (77/89) and 13. 5% (12/89) in healthy subjects. There were significant differences in the geno-type frequencies of TGTG/TGTG and TGTG/del+del/del between the two groups (χ2=6. 870, P=0. 009). The genotypes of TGTG/del and del/del at rs17235416 were risk factors for TB ( OR=0. 376; 95%CI:0. 178-1. 794 as compared with the TGTG/TGTG genotype in Tibetan people in Qinghai. Conclusion This study suggested that the NRAMP1 gene polymorphisms at rs3731865 and rs1723409 sites had no correlation with the susceptibility to TB in Tibetans in Qinghai. However, the NRAMP1 gene polymorphisms at rs17235416 site were correlated with the susceptibility to TB. The TGTG/del alleles at the rs17235416 site might be the risk factors for tuberculosis in Tibetans in Qinghai.