At present, fingerprint has become an effective mean recognized internationally in controlling the quality of Chinese materia medica (CMM) or natural products. In recent years, there are some exploratory studies on the fingerprint of natural product, while only the injection of CMM has taken the fingerprint as one of the quality criteria. Other fingerprint studies on natural products were all staying in the researching phase. There are many reasons for the bottleneck of natural product fingerprint research, such as the component complexity of natural product. There are always a lot of impurity peaks in the analytic result of fingerprint, while it is very difficult to dissociate these impurity peaks by forthcoming analytic methods. Therefore we propose to construct the "interval fingerprint". The studies and analyses on the construction program, approach, model, and application problem of the "interval fingerprint" have been carried out with Shen'an Granule as the example.

The research on fingerprint pharmacokinetics will help entirely explore the internal diversity information of drugs especially natural products, and also can combine with the drug effect. Using fingerprint technology to study pharmacokinetics will more literally reflect the entirety of drugs and find the diversity regularity of the absorption, distribution, metabolism, and egestion of drugs. Using fingerprint technology to study pharmacokinetics of Chinese materia medica (CMM) is one of the critical technologies in modernization of CMM, and these researches will push the study on administration mechanism and development of CMM. Therefore, we propose to construct the "fingerprint pharmacokinetics" in our research. This thesis fairly analyzses the formation, research situation, application analysis, and application prospect of "fingerprint pharmacokinetics".

Background Posterior capsule opacification (PCO) is a main cause for visual acuity decline after modern extracapsular cataract surgery.Objective The aim of this study was to investigate the effect of rapamycin on PCO formation following phacoemulsification combined with intraocular lens (IOL) implantation in rabbit eyes.Methods Thirty New Zealand albino rabbits were randomized into three groups according to the difference in the implanted IOLs:conventional IOL without modification,IOL coated by a polymer material and IOL with sustained released rapamycin.Phacoemulsification combined with intraocular lens implantation surgery was performed in the left eye.The anterior ocular segment and PCO formation in the rabbit eyes were examined by slit lamp biomicroscope 1-7 days after operation,and the flare and inflammatory response of the anterior chamber as well as the degree of PCO severity were graded based on the criteria of Yang.The differences in examination outcomes were compared by the Kruskal-Wallis H test.The animals were sacrificed 12 days after surgery and eye specimens were prepared for histopathological examination to evaluate the biological behavior of lens epithelial cells (LECs) on the posterior capsule.Results The coated area of the implanted lens was semi-transparent with a smooth surface.The number of eyes with aqueous flare at grades 3 and 4 insignificantly increased but those with an inflammatory response at grades 3 and 4 significantly increased in the conventional IOL group and the polymer modified IOL group,compared with the rapamycin modified IOL group on the first day after operation (H =4.038,P =0.133 ; H =8.604,P =0.014).On the seventh day,the number of eyes with aqueous flare at grades 3 and 4 and inflammatory response at grades 3 and 4 significantly increased in the conventional IOL group and the polymer modified IOL group,compared with the rapamycin modified IOL group (H =8.891,P =0.012 ; H =7.664,P =0.0220).The histopathological examination showed that marked proliferation of LECs appeared between the anterior and posterior capsule in the conventional IOL group and the polymer modified IOL group;however,less LECs and regenerative cortex were seen in the rapamycin modified IOL group.Conclusions IOL loaded with rapamycin can inhibit the inflammatory response and alleviate the severity of PCO after phacoemulsification combined with IOL implantation.The implantation of IOL loaded with rapamycin may be a new approach to the prevention and treatment of PCO.

OBJECTIVETo study the effect and mechanism of methyl protodioscin (MPD), an active ingredients of yamogenin, in protecting cardiomyocytes (CMC) against anoxia/reoxygenation (A/R) injury.

METHODSCultured CMCs of neonatal SD rats were randomly divided into three groups, cells in Group A were untreated normal cells, cells in Group B and C were made to injury CMC model by A/R, and only those in Group C were treated with MPD. Levels of ATPase activity and lactate dehydrogenase (LDH) in cell membrane of CMCs were determined. Besides, the mRNA expression of sodium-calcium exchanger (NCX) in MPD treated CMCs was detected.

RESULTSAs compared with Group B, the degree of CMC injury was significantly milder and the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase were higher in Group C after cells were treated with MPD in concentration of 10 microg/mL and 50 microg/mL. The mRNA expression of NCX in CMCs was down-regulated after MPD treatment (P < 0.05).

CONCLUSIONMPD could maintain the low calcium internal environment in CMCs by way of protecting the membranous function of Na+ -pump and Ca2+ -pump, and influencing the Ca2+ transmembrane transportation in CMCs.

Animals ; Cell Hypoxia ; Cells, Cultured ; Diosgenin ; analogs & derivatives ; pharmacology ; Myocardial Reperfusion Injury ; metabolism ; Myocytes, Cardiac ; drug effects ; metabolism ; Oxygen ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology

Previous studies have shown that paeonol can antagonize acute myocardial ischemia and infarction in rat. This study further researched the effects of paeonol on blood pressure and blood flow in the artery of spontaneously hypertensive rats and its mechanisms related on vasomotion. Firstly, thirty spontaneously hypertensive rats were randomly divided into spontaneously hypertensive control group and paeonol-treating groups of high dose and low dose, and also, the other ten Wistar rats as healthy control group. Before and after the intraduodenal administration of the drug, arterial blood pressure was measured by carotid artery and blood flow through the renal artery and carotid artery in vivo were measured by animal flowmeter. The same volume of solvent was given to the spontaneously hypertensive control group and the healthy control group, and the other operations were same. In order to further study the effect of paeonol on vasomotor function, the superior mesenteric artery, renal artery and coronary artery of the spontaneously hypertensive rat were removed and separated, precontracted by a certain concentration of potassium chloride (KCl) and 5-serotonin (5-HT) respectively, and dilatory responses were assessed by cumulative addition of paeonol. Results showed that after duodenal one-time delivery of paeonol, the blood pressure significantly lowered, the renal arterial blood flow and the carotid arterial blood flow significantly increased in spontaneously hypertensive rat. And also, paeonol relaxed the mesenteric artery, renal artery and the coronary artery of spontaneously hypertensive rat in a concentration-dependent manner. These results indicated that the effect of paeonol on decreasing arterial blood pressure and increasing the arterial blood flow was related to its vasodilative effect.
Acetophenones ; pharmacology ; Animals ; Blood Pressure ; drug effects ; Male ; Rats ; Rats, Inbred SHR ; Regional Blood Flow ; drug effects ; Vasodilator Agents ; pharmacology

OBJECTIVETo evaluate the sensitization effect of polysorbate 80 and polysorbate 80 contained Houttuynia cordata Injection in different concentrations on Beagle.

METHODSBeagles, a kind of animal highly sensitive to sensitizing agents, were randomly divided into 18 groups, 3 in each group. They received respectively the intravenous infusion of polysorbate 80 made by different factories in different concentrations (0.25%, 0.10%, 0.05%), and Houttuynia cordata Injection containing polysorbate 80 in concentration of 0.25% or 0.30%, with the constant infusing speed of 5 mL/min and volume of 10 mL/kg. Changes of animals' condition were observed before infusion and in the 24 h after infusion, time of symptom appearance and disappearance was recorded, and the grade of response was determined. Moreover, blood samples of animals were collected before infusion and 10 min after ending infusion for measuring histamine content in plasma using ELISA. Then the sensitization effect was comprehensively estimated by combined consideration of the responding grade and histamine level.

RESULTSNo typical symptom of anaphylactoid reaction and over 1-fold increase of histamine level was found in all groups that received intravenous infusion of polysorbate 80 or polysorbate 80 contained Houttuynia cordata Injection in different concentrations. Estimation showed that all test solutions didn't induce typical anaphylactoid reaction on Beagle.

CONCLUSIONSConsidering both the appearance of symptoms and the elevation of blood content of histamine could be taken as the criteria for comprehensive diagnosis of anaphylactoid reactions. The solubilization effect and safety (for foreclose anaphylactoid reaction) of polysorbate 80 could be ensured by controlling its quality and concentration below 0.25% or 0.30%.

Anaphylaxis ; chemically induced ; Animals ; Dogs ; Houttuynia ; adverse effects ; Injections ; Polysorbates ; administration & dosage ; adverse effects

OBJECTIVETo study the factors affecting cyclodextrin (CD) inclusion of the volatile components in compound traditional Chinese medicines and evaluate the stability of the inclusion compound.

METHODSThis study took Gengnian compound as an example to examine the factors affecting the inclusion process according to the inclusion compound utilization ratio. Orthogonal design method was employed optimize the parameters in the inclusion process. The moisture absorption rate of the beta-CD inclusion compound was determined in different humidity and Q10 was used to predict its.

RESULTSThe inclusion method, inclusion compound dosage, temperature, inclusion time, and the drying method could all obviously influence the inclusion process. The results of orthogonal design study showed that the optimal beta-CD inclusion of Gengnian compound volatile components could be achieved by adding 8-fold volume of beta-CD and stirring for 3 h at room temperature. Stability experiment showed that the humility did not significantly influence the inclusion compound, which can be stable for 1.26 years.

CONCLUSIONThis study comprehensively examines the factors affecting the inclusion process and the stability of the inclusion compound, and provides experimental basis for application and study of the inclusion technology.

Drug Combinations ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; Oils, Volatile ; analysis ; chemistry ; isolation & purification ; Technology, Pharmaceutical ; methods ; beta-Cyclodextrins ; chemistry

OBJECTIVETo compare the acute myocardial infarction models in Beagle dogs and mongrel dogs, and study whether the Beagle dog model is sensitive to drug intervention.

METHODThe acute myocardial infarction model of dog was set up through ligation of anterior descending branch of coronary artery in dogs, in order to observe morphological changes of the heart and determine artery length and heart coefficient of exposed anterior descending branch of coronary artery. The epicardium electrocardiogram (sigmaST, N-ST) was used to measure the degree of myocardial ischemia. The quantitative histological assay (nitroblue tetrazolium, N-BT stain) was adopted to determine the area of myocardial infarction.

RESULTThere was no significant difference between Beagle dogs and mongrel dogs in terms of sigmaST, N-ST and ischemia area. The diltiazem group of Beagle dogs showed obvious reduction in the ischemia area (P < 0.05 and P < 0.01), with notable decline in sigmaST and N-ST, however, it had no statistical difference compared with the Beagle dog model group. Beagle dogs had clear coronary branches, longer exposed arteries and less difference in organ coefficient, which were suitable for the preparation of the myocardial infarction model, whereas mongrel dogs had irregular coronary branches and exposed arteries, with greater individual difference.

CONCLUSIONBeagle dogs are superior to mongrel dogs in the preparation of the acute myocardial infarction model, which is sensitive to for drug intervention.

Acute Disease ; Animals ; Disease Models, Animal ; Dogs ; Electrocardiography ; Female ; Male ; Myocardial Infarction ; drug therapy ; pathology ; Myocardium ; pathology

OBJECTIVETo evaluate the in vitro and in vivo function of anti-human bladder tumor human-mouse chimeric antibody ch-BDI and its future clinical application.

METHODSWith ch-BDI in high-expression cell-line medium, affinity chromatography was used for the purification. Labeled with (99m)Tc through reduction method, its immunoreactive fraction and association constant were measured. The constant was injected into nude mice with xenografted human bladder tumor. The biodistribution of the labeled ch-BDI was studied with radioimmunoimaging.

RESULTSch-BDI showed desirable immunoreactive fraction (76%) and association constant (3.56 x 10(9) M(-1)) in vitro and a terrific specific targeting effect in vivo.

CONCLUSIONch-BDI has fairly good function against human bladder tumor both in vitro and in vivo, and is promising in clinical use.

Animals ; Antibodies, Monoclonal ; immunology ; Antibodies, Neoplasm ; immunology ; Antibody Affinity ; Humans ; In Vitro Techniques ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Recombinant Fusion Proteins ; immunology ; Urinary Bladder Neoplasms ; immunology

OBJECTIVETo observe the efficacy and the adverse effects of erlotinib in the treatment for advanced non-small cell lung cancer (NSCLC) in Chinese patients.

METHODSFrom November 2005 to March 2009, a total of 519 patients with unresectable, local advanced, relapsed or metastatic NSCLC were enrolled in the trial. All the patients were treated with erlotinib 150 mg/day until disease progression or intolerable toxicity or for other reasons. The response rate, time to disease progression, overall survival and toxicity were analyzed.

RESULTSOf these 519 patients, 1 case had complete response, 127 cases had partial response and 263 cases had stable disease, resulting in an overall response rate (CR + PR) of 26.7%, disease stable rate of 54.9% and disease control rate (CR + PR + SD) of 81.6%. The median time to progression was 6.44 months and median overall survival was 15.37 months. The major erlotinib treatment-related adverse events (AE) were mild (CTC AE 1/2), only 3 cases had severe adverse effect, 1 case had interstitial lung disease and died of respiratory failure.

CONCLUSIONThe study presents excellent response rates, time to progression and overall survival of erlotinib treatment for advanced NSCLC in Chinese patients, and its adverse events are tolerable.

Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease Progression ; Erlotinib Hydrochloride ; Exanthema ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Lung Diseases, Interstitial ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Quinazolines ; adverse effects ; therapeutic use ; Receptor, Epidermal Growth Factor ; adverse effects ; antagonists & inhibitors ; therapeutic use ; Remission Induction ; Survival Rate