To enhance the quality and efficiency of ozagrel by investigating the differences between the ozagrel polymorphs in bioavailability. Solid ozagrel in different polymorph forms were orally administered to SD rats. An HPLC method was established to determinate plasma level of ozagrel. The bioavailabilities of two polymorph forms were calculated and compared. The pharmacokinetic parameters of ozagrel, were as follows: Cmax was 32.72 ± 17.04 and 34.01 ± 19.13 mg · L(-1), respectively; AUC0-t was 61.14 ± 14.76 and 85.56 ± 18.08 mg · L(-1) · h, respectively; t½ was 1.53 ± 0.51 and 4.73 ± 3.00 h, respectively. There was no significant difference in pharmacokinetic parameters between form I and II polymorphs of ozagrel while the t½ of form II is longer, which indicates that the use of form II polymorph as pharmaceutical product may prolong the effective action time in clinics. This would help the polymorph quality control in drug production.
Animals ; Biological Availability ; Chromatography, High Pressure Liquid ; Methacrylates ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the clinical results of using end plate rings in preventing subsidence of titanium cage in anterior cervical corpectomy and fusion (ACCF) surgery.

METHODSThe clinical data of 71 patients with cervical spondylotic myelopathy underwent ACCF in single segment from February 2008 to February 2011 were retrospectively analyzed. There were 38 males and 33 females, aged from 39 to 74 years old with a mean of 53.8 years. Thirty-three were used end plate rings and thirty-eight were not used (end plate rings group and no end plate ring group, respectively). The Japanese Orthopaedic Association (JOA) score, Odom's scale, imaging data were used to evaluate the clinical effects. Imaging data including Cobb angle of fusion segment, intervertebral height of anterior border (Da) and posterior border (Dp), the mean intervertebral height (Dm).

RESULTSAll patients were followed up from 13 to 34 months with an average of 19.5 months. Between two groups, there was no significant difference in Cobb angle of fusion segment and the mean intervertebral height (Dm) before surgery and one week after surgery. Whereas, one year after surgery, the Cobb angle of end plate ring group was (9.4 ± 3.8) degrees, and contral group was (7.5 ± 3.9) degrees, which was significantly lower than that of end plate ring group. Meanwhile, the Dm of end plate ring group was (57.3 ± 2.2) mm, and no end ring group was (55.2 ± 2.6) mm which was significantly lower than that of end plate ring group. The subsidence in end plate ring group was 57.6%, and was 78.9% in no end plate ring group. There was no significant difference in JOA score before and after surgery between two groups. At 1 year after operation, 90.9% (30/33) got excellent or good results in end plate ring group, 89.5% (33/38) got excellent or good results in contral group.

CONCLUSIONThe use of end plate rings could not completely prevent the subsidence of titanium cage, however, which can decrease the occurrence rate of the subsidence and lessen its degree.

Adult ; Aged ; Bone Plates ; Cervical Vertebrae ; pathology ; surgery ; Female ; Humans ; Male ; Middle Aged ; Orthopedic Fixation Devices ; adverse effects ; Spinal Fusion ; instrumentation ; methods ; Spondylosis ; pathology ; surgery ; Titanium

Comparing to Chitosan, Chitosan-oligosaccharides have several special functions, such as water-soluble, antitumor activity, immunostimulating effects, and antimicrobial activity. The chitosan-oligosaccharide, the molecular weight of which was about 5000, was used as research model. According to the agarose gel electrophoresis and UV spectrophotometer it was proved that electrostatic interaction was playing a very important role in the formation process of chitosan-oligosaccharide/DNA complex. The potential of adsorbing DNA on chitosan-oligosaccharide was analyzed by gel electrophoresis and UV spectrophotometer, and it was indicated that chitosan-oligosaccharide can improve the storage and structure stability of DNA. To check its protection ability to DNA by DNase I digestive experiment, the result showed that chitosan-oligosaccharide could load with plasmid effectively and protect DNA from being digested by DNase I. It was proved that chitosan-oligosacchide was safe and effective for gene delivery and will have a very good future in the field of gene therapy.
Chitosan ; chemistry ; DNA ; chemistry ; Gene Transfer Techniques ; Genetic Vectors ; Nanoparticles ; chemistry ; Oligosaccharides ; chemistry

AIMTo study the effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino) propane hydrochloride(DDPH) on brain ischemia injury in rats.

METHODSBy using the middle cerebral artery occlusion (MCAO) induced by nylon surgical thread inserted through the internal carotid artery into the anterior cerebral artery in rats, the effects of DDPH on neuron defects(ND) and infarct size(IS) were investigated. Using incomplete cerebral ischemia in rats, the effects of DDPH on superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in brain tissue and pathological changes in rats were studied.

RESULTSDDPH at the dose of 10 mg.kg-1 i.p. 30 min before ischemia decreased the ND 3 h after ischemia. The IS declined 24 h after ischemia as well. Meanwhile, DDPH was found to increase SOD activity and reduce the MDA content, as well as mitigate pathological damage, of neuron after brain ischemia in rats.

CONCLUSIONDDPH showed protective effects on brain ischemia, probably related to its properties of calcium antagonistic effect and increasing the activity of superoxide dismutases.

Animals ; Brain ; metabolism ; pathology ; Brain Ischemia ; metabolism ; pathology ; Female ; Infarction, Middle Cerebral Artery ; pathology ; Male ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; pharmacology ; Phenethylamines ; pharmacology ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; pathology ; Superoxide Dismutase ; metabolism

OBJECTIVEThe aim of this study was to explore the possibility of creating a toxin, C-CPE-ETA', by fusing C-terminal high affinity binding domain of CPE (C-CPE) with a truncated form of Pseudomonas aeruginosa exotoxin A (ETA') and to examine whether C-CPE-ETA' could specifically target CLDN-3, 4 molecule and the targeted toxin was cytotoxic against CLDN-3,4-overexpressing ovarian cancer.

METHODSCLDN-3 and CLDN-4 expressions were analyzed at the mRNA level in three ovarian cancer cell lines and epithelial ovarian cancer tissues from 20 patients. After transforming an expression plasmid of C-CPE-ETA' into E. coli BL21 (DE3) plysS strain, the recombinant protein was purified using His-Bind resin chromatography column and analyzed by Western blot and Coomassie blue staining. The specific binding, proapoptotic and cytolytic activities were evaluated by flow cytometry, fluorescence microscopy with the JC-1 probe and MTT assay in CLDN-3,4-overexpressing ovarian cancer cells.

RESULTSQuantitive RT-PCR results showed there existed high levels of CLDN-3 and CLDN-4 in ovarian cancer cells, CAOV3, OVCAR3 and SKOV3. Moreover, high expressions of CLDN-3 and CLDN-4 were observed in 90.0% (18/20) and 60.0% (12/20) of ovarian cancer tissues, with an expression level 10-fold higher than that in the normal ovarian tissue. A 58 000 recombinant protein C-CPE-ETA' was demonstrated by Western blot and Coomassie blue staining. Purified and recombinant C-CPE-ETA' was bound with high affinity to CLDN-3,4-overexpressing ovarian cancer cells, CAOV3, OVCAR3 and SKOV3 cells. C-CPE-ETA' was strongly proapoptotic and cytotoxic towards the CLDN-3,4-overexpressing ovarian cancer cells. The concentration of IC(50) was 7.364 ng/ml for CAOV3 cells, 8.110 ng/ml for OVCAR3 cells and 22.340 ng/ml for SKOV3 cells, respectively. However, control CLDN-3,4-deficient cell line HUVEC was not susceptible to the recombinant C-CPE-ETA' at a concentration up to 10 µg/ml.

CONCLUSIONSThe C-CPE-ETA' protein exhibits remarkably specific cytotoxicity for CLDN-3,4-overexpressing ovarian cancer cells. Its therapeutic potential warrants further development for ovarian cancer molecular targeted therapy.

ADP Ribose Transferases ; metabolism ; physiology ; Apoptosis ; Bacterial Toxins ; metabolism ; Cell Line, Tumor ; Claudin-3 ; Claudin-4 ; Claudins ; genetics ; metabolism ; Enterotoxins ; metabolism ; physiology ; Exotoxins ; metabolism ; physiology ; Female ; Humans ; Immunotoxins ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Recombinant Fusion Proteins ; metabolism ; physiology ; Virulence Factors ; metabolism ; physiology

Objective To explore the clinical outcomes of patients with hypertensive intracerebral hemorrhage in the thalamus received stereotactic combined with microsurgical treatment,and find the best treated method. Methods Forty-three patients with hypertensive intracerebral hemorrhage in the thalamus,admitted to our hospital from October 2009 to March 2011,were selected in our study; these patients were divided into stereotactic combined with microsurgical treatment group (observation group,n=22) and direct surgery group (control group,n=21).Preoperative hematoma,and hematoma at 1 week and 1 month after the treatments under CT were compared; clinical curative effect at 1 month after the treatments and activities of daily living (ADL) 3 months after the treatments were compared. Results The hematoma in the observation group 1 week and 1 month after the treatments was statistically different as compared with that in the control group (P＜0.05).Clinical curative effect in the observation group (average rank=18.022) was better than that in the control group (26.166) with significant differences (P＜0.05); the total effective rate in the observation group was 77.3％ and that in the control group was 52.4％ with significant differences (P＜0.05).ADL scale indicated that the ability of the observation group (average rank=18.363) were better than that in the control group (25.809) with significant differences (P＜0.05).The postoperative complication rate in the observation group (22.7％) was lower than that in the control group (42.8％) with significant differences (P＜0.05). Conclusion Stereotactic combined with microsurgical treatment in patients with hypertensive intracerebral hemorrhage in the thalamus is safe and effective; this treatment can improve the postoperative living quality and enjoy few complications,which is worth in the clinical application.

OBJECTIVETo study the pattern of blood-brain barrier (BBB) permeability changes during whole brain radiotherapy (WBRT) for metastatic brain tumor.

METHODSTwenty patients with metastatic brain tumors receiving WBRT by 6 MV X-ray underwent (99)mTc-DTPA brain SPECT before and during WBRT (20, 40 Gy) and at 2 weeks after the end of irradiation. A frame of transverse (99)mTc-DTPA brain SPECT image that best displayed the brain metastasis was chosen, and the regions of interest (ROI) were defined in the tumor foci (T), the contralateral normal brain tissue (N) and the background outside the soft tissues around the cranium (B). The radioactive counts of every ROI were measured and the ratios of the total counts (T/B and N/B) before and during WBRT (20 Gy, 40 Gy) and at 2 weeks after the irradiation were calculated.

RESULTSThe average T/B and N/B in the 20 patients with 30 brain metastases was 142.2-/+51.1 and 82.6-/+42.3 before WBRT, 260.3-/+121.5 and 150.7-/+72.5 during 20 Gy WBRT, 251.6-/+118.3 and 161.8-/+68.4 during 40 Gy WBRT, and 250.3-/+117.2 and 158.6-/+73.5 at 2 weeks after the irradiation, respectively. The measurements during WBRT (20 and 40 Gy) and at 2 weeks after the irradiation group underwent no significant variations (P>0.05), but showed significant differences from those before WBRT (P<0.05).

CONCLUSIONSIrradiation causes direct damage of the BBB function, and the permeability of the BBB increases significantly during and within 2 weeks following 20 and 40 Gy WBRT, which provides the optimal time window for interventions with chemotherapy.

Adult ; Aged ; Blood-Brain Barrier ; diagnostic imaging ; physiopathology ; Brain Neoplasms ; diagnostic imaging ; radiotherapy ; secondary ; Capillary Permeability ; physiology ; Cranial Irradiation ; Female ; Humans ; Male ; Middle Aged ; Sodium Pertechnetate Tc 99m ; Tomography, Emission-Computed, Single-Photon

BACKGROUNDComputed tomography (CT)-guided transthoracic lung biopsy is a well-established technique for the diagnosis of pulmonary lesions. The objective of this study was to evaluate the diagnostic efficiency and complication rate of CT-guided lung biopsy in a Chinese population.

METHODSCT-guided cutting needle lung biopsies were performed in our institution on 1014 patients between January 2000 and October 2010. A chest radiograph was taken after the biopsy. Data about basic patient information, final diagnosis, and complications secondary to biopsy procedure (pneumothorax and bleeding) were extracted.

RESULTSThe diagnostic efficiency of CT-guided lung biopsy was 94.8%; only 53 patients did not get a final diagnosis from lung biopsy. Final diagnoses found 639 malignant lesions (63.0%) and 322 benign lesions (31.8%). Pneumothorax occurred in 131 patients and 15 required insertion of an intercostal drain. Small hemoptysis occurred in 41 patients and mild parenchymal hemorrhage occurred in 16 patients. The overall complication rate was 18.5%.

CONCLUSIONSCT-guided cutting needle biopsy of pulmonary lesions is a relatively safe technique with a high diagnostic accuracy. It can be safely performed in clinical trials.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; methods ; Female ; Humans ; Lung ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Tomography, X-Ray Computed ; methods ; Young Adult

OBJECTIVETo observe the exercise single photon emission computed tomography (SPECT) myocardial perfusion imaging of patients with myocardial bridge and assess the association between myocardial ischemia and extent of myocardial systolic compression.

METHODSSeventeen patients with myocardial bridge diagnosed by coronary angiogram were included and underwent exercise SPECT myocardial perfusion imaging.

RESULTSAbnormal SPECT perfusion imaging was evidenced in 12 out of 17 patients with myocardial bridge (2 out of 6 patients with systolic compression induced stenosis < 50%, 3 out of 4 patients with systolic compression induced stenosis between 50% - 75% and 7 out of 7 patients with the systolic compression induced stenosis between 75% - 100%).

CONCLUSIONExercise stress SPECT myocardial perfusion imaging could detect myocardial ischemia in patients with myocardial bridge and abnormal perfusion is positively related to the extent of systolic compression induced stenosis.

Adult ; Aged ; Coronary Angiography ; Exercise Test ; Female ; Heart ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Myocardial Bridging ; diagnostic imaging ; Myocardium ; Technetium Tc 99m Sestamibi ; Tomography, Emission-Computed, Single-Photon ; methods

Embolization therapy has been used as the initial treatment for spinal dural arteriovenous fistula (SDAVF) only for certain patients or in certain medical institutions due to its minimal invasiveness, but the recurrence of embolization remains a clinical challenge. The recurrent patient usually exhibits a gradual onset of symptoms and progressive deterioration of neurological function. Developing paraplegia several hours after embolization is commonly seen in patients with venous thrombosis-related complications, for which anticoagulation therapy is often administered. This article reports on a SDAVF patient who had weakness of both lower extremities before embolization and developed complete paraplegia several hours after embolization therapy, later confirmed by angiography as fistula recurrence. The symptoms were relieved gradually after second embolization. The pathophysiology of this patient is also discussed.
Aged ; Central Nervous System Vascular Malformations ; physiopathology ; therapy ; Embolization, Therapeutic ; methods ; Humans ; Paraplegia ; diagnosis