Animals ; Bone Marrow ; metabolism ; Cell Division ; physiology ; Hematologic Diseases ; therapy ; Hematopoiesis ; physiology ; Hematopoietic Stem Cells ; cytology ; Humans ; Renin-Angiotensin System ; physiology

Objective To investigate celecoxib self-microemulsifying drug delivery system (CXB-SMEDDS) that was developed to increase the dissolution rate and oral bioavailability of celecoxib.Methods The formulation of CXB-SMEDDS was optimized by pseudo-ternary phase diagrams analysis.The appearance, morphology, particle size distribution and in vitro drug release behavior of CXB-SMEDDS were investigated after diluted by water.The bioavailability of CXB-SMEDDS was determined by oral administration to rats compared with CXB suspension.Results An optimized formulation was selected: Medium chain triglycerides as oil phase, Tween 20 as surfactant, Transcutol HP as cosurfactant.The ratio of oil phase, surfactant and cosurfactant was 2∶9∶9.Upon mixing with water, CXB-SMEDDS formed a clear and transparent microemulsion solution with homogeneous small spherical under transmission electron microscopy.For particle size of CXB-SMEDDS was found to be (57.6±14.2) nm.The in vitro dissolution test indicated a significant improvement in release characteristics of CXB.The AUC of CXB-SMEDDS and CXB suspension were (5.54±0.94) and (3.32±0.59) mg·L-1·h, respectively.The relative bioavailability was 166.9%.Conclusion The SMEDDS can significantly increase celecoxib dissolution in vitro and bioavailability in vivo.

Objective:To prepare celecoxib nanostructured lipid carriers and investigate the characteristics of tissue distribution in rats. Methods:Celecoxib nanostructured lipid carriers were prepared by a melt-emulsion ultrasonication and low temperature-solidifi-cation method. The physicochemical properties of nanostructured lipid carriers were studied, such as particle size distribution, zeta po-tential and morphology. The concentration of celecoxib in different tissues was determined after tail vein injection of celecoxib nano-structured lipid carriers in rats. Results:The obtained celecoxib nanostructured lipid carriers were spherical with the average particle size of (103. 5 ± 32. 6) nm and zeta potential of ( -37. 3 ± 5. 1) mV. The re of celecoxib nanostructured lipid carriers in liver, spleen, brain and muscle respectively was 3. 43, 2. 99, 2. 38 and 2. 93 times higher than that of celecoxib injection. Conclusion:The biodistribution of celecoxib is changed by the nanostructured lipid carriers. Celecoxib nanostructured lipid carriers have the characteris-tics of liver, spleen and muscle targeting, which is benefit to improving the efficacy.

Objective:To prepare celecoxib nanosuspension ( CXB-NSs) and study the pharmacokinetics of CXB-NSs in rats. Methods:CXB-NSs were prepared by an anti-solvent precipitation and high pressure homogenization method. The particle size, polydispersion index ( PdI) and zeta potential of the nanosuspension were studied. Totally 12 Wistar rats were randomly divided into CXB-NSs group and CXB suspension group, and gastric drug dose was 100 mg·kg-1 . CXB concentration in plasma was determined by HPLC and the pharmacokinetic parameters were calculated by 3P97 software. Results: The particle size, polydispersion index, zeta potential of CXB-NSs was (442. 5 ± 61. 9) nm, 0. 312 ± 0. 057 and ( -31. 6 ± 3. 9) mV, respectively. AUC (0-t) of CXB suspension and CXB-NSs was (5.13 ±0.77) and (13.51 ±3.18) mg·L-1·h, half time (t1/2) was (12.31 ±1.91) and (12.73 ±1.83) h, Tmax was (2. 48 ± 0. 37) and (1. 41 ± 0. 27) h and Cmax was (0. 94 ± 0. 31) and (2. 38 ± 0. 25) mg·L-1 , respectively. Conclusion:CXB-NSs can remarkably increase bioavailability in rats.

OBJECTIVE:To prepare and characterize celecoxib-loaded PLGA nanoparticles. METHODS:Emulsification-solvent evaporation method was adopted to prepare celecoxib-loaded PLGA nanoparticles. With encapsulation efficiency and particle size as the indexes,Plackett-Burman design was preferred to screen the formulation and variables which had a significant effect on the property of nanoparticles. And then Box-Behnken response surface method was used to further optimize selected variables including mass concentration of PLGA,ultrasonic power and ultrasonic time,followed by verification. Malvern particle size analyzer was used to determine the particle size distribution of nanoparticles and Zeta potential of nanoparticle by the optimal formulation technol-ogy,and transmission electron microscope was used to observe the morphology of the nanoparticles,and their drug release in vitro behavior and stability(25,5 ℃)were also observed. RESULTS:The optimal formulation and technology was as follows as PLGA mass concentration of 30.0%,ultrasonic power of 180 W and ultrasonic time of 8 min. For the prepared nanoparticles,encapsula-tion efficiency and particle size were (85.7 ± 4.1)% and (226.1 ± 36.1) nm (n=3) respectively;particle size distribution was (176.2±41.2)nm,polydispersity index was 0.211±0.021,and Zeta potential was(-37.3±1.6)mV. Under the electron micro-scope,the nanoparticles were homogeneous in particle size and distributed spheroidally,with 24 h accumulative release of 52.4%. They were stable within 3 months at 5℃. CONCLUSIONS:Celecoxib-loaded PLGA nanoparticles have been prepared successfully.

Foreign Bodies ; Humans ; Male ; Maxillary Sinus ; Middle Aged

Although previous reports showed drug-eluting stent (DES) could effectively inhibit neointima formation, in-stent restenosis (ISR) remains an important obstacle. The purpose of this study was to investigate different effects of paclitaxel on proliferation and cell cycle regulators between vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) of rats in vitro. The cultured VSMCs and VECs of rats from the same tissues were examined by using immunohistochemistry, flow cytometry and Western blotting in control and paclitaxel-treated groups. The results showed paclitaxel could effectively inhibit proliferation of VSMCs and VECs. However, as compared with VECs, proliferation of VSMCs in paclitaxel-treated group decreased less rapidly. The percentage of cells in G0-G1 and G2-M phases was reduced, and that in S phase increased after treatment for 72 h. The expression of cyclin D1 and B1, p27 and PCNA in VSMCs of paclitaxel-treated group was up-regulated, but that of p21 down-regulated as compared with VECs. It is concluded that there are significant differences in the expression of cell cycle regulators and proliferation rate between paclitaxel-treated VSMCs and paclitaxel-treated VECs, suggesting that the G1-S checkpoint regulated by paclitaxel may play a critical role in the development of complications of DES, which provides new strategies for treatments of ISR.

OBJECTIVETo compare the effect,safety,and advantage of flexible fixation with paperboard and pad versus short leg plaster in treating the fifth metatarsal base fracture,and establish the standard of diagnosis and treatment of the fifth metatarsal base fractures in flexible fixation with paperboard and pad.

METHODSFrom June 2010 to March 2013,59 patients with the fifth metatarsal base fracture were treated with paperboard and pad fixation or short leg plaster. Patients were enrolled and divided into paperboard and pad treatment group (paperboard group) and short leg plaster treatment group (plaster group) randomly according to the random number table. In paperboard group,there were 29 cases including 9 males and 20 females with an average age of (51.79±11.40) years old; the average course of injury was (11.59±6.58) hours. In plaster group, there were 30 cases including 9 males and 21 females with an average age of (52.13+17.34) years old ;the average course of injury was (11.03±7.06) hours. According to whether the fracture line across the articular surface, in paperboard group there were 14 cases of type A,15 of type B; in plaster group,16 of type A, 14 of type B. According to the degree of dislocation,in paperboard group there were 16 cases of degree I ,13 of degree II ; in plaster group,20 were degree I ,10 were degree II. Fracture was restored according to the type in manual. Patients in paperboard group were treated with paperboard and pad, and patients in plaster group were treated with short leg plaster. Fracture was fixed for 4 to 6 weeks according to fracture healing. On the 2nd, 4th,6th, 8th week and 3rd, 6th month after fixation, patients were followed up, and the foot function score was used to evaluate the function of injured foot. X-ray of injured foot was taken on the 2nd, 4th, 6th and 8th week were used to assess fracture healing.

RESULTSAll patients got complete follow-up. The X-ray result showed that all fracture reached at clinical healing on the 8th week after fixation without skin ulcer,nonunion and displacement of fracture. From the 4th to 8th week after fixation, paperboard group had a higher X-ray score than plaster group, but the difference between two groups had no statistically significance. Repeated analysis result showed that there was interact at different time point and between groups,the difference had statistically significance (P<0.01). The foot function score showed that at all time point, paperboard group had a higher score than plaster group, and on the 2nd, 4th, and 6th week, it had statistically significant difference(P<0.01) between two groups. On the 6th months after fixation,the excellent and good rate of paperboard group was 93.10%, higher than that of plaster group, which was 86.67%. But it had no statistically difference(P=0.483) between two groups.

CONCLUSIONUsing paperboard and pad fixation to treat the fifth metatarsal base fracture has the advantage of simplicity operating,reliable fixation, satisfactory effects, easily obtainable material.

Adult ; Aged ; Casts, Surgical ; Female ; Foot Injuries ; physiopathology ; surgery ; Fracture Fixation ; instrumentation ; methods ; Fracture Healing ; Fractures, Bone ; physiopathology ; surgery ; Humans ; Male ; Metatarsal Bones ; injuries ; physiopathology ; surgery ; Middle Aged

Objective To explore the safety and effectiveness of percutaneous vertebrophasty(PVP)in the treatment of the metastatic tumor involved axis.Methods Ten patients(8 male,2 female)with osteolytic metastases involved axis were treated with PVPs.The anterolateral approach with fluoroscopy guidance was selected in 9 cases,while the posterolateral approach with CT guidance was selected in 1 case.Results Successful unilateral-paracentesis for PVP were achieved in all patients without intervention related complications such as bleeding and symptomatic polymethylmethacrylate(PMMA)leakage.CT scan taken following PVP showed that over 70% of the osteolytic metastatic area was well filled with PMMA in all cases.Varying degrees of pain relief were observed(CR in 7 cases,PR in 3 cases)within 7 days.All patients could support their heads without brackets.During a 3 to 24 months follow up after the procedures,No aggravated pain was found in the group.Two patients died in 4 months,3 Patients died in 8 to 11 months 4 patients died in 13 to 15 months,and 1 patient still was alive after 24 months.Conclusion Anterolateral or posterolateral approach to Aixs in PVP is safe and effective in treating osteolytic metastatic tumors.

Objective To investigate the features of intravertebral vacuum phenomenon (IVP)in vertebral compression fractures (VCFs). Methods Two hundred and nine patients with VCFs underwent percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP). The biopsies and the images of X-ray, CT, MRI of VCFs were obtained. The consistency between IVP and osteonecrosis on histology and the positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity and Youden index of IVP for diagnosing local osteonecrosis in VCFs were analyzed. Fisher exact probability test was used to analyze the coherence between IVP and osteonecrosis. Results Histological examination revealed 146(69.9%) osteoporoses, 10 (4.8%) osteonecroses with osteoporoses, 53 (25.4%) neoplasms. Prior to surgery,10 cases of IVP were found. Plain radiograph showed horizontally oriented lucent cleft in the vertebral body;CT further confirmed the location of gas;T_1-weighted MR image appeared hypointensity,while the signal intensity of T_2-weighted MR image differed, depending on the duration of recumbency. Nine of 10 patients with IVP showed osteonecrosis on histology, while 9 of 10 patients with osteonecrosis contained IVP. The association of osteonecrosis on histology and the IVP was statistically significant(P <0.01). The PPV, NPV, sensitivity, specificity, and Youden index for diagnosing local osteonecrosis was 90% (9/10), 99.5% (198/199), 90.0% (9/10), 99.5% (198/199), and 0.9, respectively. Conclusion The IVP is stongly suggestive of local osteonecrosis in vertebral compression fracture.