OBJECTIVE: To study the pharmacokinetics of cefotetan disodium for injection in Chinese healthy volunteers. METHODS: Thirty healthy volunteers were randomly divided into 3 groups with 5 males and 5 females in each group. The volunteers in each group were administered a single dose of cefotetan disodium of 0.5, 1.0, or 2.0 g, respectively. Those who got dose of 1.0 g were administered twice daily for 7 d. The concentrations of cefotetan disodium in plasma were determined by HPLC while the pharmacokinetic parameters were calculated by DAS software. RESULTS: The main pharmacokinetic parameters of cefotetan disodium after single-dose intravenous administration were as follows: ρmax(68.03 ± 15.95), (110.77 ± 17.67), (225.34 ± 19.63) mg · L-1; AUC0-15(242.88 ± 56.60), (415.22 ± 54.24), (856.18 ± 82.72) mg · h · L-1; t1/2(3.67 ± 0.48), (3.69 ± 0.40), (3.53 ± 0.26) h, respectively. The main pharmacokinetic parameters of cefotetan disodium after multiple-dose administration were as follows: ρmax(123.60 ± 15.74) mg · L-1; AUC0-15 (444.38 ± 62.78) mg · h · L-1; AUCSS(426.87 ± 59.36) mg · h · L-1; t1/2(3.29 ± 0.36) h; ρav(35.57 ± 4.95) mg · L-1, respectively. CONCLUSION: Cefotetan disodium for injection displays linear pharmacokinetics in the dose range of 0.5 to 2.0 g after single intravenous dosing. There is no significant accumulation after repeated dosing. There is no significant difference in the pharmacokinetic parameters between female and male subjects. Copyright 2012 by the Chinese Pharmaceutical Association.

The aim of the study was to observe osseointegration of dental implants in osteoporotic rats. Rats were randomly divided into groups A(SHAM) and B(OVX), and pure titanium screws were implanted in the distal half of the right femurs. 1 5 and 3 months after implantation, half of the rats in each group were sacrificed and right femurs were observed by X ray photography, scan electron microscopy as well as light microscopy. The results showed that 1.5 and 3 months after implantation, the osseointegration index (OI) of group A was higher than that of group B. But the OI of each group was almost the same at different intervals. 1 5 months after implantation, the amount of new bone formation in group A was more abundant than that in group B, and it increased in group A but decreased in group B 3 months after implantation.The results confirmed that with higher BMD osseointegration was better. Osteoporotic changes could decrease OI and the amount of new bone formation at implant bone interface in rats. Osseointegration would not improve without outside factors.

· AIM: To summarize the clinical features of Chinese primary congenital glaucoma and to investigate the discrepancies of the clinical features between the Chinese and Indian patients.congenital glaucoma patients were reviewed. The clinical features were summarized as several quantifiable clinical parameters and the severity of the disease was evaluated. Both the quantified clinical features and severity were statistically compared with those of the Indian patients, which were cited from the previous published articles.included in the study. In Chinese patients, sex ratio (male to female )was about 2:1, family history was presented in 3 patients (7.5%) and consanguinity was found in one patient (2.5%). The main symptoms and signs observed in Chinese patients spanned a wide spectrum of manifestations. The most frequent signs noted on the initial examination were enlarged eyeball (42.5%) and decreased visual acuity (35.0%). Compared with Indian patients, Chinese patients had a later onset, a delayed diagnosis, more severe corneal changes and more severe optic nerve damages (P＜0.01). The combined tabeculectomy and trabeculotomy operation was preferred by both Chinese and Indian doctors whereas a higher proportion of Indian patients received the combined operation (P＜0.01). The proportions of the severity grade were different between Chinese and Indian patients. Most Chinese patients were in the severe grade while most Indian patients were in the very severe grade (P＜0.01).patients were sporadic and non-consanguineous.Compared with Indian patients, Chinese patients had a relative later onset, a delayed diagnosis and treatment.More attempts are needed in Chinese PCG prevention and treatment.

OBJECTIVETo explore effective pretreated methods for hydrosalpinx before frozen embryo transfer (FET).

METHODSA randomized controlled study was performed on 229 FET cycles of hydrosalpinx patients. They were assigned to two groups by random digit table, Group A (94 cases), Group B (89 cases), and Group C (46 cases). Patients in Group A received transvaginal aspiration of hydrosalpinx combined with auricular point sticking. Those in Group B received transvaginal aspiration of hydrosalpinx group. Those in Group C received no transvaginal aspiration of hydrosalpinx. Pregnancy outcomes of FET, endometrial and subendometrial blood flow distribution on the embryo transfer day were compared among the three groups.

RESULTSThere was no statistical difference in the endometrial thickness on FET day, the number of transfer embryos, the number of transferred good quality embryos among the three groups (P > 0.05). The clinical pregnancy rate and the embryo implantation rate were significantly higher in Group A than in Group C (P < 0.05), and the clinical pregnancy rate was significantly higher in Group A than in Group B (P < 0.05). The early abortion rate and the transfer cycle cancel rate were significantly lower in Group A than in Group C (P < 0.05). Type A endometrial and subendometrial blood flow distribution was dominant in Group A, which was significantly higher in Group A than the rest two groups (P < 0.05). Type A distribution rate was also significantly higher in Group B than in Group C (P < 0.05).

CONCLUSIONTransvaginal aspiration of hydrosalpinx combined with auricular point sticking before FET could improve the endometrial receptivity and improve outcomes of IVF.

Embryo Implantation ; Embryo Transfer ; methods ; Female ; Fertilization in Vitro ; methods ; Humans ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate

Objective:The recombinant human retinal pigment epithelium-derived factor(PEDF)protein to be obtained and the angiogenesis of the rPEDF to be identified.Methods: PEDF gene gene was amplified by PCR and cloned into pET32a,rPEDF protein was expressed in E.coli BL21 and confirmed by SDS-PAGE and Western blot.The rPEDF was purified by Ni-NTA on denature condition.The concentration of the rPEDF was determined by Bradford method.The angiogenesis of the rPEDF was determined by chick chorioallantoic membrane(CAM) method.Results: The expression plasmid pET32a-PEDF was constructed successfully.The rPEDF was expressed with stable efficiency in E.coli BL21.The results of the CAM experiment showed that the rPEDF had notable angiogenesis effect in the concentration 0.4、0.04 ng/ml,but had no effect in 4 ng/ml.Conclusion:The PEDF gene was cloned and expressed efficiently,the angiogenesis of the rPEDF to be identified and the activity was worked in certain range.The results can facilitate studying its function and spreading its application.

Objective To evaluate the relationship between carotid plaque neovascularization and coronary heart disease using contrast-enhanced ultrasound. Methods We studied carotid plaques in 312 patients with coronary artery disease by contrast-enhanced ultrasound [51 patients with acute coronary syndrome (ACS) and 261 patients with stable coronary artery disease (sCAD) ]. We analyzed sonographic features of each plaque, including the enhancement intensity of plaque (A value), the ratio of plaque to carotid artery lumen in enhancement intensity (Ratio), plaque thickness and plaque echo (soft plaque, hard plaque, mixed plaque, calcified plaque). Results The average thickness of plaque in patients with ACS and in patients with sCAD had no significant difference in statistics [(2.6±0.4) mm vs (2.9±0.8) mm, t=-1.903, P=0.058) ]. The group with ACS:soft plaque 43 (84.3%, 43/51), mixed plaque 8 (15.7%,8/51), no hard plaque and calcified plaque. And the group with sCAD:soft plaque 174 (66.7%,174/261), hard plaque 19 (7.3%,19/261), mixed plaques 16 (6.1%,16/261), calcified plaque 52 (19.9%,52/261). The percentage of soft plaque in the acute coronary syndrome group was significantly higher than that in stable coronary artery disease group (χ2=6.274,P=0.012). The A value and Ratio in patients with ACS were prominently larger than those in patients with sCAD [ (11.3±3.2) vs (8.9±3.3) dB, t=7.150,P<0.01;0.6±0.2 vs 0.4±0.2, t=7.419,P<0.01].Conclusion Carotid artery plaque neovascularization density was significantly higher in patients with ACS than that in patients with sCAD by using contrast-enhanced ultrasound, revealing that the neovascularization density is closely related to clinical symptoms of patients with coronary heart disease.

Background Retinitis pigmentosa (RP)is a common hereditary blinding eye disease in ophthalmology.Current researches documented that RP may have the common pathophysiologic basis to Alzheimer disease and chronic neurodegenerative disease.Understanding this mechanism will offer a new therapeutic target for RP.Objective The purpose of the present study was to investigate the roles of cyclin-dependent kinase 5 (Cdk5)/P25 activation in the apoptosis of retinal neural cells of RCS rats.Methods Eighteen SPF RCS rats and 18 RCS-rdy+ rats were randomized into 17-,25-and 35-day groups respectively and 6 rats for each.The rats were sacrificed at corresponding time points and retinal hemogenete was prepared.Expressions of CdkS,P35,P25 and tau phosphorylation in the retinas were detected by Western blot,and the kinase activity of Cdk5/P25 was analyzed by quantitative colorimetric assay.Results The expressing level of P35 protein(A340) in the retinas of 17-day-old RCS rats was near that of 17-day-old RCS-rdy+ rats(t =0.52,P＞0.05).In 25-and 35-day-old RCS rats,the expressing levels of P35 protein were 2.20±0.48 and 1.23±0.14,which were higher than those of RCS-rdy+ rats(1.43±0.13 and 0.93±0.10),showing significant differences between them(t =3.78,4.28,P＜0.05).The expression of P25 was undetectable at postnatal 17 days in RCS rats and RCS-rdy+ rats,but it showed significantly higher in RCS rats(0.300±0.003 and 0.230±0.004) than that in RCS-rdy+ rats(0.040±0.004 and 0.070±0.004) at postnatal 25 days and 35 days(t=121.81,77.51,P＜0.01).No significant difference was found in the expression of Cdk5 in RCS rats and RCS-rdy+ rats at different ages (t =-0.60,0.19,1.62,P＞ 0.05).The kinase activity of Cdk5/P25 did not show significantly different between RCS and RCS-rdy+ rats at postnatal 17 days(t =0.19,P＞0.05),but significantly higher kinase activity of Cdk5/P25 was seen in RCS rats (0.0058 ±0.0005 and 0.0056±0.0004) than that in RCS-rdy+ rats(0.0038±0.0003 and 0.0032 ±0.0007) at postnatal 25 days and 35 days (t =8.07,5.97,P＜ 0.01).No expression of tau phosphorylation was detected in RCS rats at postnatal 17 days,but significantly higher tau phosphorylation level was seen in RCS rats at postnatal 25 days and 35 days(1.80±0.22 and 1.23±0.17),which were significant different in comparison with RCS-rdy+ rats at postnatal 25 days and 35 days(1.60 ±0.20 and 1.04 ±0.12)(t=4.71,3.17,P＜0.05).Conclusions The Cdk5/P25 kinase activity shows a consistent trend with theexpressions of P25 and tau phosphorylation in the RCS rats,indicating that the upregulation of P25 induces the enhance of enzyme activity of Cdk5,which phosphorylate its substrates to result in more apoptosis of retinal neural cells.

OBJECTIVE Glioblastoma multiforme (GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis. No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de-veloping new agents to treat GBM is important. This study aimed to evaluate the anti-tumor effect of evodiamine (Evo) on GBM cells, and to determine the underlying mechanisms involved. METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and 48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo-diamine(0-10 μmol·L-1)for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species(ROS)production was detected using dichlorofluorescein diacetate (DCFH-DA) staining. The changes in mitochondrial mem-brane potential (MMP) were assessed by JC-1 after cells were treated with evodiamine. The expres-sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c, Caspase-3, cleaved Caspase-3, PRAP, and cleaved PARP were measured by Western blot analy-ses. RESULTS According to MTT assay results, Evo significantly inhibited the cell proliferation in a time- and dose-dependent manner. Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disruption. Finally, Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos-phorylation(p38 and JNK,but not ERK)to regulate apoptotic proteins(Bax,Bcl-2,Cytochrome c,Cas-pase-3, and PARP). CONCLUSION In summary, Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.

OBJECTIVETo observe the therapeutic effects of beta-elemene combined DC/Dribble vaccine in treating mice with hepatic cancer, thus exploring their anti-tumor mechanisms.

METHODSDentritic cells were derived from Balb/c mice's spleen and their phenotypes were identified. Using hepatic cancer cell line BNL1MEA.7R.1 (abbreviated as BNL) originated from Balb/c mice as target cell, DC/Dribble vaccine was prepared via raising the antigen representing carrier autophagosomes (DRips in Blebs, DRibbles), which were rich in tumor antigen information. The mice previously immunized were divided into 4 groups, i.e., the control group, the beta-elemene group, the vaccine group, and the combined group. The PBS was subcutaneously and intraperitoneally injected to mice in the control group. The beta-elemene was intraperitoneally injected at the daily dose of 50 mg/kg to mice in the beta-elemene group and the combined group for 7 successive days. DC/Dribble vaccine was injected into the lymph node of mice in the vaccine group and the combined group on the 1st day, and DC/Dribble vaccine was subcutaneously injected on the 3rd day and the 5th day. All the mice were sacrificed on the 10th day. Their spleens were obtained sterilely, and the suspension was incubated with or without Dribble. The cells were inoculated for 72 h. The contents of IFN-gamma in the supernatant were measured by ELISA. In addition, the spleen cells obtained from the combined group were incubated with different stimulations for 72 h, which were then divided into the control group, the DRibble group, the DC group, and the DC/Dribble vaccine group. The supernatant of cultured cells were collected and the contents of IFN-gamma were measured by ELISA. The liver tumor-bearing mouse model was established, and then the BNL bearing mice were randomly divided into 4 groups, i.e., the control group, the beta-elemene group, the vaccine group, and the combined group. The treatment ways were the same as the immune ways. The tumor size and the survival period were observed in each group. On the 23rd day the mice were sacrificed. The tumor tissue was stripped and stained by HE staining. The pathomorphological manifestations of the tumor tissue were observed by light microscope.

RESULTSIn vitro detection of mice immunized previously by different ways showed that the secretion of IFN-gamma was significantly higher in the combined group than in the rest groups (P < 0.01). The secretion of IFN-gamma was significantly higher in the beta-elemene group and the vaccine group than in the control group (P < 0.01). The spleen cells could be stimulated to secrete a large amount of IFN-gamma in the vaccine group and the Dribble group (P < 0.01). When the beta-elemene was 10 microg/mL as the stimulating dose, the secretion of IFN-gamma obviously increased (P < 0.01). In vivo observation showed that the growth velocity of tumors in mice of the combined group was slowed down. There was statistical difference in the tumor area or the survival period of mice in the combined group, when compared with the other groups (P < 0.01). In HE staining, the surrounding connective tissues of the tumor were wrapped tightly and compactedly, with infiltration of a large amount of inflammatory cells.

CONCLUSIONSbeta-elemene combined DC/Dribble vaccine could induce specific immune cells to secrete secretory cells, thus exerting its anti-tumor effect. Its immunological effects might be associated with enhancing the DC antigen presenting function.

Animals ; Cancer Vaccines ; immunology ; Cell Line, Tumor ; Dendritic Cells ; drug effects ; immunology ; Female ; Liver Neoplasms ; drug therapy ; immunology ; Mice ; Mice, Inbred BALB C ; Sesquiterpenes ; pharmacology

OBJECTIVEUsing olfactory event related potentials (OERP) and magnetic resonance to evaluate olfactory function in patients with posttraumatic anosmia.

METHODSTwenty four patients with posttraumatic anosmia were reviewed retrospectively. A thorough medical history, physical examination, nasal endoscopy, T&T olfactory testing, olfactory event-related potentials, brain computed tomography scan and magnetic resonance image of olfactory pathway were performed in all patients.

RESULTSSubjective olfactory testing indicated 20 of 24 patients were birhinal anosmia, 2 with right nostril anosmia and left impairment, 2 with left anosmia and right normal. No OERP were obtained in 24 (20 were birhinal, 4 was monorhinal), except 4 cases with single nostril. Magnetic resonance imaging revealed the injures to the olfactory bulbs (100%), rectus gyrus (91.7%), orbital gyrus (67%), olfactory tracts (8%) and temporal lobes (8%).

CONCLUSIONSOERP can objectively evaluate posttraumatic olfactory function, and magnetic resonance of olfactory pathway can precisely identify the location and extent of injures.

Adult ; Craniocerebral Trauma ; complications ; Evoked Potentials ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Olfaction Disorders ; etiology ; pathology ; physiopathology ; Retrospective Studies