The expression of brain aquaporin 4 (AQP4) is different at the different stages of cellular differentiation, and distribution of brain AQP4 is affected by the existence of endothelial cells. Other factors including osmolality, ammonia, hypoxia, temperature, hormone, C-type natriuretic peptide, lead, complement inhibitor, lipopolysaccharide can also influence AQP4 expression in astrocytes. However, the regulating mechanisms for brain AQP4 expression are not clear. Protein interaction, protein kinase C (PKC) through protein phosphorylation, mitogen-activated protein kinase signal pathway, Ca2+ signaling cascade signal pathway and transcription factor pathway have been proposed, among which phosphorylation of PKC for the inhibition of AQP4 is frequently studied.

Objective To investigate the value of hysteroscopy combined with B-ultrasonography in the diagnosis and treatmeant of early cornual pregnancy (within 7 weeks of pregnancy). Methods A total of 28 cases of early cornual pregnancy diagnosed and treated by hysteroscopy combined with B-ultrasonography from January 1999 to December 2004 were analyzed retrospectively. Results The operation were carried out successfully on one session in 27 cases, while placental remnants were found after the second curettage in 1 case, in which after an injection of methotrexate was given under hysteroscope, the serum ?-HCG decreased to a normal level 2 week later. No intra- or post-operative complications were recorded. Follow-up observations for 4~36 months (mean, 20 months) in the 28 cases found 6 cases of pregnancy out of 11 patients with childbearing demand. Conclusions Hysteroscopy combined with B-ultrasonography in the diagnosis and treatment of early cornual pregnancy is a preferable method with advantages of highly efficacy, safety and mini-invasion.

OBJECTIVE: To establish a RP-HPLC method for the determination of 5-fluorouracil(5-Fu)in magnetic micropheres (MMS), and to evaluate the target ability of 5-Fu magnetic microspheres in mice. METHODS: 5-Fu-MMS was digested with 0.5% pepsin, and then free 5-Fu was extracted from tissue with ethyl acetate, and detected by a validated RP-HPLC method. RESULTS: The calibration curve was linear over the range of 0.1～25mg?L-1 and the limit of quantization was 0.1mg?L-1. The tissue distribution of 5-Fu-MMS in the liver was significantly increased as compared to control(P

To determine the pharmacokinetics and bioequivalence of epinastine (EPN) hydrochloride, a promising histamine H1 receptor antagonist, in healthy Chinese volunteers under fasting conditions. METHODS: EPN hydrochloride test and reference tablets were administered as a single dose on two treatment days separated by a 1-week washout period. After dosing, serial blood samples were collected for a period of 36 h, and plasma EPN hydrochloride concentrations were determined by a validated reversed-phase HPLC method and pharmacokinetic parameters were calculated with DAS software. RESULTS: Plasma concentration-time profiles were adequately described by a two-compartment open model. The compound was rapidly absorbed and cleared slowly from plasma with a half-life of approximately 10 h. The main pharmacokinetic parameters of EPN hydrochloride test and reference tablets were as follow: tmax were (2.2±0.5) and (2.0±0.4)h, Cmax were (66±16)and (68±13)μg/L, t1/2 were(10.1±1.3) and (10.4±2.4)h, AUC0-36 were (592±88) and (601±94)μg·h·L-1, respectively. The relative bioavailability of test tablets was (99±13)%. CONCLUSION: The results indicate that the two formulations of EPN hydrochloride tablets are bioequivalent in the rate and extent of absorption.

AIM: To compare the bioavailability of the test and reference formulation of secnidazole (2 g) tablets under fasting conditions. METHODS: This bioequivalence study was carried out in 20 healthy male Chinese volunteers according to a single dose, two-sequence, crossover randomized design. Fifteen blood samples per period were collected over 96 h, and plasma secnidazole concentrations were determined by locally validated high performance liquid chromatography (HPLC) assay and pharmacokinetic parameters were analyzed by the non-compartmental and compartmental methods. RESULTS: Plasma concentration-time profiles were adequately described by a one-compartment open model with first-order absorption. The main pharmacokinetic parameters of secnidazole test and reference tablets were as follows: tmax were (2.30±1.06) and (2.28±1.10) h, Cmax were (49.63±6.35) and (46.17±4.24) mg/L, t1/2 were (28.84±3.41) and (29.05±4.01) h, AUC0-96 were (1832.06±180.15) and (1847.14±204.14) mg·h-1·L-1, respectively. The relative bioavailability of test tablets was (99.99±11.92)%. CONCLUSION: The results indicate that the two formulations of secnidazole tablets are bioequivalent in the rate and extent of absorption.

AIM: To study pharmacokinetics and relative bioavailability of pantoprazole sodium enteric-coated test and reference tablets in healthy volunteers. METHODS: A single oral dose of 40 mg pantoprazole sodium enteric-coated test and reference tablets were given to 20 male healthy volunteers in a randomized two-way crossover design. Plasma concentrations of pantoprazole were determined by HPLC method. Pharmacokinetic parameters and relative bioavailability were calculated with DAS program to evaluate the bioequivalence of the two preparations. RESULTS: Plasma concentration-time profiles were adequately described by a two-compartment open model. The main pharmacokinetic parameters of pantoprazole sodium test and reference tablets were as follow: The values of Tmax were (3.18±0.54) and (3.30±0.47) h, Cmax were (2.98±0.83) and (2.91±0.87) mg·L-1, T1/2β were (1.86±0.41) and (1.72±0.48) h, AUC0-t were (9.51±3.71) and (9.77±4.55) mg·h·L-1, respectively. The relative bioavailability of test tablets was (102.3±19.6)%. CONCLUSION: The two preparations of pantoprazole sodium are bioequivalent.

OBJECTIVE:To establish a HPLC method for the determination of mycophenolic acid (MPA) in human plasma and to study its pharmacokinetics in human body.METHODS:After sedimentation by methanol,plasma sample of MPA was determined directly on Symmetry Shield C18 column with column temperature at 30℃,detective wavelength at 218mn and sample size at 20?L.The mobile phase consisted of acetonitrile-water-triethylamine(40∶60∶0.3) with a flow rate of 1.0mL?min-1.RESULTS:The calibration curve was linear over the range of 0.2～50mg?L-1(r=0.999 6)and the limit of quantitation was 0.2mg?L-1.The mean methodological recovery was 101.94% and the mean extraction recovery was 87.06%.The RSD of both the intra-day and the inter-day were less than 6%.The pharmacokinetic study showed that MPA had enterohepatic circulation in human body,which resulted in the occurrence of double peaks,and the concentration-time curves of MPA were fitted to one-compartment open model.CONCLUSION:This method is sensitive,rapid,specific,accurate and precise,and can be used for the study of pharmacokinetics of MPA.

ObjectiveTo determine whether glutamate induces the alteration of aquaporin 4 (AQP4) expression in cultured rat astrocytes. MethodsThe secondary cultured astrocytes were treated with 1 mmol/L L-glutamate for 1 h, 3 h, 6 h, 12 h, 24 h and 48 h. The morphologic changes of astrocytes were observed through microscope after GFAP immunostaining and AQP4 mRNA expression were detected with real-time PCR. ResultsThe astrocytes swelled when exposed to glutamate for 1 h and remained with prolonged treatment. Meanwhile, the AQP4 mRNA expression were early down-regulated and subsequently up-regulated, featured with the lowest AQP4 mRNA level at 12 h after treatment (P<0.01) and higher at 48 h (P<0.05). ConclusionAquaporin 4 may be involved in the occurrence and development of astrocyte swelling induced by glutamate.

Objective To reproduce a scratch-wound model in cultured rat astrocytes (AST).Methods The secondary cultured AST prepared from newborn Wistar rat cerebral cortex were scratched with plastic pipette tips. The morphologic change of AST was observed through microscope at 10 min before and 1, 3, 6, 12, and 24 h after injury, meanwhile the lactate dehydrogenase (LDH) leakages in the cultured medium were determined.Results Immediately after injury the edge of the scratch was lined with irregularly shaped cell. 6 h after injury the AST processes began extending to cell-free area, and elongated further at 12 and 24 h after injury, with presented of new generated cells in the denuded area. At different times after injury, the LDH leakages of the experiment group were higher than that before injury ( P<0.05), and were higher than that of the control group ( P<0.05).Conclusion According to observed AST morphologic changes and determined LDH leakages in culture medium, the scratch-wound model in cultured rat AST is successfully reproduced.

Objective To investigate the protective effect of methylene blue (MB) on blood-brain barrier (BBB) injury after focal cere-bral ischemia-reperfusion in rats. Methods 18 male Sprague-Dawley rats were randomly divided into sham-operated group (n=6), model group (n=6) and MB treatment group (n=6). The left middle cerebral arteries were occluded for 1 hour and reperfused. MB was infused intra-venously immediately after reperfusion (3 mg/kg) and again 2 hours post-reperfusion (1.5 mg/kg), while normal saline was administered in the model group. The sham-operated group was treated as same as the model group without occlusion and infusion. HE staining was used to observe the histological injury in the cortex around the infarcted region 47 hours after reperfusion, while albumin immunohistochemistry was used to evaluate the permeability of the BBB, and immunohistochemistry and double immunofluorescence staining were used to exam-ine the expressions of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP-4). Results HE staining showed that cells and blood ves-sels were not intact in the cortex around the infarcted region in the model group and they were better in the MB treatment group. The expres-sions of the albumin, GFAP and AQP-4 were higher in the model group than in the sham-operated group (P<0.01), and were lower in MB treatment group than in the model group (P<0.05). The double immunofluorescence staining showed the colocalization of GFAP and AQP-4 in the astrocytes. Conclusion MB may ameliorate the BBB disruption induced by focal cerebral ischemia-reperfusion through reducing glio-cyte proliferation and down-regulation of AQP-4 expression in rats.