1.Effect of Food on the Pharmacokinetics of Pirfenidone Capsules in Healthy Volunteers
Zhongfang LI ; Jianhong WU ; Hui CHEN ; Ying LUO ; Fandian ZENG ; Shaojun SHI
China Pharmacist 2018;21(10):1731-1734
Objective: To compare the pharmacokinetics and bioavailability of pirfenidone in the fasted and fed states in healthy volunteers. Methods: An open-label, randomized crossover study was conducted in 12 healthy subjects. Food effects were examined by comparing pharmacokinetic data of pirfenidone after administration of a single oral 400 mg dose under fasted or fed conditions. Plas-ma pirfenidone concentration was determined by an HPLC method and its pharmacokinetic parameters were calculated with DAS v2. 0 software. Results: Under fasted and fed conditions, the concentration-time profiles of pirfenidone were fitted a one-compartment model and the pharmacokinetic parameters were as follows: t1/2were (2. 16 ± 0. 47) and (2. 05 ± 0. 42) h;tmaxwere(0. 69 ± 0. 16)and (1. 46 ± 0. 40)h;Cmaxwere (12. 95 ± 1. 79) and (9. 16 ± 2. 87) mg·L-1;AUC0-12were (44. 97 ± 15. 06) and (36. 19 ± 14. 44) mg·h·L-1;AUC0-∞were (46. 55 ± 16. 79) and (37. 41 ± 15. 43) mg·h·L-1, respectively. When compared with that of the fasted group, tmaxwas significantly increased (P<0. 001) while Cmaxand AUC were remarkedly decreased in the fed group (P<0. 001 and P<0. 01, respectively). Conclusion: Concomitant food intake significantly influences the pharmacokinetics and bioavail-ability of pirfenidone as indicated by reducing its extent and rate of absorption, which is associated with better tolerability.
2.Distribution of Astrocytic Syntrophin in Hippocampus from Human Mesial Temporal Lobe Epilepsy
Xiaoxuan WANG ; Zhenrong SUN ; Min WU ; Zhongfang SHI ; Xu YAN ; Lixin XU ; Liping DONG ; Shaohua YANG ; Fang YUAN
Chinese Journal of Rehabilitation Theory and Practice 2017;23(3):292-297
Objective To investigate the expression changes of astrocytic syntrophin in hippocampus from human mesial temporal lobe epilepsy (MTLE). Methods From April, 2015 to July, 2016, 17 cases of hippocampus, collected from temporal lobectomy, were divided into MTLE group (n=13) and non-MTLE group (n=4) according to hematoxylin and eosin staining, glial fibrillary acidic protein and neuronal nu-clei immunohistochemical staining. Immunofluorescence double labeling and immunofluorescence histochemistry were used to observe the expression of syntrophin. Results The proliferation of astrocytes increased and neurons reduced in the hippocampus of MTLE group. Syntro-phin was found in the membrane and foot processes of astrocyte, that was enriched along perivascular astrocyte end-feet domain in non-MTLE group, but lost in MTLE group. While the whole expression of syntrophin was more in MTLE group than in non-MTLE group (t=5.421, P<0.001). Conclusion The distribution of syntrophin in hippocampus astrocytes may be related to the development of MTLE.
3.Expression of Aquaporin 4 in Astrocytes of Rats in Vitro
Lixin XU ; Liping DONG ; Zhongfang SHI ; Xu YAN ; Shaohua YANG ; Fang YUAN
Chinese Journal of Rehabilitation Theory and Practice 2017;23(9):1051-1055
Objective To explore the expression of aquaporin 4 (AQP4) in primary and secondary cultured rat astrocytes. Methods Rat cortical astrocytes from a newborn (one day) Wistar rat were cultured. Astrocytes were identified with immunofluorescence staining of glial fibrilillary acidic protein (GFAP). The expression of AQP4 was determined with real-time quantitative polymerase chain reaction and immu-nofluorescence staining three, five, seven and nine days of primary culture, and nine days of secondary culture. Results The purity of GFAP-positive cells was more than 95%. The expression of AQP4 mRNA was found three days of primary culture, remained unchanged five days of primary culture (P>0.05), and increased seven and nine days of primary culture (P<0.05). The expression of AQP4 mRNA was not different between nine days of primary culture and nine days of secondary culture (P>0.05). AQP4 immunofluorescence staining showed the same trend of AQP4 mRNA. Conclusion AQP4 may express since three days of primary culture in rat astrocytes in vitro, and increase slowly until nine days of primary culture.
4.Comparison of the differences in glutamate-induced astrocyte swelling between Wistar and Sprague-Dawley rats
Zhongfang SHI ; Lixin XU ; Yi LU ; Liping DONG ; Xu YAN ; Shaohua YANG ; Fang YUAN
Acta Laboratorium Animalis Scientia Sinica 2016;24(5):454-459
Objective To compare the differences between the cell swelling of cultured astrocytes ( AST) from Wistar and Sprague-Dawley ( SD) rats after incubation with glutamate.Methods Primary cultured AST derived from the cerebral cortex of one-day-old Wistar or SD rats were prepared.The cultured AST received 1 or 10 mmol/L glutamate treat-ment for 48 h on the tenth day after subculture.The viability of AST was determined by lactate dehydrogenase ( LDH) kit to assess the cell injury, and the perimeter of AST was measured using Image Pro Plus software after glial fibrillary acidic protein immunofluorescence staining to evaluate the astrocyte swelling.Then, the expression of aquaporin 4 ( AQP4 ) in cultured AST was detected by quantitative reverse transcription polymerase chain reaction.Results No significant differ-ence was found in the LDH release after the glutamate treatment in cultured AST from these two strains (P>0.05).The perimeter of AST from normal Wistar rats was shorter than that from SD rats, but was longer after the treatment of glutamate (P<0.05).Meanwhile, AQP4 expression in the Wistar rats was significantly higher than that from SD rats after incuba-tion with 1 mmol/L glutamate ( P<0.05 ) .Conclusions These results suggeste that cultured AST from Wistar rats are more susceptible to glutamate-induced swelling than that from SD rats, and there are differences between the effects of glu-tamate on AQP4 expression in astrocytes of Wistar and SD rats.
5.Effect of Methylene Blue on Blood-brain Barrier after Focal Cerebral Ischemia-reperfusion in Rats
Min WU ; Qing FANG ; Zhongfang SHI ; Lixin XU ; Liping DONG ; Xu YAN ; Shaohua YANG ; Fang YUAN
Chinese Journal of Rehabilitation Theory and Practice 2016;22(2):125-131
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.
6.Exploration of capacity-building of scientific research of medical and nursing postgraduate
Fang YUAN ; Wei ZHANG ; Zhongfang SHI
Chinese Journal of Modern Nursing 2014;20(8):962-964
The capacity-building of scientific research is an important part as well as the main purpose of medical and nursing postgraduate training .However , there are still many gaps and deficiencies in the process of the capacity-building of scientific research .In this paper , the authors described the existed specific problems in the capacity-building of scientific research of medical and nursing postgraduate , and also deeply explored the approaches of capacity-building of scientific research of postgraduate including enhancing the awareness of research , cultivating scientific thinking , focusing on reading the literature , improving the ability of operation and writing of thesis and so on .
7.Effect of cell culture experiment teaching on scientific research ability of medical and nursing graduate students
Chinese Journal of Modern Nursing 2014;20(23):2964-2965
With the rapid development of medical and health service , the medical and educational managers payed more attention to the education of medical and nursing graduate students .The training of scientific research ability had an important place in the whole cultivation system of medical and nursing graduate students.The experimental teaching including biochemistry , molecular biology and cell culture played an important role in the training of scientific research ability of the medical and nursing graduate students .The cell culture experiment teaching not only made the students learn the relevant knowledge of cell culture ; also made them aware of the importance of sterile concepts , which was very important to the clinical and nursing work in the future; further, the scientific research ability including the innovation , thinking, observation, practice, planning and coordinate ability was trained in the teaching of cell culture experiment , which could improve the scientific research ability in the medical and nursing graduate students .
8.Sensitivity of Human Glioblastoma Multiforme Cell Line BT325 to Antineoplastic Drugs
Ming HAN ; Fang YUAN ; Liping DONG ; Zhongfang SHI ; Hui YUAN ; Shaohua YANG
Chinese Journal of Rehabilitation Theory and Practice 2011;17(9):840-843
Objective To examine the sensitivity of human glioblastoma multiforme cell line BT325 to 5 antineoplastic drugs, including cisplatin (DDP), teniposide (VM26), nimustine (ACNU), temozolomide (TMZ) and vincristine (VCR). Methods BT325 cells were incubated in DMEM with 10% or 20% fetal bovine serum (FBS) or without FBS respectively. The cell numbers were counted at 24 h, 48 h, 72 h,96 h, 120 h, and 144 h, then platting and growth curve were drafted. Cell counting kite-8 was used to detect the influence of 5 drugs with different concentrations on human glioma cell line BT325. Results DDP and VM26 significantly suppressed BT325 cells(>75%) viability in a dose-dependent manner, while VCR inhibited BT325 cells (50%) growth without dose-effect relationship. In contrast, ACNU and TMZwere not effective on the viability of BT325 cells. Conclusion BT325 cells were very sensitive to chemotherapeutic drugs DDP amd VM26.
9.Glutamate-induced Dynamic Expression of Aquaporin 4 in Cultured Rat Astrocytes
Yang LU ; Zhongfang SHI ; Fang YUAN ; Ming HAN
Chinese Journal of Rehabilitation Theory and Practice 2010;16(1):29-31
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.
10.Pharmacokinetics and bioequivalence of epinastine hydrochloride,a histamine H1 receptor antagonist, in healthy Chinese volunteers
Shaojun SHI ; Zhongfang LI ; Huating CHEN ; Fandian ZENG
Chinese Journal of Clinical Pharmacology and Therapeutics 2007;12(2):214-218
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.


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