1. Bioavailability study of self-microemulsifying drug delivery system of a novel anti-stroke compound TID-101 in rats
Journal of International Pharmaceutical Research 2016;43(4):731-735
Objective: To establish and validate a LC-MS/MS method for quantitative analysis of a new anti-stroke compound TID-101 in rat plasma and to study the pharmacokinetics and bioavailability of TID-101 self-(micro)emulsified drug delivery system(SMEDDS). Methods: The plasma samples were treated with methanol for precipitating protein. The chromatographic separation was achieved with a acetonitrile-water mobile phase. Detection of TID-101 and the internal standard (IS) dexamethasone acetate was achieved by electrospray ionization (ESI) source in the negative ion mode at m/z 353.4→323.2 and m/z 433.4→353.4. The method was applied for pharmacokinetics study of TID-101 between SMEDDS in rats. Results: The method was linear over TID-101 concentration range from 10-95 000 ng/ml with the correlation coefficients (r) of 0.9998. The intra-run and inter-run relative standard deviations(RSD) were less than 15% and the average absolute recovery values were 83.4-87.0%. The validated method was applied to a pharmacokinetic study in rats after intravenous administration of TID-101 fat emulsion injection and oral administration of TID-101 suspension and SMEDDS. The bioavailability of TID-101 API and SMEDDS was 2.8% and 14.9%, respectively. Conclusion: The analysis method is simple, accurate, and sensitive for assaying the in vivo pharmacokinetic study of TID-101 in rats. SMEDDS could effectively enhance the oral bioavailability of TID-101.
2.Influencing factors for health-related quality of life in patients with chronic liver disease
Feng GAO ; Ru GAO ; Guang LI ; Yu WANG ; Jianyu HAO ; Jidong JIA
Chinese Journal of General Practitioners 2013;(6):438-442
Objective To investigate the factors affecting health-related quality of life (HRQOL) in patients with chronic liver disease (CLD).Methods HRQOL was measured with SF-36v2 Chinese version.All patients with CLD diagnosed between December 2009 and May 2011 in Liver Research Center,Beijing Friendship Hospital and Digestive Department,Beijing Chaoyang Hospital were enrolled in this study.Patients with CLD were divided into 4 groups according to their Child-Turcotte-Pugh scores:no cirrhosis,Child's classes A,B,and C.Demographic and clinical data were collected in each group.Results A total of 392 patients with CLD and 91 healthy controls were included.HRQOL in patients with CLD was lower than that in healthy controls.Physical component score (PCS) in healthy controls was 54.6 ± 5.5,and in CLD was 47.8 ± 8.8 (t =9.343,P < 0.01).Mental component score (MCS) in healthy controls was 56.4 ± 8.1,and in CLD was 51.7 ± 7.4 (t =5.302,P < 0.01).Increasing severity of CLD from no cirrhosis to advanced cirrhosis was associated with a decrease on HRQOL,PCS scores were 53.1 ± 5.9,48.7 ± 6.6,42.4 ± 7.1 and 37.2 ± 8.9 (F =93.353,P < 0.01) ; MCS scores were 53.2 ± 4.8,52.7 ±6.5,51.8 ±7.5,and 46.8 ± 7.5 (F =11.325,P <0.01),for no patients with cirrhosis,Child's classes A,B and C respectively.Stepwise linear regression analysis showed that severity of disease,age,present ascites,present varices,and prothrombin time had significant effects on physical health area (F =100.893,P < 0.010).Severity of disease,female gender,present varices,total bilirubin,prothrombin time and hemoglobin had significant effects on mental health area (F =19.237,P < 0.010).Conclusions Patients with CLD have reduced HRQOL.Increasing severity of CLD is associated with a decreasing HRQOL.Old age,female gender,advanced stage of CLD,present ascites,hyperbilirubinemia and prolonging prothrombin time are risk factors for reducing HRQOL.
4.Expression, purification and antibody preparation of beta-hemolysin from Staphylo-coccus aureus
Chenghua LIU ; Di LI ; Yaping GAO ; Peng JIN ; Yu LIU ; Guang YANG
Military Medical Sciences 2016;40(2):127-132
Objective To express the beta hemolysin ( Hlb), an important toxin secreted by Staphylococcus aureus ( S.aureus) and the mutant protein Hlb H-149-N , to detect the hemolytic activity of Hlb and Hlb H-149-N on sheep erythrocytes , and to prepare the specific antibodies against Hlb which can inhibit the hemolytic activity of Hlb .Methods Hlb gene was amplified by PCR using S.aureus NCTC-8325 genome DNA as template.The expression vector pET-28a-hlb was constructed and transformed into E.coli BL21(DE3).The expression vector pET28a-hlbH-149-Nwas constructed through point mutation.The recombinant Hlb and Hlb H-149-N protein were expressed and purified by Ni 2+affinity chromatography .The hemolytic activity of Hlb and Hlb H-149-N was measured by sheep erythrocyte lysis assay .Results Recombinant Hlb protein and the mutant were obtained .Further investigations showed that Hlb could significantly induce the lysis of SRBC while HlbH-149-N could not.The specific polyclonal antibodies against Hlb (anti-Hlb) were prepared.It was found that anti-Hlb recognized Hlb and Hlb H-149-N .Moreover , it was found that anti-Hlb blocked the hemolytic activity of Hlb .Conclusion The recombinant Hlb protein with high hemolytic activity and Hlb H-149-N without hemolytic activity are obtained while its neutralized antibody is pepared .Hlb from S.aureus has different hemolytic effects on erythrocytes from various species .Our findings will facilitate the investigation on the role of Hlb in the pathogenesis of S.aureus.
5.Re: Nerve sparing laparoscopic radical prostatectomy.
Xin GAO ; Jiang-Guang QIU ; Bing ZHANG ; Yu-Bing CAI ; Liang-Qin HONG
Asian Journal of Andrology 2003;5(4):338-338
Aged
;
Humans
;
Male
;
Middle Aged
;
Penis
;
innervation
;
Prostatectomy
;
methods
;
Prostatic Neoplasms
;
surgery
6.Airway management and anesthesia for tracheal masses in 15 patients.
Hui GAO ; Jie YI ; Yu-guang HUANG
Acta Academiae Medicinae Sinicae 2013;35(3):322-326
OBJECTIVETo summarize our experiences in anesthetic management for the resection of tracheal masses.
METHODSThe clinical data of 15 patients with tracheal masses in Peking Union Medical College Hospital from 2002 to 2012 were analyzed retrospectively. Remarkable dyspnea and tracheal stenosis were observed in 12 patients. Standard orotracheal intubation was carried out in patients with less than 50% of tracheal lumen obstructed. The location of masses was critical for those with severe tracheal stenosis. Local anesthetics were applied and tracheostomy were performed in patients with masses located at the upper part of the trachea. Intubation above the masses was established in patients with masses located at the lower part of the trachea. Percutaneous cardiopulmonary support was introduced before anesthetic induction in a patient with severe respiratory distress and hypercapnea,then an endotracheal tube successfully passed the stenosis guided by a fiberoptic bronchoscope. General anesthesia was induced intravenously and muscle relaxants were applied in all patients. Succinylcholine was administrated in 5 of 6 difficult patients.
RESULTSAirway management and anesthesia were performed successfully in all the 15 patients. After the operations,patients were extubated and discharged from the hospital without difficulty in respiration.
CONCLUSIONSThe successful airway management of tracheal masses depends on the degree and location of stenosis and the severity of dyspnea. Extracorporeal circulation is an optimal choice for those with critical airway occlusion and adequate oxygenation can not be accomplished with conventional anesthesia.
Adolescent ; Adult ; Aged ; Airway Management ; methods ; Anesthesia ; Extracorporeal Circulation ; Female ; Humans ; Intubation, Intratracheal ; Male ; Middle Aged ; Retrospective Studies ; Tracheal Stenosis ; surgery ; Tracheostomy ; Young Adult
8.The analgesic action of oxysophoridine and its effect on the expression of PKC? in central nervous system of mice
Jinxian GAO ; Lijun TAO ; Jianqiang YU ; Shaoju JIN ; Guang YANG ; Yonghui XU ; Yuanxu JIANG
Chinese Pharmacological Bulletin 2003;0(11):-
Aim To study the analgesic action of oxysophoridine and its effect on the expression of protein kinase C?(PKC?) in dorsal horn of spinal cord(it should be expressed as in dorsal horn of the spinal),cerebral cortex and thalamus of the mice.Methods Hot plate test was used to observe and analyze the analgesic strength and action position of OSR through iv and icv approaches,immunohistochemistry(SABC) was taken to inspect the expression of PKC? in dorsal horn of spinal cord(it should be expressed as in dorsal horn of the spinal),cerebral cortex and thalamus of the mice after administrating OSR.Results The foot-licking latencies of mice were prolonged both iv OSR(500、250、125 mg?kg-1)and icv OSR(100,50,25 mg?kg-1)in the hot plate test(P
9.The analysis of clinical correlated factors of renal damage in henoch-schonlein purpura
yu-qing, JIAO ; si-guang, LU ; li-li, GAO ; chen, DONG
Journal of Applied Clinical Pediatrics 1986;0(01):-
Objective To study the clinical correlated factors of renal damage in henoch-schonlein purpura (HSP).Methods One hundred cases with HSP were retrospectively studied. Accoding to the urinary route examination, the patients were devided into 2 groups, HSP with (49 cases) and without renal damaged (51 cases). In addition, the group of HSP with renal damaged was further diveded into 2 groups, HSP with urinary abnormality passingly (27 cases) and persistently (22 cases). Clinical indicators were statistical analysed.Results To be compared with HSP without renal damaged, age,apread of the purpura, abdominal pain,hemorrhage of digestive tract were higher in HSP with renal damaged (P
10.Effects of fluorosis on osteoclasts's quantity and bone resorption function in vitro
Guang, DU ; Mao-juan, YU ; Xiao-ya, XU ; Wei-fang, JIN ; Jian-jun, GAO
Chinese Journal of Endemiology 2011;30(3):266-269
Objective To determine the effects of fluoride on osteoclasts's quantity and bone resorption function in vitro and its mechanisms. Methods The osteoclasts and bone marrow stromal cells(BMSCs) isolated from long bone of new born rats were cultured respectively in TC199 medium (containing 10% fetal bovine serum) with fluoride. The osteoclasts were inoculated in 96-well culture plate and ivory slice, BMSCs were inoculated in 6- well culture plate, respectively, medium were changed after 2 hours incubation. They were divided into control group, low-dose fluoride, medium-dose fluoride and high-dose fluoride groups, the doses of sodium fluoride were 0,2.5 × 10-5,5.0 × 10-5,10.0 × 10-5 mol/L, respectively. Tartrate-resistant acid phosphatase(TRAP) staining positive cells were counted under light microscope after TRAP staining on the 2nd and the 5th day and the pit formed in ivory slices were measured by histomorphometry after staining with toludine blue. The expression of receptor activator of NK-κβ ligand(RANKL) and osteoprotegerin(OPC) was detected by real-time fluorescence quantitative (337.5 ± 70.5), (447.5 ± 43.4), (472.9 ± 34.8), (475.3 ± 24.3)/well in the control group, the low-dose, mediumdose and high-dose fluoride groups, respectively. The differences were statistically significant between these groups and the control group (all P < 0.05). After in vitro culture for 5 days, the numbers of osteoclasts were (92.5 ± 22.1), (123.0 ± 26.4), (135.5 ± 22.2), (136.9 ± 23.0) per well in the control group, the low-dose, medium-dose and high-dose fluoride groups, respectively. The differences were statistically significant between these groups and the (0.088 ± 0.030), (0.100 ± 0.018), (0.152 ± 0.015), (0.242 ± 0.031 )mm2 per piece in the control group, the lowdose, medium-dose and high-dose fluoride groups, respectively. The values of medium-dose and high-dose fluoride BMSCs in the control group, the low-dose, medium-dose and high-dose fluoride groups were 100.00 ± 56.02, 144.95 ± 97.21,223.25 ± 184.48,193.98 ± 137.93, respectively. The values of medium-dose and high-dose fluoride groups were significantly higher than that of control group (all P < 0.05). Conclusions Fluoride can cause increase in the number of osteoclasts in vitro and promote their cell differentiation and bone resorption activity, which may be related to increased expression ratio of RANKL/OPG mRNA in BMSCs.