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.

Chondroma ; surgery ; Cricoid Cartilage ; Humans ; Male ; Middle Aged

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.

Objective To assess the application of Xpert MTB/RIF assay in rapid diagnosis of tuberculous lymphadenitis.Methods Lymph node samples were collected from 1 02 clinically diagnosed patients with lymph node tuberculosis and 65 patients with other lymph node diseases from Zhejiang Provincial Hospital of Traditional Chinese and Western Medicine during January 201 4 and February 201 5. Xpert MTB/RIF,pathological examination and mycobacterium tuberculosis culture were conducted in all specimens of two groups.Taking clinical comprehensive diagnosis as the gold standard,the diagnostic sensitivity,specificity,positive predictive value,negative predictive value and diagnosis efficacy of three detection methods were assessed.The sensitivity of Xpert MTB/RIF in determining rifampicin resistance was analyzed using drug susceptibility testing as gold standard.Results The mean detection time of Xpert MTB/RIF was (2.2 ±0.2)h.Among 1 02 patients,Xpert MTB/RIF achieved higher sensitivity (96.1 %, 98 /1 02 ) than pathological examination (76.5%,78 /1 02 ) and mycobacterium tuberculosis culture (33.3%,34 /1 02)(χ2 =1 6.558 and 87.91 9,both P <0.01 ).Among 65 patients with other lymph node diseases,the specificity of all three detection methods was 1 00%.The receiver-operating-characteristic curve analysis demonstrated that diagnostic performance of Xpert MTB/RIF was better than that of other two methods.In 8 patients resistant to rifampicin confirmed by drug susceptibility testing,Xpert MTB/RIF detected 6 resistant-resistant patients.Conclusion Xpert MTB/RIF shows higher sensitivity and specificity in diagnosis of lymph node tuberculosis with the advantages of easy and rapid performance.

Objective To investigate the relationship between impaired fasting glucose(IFG) and the distribution of body fat in adolescents.Methods Stratified cluster sampling was used to select 3874 adolescents aged 13-18 years for this cress-sectional study.Measurements included height,weight,waist circumference,hip circumference and fasting plasma glucose (FPG).Family history of diabetes was determined by using a serf-administered questionnaire.Participants were divided into normal fasting glucose group(FPG＜5.6 mmol/L,n=3738) and impaired fasting glucose group (5.6 mmol/L≤FPG ＜ 7.0 mmoL/L,n=136) according to their FPG levels. Results (1) After adjusting for age and sex using covariance analysis,the impaired fasting glucose group showed increased levels of body mass index,weight circumference,waist/hip ratio,waist/height ratio,as compared to the normal fasting glucose group (P＜ 0.05).(2) After the age and gender were adjusted,body mass index,weight circumference,waist/hip ratio and waist/height ratio were positively correlated with FPG level (P＜0.05).Among the partial relation coefficients, that between waist/height ratio and FPG(r'=0.0925) was the highest (3) In multiple regression analyses,age (β=-0.102,P＜0.05),family history of diabetes (β=0.186,P＜0.05) and waist/height ratio (β=0.842,P＜0.05) were consistently associated with FPG.Conclusion Central obesity was an important predictor of IFG in adolescents.Waist/height ratio may be an useful index of central obesity and an important predictor of IFG in adolescents.

Objective To investigate the intranasal anatomic abnormalities and clinical features of mucosal contact point headache, as well as the outcomes of endoscopic surgery. Methods The clinical data of 29 patients with mucosal contact point headache, received treatment in our hospital from October 2008 and May 2010, were reviewed retrospectively. All cases received CT scans, endoscope examinations and local anesthesia tests. Endoscopic surgery was performed to correct the contact points for these cases. They were followed-up for at least 1 year; and the changes of intensity, duration and frequency of headache of these patients were observed. Results Most common anatomic abnormalities included septal spurs in contact with the turbinates, uncinate process hypertrophy,pneumatized middle turbinates, abnormal curve of middle turbinate and large ethmoid bulla. The intensity, duration and frequency of headache after surgery decreased significantly as compared with those before the surgery (P<0.05). Nineteen of the 29 patients (65.52%) got benefits from surgical intervention, and 8 patients (27.59%) had complete relief of headache. Pain was the same as before the surgery in 10 cases (34.48%) in the follow-up period. Conclusion Intranasal contact points must be considered in patients who have no other obvious cause of headache. Significant relief of headache can be obtained by endoscopic surgery in selected cases.

AIMTo investigate the effect of inhalation of cyclosporin (CsA) on antigen-induced airway inflammation in Sprague-Dawley rats.

METHODSRats were sensitized with antigen (ovalbumin, OA). After two weeks, the sensitized rats were pretreated with aerosol CsA (5, 10, 20 g x L(-1)), once per day for 7 days. Then, the sensitized rats were challenged with OA (10 g x L(-1), once per day) for 2 days at day 20 after sensitization. The number of eosinophils in bronchoalveolar lavage fluid (BALF) and peripheral blood, histological changes of lung tissue, and TNF-alpha content in BALF were investigated.

RESULTSInhalation of CsA significantly reduced the number of eosinophils in BALF and peripheral blood, inflammatory infiltration and tissue edema of lung tissue, decreased the content of TNF-alpha in BALF.

CONCLUSIONInhalation of CsA inhibited airway inflammation in rats, and the mechanism is related to inhibition of TNF-alpha release.

Administration, Inhalation ; Animals ; Asthma ; chemically induced ; metabolism ; pathology ; Bronchoalveolar Lavage Fluid ; chemistry ; Cyclosporine ; administration & dosage ; pharmacology ; Eosinophils ; pathology ; Female ; Immunosuppressive Agents ; pharmacology ; Leukocyte Count ; Lung ; pathology ; Male ; Ovalbumin ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

AIMTo establish an antigen-specific asthmatic model of guinea pig induced by protein antigen extracted from Dermatophagoides farinae (Der f), and study the desensitization of dust mite drops (DMD, extracted from Der f) in a dose progressive manner and long-term sublingual administration.

METHODSTo sensitize the guinea pigs, the protein antigen emulsified in aluminium hydroxide gel was subcutaneously and intraperitoneally injected. To observe early-phase reaction of asthma, lung resistance (R(L)) and lung dynamic compliance (Cdyn) in the sensitized guinea pigs were determined by intravenously injecting antigen. To observe late-phase reaction of asthma, the sensitized guinea pigs were challenged with aerosolized antigen for 7 days. Subsequently, methacholine (Mch) in a cumulative dose-manner induced-airway hyperreactivity (AHR), inflammatory cells numbers in bronchoalveolar lavage fluid (BALF) and pathological changes of lung tissue were measured in the model. From the first day of sensitization, the guinea pigs in treatment group sublingually received DMD in a dose progressive manner. The model group sublingually received equivalent saline. The normal control group did not receive any treatment.

RESULTSThe guinea pigs in model group showed a significant increase in R(L) and decrease in Cdyn, and developed a marked AHR to Mch. The number of total leukocytes and eosinophils increased significantly in BALF. Serious infiltration of eosinophils was observed in pathological section of lung tissue. Compared with model group, DMD treatment group exhibited a significant amelioration for early-phase and late-phase reaction of asthma.

CONCLUSIONDMD in a dose progressive manner and long-term sublingual administration displays a significant desensitization on Der f antigen-specific asthmatic reaction. The results provided experimental evidence for clinical therapy.

Administration, Sublingual ; Airway Resistance ; drug effects ; Allergens ; immunology ; Animals ; Antigens, Dermatophagoides ; administration & dosage ; isolation & purification ; therapeutic use ; Asthma ; immunology ; physiopathology ; therapy ; Bronchoalveolar Lavage Fluid ; cytology ; Dermatophagoides farinae ; immunology ; Desensitization, Immunologic ; methods ; Eosinophils ; drug effects ; pathology ; Female ; Guinea Pigs ; Leukocyte Count ; Lung Compliance ; drug effects ; Male

OBJECTIVETo compare the bronchofilating and antiallergic effects with piclamilast with ciclamilast, the second-generation phosphodiesterase 4 (PDE4) selective inhibitors.

METHODSEffects of piclamilast and ciclamilast on airway smooth muscle (ASM) at resting tension, carbachol-induced contraction and the synergistic effect of two agents on isoproterenol-induced bronchorelaxation were evaluated in the isolated tracheal strips of guinea pig in a cumulative manner in vitro. Slow reaction substance of anaphylaxis (SRS-A) release from lung tissues of the sensitized guinea pigs after antigen challenge was examined by bioassay. Antiallergic effect of piclamilast, ciclamilast and rolipram on the isolated ASM of sensitized guinea pigs were evaluated with Schultz-Dale reaction.

RESULTSPiclamilast and ciclamilast showed bronchorelaxant effect in ASM at resting tension. EC50 values of piclamilast and ciclamilast were 1.00 x 10(-5) mol/L and 0.84 x 10(-5) mol/L. Piclamilast and ciclamilast could both enhance the bronchodilating effect of isoproterenol in the isolated ASM of guinea pig, reduce the amount of SRS-A released from lung tissues of the sensitized guinea pigs and also inhibit ovalbumin (OA)-induced bronchoconstruction (Schultz-Dale reaction).

CONCLUSIONThe results indicate the bronchodilating effect of ciclamilast is as potent as piclamilast, but the antiallergic effect of ciclamilast is significantly more potent than that of piclamilast.

Animals ; Anti-Allergic Agents ; pharmacology ; Benzamides ; pharmacology ; Bronchodilator Agents ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Guinea Pigs ; In Vitro Techniques ; Isoproterenol ; pharmacology ; Male ; Phosphodiesterase Inhibitors ; pharmacology ; Pyridines ; pharmacology

OBJECTIVETo study inhibitory the effects of Cryptoporus volvatus ferment substance(CVFS) on leukotriene production in vitro from neutrophils in rats.

METHODSNeutrophil aggregation was induced by intraperitoneal injection of glycogen in rats. After 16 h, intraperitoneal lavage fluid(PLF) was collected and neutrophils were removed. Neutrophils were stimulated by calcium ionophore A23187 in vitro to produce leukotriene B(4), C(4), D(4). The concentrations of leukotriene B(4), C(4) and D(4) were measured by reversed-phase high-performance liquid chromatography(HPLC).

RESULTCVFS at 0.25, 1, 4 mg x L(-1)decreased leukotriene B(4), C(4), D(4) release from neutrophils in a concentration-dependent manner. Inhibitory rate of CVFS 0.25, 1, 4 mg x L(-1 )on A23187-induced leukotriene B(4) production was 27.4%, 54.2% and 78.8%(P<0.05), respectively. Inhibitory rate of leukotriene C(4) production was 65.1%, 74.3 and 79.0%(P<0.05), respectively. Inhibitory rate of leukotriene D(4) production was 55.6%, 60.9% and 72.8%(P<0.05), respectively.

CONCLUSIONThe results suggest that suppression of leukotriene release may be a mechanism of the anti-inflammation and anti-asthma effects of CVFS.

Animals ; Anti-Asthmatic Agents ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Fermentation ; Leukotriene B4 ; secretion ; Leukotriene C4 ; secretion ; Leukotriene D4 ; secretion ; Male ; Neutrophils ; drug effects ; physiology ; Polyporaceae ; metabolism ; Rats ; Rats, Sprague-Dawley