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.

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.

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

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.

To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, β-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, β-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues.
Amides ; chemical synthesis ; pharmacology ; Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Fluoroquinolones ; chemical synthesis ; pharmacology ; HL-60 Cells ; Humans ; Ketones ; chemical synthesis ; pharmacology ; Rhodanine ; chemical synthesis ; pharmacology

To discover novel antitumor fluoroquinolone lead compounds from a rational modification for antibacterial fluoroquinolones, a fused heterocyclic ketone corresponding to thiazolo[2,3- b][1,2,4]triazolone used as a bioisosteric replacement of the C-3 carboxylic acid group of ciprofloxacin 1, and further modification by a Claisen condensation reaction with substituted benzaldehydes formed novel fluoroquinolone C-3 fuse heterocyclic α, β-unsaturated ketones as the title compounds (6a-6r), separately. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS, and the in vitro anti-proliferative activity against human hepatoma Hep-3B cells, pancreatic Capan-1 cells and leukemia HL60 cells was evaluated by a MTT assay. The preliminary results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. In particular, compounds carrying an electron-withdrawing carboxyl (6k, 6m) or sulfonamide substituent (6q, 6r) attached to benzene ring were comparable to or better than constractive drug doxorubicin against Capan-1 cells. As such, it suggests that it is favorable for a fused heterocyclic α, β-unsaturated ketone scaffold instead of the C-3 carboxylic acid group to improve the antitumor activity of fluoroquinolones.
Anti-Bacterial Agents ; Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Ciprofloxacin ; analogs & derivatives ; Fluoroquinolones ; chemical synthesis ; pharmacology ; HL-60 Cells ; Humans ; Ketones ; pharmacology ; Structure-Activity Relationship

To discover an efficient strategy for the conversion of the antibacterial activity of fluoroquinolones into the antitumor activity, the three series of C-3 s-triazole-based derivatives including sulfide ketones (6a-6g), thiosemicarbazones (7a-7g) and fused heterocyclic thiazolotriazoles (8a-8g) were synthesized from ciprofloxacin (1), respectively. The structures were characterized by elemental analysis and spectral data. The antitumor activity was tested against three tumor cell lines (Hep-3B, Capan-1 and HL60) using the MTT assay. The three types of compounds all exhibited stronger anti-proliferative activities than ciprofloxacin in the test. The order of their activities was in compounds 7>8>6, and the order of selectivity against cancer cell lines was Capan-1, Hep-3B and HL60. Meanwhile, the SAR revealed that some compounds with electron-drawing group substituted such as fluoro- and nitro-phenyl compounds (6f, 7f, 8f) and (6g, 7g, 8g) displayed more significant activity than the control compounds, especially the IC50 values of thiosemicarbazone compounds 7f and 7g against Capan-1 was comparable to doxorubicin. Thus, a five-membered triazole as the C-3 bioisostere modified with the functionalized side-chain of sulfide-ketone thiosemicarbazone warrants special attention and further investigation.
Anti-Bacterial Agents ; chemistry ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Ciprofloxacin ; chemistry ; Doxorubicin ; pharmacology ; HL-60 Cells ; Humans ; Ketones ; pharmacology ; Sulfides ; pharmacology ; Triazoles ; pharmacology

OBJECTIVETo investigate the immunoregulatory effects of pertussis protein on airway inflammatory, IFN-gamma/IL-4 ratio in bronchoalveolar lavage fluids(BALF) and airway hyperresponsiveness (AHR) in the sensitized mice.

METHODSThe sensitized mice were reexposed to ovalbumin and the airway response to methacholine injection was monitored. Inflammatory cells and cytokines IFN-gamma/IL-4 ratio in BALF were measured. Lung tissue specimens were collected for histological examination.

RESULTIntramuscular injection or intranasal instillation of pertussis protein inhibited changes in lung resistance and lung dynamic compliance, upregulated IFN-gamma/IL-4 ratio and decreased eosinophil accumulation in a dose-dependent manner. Pathological examination showed that goblet cell hyperplasia and inflammatory cells infiltration in lung tissue were suppressed by pertussis protein.

CONCLUSIONPertussis protein inhibits the inflammation and regulates the function of lungs in asthma mice, suggesting its potential application in treatment of asthma.

Albumins ; Animals ; Asthma ; chemically induced ; immunology ; therapy ; Bacterial Proteins ; immunology ; pharmacology ; Bacterial Toxins ; immunology ; pharmacology ; Bronchoalveolar Lavage Fluid ; chemistry ; Interferon-gamma ; analysis ; Interleukin-4 ; analysis ; Male ; Methacholine Chloride ; Mice ; Mice, Inbred ICR