A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76.4% ± 36.2%, respectively, after intravenous administration of racemic- and R-ibuprofen. This study provides a theoretical basis for the safety of ibuprofen formula of injection drug.

A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76.4% ± 36.2%, respectively, after intravenous administration of racemic- and R-ibuprofen. This study provides a theoretical basis for the safety of ibuprofen formula of injection drug.
Animals ; Chromatography, High Pressure Liquid ; Dogs ; Ibuprofen ; blood ; pharmacokinetics ; Stereoisomerism

OBJECTIVETo evaluate the efficacy of ultrasound-guided fine-needle aspiration (US-FNA) in the diagnosis of thyroid nodules.

METHODSUS-FNA was performed for 175 thyroid nodes in 168 patients aged 4 to 75 years in Peking Union Medical College Hospital from November 2004 to December 2008. The diagnostic data obtained from US-FNA were compared with those confirmed by surgical pathology and clinical follow-up. The US-FNA results were classified as benign, malignant, suspicious, or unsatisfactory.

RESULTSAmong these 175 thyroid nodules, surgical pathology and clinical follow-up confirmed that there were 39 malignant nodules and 136 benign nodules, while US-FNA showed that 124 aspirates (70.9%) were benign, 24 (13.7%) were malignant, 14 (8.0%) were suspicious, and 13 (7.4%) were unsatisfactory for interpretation. For US-FNA, the sensitivity was 81.1%, specificity was 93.6%, accuracy was 90.7%positive predictive value was 78.9%and negative predictive value was 94.4%. Post-puncture bleeding was observed in 3 nodules (1.7%).

CONCLUSIONUS-FNA is accurate and reliable in diagnosing thyroid nodules.

Adolescent ; Adult ; Aged ; Biopsy, Fine-Needle ; methods ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Sensitivity and Specificity ; Thyroid Nodule ; diagnostic imaging ; pathology ; Ultrasonography ; Young Adult

Objective To compare the efficacy of ultrasound-guided fine-needle aspiration(US-FNA)biopsy in diagnosing solid and complex thyroid nodules with different size. Methods One hundred and seventy-five thyroid FNA biopsies were prospectively performed on 168 patients ranging from 4 to 75 years of age. Sixty-three nodules were surgically excised and the others were clinically followed-up. The cytology diagnoses were categorized into four groups: benign, malignant, suspicious and unsatisfactory. Results There was no significant complication in the all 115 solid and 60 complex thyroid lesions and there were 36and 3 malignant nodules respectively in solid and complex thyroid nodules. The nondiagnostic rates of solid and complex nodules were 7％ and 8％. The accuracy of US-FNA in diagnosing complex thyroid nodules was comparatively equal to that of in solid thyroid nodules. In solid thyroid nodules, the sensitivity and accuracy in ≤1 cm group were similar to that of in ＞1 cm group. Conclusions US-FNA was an accurate and reliable method to diagnose thyroid solid and complex lesions.

OBJECTIVERecent studies showed that adenosine played important roles in vasodilation. This study aimed to investigate the effects of adenosine, its A1 and A2b receptor agonists on pulmonary artery hypertension (PAH) induced by chronic hypoxia in rats by continuously subcutaneous administration with an osmotic pump for 14 days, and to see if rennin angiotensin system and inducible nitric oxygen synthase (iNOS)/nitric oxide (NO) mediate the effects.

METHODFifty-six male SD rats were randomly assigned to seven groups. Each group included eight rats. They were normoxic group, hypoxic group, adenosine-treated group [adenosine was administered at a dose of 150 µg(kg·min) under the hypoxic condition], adenosine A1 receptor agonist CPA-treated group [CPA was administered at a dose of 20 µg/(kg·min) under the hypoxic condition], CPA plus selective adenosine A1 antagonist DPCPX-treated group [CPA and DPCPX were administered simultaneously under the hypoxic condition, the dose of CPA was the same as the above, and the dose of DPCPX was 25 µg/(kg·min)], adenosine A2b receptor agonist NECA-treated group [NECA was administered at a dose of 30 µg/(kg·min) under the hypoxic condition], NECA plus selective adenosine A2b receptor antagonist MRS-treated group[ NECA and MRS1754 were administered simultaneously under the hypoxic condition, the dose of NECA was the same as the above, and the dose of MRS1754 was 50 µg/(kg·min)]. Osmotic pumps containing adenosine or selective adenosine A1 receptor agonist (CPA), or nonselective but potent adenosine A2b receptor agonist (NECA) were placed subcutaneously 7 days after hypoxia and continuously administered the agents for 14 days.Mean pulmonary artery pressure (mPAP) was detected after administration of the agents. Then blood samples were taken from heart for measurement of renin activity, angiotensin II (AngII) and endothelin-1 (ET-1) concentration by radioimmunoassay, NO by measuring nitrate. Small pulmonary arteries were prepared for immunoreactivity staining of proliferating cell nuclear antigen (PCNA) and iNOS.

RESULT(1) Chronic hypoxia induced PAH [mPAP: (31.38 ± 3.42) mm Hg]. Adenosine or CPA or NECA administered for 14 days by subcutaneous route attenuated the mPAP [(21.17 ± 3.56) mm Hg, (22.88 ± 2.95) mm Hg, (19.81 ± 2.39) mm Hg, respectively], which showed significant difference when compared with hypoxia group (P < 0.05 respectively). (2) Plasma rennin activity and AngII level in hypoxia group [(2.51 ± 0.25) ng/(ml·h), (83.01 ± 9.38) pg/ml] were significantly higher than that in normoxic group (P < 0.05, respectively).(3) Adenosine treatment decreased the rennin activity and AngII level when compared with hypoxic group(P < 0.05, respectively);CPA and NECA attenuated respectively the rennin activity and AngII level of rats induced by chronic hypoxia (P < 0.05, respectively). (4) Adenosine administration for 14 days attenuated the wall thickness induced by chronic hypoxia (P < 0.05). CPA showed no effect on wall thickness, but NECA significantly attenuated the wall thickness (P < 0.05). (5) The number of iNOS staining positive cells in small pulmonary artery was higher in hypoxia group than in that in normoxic rats (23.75 ± 7.91 vs. 8.00 ± 2.20, P < 0.05). Adenosine or CPA, or NECA administration increased respectively the iNOS expression in rats treated with chronic hypoxia. Chronic hypoxia caused significant decrease of nitric oxide level. Adenosine treatment increased the nitric oxide level in rats treated with chronic hypoxia. CPA and NECA also increased respectively the nitric oxide level in rats treated with chronic hypoxia. Chronic hypoxia caused significant increase of ET-1 level. The ET-1 level in rats treated with adenosine, CPA or NCEA respectively were lower than that in chronic hypoxia rats (P < 0.05). (6) Adenosine treatment partially attenuated the number of PCNA-positively stained cells. NECA treatment also attenuated the PCNA expression, but CPA showed no effect.

CONCLUSIONAdenosine and its agonists CPA, NECA administered continually by subcutaneous route attenuate mPAP of rats induced by chronic hypoxia. CPA attenuates mPAP through reduction of RA/AngII activity and balance of NO/ET-1 level. NECA attenuates mPAP by inhibiting PCNA expression and proliferation of mooth muscle of pulmonary artery.

Adenosine ; administration & dosage ; pharmacology ; Angiotensin II ; blood ; Animals ; Disease Models, Animal ; Endothelin-1 ; metabolism ; Hypertension, Pulmonary ; drug therapy ; etiology ; metabolism ; Hypoxia ; complications ; Male ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type II ; metabolism ; Proliferating Cell Nuclear Antigen ; metabolism ; Pulmonary Artery ; drug effects ; physiopathology ; Purinergic P1 Receptor Agonists ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Renin ; blood

OBJECTIVETo investigate the vascular activity of extract from mulberry leaves (EML) on rat thoracic aorta and the underlying mechanism.

METHODSIsolated thoracic rings of Sprague-Dawley rats were mounted on the organ bath and the tension of the vessel was recorded.

RESULT(1) EML produced a concentration-dependent vasorelaxation of aorta preconstricted by high K(+) (60 mmol/L) or 10(-6) mol/L phenylephrine (PE) in endothelium-intact and endothelium-denuded arteries. (2) EML at EC(50) concentration reduced the calcium dose-response curve. (3) After incubation of aorta with verapamil, EML induced vasocontraction of aorta preconstricted by PE, which was abolished by ruthenium red.

CONCLUSIONThe vascular effect of EML is biphasic, the vasorelaxation is greater than the vasocontraction. The vasorelaxation induced by EML may be mediated by inhibition of voltage-and receptor-dependent calcium channels in vascular smooth muscle cells, while the vasocontraction is via activation of ryanodine receptor in endoplasmic reticulum.

Acetates ; isolation & purification ; pharmacology ; Animals ; Aorta, Thoracic ; drug effects ; physiology ; Dose-Response Relationship, Drug ; In Vitro Techniques ; Male ; Morus ; chemistry ; Plant Extracts ; isolation & purification ; pharmacology ; Plant Leaves ; chemistry ; Potassium ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Ryanodine Receptor Calcium Release Channel ; physiology ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects

OBJECTIVETo investigate the clinical feasibility and technical characteristics of immediate loading and to access the short-term clinical results of treatment.

METHODSThis study included 3 completely edentulous patients and 24 patients who were partially edentulous from March 1999 to December 2003. 21 implants were immediately loaded and provided support for mandibular overdenture for 3 fully edentulous patients. 30 implants were placed in 21 partially edentulous patients and implants were immediate loaded in edentulous mandibular providing support for fixed provisional prosthesis within 6 months. Then, metal-ceramic crowns were completed. All patients were followed up by 1, 3, 6, 12 months and the patients were checked every 12 months.

RESULTSA total of 42 implants were loaded immediately. From March 1999 to December 2003, no implants were lost during follow-up (range 3 to 49 months, mean of 28 months). No infections, nerve or sinus damage or other sequelae occurred. No implants exhibited peri-implant radiolucencies. Moreover, immediate loading seems to increase the ossification of the alveolar bone around endosseous implants. Patients were satisfied with the treatment.

CONCLUSIONSThe data and the experience described in this study indicate that immediate loading with restorations using appropriate surgical and restorative techniques can predicate the completely edentulous and partially edentulous mandible in some cases. Further study is needed to determine the long-term result of immediately loaded implants.

Adult ; Dental Abutments ; Dental Implantation, Endosseous ; methods ; Dental Implants ; Dental Prosthesis Design ; Dental Prosthesis Retention ; instrumentation ; Dental Prosthesis, Implant-Supported ; Denture, Complete, Immediate ; Denture, Partial, Immediate ; Female ; Humans ; Jaw, Edentulous ; surgery ; Jaw, Edentulous, Partially ; rehabilitation ; surgery ; Male ; Middle Aged

OBJECTIVETo investigate if magnetic- attached overdenture supported by microimplants of 2.5 mm in diameter was able to function properly.

METHODSFourteen microimplants were placed in 4 patients. Implants were exposed 3 months later and magnetic abutments were connected directly. X-ray was taken during the 3 year follow-up to examine marginal bone level. Peri-implant soft tissue was also checked. Denture retention, chewing stability and overall satisfaction with the microimplants retained overdenture were evaluated.

RESULTSAll of the 14 microimplants achieved initial primary stability without infection or any other postoperative complications. No implant was lost during the follow-up period. Only one magnetic abutment fractured one year after restoration and was replaced. X-ray showed highly stable marginal bone level around the microimplants. The patients were satisfied with the restoration.

CONCLUSIONSThe microimplants retained overdenture leads to a significant improvement of function despite of the small dimensions of these implants. In particular for elder patients with severe residual ridge resorption, this treatment represents a less invasive alternative compared to conventional implant systems.

Aged ; Dental Implantation, Endosseous ; methods ; Denture, Overlay ; Female ; Follow-Up Studies ; Humans ; Jaw, Edentulous ; rehabilitation ; Magnetics ; instrumentation ; Male

OBJECTIVETo evaluate the clinical effects of implants supported magnet-retained overdenture.

METHODSFrom November 1999 to March 2005, 25 cases with edentulous jaws underwent implant-supported magnet-retained overdenture. Among them, 14 patients were male, 11 patients were female. The average age of the patients was 67.6 years. (Range 45 - 79 years). Ninety-five implants used included Komet (18), IMZ (11), Frialit-2 (12), Ankylos (10), Camlog (44). The fellow-up time was from 6 months to 70 months. Clinical examination and radiographs were conducted.

RESULTSNo infections, nerve or sinus damage or other sequelae occurred. The overdentures were stable and functioned effectively. From November 1999 to March 2005, One Komet abutment was fracture and 1 Frialit-2 implant was lost because of overloading during follow-up. The remaining implants achieved successful osseointegration. Patients were satisfied with the treatment.

CONCLUSIONSImplant-supported magnet-retained overdenture was a predictable and reliable method, especially for old patients with edentulous jaws.

Aged ; Dental Implantation ; methods ; Dental Prosthesis, Implant-Supported ; Denture, Overlay ; Female ; Follow-Up Studies ; Humans ; Jaw, Edentulous ; rehabilitation ; Magnetics ; instrumentation ; Male ; Middle Aged

Objective:To explore the hospital-institute integration mode based on project cooperation.Methods:Focusing on the management innovation of clinical and basic scientific research cooperation mode, the method of hospital-institute integration mode based on project cooperation and the key points in practice were discussed, to develop better understandings of the construction and development such mode.Results:Several key points of developing hospital-institute integration mode based on project cooperation were proposed. Main measurements adopted including the integration of scientific research and clinic service, comprehensive construction of management concept, scientific research capacity, teaching organization and service concept, cultivation of high-level research talents, construction of research departments, according to which formed the main structure of the hospital. Furthermore, it is important to change the development mode in time to promote the healthy development of the hospital.Conclusions:It is a new direction of the clinical and basic research cooperation innovation to encourage the hospital-institute integration mode based on project cooperation. It is also an effective strategy to promote the improvement of diagnosis and treatment level under the new medical reform situation.