The Effect of Silibinin on the Pharmacokinetics of Ivabradine and N-Desmethylivabradine in Rats.

The objective of this work was to investigate the effect of orally administered silibinin on the pharmacokinetics of ivabradine and its active metabolite N-desmethylivabradine in rats. Twelve healthy male Sprague-Dawley rats were randomly divided into 2 groups: the control group (received oral 1.0 mg/kg ivabradine alone) and the combination group (1.0 mg/kg ivabradine orally coadministered with 30 mg/kg silibinin). The plasma concentration of ivabradine and N-desmethylivabradine were estimated by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and different pharmacokinetic parameters were calculated using the DAS 2.0 software. The pharmacokinetic parameters of t1/2, Cmax, AUC(0-t) and AUC(0-∞) of ivabradine in the combination group were significantly higher than those in the control group (p < 0.01). However, silibinin has no effect on the pharmacokinetics of N-desmethylivabradine. This study demonstrates that silibinin increase plasma concentration of ivabradine. Henceforth, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing ivabradine to patients already taking silibinin.

Repair of coronary artery ostium with a ring-shaped bovine pericardial patch.

As an approach to coronary artery ostial injury in type A aortic dissection and infective endocarditis, we describe a technique of coronary ostial repair using a ring-shaped bovine pericardial patch. The inner and outer rims of the patch were sutured to the involved coronary ostium (to close the ostial tear) and to the aortic wall (to cover the sinus), respectively. Four patients were successfully managed and computed tomographic coronary arteriogram at follow-up showed patent coronary ostia and arteries. The favourable preliminary results imply that this technique is a simple, safe and effective approach to coronary ostial repair in patients with type A aortic dissection or infective endocarditis.

Simultaneous Determination of Celecoxib, Dezocine and Dexmedetomidine in Beagle Plasma Using UPLC-MS/MS Method and the Application in Pharmacokinetics.

BACKGROUND: An efficient, fast and sensitive ultra high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for simultaneous determination of celecoxib (CEL), dezocine (DEZ) and dexmedetomidine (DEX) in beagle plasma were established. METHODS: The beagle dogs plasmawas precipitated by acetonitrile. The column was Acquity UPLC BEH C18 column and the mobile phase was acetonitrile-formic acid with gradient mode, and the flow rate was set at 0.4 mL/min. Under the positive ion mode, CEL, DEZ, DEX and Midazolam (internal standard, IS) were monitored by multiple reaction monitoring (MRM) as the following mass transition pairs: m/z 381.10→282.10 for CEL, m/z 246.20→147.00 for DEZ, m/z 201.10→94.90 for DEX, and m/z 326.10→291.10 for IS. RESULTS: This UPLC-MS/MS method had good linearity for CEL, DEZ and DEX. The RSDs of inter-day and intra-day precision were the values of 0.31-7.66% and 0.11-9.63%, respectively; the RE values were from -6.05% to 10.98%. The extraction recovery was more than 79%, and the matrix effect was around 100%. The RSDs of stability were less than 8.96%. All of them met the acceptance standard of biological analysis method recommended by FDA. CONCLUSION: This UPLC-MS/MS method is an effective tool for the simultaneous determination of CEL, DEX and DEX, and has been successfully applied to the study of pharmacokinetics in beagle dogs.

Machinability: Zirconia-reinforced lithium silicate glass ceramic versus lithium disilicate glass ceramic.

Diamond grinding used in dental adjustment of high-strength zirconia-reinforced lithium silicate glass ceramic (ZLS) and lithium disilicate glass ceramic (LDGC) is challenging in restorative dentistry. This study aimed to compare the machinability of ZLS and LDGC in diamond grinding in terms of machining forces and energy, debris, surface and edge chipping damage. Grinding experiments in simulation of dental adjustment were conducted using a computer-assisted high-speed dental handpiece and coarse diamond burs. A piezoelectric force dynamometer and a high-speed data acquisition system were used for on-processing monitoring for assessment of grinding forces and energy. Grinding debris and grinding-induced surface and edge chipping damage were examined using scanning electron microscopy. The results show that grinding of ZLS required higher tangential and normal forces and energy than LDGC (p < 0.05). ZLS was ranked the most difficult to machine among dental glass ceramics based on a machinability index associated with the material mechanical properties. The higher machinability indices of ZLS and LDGC pose a challenge for clinicians to conduct high-efficient material removal for dental adjustment and repair. Both ZLS and LDGC debris were micro fractured particles but the former were smaller than the latter due to the finer microstructure of ZLS. Ground ZLS surfaces contained more irregular microchipping and microfracture in comparison with LDGC surfaces with intergranular fracture or grain dislodgement. Grinding-induced edge chipping damage remained a serious issue for both ZLS and LDGC, which depths ranged approximately 20-100 µm and significantly increased with the material removal rate (p < 0.01). As the zirconia-reinforcement in ZLS only slightly reduced edge chipping damage (p > 0.05), continued efforts are required to explore new reinforcement technologies for optimized LDGC.

Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS.

A sensitive and reliable ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of parecoxib and its metabolite valdecoxib in beagles. The effects of dexmedetomidine on the pharmacokinetics of parecoxib and valdecoxib in beagles were studied. The plasma was precipitated by acetonitrile, and the two analytes were separated on an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm); the mobile phase was acetonitrile and 0.1% formic acid with gradient mode, and the flow rate was 0.4 mL/min. In the negative ion mode, the two analytes and internal standard (IS) were monitored by multiple reaction monitoring (MRM), and the mass transition pairs were as follows: m/z 369.1 → 119.1 for parecoxib, m/z 313.0 → 118.0 for valdecoxib, and m/z 380.0 → 316.0 for celecoxib (IS). Six beagles were designed as a double cycle self-control experiment. In the first cycle, after intramuscular injection of parecoxib 1.33 mg/kg, 1.0 mL blood samples were collected at different times (group A). In the second cycle, the same six beagles were intravenously injected with 2 µg/kg dexmedetomidine for 7 days after one week of washing period. On day 7, after intravenous injection of 2 µg/kg dexmedetomidine for 0.5 hours, 6 beagle dogs were intramuscularly injected with 1.33 mg/kg parecoxib, and blood samples were collected at different time points (group A). The concentration of parecoxib and valdecoxib was detected by UPLC-MS/MS, and the main pharmacokinetic parameters were calculated by DAS 2.0 software. Under the experimental conditions, the method has a good linear relationship for both analytes. The interday and intraday precision was less than 8.07%; the accuracy values were from -1.20% to 2.76%. C max of parecoxib in group A and group B was 2148.59 ± 406.13 ng/mL and 2100.49 ± 356.94 ng/mL, t 1/2 was 0.85 ± 0.36 h and 0.85 ± 0.36 h, and AUC(0-t) was 2429.96 ± 323.22 ng·h/mL and 2506.38 ± 544.83 ng·h/mL, respectively. C max of valdecoxib in group A and group B was 2059.15 ± 281.86 ng/mL and 2837.39 ± 276.78 ng/mL, t 1/2 was 2.44 ± 1.55 h and 2.91 ± 1.27 h, and AUC(0-t) was 4971.61 ± 696.56 ng·h/mL and 6770.65 ± 453.25 ng·h/mL, respectively. There was no significant change in the pharmacokinetics of parecoxib in groups A and B. C max and AUC(0 - ∞) of valdecoxib in group A were 37.79% and 36.19% higher than those in group B, respectively, and t 1/2 was increased from 2.44 h to 2.91 h. V z /F and CL z /F were correspondingly reduced, respectively. The developed UPLC-MS/MS method for simultaneous determination of parecoxib and valdecoxib in beagle plasma was specific, accurate, rapid, and suitable for the pharmacokinetics and drug-drug interactions of parecoxib and valdecoxib. Dexmedetomidine can inhibit the metabolism of valdecoxib in beagles and increase the exposure of valdecoxib, but it does not affect the pharmacokinetics of parecoxib.

[Staged total cavopulmonary connection for complex congenital heart diseases].

OBJECTIVE: To review the experience of staged total cavopulmonary connection (TCPC) in complex congenital heart diseases. METHODS: From June 1998 to March 2008, 22 patients underwent staged TCPC for complex congenital heart diseases. Among them, 9 were univentricular and pulmonary artery valve stenosis; 3 were univentricular and pulmonary artery atresia; 1 was transposition of great arteries, crisscross heart and pulmonary artery valve stenosis; 1 was complete atrioventricular canal defects, left ventricular hypoplasia, pulmonary artery atresia and atrioventricular valvular regurgitation; 1 was complete atrioventricular canal defects, left ventricular hypoplasia, pulmonary artery valve stenosis and atrioventricular valvular regurgitation after Glenn procedure; 1 was mirror image dextrocardia, single ventricle, pulmonary artery atresia, major aortopulmonary collateral arteries (MAPCAs) and right pulmonary arteriovenous fistula after Glenn procedure; 4 were tricuspid atresia and pulmonary artery valve stenosis; 1 was tricuspid atresia and pulmonary atresia; 1 was mirror image dextrocardia, double-outlet of right ventricle, left ventricular hypoplasia, pulmonary artery valve stenosis, tricuspid incompetence, and MAPCAs. Among them, 5 patients received systemic-to-pulmonary artery shunt, bidirectional Glenn procedure and TCPC. Seventeen patients received bidirectional Glenn procedure, the mean age was (5.9+/-4.4) years old. Pulmonary artery pressure pre-Glenn procedure was 17 to 20 mm Hg (1 mm Hg=0.133 kPa). Atrioventricular valve incompetence in 3 patients. Nakata index was less than 200 mm2/m2 in 4 patients before the first stage operation. The age of TCPC procedure was (9.6+/-4.9) years old, the interval time was (3.7+/-1.2) years. RESULTS: There was one in-hospital death, the mortality was 4.5%. The patient with univentricular and pulmonary atresia, received systemic-to-pulmonary artery shunt, bidirectional Glenn procedure and TCPC and died of pneumorrhagia. Other patients were recovered well, postoperative central venous pressure was 12 to 18 mm Hg, percutaneous oxygen saturation was 90% to 96%. The cardiac function were in NYHA class I to II. CONCLUSIONS: The staged TCPC was a good procedure in high-risk Fontan candidates. The results were satisfactory for those patients. This staged strategy may extend the operative indications for the Fontan procedure.

[Coronary artery bypass grafting in patients over 70 years old].

OBJECTIVE: To retrospectively analyze the experiences, indications, technique, and results of coronary artery bypass grafting (CABG) in patients over 70 years old. METHODS: Ninety-one patients received coronary artery bypass grafting from March 2004 to March 2008. Ages ranged from 70 to 83 years old, 22 patients over 75 years old. Conventional CABG (CCABG) in 72 patients, off-pump CABG (OPCAB) in 19 patients. Clinical data has no significant differences in two groups. The rate of using left internal mammary artery was 96.7%. The number of grafts in CCABG and OPCAB group were 2 to 5 (3.5 +/- 0.8) and 1 to 4 (2.9 +/- 0.7) respectively. RESULTS: In-hospital death in 2 cases, both were from chronic obstructive pulmonary disease and pulmonary infection. Cerebral infarction in 1 case and pulmonary infection in 2 cases in CCABG group, but no significant difference between two groups, and no difference in intubation, ICU stay, respiratory failure, renal function failure. But number of grafts in CCABG was significantly more than that in OPCAB (P < 0.01). Postoperative follow-up was 3 to 36 months, 1 case with recurrent angina in OPCAB. CONCLUSIONS: According to the characteristic of coronary artery disease in elderly, fully revascularization and improving myocardial blood supply, patients over 70 years old with CABG can obtain the same efficacy as younger patients. There were not significant difference between CCABG and OPCAB.

[Surgical treatment of complex congenital heart diseases with extracardiac conduit total cavopulmonary connection].

OBJECTIVE: To report the experience of extracardiac conduit total cavopulmonary connection (ECTCPC) in surgical treatment of complex congenital heart diseases. METHODS: From 1998 to 2006, 68 patients underwent ECTCPC for complex congenital heart diseases. Among them, 45 had functional univentricle with transposition of the great artery (TGA) and pulmonary artery valve stenosis, 19 had tricuspid atresia with hypoplasia of right ventricle, 4 had Ebstein's anomaly with hypoplasia of right ventricle. Six had left superior vena cava, 18 had received Bidirectional Glenn operation; Fifty-seven cases were performed under cardiopulmonary bypass with general anesthesia and hypothermia, 11 cases were performed without cardiopulmonary bypass. RESULTS: There were two death, the mortality was 2.9%. All patients were followed up from 1 to 8 years with no clinical symptoms and have been doing well. The arterial oxygen saturation was 90% - 96%, the cardiac function were in NYHA class I - II. CONCLUSION: The extra cardiac conduit TCPC is a simple procedure and superior to other type of Fontan procedure in most patients.

Relationship of remote sensing normalized differential vegetation index to Anopheles density and malaria incidence rate.

OBJECTIVE: To study the relationship of remote sensing normalized differential vegetation index (NDVI) to Anopheles density and malaria incidence rate. METHODS: Data of monthly average climate, environment, Anopheles density and malaria incidence rate, and remote sensing NDVI were collected from 27 townships of 10 counties in southeastern Yunnan Province from 1984 to 1993. The relationship of remote sensing ecological proxy index, NDVI, to Anopheles density and malaria incidence rate was studied by principal component analysis, factor analysis and grey correlation analysis. RESULTS: The correlation matrix showed that NDVI highly correlated with Anopheles density in 4 townships of Mengla, Jinghong, and Yuanjiang counties, but in other 23 townships the relationship was not clear. Principal component and factor analyses showed that remote sensing NDVI was the representative index of the first principal component and the first common factor of Anopheles density evaluation. Grey correlation analysis showed that in rainy season NDVI had a high grey correlation with Anopheles density and malaria incidence rate. The grey correlation analysis showed that in rainy season the grey degree of NDVI correlated with Anopheles. Minimus density was 0.730, and 0.713 with Anopheles sinensis density, and 0.800 with malarial incidence rate. CONCLUSION: Remote sensing NDVI can serve as a sensitive evaluation index of Anopheles density and malaria incidence rate.

Greenhouse cultivation mitigates metal-ingestion-associated health risks from vegetables in wastewater-irrigated agroecosystems.

Wastewater irrigation can elevate metal concentrations in soils and crops and increase the metal-associated health risks via vegetable ingestion in arid and semiarid northwestern China. Here, we investigated the As, Cd, Cr, Cu, Ni, Pb, and Zn concentrations in four vegetable species from Dongdagou and Xidagou farmlands in Baiyin, Gansu, China. We evaluated the effects of irrigation type (Dongdagou: industrial wastewater; Xidagou: domestic wastewater) and cultivation mode (open field and greenhouse) on the vegetable metal concentration, metal partitioning, soil-to-plant bioconcentration factor (BCF), and the health risk index. All stream waters, soils, and vegetables were found most severely polluted by As and Cd, with higher severity in the industrial-wastewater-irrigated Dongdagou than the domestic-wastewater-irrigated Xidagou. All vegetables had higher or, at least, comparable metal mass allocated in the shoot than in the root. Greenhouse cultivation could reduce metal-ingestion-associated health risks from edible vegetable biomass by decreasing the soil to plant bioaccumulation (BCF) and the metal concentration. This effect was always significant for all vegetables within Xidagou, and for carrot within Dongdagou. This mitigation effect of greenhouse cultivation could be attributed to the metal sorption by a higher level of soil organic matter and faster growth rate over metal uptake rate in greenhouses compared to open fields. Such mitigation effect was, however, insignificant for leafy vegetables within Dongdagou, when much more severely polluted water for irrigation was applied in greenhouses compared to open fields within Dongdagou. The present study highlights greenhouse cultivation as a potential mitigating approach to providing less-polluted vegetables for residents in the severely polluted area in addition to the source pollution control.

[Valve-sparing aortic root replacement in patients with aortic root disease].

OBJECTIVE: To review the results of the valve-sparing operation (David procedure) in patients with aortic root disease. METHODS: Twenty-nine patients with aortic root disease, 20 males and 9 females, aged 39 +/- 17 (10-64), 10 being of heart functional class I, 15 of class II, and 4 of class III, and 15 with gentle, 9 with moderate, and 5 with severe aortic insufficiency underwent David procedure, one undergoing the aortic valve-sparing reimplantation (David I), 25 undergoing aortic valve-sparing remodeling (David II), and 3 undergoing a new modified aortic valve-sparing operation. After the operation the patients were followed up for 29 +/- 15 months (5-74 months). RESULTS: No intra-operative death was found. The mean extracorporeal circulation time was 126 min +/- 25 min, and the aortic crossclamp time was 87 min +/- 22 min. All patients recovered to heart functional class I. Post-operatively 11 patients showed no normal, eight gently and two moderate aortic regurgitation. CONCLUSION: The valve-sparing operation is an ideal operation to the aortic root aneurysm with more or less normal aortic leaflets and valvular ring normal.

[Dynamic changes of the relationships between economic growth and environmental pressure in Gansu Province: a structural decomposition analysis].

Based on the ideology of macro environmental economics, a function of environmental pressure represented by pollutant emission was built, and the relative importance of the driving factors in the dynamic changes of the relationships between economic growth and environmental pressure in Gansu Province in 1990 - 2005 was analyzed by using structural decomposition analysis (SDA) model combining with 'refined Laspeyres' method. In the study period, the environmental pressure in the Province was mainly caused by the emission of waste gases and solids in the process of economic growth, and showed a rapid increasing trend at the late stage of the period. Population factor had less impact on the increase of this environmental pressure, while economic growth factor had obvious impact on it. Technological progress did mitigate, but could not offset the impact of economic growth factor, and the impacts of economic growth and technological factors on the environmental pressure differed with the kinds of pollutants.