Objective To explore the effects of detecting of γ-glutamyltransferase( γ-GT)and leucine aminopeptidase(LAP)in urine on early diagnosis of kidney injury induced by zoledronic acid. Methods The patients with malignant tumor bone metastasis and received zoledronic acid from February 2012 to July 2014 in the General Hospital of Shenyang Military Command were enrolled into this study. The patient received IV infusion of zoledronic acid 4 mg,once for 25 to 35 days,finished within 30 minutes. The therapy was applied 3 times continuously. The patients' urine and venous blood samples were taken before and after each medication's morning. The levels of γ-GT,LAP in urine and serum creatinine were detected and compared. Results A total of 100 patients comprised 48 males and 52 females with a mean age of (60 ± 11)years(25-82 years)were enrolled into the study. The levels of γ-GT,LAP in urine and serum creatinine before and after receiving zoledronic acid in the first time were(8 ± 5),(7 ± 5)U/ L;(332 ± 110),(375 ± 113)nmol·s-1 ·L-1;(52 ± 12),(54 ± 12)μmol/ L,respectively. The levels of γ-GT, LAP in urine and serum creatinine before and after receiving zoledronic acid the second time were(10 ± 4), (12 ± 5)U/ L;(407 ± 104),(377 ± 126)nmol·s-1 ·L-1;(51 ± 13),(53 ± 13)μmol/ L,respectively. The levels of γ-GT,LAP in urine and serum creatinine before and after receiving zoledronic acid the third time were(16 ± 8),(19 ± 9)U/ L;(549 ± 159),(662 ± 199)nmol·s-1 ·L-1;(52 ± 15),(53 ± 14)μmol/ L,respectively. The differences of levels of γ-GT,LAP in urine before and after 3 times of medication were statistically significant( all P < 0. 05). But the differences of levels of serum creatinine were not statistically significant(all P > 0. 05). The differences of levels of γ-GT,LAP in urine after 3 times of
medication were statistically significant(all P < 0. 05). But the The differences of levels of serum creatinine were not statistically significant(all P > 0. 05). Conclusions The change in levels of γ-GT and LAP in urine was earlier than that of serum creatinine in patient with kidney injury induced by zoledronic acid. γ-GT and LAP in urine can be the early diagnostic marker of kidney injury induced by zoledronic acid.

Objective To explore the effects of detecting of γ-glutamyltransferase( γ-GT)and leucine aminopeptidase(LAP)in urine on early diagnosis of kidney injury induced by zoledronic acid. Methods The patients with malignant tumor bone metastasis and received zoledronic acid from February 2012 to July 2014 in the General Hospital of Shenyang Military Command were enrolled into this study. The patient received IV infusion of zoledronic acid 4 mg,once for 25 to 35 days,finished within 30 minutes. The therapy was applied 3 times continuously. The patients' urine and venous blood samples were taken before and after each medication's morning. The levels of γ-GT,LAP in urine and serum creatinine were detected and compared. Results A total of 100 patients comprised 48 males and 52 females with a mean age of (60 ± 11)years(25-82 years)were enrolled into the study. The levels of γ-GT,LAP in urine and serum creatinine before and after receiving zoledronic acid in the first time were(8 ± 5),(7 ± 5)U/ L;(332 ± 110),(375 ± 113)nmol·s-1 ·L-1;(52 ± 12),(54 ± 12)μmol/ L,respectively. The levels of γ-GT, LAP in urine and serum creatinine before and after receiving zoledronic acid the second time were(10 ± 4), (12 ± 5)U/ L;(407 ± 104),(377 ± 126)nmol·s-1 ·L-1;(51 ± 13),(53 ± 13)μmol/ L,respectively. The levels of γ-GT,LAP in urine and serum creatinine before and after receiving zoledronic acid the third time were(16 ± 8),(19 ± 9)U/ L;(549 ± 159),(662 ± 199)nmol·s-1 ·L-1;(52 ± 15),(53 ± 14)μmol/ L,respectively. The differences of levels of γ-GT,LAP in urine before and after 3 times of medication were statistically significant( all P < 0. 05). But the differences of levels of serum creatinine were not statistically significant(all P > 0. 05). The differences of levels of γ-GT,LAP in urine after 3 times of
medication were statistically significant(all P < 0. 05). But the The differences of levels of serum creatinine were not statistically significant(all P > 0. 05). Conclusions The change in levels of γ-GT and LAP in urine was earlier than that of serum creatinine in patient with kidney injury induced by zoledronic acid. γ-GT and LAP in urine can be the early diagnostic marker of kidney injury induced by zoledronic acid.

Objective To manufacture magnetic microbubbles with dual-response to ultrasound and magnetic fields.Methods Microbubbles of ultrasound contrast agent (ST68) based on a surfactant were prepared by the acoustic cavitation method.Fe3O4 magnetic nanoparticles with negative charge were synthesized using the polyol procedure.Magnetic microbubbles were generated by depositing polyethylenimine and Fe3O4 magnetic nanoparticles alternately onto the microbubbles using the layer-by-layer self-assembly.In vitro ultrasonography was performed on a silicone tube with/without magnetic microbubbles (3 × 108/ml) by a self-made device to observe the movement of magnetic microbubbles under the effects of magnetic field.In vivo imaging was performed on the kidney of New Zealand rabbits before and after the injection of magnetic microbubbles.Results The Fe3O4 nanoparticles carried a stable negative charge of (-24.6 ± 6.7) mV and more than 98％ of the particles were less than 8 μm in diameter,meeting the size requirement of an ultrasound contrast agent for intravenous administration.There was no echoic signal in the silicone tube before injection of magnetic microbubbles,but there were strong echoic signals after injection.After applying a magnetic field,the magnetic microbubbles moved along the direction of the magnetic flux.In vivo ultrasound imaging could not visualize the kidney before injection of magnetic microbubbles,but could remarkably visualize the kidney after injection.Conclusions The magnetic microbubbles exhibit favorable magnetic targeting and ultrasound contrast enhancement characteristics.Such properties may serve as the foundation to study their potential for simultaneous diagnosis and treatment in the future.

Objective To fabricate an ultrasound/fluorescence bi-modal contrast agent by encapsulating fluorescent quantum dots into polymeric ultrasound contrast agent microbubbles.Methods Polylactic acid (PLA,500 mg),(1R)-(+)-camphor (50 mg) and CdSe/ZnS quantum dots (0.5 ml,2.3 μmol/L)were dissolved or dispersed in dichloromethane (10 ml) to form in an organic phase.Ammonium carbonate solution and poly (vinyl alcohol) solution were employed as the internal and external water phase,respectively.The fluorescent microbubbles were generated using double emulsion solvent evaporation and lyophilization methods.The morphology and illumination were characterized by scanning electron microscopy (SEM) and fluorescence spectrophotometry.Synchronized contrast-enhanced ultrasound and fluorescence imaging was acquired by injecting fluorescent microbubbles into the silicone tube coupled to a self-made ultrasound/fluorescence imaging device.Ultrasound/fluorescence bi-modal in vivo imaging was acquired on the kidney of New Zealand rabbits and suckling mice.Results The fluorescent microbubbles were hollow spheres with an averaged diameter of (1.62 ± 1.47) μm.More than 99％ of these microbubbles were less than 8 μm in diameter,which meeted the size criteria for ultrasound contrast agents.The fluorescence emission peak of the microbubbles appeared at 632 nm,indicating that good luminescence properties of quantum dots were maintained.In vitro ultrasound/fluorescence imaging showed no echoic signal when the silicone tube was filled with saline,but there was a strong echo when filled with fluorescent microbubbles.The liquid column with fluorescent microbubbles emitted red luminescence under ultraviolet irradiation.The kidney of the rabbit was remarkably enhanced after the administration of fluorescent microbubbles.Bright fluorescence could be observed at the injection site of the suckling mice via subcutaneous injection.Conclusions A bi-modal but single contrast agent based on polymeric microbubbles has been successfully fabricated for the use of ultrasound and fluorescence imaging.It retains the good characteristics of both echogenicity and fluorescence,which complement each other in case of limitations imposed by uni-modal,single agents.