1.Effect of diameter of adriamycin polybutylcyanoacrylate nanoparticles on liver targeting.
Liang-fang SHEN ; Xin WANG ; Cheng WANG ; Kai ZHAO ; Xin-ju LIU ; Hai-ju SHEN
Journal of Central South University(Medical Sciences) 2006;31(5):732-741
OBJECTIVE:
To observe the different tissue distributions of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the mice body after the injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice livers.
METHODS:
One hundred and eighty mice were randomly divided into 6 groups with 30 mice in each group: non-conjugated free ADM (Group 1); (22.3+/-6.2) nm in diameter ADM-PBCA-NP group (Group 2); (48.6+/-9.2) nm ADM-PBCA-NP group (Group 3); (101.9+/-20.3) nm ADM-PBCA-NP group (Group 4); (143.5+/-23.5) nm ADM-PBCA-NP group (Group 5), and (194.2+/-28.4) nm ADM-PBCA-NP group (Group 6). A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours after the injection, respectively. The adriamycin concentrations in the collected livers, kidneys, spleens, hearts, lungs and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector.
RESULTS:
Compared with that of the control group, adriamycin was hardly detected in the heart muscles of the treatment groups (P<0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissues. The adriamycin concentrations of the mice liver and spleen in the experimental groups was significantly higher than those in the control group, except for the group with the nanoparticles diameters of (22.3+/-6.2) nm (P<0.05). The ADM-PBCA-NP in (101.9+/-20.3) nm diameter had the highest liver distribution, and the second highest adriamycin distribution in the liver was the group of (143.5+/-23.5) nm diameter (P<0.05). Adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBCA-NP in (22.3+/-6.2) nm diameter was not distributed in the tissues of the livers, kidneys, hearts, spleens, and lungs.
CONCLUSION
ADM-PBCA-NP with a 100 - 150 nm diameter range has the best liver targeting with slow medicine release. It also decreases the medicine distribution in the heart and other organs. In the treatment of liver cancer, the polybutylcyanoacrylate nanoparticle system has a good liver targeting ability, which increases the anticancer activity and markedly decreases the toxicity of adriamycin.
Animals
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Antibiotics, Antineoplastic
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administration & dosage
;
pharmacokinetics
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Doxorubicin
;
administration & dosage
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pharmacokinetics
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Drug Carriers
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Drug Delivery Systems
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Enbucrilate
;
administration & dosage
;
pharmacokinetics
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Liver
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metabolism
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Male
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Mice
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Nanoparticles
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Particle Size
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Random Allocation
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Tissue Distribution
2.Liver targeting and the delayed drug release of the nanoparticles of adriamycin polybutylcyanoacrylate in mice.
Liang-fang SHEN ; Yang-de ZHANG ; Hai-ju SHEN ; Shan ZENG ; Xin WANG ; Cheng WANG ; Yuan LE ; Hong SHEN
Chinese Medical Journal 2006;119(15):1287-1293
BACKGROUNDLiver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are currently under hot investigation with great clinical significance. This study was aimed to investigate the different tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the mice body after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice liver.
METHODSOne hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in each group (5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycin injection was employed as the control group). A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin concentrations in the respectively collected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector.
RESULTSCompared with the control group, adriamycin was hardly detected in the heart muscle of the treatment groups (P < 0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. The adriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher than that in the control group, except for the group with the nanoparticles diameters of (22.3 +/- 6.2) nm (P < 0.05). The ADM-PBCA-NP in (101.0 +/- 20.3) nm diameter had the highest liver distribution, and the second highest adriamycin distribution in liver was the group of (143.0 +/- 23.5) nm diameter (P < 0.05). Moreover, adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBCA-NP in (22.3 +/- 6.2) nm diameter was not distributed in the tissue of the liver, kidney, heart, spleen, and lung.
CONCLUSIONSADM-PBCA-NP in 100 - 150 nm diameter range has the best liver targeting with a characteristic of slow medicine release. It also decreases the medicine distribution in the heart, kidney and lung. In the treatment of liver cancer, the polybutylcyanoacrylate nanoparticles system has a good liver targeting ability, which increases the anticancer activity and markedly decreases the toxicity of adriamycin.
Animals ; Antineoplastic Agents ; administration & dosage ; Doxorubicin ; administration & dosage ; Drug Delivery Systems ; Enbucrilate ; administration & dosage ; Liver ; metabolism ; Mice ; Nanostructures ; Tissue Distribution
3.Evaluation of aminoglycoside resistance phenotypes and genotyping of acetyltransferase in Escherichia coli.
Hai-shen KONG ; Xue-fen LI ; Ju-fang WANG ; Min-jin WU ; Xiao CHEN ; Qing YANG
Journal of Zhejiang University. Medical sciences 2006;35(1):83-86
OBJECTIVETo investigate the prevalence of aminoglycoside resistance and genotyping of acetyltransferase in Escherichia coli.
METHODSResistance phenotypes to 12 antibiotics of 44 Escherichia coli isolates were analyzed using agar dilution method and 3 aminoglycoside resistance genes aac(3)-I, II and aac(6')-I were determined by PCR method.
RESULTSIn 44 clinical isolates, the occurrence of ESBLs was 45.45%, resistance rates were discrepant for amikacin (18.18%), gentamicin (56.82%) and tobramycin (61.36%), the prevalence of phenotype TG (tobramycin and gentamicin) indicative of aac(3)-II production and TGA (tobramycin, gentamicin and amikacin) indicative of aac(6')-I production were 36.36% and 18.18%, respectively. The most common aminoglycoside resistance genotype of acetyltransferase was aac(3)-II (52.27%) and aac(6')-I was lower (29.55%), but no aac(3)-I was detected.
CONCLUSIONAt least 2 acetyltransferase genes exist in this area i.e. aac(3)-II and aac(6')-I.
Acyltransferases ; genetics ; Amikacin ; pharmacology ; Aminoglycosides ; pharmacology ; Drug Resistance, Bacterial ; genetics ; Escherichia coli ; enzymology ; genetics ; Genotype ; Gentamicins ; pharmacology ; Phenotype ; Tobramycin ; pharmacology
4.Repair of the large skin and vessel defect of upper arm with free anterolateral thigh flap.
Jin-sheng LI ; Ju-fang ZHANG ; Hai-yan SHEN ; Hong-jun WU
Chinese Journal of Plastic Surgery 2010;26(1):12-14
OBJECTIVETo explore an effective method for repairing the large skin and vessel defect of upper arm.
METHODSThe large skin defect was repaired by the free anterolateral thigh flap. The vessel defect was reconstructed with the end branch of descending branch from lateral femoral circumflex artery, or the large muscular branch through bridge-like vascular anastomosis.
RESULTSSince 2003, 5 cases were treated. All the flaps survived completely with a soft tissue texture. They were followed up for 8-24 months. The cosmetic and functional results were both satisfactory with less morbidity in the donor sites. The blood supply of the flap and the end of extremities was not affected by weather.
CONCLUSIONSAnterolateral thigh flap is very suitable for large skin and vessel defect of upper arm.
Adolescent ; Adult ; Arm Injuries ; surgery ; Dermatologic Surgical Procedures ; Female ; Humans ; Male ; Middle Aged ; Skin ; injuries ; Skin Transplantation ; methods ; Soft Tissue Injuries ; surgery ; Surgical Flaps ; Thigh ; surgery ; Young Adult
5.Endoscopic mucosal resection in the treatment of 2609 cases with colorectal polyps.
De-chang DENG ; Xiao-ming FANG ; Hai-hong JU ; Wen-xiao SHEN ; Hai-fei YE
Chinese Journal of Gastrointestinal Surgery 2012;15(12):1301-1303
OBJECTIVETo explore the safety and effectiveness of endoscopic mucosal resection (EMR) in the treatment of colorectal polyps.
METHODEMR was applied in the treatment of colorectal polyps.
RESULTSA total of 3578 polyps in 2609 patients were all completely resected except 2 cases and the integrated rate of samples was 99.6%. Intra- and post-operation complications occurred in 22 cases(0.8%), including 7 intraoperative bleeding, 5 postoperative bleeding, and 10 thermal burn, which were cured by symptomatic treatment. A total of 1530 (58.6%) cases were followed-up with 3-12 months and no relapse was found in former place of excision.
CONCLUSIONEMR can be applied in resection of colorectal polyps effectively and safely.
Aged ; Endoscopy, Gastrointestinal ; Humans ; Intestinal Mucosa ; surgery ; Intestinal Polyps ; surgery ; Postoperative Hemorrhage ; Recurrence
6.Therapeutic effect of ankle bath associated with chiropractic technique on the patients with ankle fractures in later period
Yong-Xiu ZHUANG ; Ping LI ; Ju-Hua SHEN ; Xiao-Yan CHEN ; Xiao-Fang LIU ; Hui-Yan PENG
Chinese Journal of Modern Nursing 2012;18(19):2279-2282
Objective To observe the therapeutic effect of ankle bath by traditional Chinese medicine associated with chiropractic technique on the patients with ankle fractures in later period so as to explore the nursing and its influencing factors.Methods From June 2009 to December 2011,a total of 76 cases with ankle fractures were selected and radomly divided into control group and observation group.Control group took medicine that could activate blood circulation to dissipated blood stasis,bathed ankle in warm water and took functional exercise,while the observation group received Chinese medicine bath and massage followed by functional exercise.Results After 10 days,the difference between observation group and control group in the degree of pain and activity of ankle and joint function appeared ( 14.86 ±7.21vs 8.68 ± 8.98,7.18 ± 1.91vs 4.34 ± 1.66,2.84 ± 1.46 vs 1.97 ± 1.17 ) and the difference was statistically significant ( t =3.31,6.90,2.85 ;P<0.05).And 20 days later,the improvement rate of observation group was 92.1% and 71.06% of control group,and the difference was statistically significant ( u =2.07,P < 0.05).Conclusions Bath foot by traditional Chinese medicine associated with chiropractic technique can make qi and blood be unobstructed,activate blood circulation to dissipate blood stasis,promote ankle joint swelling and analgetic,and finally enhance joint function to recover.
7.Analysis on the therapeutic effects of re-irradiation with stereotactic body radiation therapy for the advanced recurrent locally pancreatic cancer
Yuxin SHEN ; Xiaofei ZHU ; Xiaoping JU ; Yangsen CAO ; Shuiwang QING ; Fei CAO ; Yangyang GENG ; Xianzhi ZHAO ; Fang FANG ; Zhen JIA ; Lei GU ; Huojun ZHANG
Chinese Journal of Pancreatology 2018;18(3):153-158
Objective To investigate the safety and efficacy of re-irradiation with stereotactic body radiotherapy(SBRT) for treating locally recurrent advanced pancreatic cancer.Methods From 2014 to 2017,7 patients with stage Ⅲ pancreatic cancer were treated by re-irradiated with SBRT at Shanghai Changhai Hospital.SBRT was delivered via the G4 type cyberknife robotic stereotactic radiosurgery system in all the patients.The median dose of the first SBRT was 35Gy/5-7 fx,and the median dose of re-irradiation with SBRT was 31 Gy/5-8 fx.6 patients had undergone sequential chemotherapy either with gemcitabine or S-1 based therapy except one patient who refused the chemotherapy.Results There were 5 male and 2 female patients.The median overall survival (OS) of 7 patients was 30 months.Patients were re-irradiated with SBRT after a median interval of 10 months after the first SBRT.Median OS and locally relapse-free survival (LFRS) from re-irradiation were 13 months and 11 months,respectively.Three months after re-irradiation,3(42.9%) patients had partial remission and 4 patients had stable disease.Pain disappeared in 4 patients at the end of reirradiation and significant pain was alleviated in 2 patients 1 month after re-irradiation.There were no toxicities of grade 3 or higher grade during two courses of SBRT.Conclusions For patient with locally recurrent advanced pancreatic cancer,SBRT re irradiation regimen was associated with acceptable toxicity,which can effectively alleviate the pain,prolong the survival and improve the life quality.
8.Assessment of stroke volume variation and intrathoracic blood volume index on the responsiveness to volume loading in mechanically ventilated canine with hemorrhagic shock.
Song-qiao LIU ; Hai-bo QIU ; Yi YANG ; Yong-ming CHEN ; Jia-qiong LI ; Ju-fang SHEN
Chinese Journal of Surgery 2006;44(17):1216-1219
OBJECTIVETo assess the significance of stroke volume variation (SVV) and intrathoracic blood volume index (ITBI) on the responsiveness to volume loading in mechanically ventilated canine with hemorrhagic shock.
METHODSHemorrhagic shock canine model was established with the modified Wiggers' method. The heart rate (HR), mean artery pressure (MAP), central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), intrathoracic blood volume index (ITBI) and stroke volume variation (SVV) were investigated by Swan-Ganz catheter or PiCCO monitor. Graded volume loading (VL) was performed. Successive responsive VLs were performed (increase in SV > 5% after VL) until continuous change in SV < 5% (unresponsive) was reached.
RESULTSFourteen canines were studied and a total of 134 VLs were performed. In 94 VLs, an increase in SV of more than 5% was reached. In the other 40 VLs, increase in SV was less than 5%. The change of HR, MAP, ITBI, SVV in responsive were more than those of unresponsive after VL. The change of CVP, PAWP in responsive were less than those of unresponsive. Significant correlation was found between DeltaSV after VL and the baseline values of ITBI, SVV. No correlation was found between DeltaSV and HR, MAP, CVP, PAWP. Significant correlations were also found between DeltaSV and DeltaCVP, DeltaPAWP, DeltaITBI, DeltaSVV after fluid loading. No correlation was found between DeltaSV and DeltaHR, DeltaMAP. By using receiver operating characteristic analysis, the area under the curve were 0.872 for SVV and 0.689 for ITBI, more than those of HR, MAP, CVP, PAWP statistically. As SVV value of 9.5% or more will predict an increase in the SV of at least 5% in response to a VL with a sensitivity of 92.6% and a specificity of 82.5%.
CONCLUSIONSSVV and ITBI were more useful indicators than CVP and PAWP on the assessment of responsiveness to volume loading. SVV as a functional preload parameter and for on-line monitoring may help to improve the hemodynamic management.
Animals ; Blood Volume ; physiology ; Blood Volume Determination ; methods ; Dogs ; Female ; Male ; Shock, Hemorrhagic ; diagnosis ; physiopathology ; Stroke Volume ; physiology
9.Effect of lung stress index on titration of positive end-expiratory pressure at post-recruitment in three canine acute respiratory distress syndrome models.
Hai-bo QIU ; Yong-ming CHEN ; Yi YANG ; Ju-fang SHEN ; Jia-qiong LI ; Na LI ; Bin WU
Chinese Journal of Surgery 2006;44(17):1181-1184
OBJECTIVETo investigate the relationship of lung stress index and positive end-expiratory pressure (PEEP) at post-recruitment in different canine acute respiratory distress syndrome (ARDS) models.
METHODSThe ARDS models were induced by intravenous oleic acid, saline lavage and hydrochloric acid aspiration in anesthetized dogs. During volume control ventilation with constant inspiratory flow, PEEP was set to obtain a b (stress index) value between 0.9 and 1.1 (b = 1) before and post recruitment maneuver (RM). PEEP was changed to obtain b < 1 (0.6 < b < 0.8) and b > 1 (1.1 < b < 1.3). Meanwhile, the recruited volume (RV) was measured and pulmonary mechanics and gas exchange were observed.
RESULTSAt b = 1 after RM, PEEP were (10.8 +/- 2.3), (12.8 +/- 1.8) and (9.2 +/- 1.8) cm H2O in the oleic acid, saline-lavaged and hydrochloric acid aspiration groups, respectively. PEEP in saline-lavaged group was higher than that in hydrochloric acid aspiration group (P < 0.05). The ratio of partial arterial oxygen tension and fraction of inspiratory oxygen (PaO(2)/FiO(2)) at b = 1 without RM was lower than those post-RM in all three groups (P < 0.05). In oleic acid group, PaO(2)/FiO(2) at b = 1 post-RM was (399 +/- 61) mm Hg, which was higher than that at b < 1 [(307 +/- 71) mm Hg], but there was no difference between those at b = 1 and b > 1. At b = 1 after RM, PaO(2)/FiO(2) in the saline-lavaged group was higher than that in acid aspiration group, but no difference between saline-lavaged group and oleic acid group was found. At b = 1 post-RM, RV were higher than that at b = 1 before RM in all three groups (P < 0.01), but there was no significant difference among three groups. At b = 1 post-RM in three groups, pulmonary compliance were higher than those at b > 1, but airway plateau pressure were lower than those at b > 1.
CONCLUSIONSLung stress index could be a good indicator for PEEP titration at post-RM.
Animals ; Disease Models, Animal ; Dogs ; Female ; Hydrochloric Acid ; pharmacology ; Lung ; physiopathology ; Lung Compliance ; Male ; Oleic Acid ; pharmacology ; Positive-Pressure Respiration ; Respiratory Distress Syndrome, Adult ; chemically induced ; physiopathology ; therapy ; Respiratory Function Tests ; Sodium Chloride ; pharmacology
10.A research of endothelial cell-targeted therapy for cure of hypertrophic scar.
Rui SHEN ; Tian-zeng LI ; Shao-hai QI ; Hui-zhen LIANG ; Ying-bin XU ; Ju-lin XIE ; Yi-fang WU ; Xiang-sheng FENG ; Yong-jun DU
Chinese Journal of Plastic Surgery 2003;19(4):254-257
OBJECTIVETo investigate the feasibility of endothelial cell-targeted therapy to cure post-burn hypertrophic scar.
METHODSA hypertrophic scar animal model was made. Intralesional injecting of VEGF monoclonal antibody was performed for three weeks. The changes of scar in volume and morphology were observed.
RESULTS1. The volume of scar decreased. 2. The number of the capillary, the amount of collagen I and collagen III decreased. 3. Transmission electron microscope examinations demonstrated many dead or apoptotic fibroblasts and endothelial cells. Fibrocytes were seen relatively common.
CONCLUSIONVEGF induces the growth and development of hypertrophic scar in that it induces excessive and uncontrollable angiogenesis, which favors excessive collagen synthesis. Endothelial cell-targeted therapy may be a promising method to cure post-burn hypertrophic scar.
Animals ; Apoptosis ; Burns ; complications ; Cicatrix, Hypertrophic ; chemically induced ; therapy ; Collagen Type I ; Collagen Type III ; Disease Models, Animal ; Endothelial Cells ; Feasibility Studies ; Neovascularization, Pathologic ; etiology ; Vascular Endothelial Growth Factor A