PURPOSE: Poloxamer 407 (P407) thermo-sensitive hydrogel formulations were developed to enhance the retention time in the urinary bladder after intravesical instillation. MATERIALS AND METHODS: P407 hydrogels (P407Gels) containing 0.2 w/w% fluorescein isothiocyanate dextran (FD, MW 4 kDa) as a fluorescent probe were prepared by the cold method with different concentrations of the polymer (20, 25, and 30 w/w%). The gel-forming capacities were characterized in terms of gelation temperature (G-Temp), gelation time (G-Time), and gel duration (G-Dur). Homogenous dispersion of the probe throughout the hydrogel was observed by using fluorescence microscopy. The in vitro bladder simulation model was established to evaluate the retention and drug release properties. P407Gels in the solution state were administered to nude mice via urinary instillation, and the in vivo retention behavior of P407Gels was visualized by using an in vivo imaging system (IVIS). RESULTS: P407Gels showed a thermo-reversible phase transition at 4℃ (refrigerated; sol) and 37℃ (body temperature; gel). The G-Temp, G-Time, and G-Dur of FD-free P407Gels were approximately 10℃–20℃, 12–30 seconds, and 12–35 hours, respectively, and were not altered by the addition of FD. Fluorescence imaging showed that FD was spread homogenously in the gelled P407 solution. In a bladder simulation model, even after repeated periodic filling-emptying cycles, the hydrogel formulation displayed excellent retention with continuous release of the probe over 8 hours. The FD release from P407Gels and the erosion of the gel, both of which followed zero-order kinetics, had a linear relationship (r²=0.988). IVIS demonstrated that the intravesical retention time of P407Gels was over 4 hours, which was longer than that of the FD solution ( < 1 hour), even though periodic urination occurred in the mice. CONCLUSIONS: FD release from P407Gels was erosion-controlled. P407Gels represent a promising system to enhance intravesical retention with extended drug delivery.
Administration, Intravesical* ; Animals ; Dextrans ; Drug Liberation ; Fluorescein ; Hydrogel* ; Hydrogels* ; In Vitro Techniques ; Kinetics ; Methods ; Mice* ; Mice, Nude ; Microscopy, Fluorescence ; Optical Imaging ; Phase Transition ; Poloxamer* ; Polymers ; Urinary Bladder* ; Urination

PURPOSE: To evaluate the efficacy of subureteral injection types in patients with middle- to high-grade vesicoureteral reflux (VUR). MATERIALS AND METHODS: Between June 1999 and September 2010, subureteral dextranomer was applied at our clinic to 149 patients (214 refluxing ureters) with grades II, III, and IV VUR. Group 1 consisted of 54 patients (80 ureters), and group 2 consisted of 95 patients (134 ureters). The standard subureteric transurethral injection (STING) procedure was applied to group 1, and the modified STING procedure was applied to group 2. A second and if needed a third injection was applied to unsuccessfully treated patients. The mean follow-up period was 2 years. Patients were evaluated by cystography and ultrasonography in the third month of follow-up. RESULTS: VUR was resolved completely after a single injection in 54/80 ureters (67.5%) in group 1 and in 94/134 ureters (70.1%) in group 2. Overall successes after a second or a third injection were 61/80 (76.2%) and 111/134 (82.8%), respectively. There was a statistically significant difference between the groups only for grade IV reflux following multiple injections (p<0.05). CONCLUSIONS: Endoscopic treatment of VUR is a recommended treatment because it is minimally invasive, efficient, and repeatable. Our study confirmed that a modified STING procedure can be an alternative treatment to the standard technique.
Administration, Intravesical ; Adolescent ; Child ; Child, Preschool ; Dextrans/*administration & dosage ; Endoscopy ; Female ; Follow-Up Studies ; Humans ; Hyaluronic Acid/*administration & dosage ; Infant ; Male ; Reproducibility of Results ; Treatment Outcome ; Ureter/*surgery ; Urologic Surgical Procedures/*methods ; Vesico-Ureteral Reflux/*drug therapy/ultrasonography

PURPOSE: To evaluate the efficacy of subureteral injection types in patients with middle- to high-grade vesicoureteral reflux (VUR). MATERIALS AND METHODS: Between June 1999 and September 2010, subureteral dextranomer was applied at our clinic to 149 patients (214 refluxing ureters) with grades II, III, and IV VUR. Group 1 consisted of 54 patients (80 ureters), and group 2 consisted of 95 patients (134 ureters). The standard subureteric transurethral injection (STING) procedure was applied to group 1, and the modified STING procedure was applied to group 2. A second and if needed a third injection was applied to unsuccessfully treated patients. The mean follow-up period was 2 years. Patients were evaluated by cystography and ultrasonography in the third month of follow-up. RESULTS: VUR was resolved completely after a single injection in 54/80 ureters (67.5%) in group 1 and in 94/134 ureters (70.1%) in group 2. Overall successes after a second or a third injection were 61/80 (76.2%) and 111/134 (82.8%), respectively. There was a statistically significant difference between the groups only for grade IV reflux following multiple injections (p<0.05). CONCLUSIONS: Endoscopic treatment of VUR is a recommended treatment because it is minimally invasive, efficient, and repeatable. Our study confirmed that a modified STING procedure can be an alternative treatment to the standard technique.
Administration, Intravesical ; Adolescent ; Child ; Child, Preschool ; Dextrans/*administration & dosage ; Endoscopy ; Female ; Follow-Up Studies ; Humans ; Hyaluronic Acid/*administration & dosage ; Infant ; Male ; Reproducibility of Results ; Treatment Outcome ; Ureter/*surgery ; Urologic Surgical Procedures/*methods ; Vesico-Ureteral Reflux/*drug therapy/ultrasonography

OBJECTIVE: To investigate the effectiveness of treatment for severe ovary hyperstimulation syndrome (OHSS) complicated by pleural effusion and ascites after in vitro fertilization preembryo transfer (IVF-ET). METHODS: One hundred and thirty-two patients with severe OHSS in our hospital (from January 2007 to December 2010) were retrospectively analyzed and the efficacy of three therapeutic methods was compared. Twenty-five patients in group I were treated with low-molecular dextran and albumin, 67 patients in group II were treated with 6% medium molecular-weight hydroxyethyl starch, and 40 patients in group III were treated with active aspiration of pleural effusion and ascites. RESULTS: All three therapies improved the symptoms of OHSS and various blood biochemical parameters. The duration of hospitalization of group III [(7.4±4.5) d] was significantly less than those of group I [(21.4±9.2) d] or II [(15.6±6.7) d], and the cost of group III [(2656.2±1882.8) Yuan] was also significantly lower than that of group I or II [(11937.6±7989.8) and (5182.7±2991.7) Yuan, respectively]. CONCLUSION Abdominal B ultrasonography-guided trans-abdominal wall aspiration of pleural effusion and ascites combined with blood volume maintenance is an effective and economical way to treat OHSS.
Adult ; Ascites ; etiology ; therapy ; Dextrans ; administration & dosage ; Drainage ; Female ; Fertilization in Vitro ; Humans ; Hydroxyethyl Starch Derivatives ; administration & dosage ; Infusions, Intravenous ; Ovarian Hyperstimulation Syndrome ; complications ; therapy ; Ovulation Induction ; adverse effects ; Pleural Effusion ; etiology ; therapy ; Retrospective Studies ; Serum Albumin ; administration & dosage

Iron deficiency anemia (IDA) frequently occurs in infants and adolescents. IDA is the result of an interplay between increased host requirements, limited external supply, and increased blood loss. In outpatient clinics, we often see children with iron deficiency anemia. Most cases in children are caused by incomplete nutrient supplements and growth spurts. However, we can occasionally see patients with poor response despite iron supplementation. Failure of iron therapy occurs when a child does not receive the prescribed medication, when iron is given in a form that is poorly absorbed, or when there is a continuing unrecognized blood loss such as intestinal or pulmonary loss, or loss with menstrual periods. In addition, the therapeutic failure of iron medication may indicate that the original diagnosis of nutritional iron deficiency was incorrect. In this situation, we have to evaluate other etiologies of anemia. Recently, many cases relating H.pylori infection to iron deficiency anemia have been described in the literature and H.pylori infection has emerged as a cause of refractory iron deficiency anemia that is unresponsive to oral iron therapy. Also, iron deficiency anemia induced by athletics in adolescent females has been reported several times. In this article, the author reviews various etiologies of childhood iron deficiency anemia. The most important consideration in treatment of iron deficiency anemia is disclosure of the underlying cause and its recovery. Dietary habits should also be corrected. To supplement iron, 6 mg/kg of oral iron supplements (elemental iron) is recommended in ferrous salt form. If oral administration is not feasible, intravenous supplementation is recommended using forms such as iron dextran, iron gluconate, or iron sucrose.
Administration, Oral ; Adolescent ; Ambulatory Care Facilities ; Anemia ; Anemia, Iron-Deficiency ; Child ; Dextrans ; Disclosure ; Female ; Ferric Compounds ; Food Habits ; Glucaric Acid ; Gluconates ; Humans ; Infant ; Iron ; Sports ; Sucrose

The drug-loading system of DMF (dextran - magnetic layered double hydroxide - fluorouracil) was synthesized by "co-precipitation intercalated assembly - dextran composite in situ - solvent conversion" technology. The crystal-phase characteristic and slow-release performance of DMF were investigated through X-ray diffraction (XRD), infrared spectrum (IR), transmission electron microscopy (TEM), thermogravimetry (TG) and in vitro release experiment. The targeted transshipment and slow-release effect of DMF system were evaluated by in vivo animal experiment. It was showed that the XRD of DMF matched with R-sixtetragonum type layered double hydroxide and Fd-3m cubic type ferrite. IR test demonstrated that the DMF system was a supra-molecular complex consisted of Dextran (DET), magnetic layered double hydroxide (MLDH) and fluorouracil (FU) components. The two-level supra-molecular MLDH-FU presented six-edge lozenge TEM morphology, with layered characteristics. DET on the surface of DMF was capable of protecting the layered structure of MLDH-FU, improving particle dispersion properties, and strengthening the slow-release performance of the drug delivery system. The drug release model of DMF at pH 7.35 of PBS in vitro fit to the zero-order kinetics equation C = 1.1716 x 10(-5) + 4.4626 x 10(-7) t. The drug delivery system DMF could transport drugs principally to in vivo target organs with a local effect, targeted specificity, and excellent circulation transshipment performance. The pharmacokinetic process of DMF presented multi-peak phenomenon with peak attenuation and cyclic growth. The peaks appeared at 0.25, 1, 3, 5 and 9 d separately after dosing intervention. The first peak process of DMF accorded with a pharmacokinetic equation of C(FU) = 14.34 e(-0.530t) + 36.04 e(-0.321t) + 24.18 e(-0.96t), and presented the characteristic of slow absorption and fast elimination. As for subsequent peak processes, half-life increased, bioavailability increased, and plasma clearance decreased. The highest peak value of DMF was 1/37 of original value of FU, and the relative bioavailability was 419% to original FU.
Animals ; Biological Availability ; Delayed-Action Preparations ; Dextrans ; chemistry ; Drug Carriers ; Female ; Fluorouracil ; administration & dosage ; chemistry ; pharmacokinetics ; Half-Life ; Hydroxides ; chemistry ; Magnetics ; Male ; Microscopy, Electron, Transmission ; Rats ; Rats, Sprague-Dawley ; Spectrophotometry, Infrared ; Thermogravimetry ; X-Ray Diffraction

The aim of this study is to prepare cationic biodegradable dextran microspheres loaded with tetanus toxoid (TT) and to investigate the mechanism of protein loading. Positively charged microspheres were prepared by polymerization of hydroxylethyl methacrylate derivatized dextran (dex-HEMA) and dimethyl aminoethyl methacrylate (DMAEMA) in an aqueous two-phase system. The loading of the microspheres with TT was based on electrostatic attraction. The net positive surface charge increased with increasing amounts of DMAEMA. Confocal images showed fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) could penetrate into cationic dextran microspheres but not natural dextran microspheres. TT loading efficiency by post-loading was higher compared with by pre-loading. Even though TT is incorporated in the hydrogel network based on electrostatic interaction, still a controlled release can be achieved by varying the initial network density of the microspheres.
Delayed-Action Preparations ; Dextrans ; chemistry ; Drug Carriers ; chemistry ; Hydrogels ; chemistry ; Methacrylates ; chemistry ; Microscopy, Confocal ; Microspheres ; Particle Size ; Polymerization ; Serum Albumin, Bovine ; chemistry ; Tetanus Toxoid ; administration & dosage ; chemistry

OBJECTIVETo investigate the feasibility of in vivo magnetic resonance imaging (MRI) tracking of transplanted adipose-derived stem cells (ADSCs) labeled with superparamagnetic iron oxide (SPIO) in rat heart.

METHODSADSCs were labeled with poly-L-lysine (PLL)-SPIO complexes. Intracellular iron uptake was identified by Prussian blue stain and transmission electromicroscopy. Trypan blue staining was used to test the viability of the labeled cells. In vitro MRI of labeled cells was performed. SPIO-labeled ADSCs were transplanted into normal rat hearts and were in vivo imaged with MRI. Image findings on MRI were correlated with histological findings of the rat hearts.

RESULTSThe labeling efficacy of ADSCs with PLL-SPIO was nearly 100%. Light microscopy revealed the SPIO particles were located in the cytoplasm of the ADSCs by Prussian blue staining. Transmission electromicroscopy revealed that the SPIO particles were located in the endosomes in the cytoplasm. There was no significantly deference in viability between labeled and unlabeled groups demonstrated by Trypan blue test (P > 0.05). MRI showed signal loss in gel mixed with labeled cells as compared with the unlabeled cells group and blank group. Signal void on rat hearts were demonstrated on MRI and were well correlated with histological findings where Prussian-blue-stain positive cells presented.

CONCLUSIONMRI can be used to in vivo track the transplanted ADSCs labeled with SPIO into rat hearts and facilitate to understand the conditions of the labeled cells in the transplanted areas.

Adipocytes ; cytology ; Animals ; Cell Differentiation ; Contrast Media ; administration & dosage ; Dextrans ; administration & dosage ; Feasibility Studies ; Image Enhancement ; methods ; Magnetic Resonance Imaging ; methods ; Magnetite Nanoparticles ; administration & dosage ; Male ; Myocardium ; cytology ; pathology ; Rats ; Rats, Wistar ; Stem Cell Transplantation ; methods ; Stem Cells ; cytology

OBJECTIVETo study magnetic resonance enhancement features of inflammatory lymph nodes using different doses of ultrasmall superparamagnetic iron oxide (USPIO) particles in order to establish a standardized protocol for USPIO enhanced magnetic resonance imaging of lymph nodes.

METHODSA total of 12 healthy New Zealand rabbits were injected complete Freund's adjuvant in foot pad to establish popliteal inflammatory lymph node model. Different doses (45, 90, 135 micromol Fe/kg) of USPIO were injected intravenously. Magnetic resonance scans were performed before and after USPIO injection to observe the enhancement features of different groups. T2 signal intensity, T1 signal intensity, T2 x value, and T2 value were measured and T2 enhancement ratio was calculated at different time points.

RESULTSTwenty-four hours after USPIO injection, there was no statistical difference in T2 signal intensity and T2 enhancement ratio between 90 and 135 micromol Fe/kg dose groups, but both were superior to 45 micromol Fe/kg group (P < 0.05). There were no statistical differences in T2 signal intensity, T1 signal intensity, T2 value, and T2 enhance ratio among different postcontrast time delays from 6 to 24 hours in 90 micromol Fe/kg group (P > 0.05), and signal reduction of lymph nodes peaked 18 hours after USPIO injection. Better images were acquired with a postcontrast delay of 18-24 hours.

CONCLUSIONSLymph nodes can be enhanced well with a dose of 90 micromol Fe/kg. Postcontrast delay of 18-24 hours is appropriate for acquiring satisfactory enhancement images.

Animals ; Contrast Media ; administration & dosage ; Dextrans ; administration & dosage ; Image Enhancement ; methods ; Lymphadenitis ; diagnosis ; pathology ; Magnetic Resonance Imaging ; methods ; Magnetite Nanoparticles ; administration & dosage ; Male ; Rabbits ; Random Allocation

A cationic liposome was prepared with a ligand directed at folate receptor in cancer cells to improve selectivity and facilitate its access to the cancer cells. Folate-polyethyleneglycol-distearoylphosphatidylethanolamine (F-PEG-DSPE) was synthesized by reacting folic acid (F), polyoxyethylene-bis-amine (NH2-PEG-NH2), succinic anhydride (SUC) with distearoylphosphatidylethanolamine (DSPE). Folate receptor-targeted liposomes composed of DPPC/DC-Chol/F-PEG-DSPE (10:10:0.75, molar ratio) were prepared by film dispersion method. A negative charged dextran fluorescein anionic (DFA) was used as a model to explore the in vitro properties and cell uptake efficiencies of liposomal DFA on KB and HpeG2 cells. The formulations were investigated by orthogonal experiment using encapsulation efficiency as the optimized indexes. The size, 4 potential, entrapment efficiency and DFA release in vitro were investigated. The results showed that DFA loaded folate receptor-targeted liposomes had high encapsulation efficiency and the mean size approximately 144 nm. The cationic liposomes had some toxicity to HepG2 cells, and at low concentration (0.0125-0.1 micromol x L(-1)) , the toxicity was linear with the concentration of DC-chol. The folate receptor-targeted liposomes showed great effects on increasing liposome cellular uptake of DFA. In summary, the method of film dispersion method is suitable for producing DFA loaded lipsomes with high entrapment efficiency, small size and slow release. The folate receptor-targeted liposomes can efficiently deliver DFA into cells in vitro. This may represent a promising option for researches on cancer gene therapy.
Carrier Proteins ; metabolism ; Dextrans ; chemistry ; Drug Carriers ; Drug Delivery Systems ; Fluoresceins ; chemistry ; Folate Receptors, GPI-Anchored ; Folic Acid ; chemistry ; Genetic Therapy ; Hep G2 Cells ; Humans ; KB Cells ; Liposomes ; administration & dosage ; chemical synthesis ; metabolism ; Particle Size ; Phosphatidylethanolamines ; chemistry ; Polyethylene Glycols ; chemistry ; Receptors, Cell Surface ; metabolism ; Transfection