Malignant ureteral obstruction: experience and comparative analysis of metallic versus ordinary polymer ureteral stents.

BACKGROUND: To study the outcome and experience of using metallic stents in treating patients with malignant ureteral obstruction (MUO). METHODS: Seventy-six patients with MUO were assigned to the metallic stent group (MSG) or the ordinary polymer stent group (OPSG) according to the different materials. The success rate of the operation, duration of operation, patency rate serum creatinine values ,postoperative complications and QOL scores were compared between the two groups. RESULTS: In the OPSG and MSG, the success rates of the operation were 95.5% and 96.9%, respectively, and the durations of the operation were 20.6 ± 2.2 min and 50.9 ± 10.3 min (P < 0.01), respectively. There was no significant difference between the groups in serum creatinine values at 3 days after the operation (P > 0.05); however, the creatinine values at 3 days after the operation decreased significantly compared with those before the operation (P < 0.01). In the OPSG, there was no significant difference in creatinine values between 3 days and 6 months after operation, while the creatinine values 1 year after operation were increased significantly compared to those at 3 days after the operation (P < 0.05). In the MSG, there was no significant difference among creatinine values at different intervals (P > 0.05). The total rate of post-procedural complication was lower in the MSG than that in the OPSG(P < 0.05). There was no significant difference in the QOL score between the two groups before the operation (P > 0.05); however, the QOL scores at 6 months and 1 year after the operation were higher in the MSG than that in the OPSG(P < 0.05). In the MSG, there was no significant difference in the QOL score between preoperation and 6 months after surgery. Similarly, there was also no difference in the QOL score between 6 months after surgery and 1 year after surgery(P > 0.05). On the contrary, the differences of QOL score in the OPSG group were much significant between disparate time intervals (P < 0.05). CONCLUSIONS: For patients with MUO who require long-term retention of the stent, metallic stents with longer indwelling time are superior to ordinary polymeric stents.

[Silencing effect of cell-specific RNA interference plasmid pPSMAe/p-shNS-ploy(A) loaded by transgenic vector Tf-PEG-PEI targeting nucleostemin on prostate cancer cells in vitro].

OBJECTIVE: To explore the transgenic efficiency of non-viral vector Tf-PEG-PEI and the cell specific silencing effect of plasmid pPSMAe/p-shNS-ploy(A) on prostate cancer cells. METHODS: Polyethyleneimine (PEI) was modified by using polyethylene glycol and transferrin to synthesize the non-viral vector Tf-PEG-PEI. NS-specific plasmids pPSMAe/p-shNS-ploy(A) and Tf-PEG-PEI were used to transfect prostate cancer LNCap and PC-3 cells. The changes of cell morphology, proliferation ability and cell cycle were studied after down-regulating the NS gene level. RESULTS: Tf-PEG-PEI was successfully modified. After transfection, the PSMA-expressing LNCaP cells became larger and showed more pseudopodia, having a tendency to differentiate. Their cell proliferation ability was reduced, and the detection of cell cycle showed a decrease of S phase and an increase of G(1) phase after knocking down NS gene. These targets were not changed in non-PSMA-expresing PC-3 cells. CONCLUSIONS: The non-viral vector Tf-PEG-PEI has a high ability to transfer targeted gene into target cells. The cellular specificity of short-hairpin RNA transcription driven by PSMAe/p is confirmed by silencing NS gene. The use of cell specific promoter may be an effective strategy of gene therapy for prostate cancer.

[Development of glipizide push-pull osmotic pump controlled release tablets by using expert system and artificial neural network].

The purpose of this study is to develop glipizide push-pull osmotic pump (PPOP) tablets by using a formulation design expert system and an artificial neural network (ANN). Firstly, the expert system for the formulation design of osmotic pump of poor water-soluble drug was employed to design the formulation of glipizide PPOP, taking the dissolution test results of Glucotrol XL as the goal. Then glipizide PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. And in vivo evaluation was carried out between the samples which were similar to Glucotrol XL and the Glucotrol XL in Beagle dogs. The range of the factors of formulation and procedure, which could influence the drug release, was optimized using artificial neural network. Finally, the design space was found. It was found that the target formulation which was similar to Glucotrol XL in dissolution test could be obtained in a short period by using the expert system. The samples which were similar to Glucotrol XL were bio-equivalent to the Glucotrol XL in Beagle dogs. The design space of the key parameter coating weight gain was 9.5%-12.0%. It could be concluded that a well controlled product of glipizide PPOP was developed since the dissolution test standard of our product was more strict than that of Glucotrol XL.

[Effects of modification of transferrin on cytotoxicity and intracellular delivery of paclitaxel loaded PLGA nanoparticles].

OBJECTIVE: To evaluate the effects of modification of transferrin on cytotoxicity and intracellular delivery of paclitaxel loaded Poly (lactide-co-glycolide) (PLGA) nanoparticle (NPs). METHODS: PLGA NPs were formulated with microemulsion method, Polyvinyl alcohol (PVA) was used as surfactant (PVA NPs). Transferrin (Tf) was used to modify the NPs (Tf NPs). The cytotoxicity of paclitaxel solution and paclitaxel loaded PVA NPs and Tf NPs were measured in bladder cancer cell line J-82. The intracellular delivery of two kinds of NPs was measured. RESULTS: The half maximal inhibitory concentration (IC50) of paclitaxel loaded PVA NPs and Tf NPs was (44 ± 7) and (49 ± 11) ng/ml respectively and significantly lower than that of paclitaxel solution, which was (81 ± 18) ng/ml (both P < 0.05). The uptake of PVA NPs and Tf NPs by J-82 cells after 2 hours was (89 ± 19) µg/mg cellular protein and (76 ± 16) µg/mg cellular protein. The uptake of two kinds of NPs had no significantly difference. The intracellular level of NPs decreased significantly upon the withdrawal of NPs in medium. However, it became stable 2 hours later and 11.3% PVA NPs and 18.0% Tf NPs remained. The intracellular level of PVA NPs and Tf NPs had no significantly difference at any time point. NPs were distributed in cytoplasm after endocytosis. CONCLUSIONS: PLGA NPs can significantly improve the anti-neoplastic effect of paclitaxel on bladder cancer. However, modification of Tf does not change the intracellular dynamics.

Correlation between bone volume fraction in posterior implant area and initial implant stability.

OBJECTIVE: Bone volume fraction (BV/TV) was used as a quantitative indicator of bone mineral density (BMD) in the posterior dental implant area, and the relationship between it and the initial stability of the implant was analyzed. METHODS: 53 patients with posterior dental implantation were selected. Remove the bone fragments from the planting area and put them in the formalin solution. Then, the implant was placed after the operator prepared the hole step by step. Peak Insertion torque value (ITV) and Implant stability quotient (ISQ) were recorded. The BV/TV of the bone fragments was measured by Image pro Plus6.0. The correlation between it and ITV and ISQ was analyzed. RESULTS: BV/TV was correlated with ITV and ISQ in the posterior dental planting area (r=0.862, r=0.832, P < 0.05). The correlation of the parameters in the posterior part of maxilla was higher than that in the mandible. There were significant differences in BV/TV, ITV, and ISQ between the mandible and maxilla, and the implant area of the mandible was higher than that of the maxilla. CONCLUSION: BV/TV can provide an objective index for BMD in the implant area, which has an important influence on the evaluation of the initial stability of the implant.

SP1/TGF­ß1/SMAD2 pathway is involved in angiogenesis during osteogenesis.

The relationship between osteoblasts and angiogenesis is vital for bone regeneration, especially mandibular and maxillary bones. Transforming growth factor ß1 (TGF­ß1) and vascular endothelial growth factor (VEGF) are closely related to angiogenesis; however, the regulatory mechanism between them remains unknown. The present study aimed to reveal this mechanism to provide novel insight for development of potential therapeutic opportunities. Western blotting and reverse transcription­quantitative PCR was used to assess the protein and mRNA expression levels in MC3T3­E1 preosteoblast cells and HUVECs, ELISAs were used to detect the expression levels of secreted VEGF, MTT assays were used to assess the viability of the cells, migratory ability was assessed using Transwell assays, angiogenesis assays were used to analyze the formation of blood vessels, and TGF­ß1 regulation was confirmed using a dual­luciferase reporter assay. The overexpression of specificity protein 1 (SP1) or TGF­ß1 increased VEGF expression levels and secretion, and promoted angiogenesis of co­cultured HUVECs. SP1 also promoted SMAD2 phosphorylation. These effects of SP1 were all reversed by the TGF­ß1 inhibitor. The VEGF inhibitor bevacizumab also reduced the SP1/TGF­ß1/SMAD2 pathway­induced angiogenesis of preosteoblasts. In conclusion, it was demonstrated that SP1 promoted TGF­ß1 expression, activated the SMAD2 pathway and induced VEGF secretion, which may enhance angiogenic processes in preosteoblasts.

[Optimization of a floating osmotic pump system of dipyridamole using central composite design-response surface methodology].

A new type of floating osmotic pump of dipyridamole was designed in this paper. Apparatus three (Chinese Pharmacopeia 2005, appendix XD) was employed for in vitro dissolution test in order to evaluate the release and floating behavior in a same experiment. The system was optimized using central composite design-response surface methodology; where similarity factor (f2) between the dissolution profile of prepared formulation and the target dissolution profile was taken as dependent factor, usage amount of polyoxyethylene (X1, mg), NaCl (X2, mg) and pore former (PEG4000, X3, %) were taken as independent factors. The optimization model was f2 = -29.3 + 2.35X3 - 0.123X1(2) - 0.046X2(2) + 0.145X1X2 (R = 0.996). It was found that the dissolution profile could match the target dissolution profile under the condition of weight gain 8%-9%, X1 (20-34), X2 (30-57), X3 = 50. It is also found that the minimum usage percentage of pore former is 35.1%. The prediction results of the optimization model were good in the experiments.

[Comparative study of 3D printing implant guide in different implant surgeries in anterior tooth defect area].

OBJECTIVE: To study the accuracy of 3D printing implant-guided anterior tooth implantation under flap or flapless surgery. METHODS: Twenty-one cases (32 teeth) with missing teeth were divided into two groups: tooth implantation on the maxillary models under flap surgery (FP group) and tooth implantation on the maxillary models under flapless surgery (FPS group). A dental implant guide was designed and used in the two groups. The actual position of the dental implants in the two groups was compared with the preplanned deviation values of implant top, bottom, vertical distance, and angle deviation. SPSS 19.0 software was used for statistical analysis. RESULTS: The deviation values of implant top, bottom, vertical distance, and angle were significantly lower in the FP group than in the FPS group (P<0.05). CONCLUSIONS: High accuracy of tooth implantation can be realized by using the 3D printing implant guide. The different surgical methods influence the precision of tooth implantation. Clinicians can choose the surgery reasonably depending on the actual situation.

In vivo remineralization of dentin using an agarose hydrogel biomimetic mineralization system.

A novel agarose hydrogel biomimetic mineralization system loaded with calcium and phosphate was used to remineralize dentin and induce the oriented densely parallel packed HA layer on defective dentin surface in vivo in a rabbit model. Firstly, the enamel of the labial surface of rabbits' incisor was removed and the dentin was exposed to oral environment. Secondly, the hydrogel biomimetic mineralization system was applied to the exposed dentin surface by using a custom tray. Finally, the teeth were extracted and evaluated by scanning electron microscopy, X-ray diffraction, and nanoindentation test after a certain time of mineralization intervals. The regenerated tissue on the dentin surface was composed of highly organised HA crystals. Densely packed along the c axis, these newly precipitated HA crystals were perpendicular to the underlying dental surface with a tight bond. The demineralized dentin was remineralized and dentinal tubules were occluded by the grown HA crystals. The nanohardness and elastic modulus of the regenerated tissue were similar to natural dentin. The results indicated a potential clinical use for repairing dentin-exposed related diseases, such as erosion, wear, and dentin hypersensitivity.

Silicon Phthalocyanines Axially Disubstituted with Erlotinib toward Small-Molecular-Target-Based Photodynamic Therapy.

Small-molecular-target-based photodynamic therapy-a promising targeted anticancer strategy-was developed by conjugating zinc(II) phthalocyanine with a small-molecular-target-based anticancer drug. To prevent self-aggregation and avoid problems of phthalocyanine isomerization, two silicon phthalocyanines di-substituted axially with erlotinib have been synthesized and fully characterized. These conjugates are present in monomeric form in various solvents as well as culture media. Cell-based experiments showed that these conjugates localize in lysosomes and mitochondria, while maintaining high photodynamic activities (IC50 values as low as 8 nm under a light dose of 1.5 J cm-2 ). With erlotinib as the targeting moiety, two conjugates were found to exhibit high specificity for EGFR-overexpressing cancer cells. Various poly(ethylene glycol) (PEG) linker lengths were shown to have an effect on the photophysical/photochemical properties and on in vitro phototoxicity.

A Direct Electric Field-Aided Biomimetic Mineralization System for Inducing the Remineralization of Dentin Collagen Matrix.

This in vitro study aimed to accelerate the remineralization of a completely demineralized dentine collagen block in order to regenerate the dentinal microstructure of calcified collagen fibrils by a novel electric field-aided biomimetic mineralization system in the absence of non-collagenous proteins. Completely demineralized human dentine slices were prepared using ethylene diamine tetraacetic acid (EDTA) and treated with guanidine hydrochloride to extract the bound non-collagenous proteins. The completely demineralized dentine collagen blocks were then remineralized in a calcium chloride agarose hydrogel and a sodium hydrogen phosphate and fluoride agarose hydrogel. This process was accelerated by subjecting the hydrogels to electrophoresis at 20 mA for 4 and 12 h. X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) were used to evaluate the resultant calcification of the dentin collagen matrix. SEM indicated that mineral particles were precipitated on the intertubular dentin collagen matrix; these densely packed crystals mimicked the structure of the original mineralized dentin. However, the dentinal tubules were not occluded by the mineral crystals. XRD and EDX both confirmed that the deposited crystals were fluorinated hydroxyapatite. TEM revealed the existence of intrafibrillar and interfibrillar mineralization of the collagen fibrils. A novel electric field-aided biomimetic mineralization system was successfully developed to remineralize a completely demineralized dentine collagen matrix in the absence of non-collagenous proteins. This study developed an accelerated biomimetic mineralization system which can be a potential protocol for the biomineralization of dentinal defects.

Luzindole, a melatonin receptor antagonist, inhibits the transient outward K+ current in rat cerebellar granule cells.

The inhibitory effect of the melatonin receptor antagonist luzindole on voltage-activated transient outward K(+) current (I(K(A))) was investigated in cultured rat cerebellar granule cells using the whole cell voltage-clamp technique. At the concentration of 1 microM to 1 mM, luzindole reversibly inhibited I(K(A)) in a concentration-dependent manner. In addition to reducing the current amplitude of I(K(A)),luzindole accelerated the fast inactivation of I(K(A)) channels and shifted the curves of voltage-dependent steady-state activation and inactivation of I(K(A)) by +6.6 mV and -7.0 mV, respectively. The inhibitory effect of luzindole was neither use-dependent nor voltage-dependent, suggesting that the binding affinity of luzindole to I(K(A)) channels is state-dependent. Including luzindole in the pipette solution, or extracellular application of 4 P-PDOT, an antagonist of melatonin receptors, did not change the luzindole-induced inhibitory effect on the I(K(A)) current, indicating that luzindole exerts its channel blocking inhibitory action at the extracellular mouth of the channel, and that the effect is not due to action of the melatonin receptors. Our data are the first demonstration that luzindole is able to block transient outward K(+) channels in rat cerebellar granule cells in a state-dependent manner, likely associated with extracellular interaction of the drug with the I(K(A)) inactivation gate.

[Relationships between melatonin and cortisol and the status of disease in patients with bronchial asthma].

OBJECTIVE: The aim of the study was to elucidate the interaction and clinical significance between melatonin and cortisol and the status of disease in patients with bronchial asthma. METHODS: Ten mild persistent and 10 moderate-to-severe persistent asthma patients were recruited to participate in the study. Fifteen normal subjects served as contrds Salivary free melatonin and cortisol were measured simultaneously by radioimmunoassay in all subjects, and 8 salivary samples were collected in a series during a 24-hour period in each subject. The intensity of light was restricted to natural light at room during the daytime and less than 50 lux at night. RESULTS: The results showed that salivary free melatonin levels were significantly lower in mild (15.5 +/- 5.3) micro g/L and moderate-to-severe (7.1 +/- 2.5) micro g/L persistent asthma patients as compared to control subjects (28.9 +/- 8.7) micro g/L (F = 4.47, P < 0.05; F = 7.61, P < 0.01, respectively). The results also showed that salivary free cortisol levels were significantly lower in mild (3.1 +/- 0.5) micro g/L and moderate-to-severe (4.2 +/- 0.5) micro g/L persistent asthma patients as compared to control subjects (5.9 +/- 0.7) micro g/L (F = 10.45, P < 0.01; F = 5.21, P < 0.05, respectively). The amplitude of salivary free cortisol level was reduced in mild and moderate-to-severe persistent asthma patients, and salivary cortisol peak level was significantly delayed in mild and moderate-to-severe persistent asthma patients (P < 0.05, P < 0.01, respectively). There were no significant correlations between the salivary free melatonin and cortisol levels in control and mild persistent asthma patients (r = 0.174, P = 0.057; r = -0.138, P = 0.221, respectively). However, a significant negative correlation was found between the salivary free melatonin and cortisol levels in moderate-to-severe persistent asthma patients (r = -0.275, P = 0.013). CONCLUSIONS: There were lower salivary free melatonin and cortisol levels in asthmatic patients. A significant negative correlation was found between melatonin and cortisol levels in moderate-to-severe persistent asthma patients. Furthermore, the reciprocal inhibition of melatonin and cortisol was closely associated with the status of disease in asthmatic patients.

Overcome side identification in PPOP by making orifices on both layers.

The original purpose of this research was to build a database for an expert system. Unexpectedly, it was found that the color-identifying device in push-pull osmotic pump (PPOP) manufacturing process could be unnecessary. Water-insoluble drug indapamide, gliclazide and dipyridamole were employed as model drugs. Bunches of conventional formulations were designed; and traditional preparation procedures were used. In vitro drug release was studied; and the similarity between the conditions of orifice only on the side of the drug layer and orifices of the same diameter on both sides was evaluated. It was found that the drug release from PPOP could be influenced by formulation and core hardness while it could hardly be influenced by orifice size. No significant difference was observed between the dissolution profiles of orifice only on the side of the drug layer and orifices of the same diameter on both sides. Mechanism of drug release was discussed. The conclusion was that the disadvantage of side identification in PPOP manufacturing process could be overcome by drilling orifices on both sides.

The investigation of protein adsorption behaviors on different functionalized polymers films.

The adsorption of BSA and fibrinogen onto plasma-polymerized di-(ethylene glycol) vinyl ether, allylamine, and maleic anhydride films were investigated in detail by surface plasmon resonance spectroscopy (SPR). The chemical properties of the plasma polymers were initially determined by the plasma deposition conditions during the generation procedure. The analysis of the chemical structure of the films and the refractive index of plasma polymers in aqueous solution was carried out using Fourier transform infrared spectroscopy and waveguide mode spectroscopy, respectively. Using water contact angle measurement, the surface wettability of plasma polymers was also characterized. These properties have a critical influence on the behavior of protein adsorption on the surface of the plasma polymers. Protein adsorption was found to depend not only on the types of functionalized groups, but also on the plasma polymer thickness since the protein molecules penetrate into the plasma polymer network bulk. According to the size of protein molecules in aqueous solution and the amount of adsorbed proteins observed by SPR, the conformational changes of proteins could be deduced.

Alterations in circadian rhythms of melatonin and cortisol in patients with bronchial asthma.

AIM: To investigate the possible relationships between alterations in circadian rhythm of melatonin, cortisol and bronchial asthma. METHODS: Salivary melatonin and cortisol were measured simultaneously by radioimmunoassay in 10 mild intermittent or persistent patients, 11 moderate-to-severe persistent asthma patients, and 15 control subjects. Twelve salivary samples were collected in a series during a 24-h period in each subject. RESULTS: The results showed overall lower levels of salivary melatonin in asthma patients compared with control subject (P<0.01). The amplitude, peak-level, and baseline of salivary melatonin were significantly lower in mild intermittent or persistent (P<0.01, P<0.05) and moderate-to-severe persistent asthma patients (P<0.01) compared with control group. The 24-h mean level of salivary cortisol was greatly lower and the acrophase was markedly delayed in patients with mild intermittent or persistent asthma (P<0.01) and moderate-to-severe persistent asthma (P< 0.05, P<0.01) compared with control subject. CONCLUSION: Disordered circadian rhythms of salivary melatonin and cortisol were found in asthma patients, which may be involved in the pathogenesis of bronchial asthma.