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1.
Synthesis of novel nonionic surfactants has attracted attention of synthetic chemists due to the issues of the currently used commercial surfactants. The synthesis of three biocompatible triazole-based nonionic surfactants is reported for nanovesicular drug loading. The surfactants were synthesized in a three-step reaction and characterized using 1HNMR and mass spectroscopy techniques. They were investigated for their critical micelle concentration (CMC) using a UV–Visible spectrophotometer. Their biocompatibility was investigated against cell culture and in blood. All the synthesized nonionic surfactants were further explored for their nanovesicular drug loading using clarithromycin as a model hydrophobic drug. Nonionic surfactants revealed lower CMC in 35–45 μM and were less hemolytic and cytotoxic. They were capable of self-assembling in nanosize niosomal vesicles encapsulating increased amounts of drug. The results suggest the synthesized nonionic surfactants as biocompatible nanotechnology-based drug-delivery vehicles. 相似文献
2.
The kinetics of substrate removal by the liver and the resulting nonlinear changes in unbound fraction along the flow path at varying input drug concentrations were examined by a model simulation study. Specifically, we varied the binding association constant, KA, and the Michaelis-Menten constants (Km and Vmax) to examine the steady state drug removal (expressed as hepatic extraction ratio E) and changes in drug binding for (i) unienzyme systems and (ii) simple, parallel metabolic pathways; zonal metabolic heterogeneity was also added as a variable. At low KA, E declined with increasing input drug concentration, due primarily to saturation of enzymes; only small differences in binding were present across the liver. At high KA, a parabolic profile for E with concentration was observed; changes in unbound fraction between the inlet and the outlet of the liver followed in parallel fashion. Protein binding was the rate-determining step at low input drug concentrations, whereas enzyme saturation was the rate-controlling factor at high input drug concentration. Heterogeneous enzymic distribution modulated changes in unbound fraction within the liver and at the outlet. Despite marked changes in unbound fraction occurring within the liver for different enzymic distributions, the overall transhepatic differences were relatively small. We then investigated the logarithmic average unbound concentration and the length averaged concentration as estimates of substrate concentration in liver in the presence of nonlinear drug binding. Fitting of simulated data, with and without assigned random error (10%), to the Michaelis-Menten equation was performed; fitting was repeated for simulated data obtained with presence of a specific inhibitor of the high-affinity, anteriorly distributed pathway. Results were similar for both concentration terms: accurate estimates were obtained for anterior, high affinity pathways; an overestimation of parameters was observed for the lower affinity posteriorly distributed pathways. Improved estimations were found for posteriorly distributed pathways upon inhibition with specific inhibitors; with added random error, however, the improvement was much decreased. We applied the method for fitting of several sets of metabolic data obtained from rat liver perfusion studies performed with salicylamide (SAM) (i) without and (ii) with the presence of 2,6-dichloro-4-nitrophenol (DCNP), a SAM sulfation inhibitor. The fitted results showed that SAM sulfation was a high-affinity high-capacity pathway; SAM glucuronidation was of lower affinity but comparable capacity as the sulfation pathway, whereas SAM hydroxylation was of lower affinity and lower capacity. 相似文献
3.
4.
Todd M. Alam Joshua U. Otaigbe Dave Rhoades Gregory P. Holland Brian R. Cherry Paul G. Kotula 《Polymer》2005,46(26):12468-12479
Nanostructured polymer blends prepared via anionic ring opening polymerizations of cyclic monomers in the presence of a pre-made polymer melt exhibit a number of special properties over traditional polymer blends and homopolymers. Here, we report on a simple and versatile method of in situ polymerization of macrocyclic carbonates in the presence of a maleic anhydride polypropylene (mPP) matrix and a surface-active compatibilizer (i.e. PC grafted onto a mPP backbone generated in situ) to yield a micro- and nanostructured polymer blends consisting of a polycarbonate (PC) minor phase, and a polypropylene (PP) major phase. By varying the processing conditions and concentration of the macrocyclic carbonate it was possible to reduce the size of the PC dispersions to an average minor diameter of 150 nm. NMR and TEM characterizations indicate that the PC dispersions do not influence crystal content in the PP phase. Overall, the results point to a simple strategy and versatile route to new polymeric materials with enhanced benefits. 相似文献
5.
KS Atia AI El‐Batal 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2005,80(7):805-811
Glucose oxidase (EC 1.1.3.4) was immobilized on different polymeric materials using different immobilization techniques (entrapping by γ‐irradiation, and covalent binding using epichlorohydrin). Studies were carried out to increase the thermal stability of glucose oxidase (GOD) for different applications. The activity and stability of the resulting biopolymers have been compared with those of free GOD. The effect of different polyvinyl alcohol/polyacrylamide (PVA/PAAm) compositions of the copolymer carrier on the enzymatic activity of the immobilized GOD was studied. The maximum enzymatic activity was obtained with the composition ratio of PVA/PAAm of 60:40. The behaviour of the free and immobilized enzyme was analysed as a function of pH. A broadening in the pH profile (5.5–8) was observed for immobilized preparations. The activity and stability of the resulting biopolymers produced by immobilization of GOD onto different carriers have been compared, in both aqueous and organic media, with those of the free GOD. The enzyme's tolerance toward both heat and organic solvent was enhanced by immobilization onto polymers. The addition of different concentrations of organic solvents (10–50%, v/v) to the enzyme at higher temperature (60 °C) was found to stabilize the enzyme molecule. The strongest stabilizing effect on the enzymatic activity was achieved at a concentration of 10%. Copyright © 2005 Society of Chemical Industry 相似文献
6.
Interleukin-5 (IL-5) regulates the growth and function of eosinophils. It induces rapid tyrosine phosphorylation of Lyn and Jak2 tyrosine kinases. The role of tyrosine phosphatases in IL-5 signal transduction has not been investigated. In this study, we provide first evidence that SH2 protein tyrosine phosphatase 2 (SHPTP2) phosphotyrosine phosphatase plays a key role in prevention of eosinophil death by IL-5. We found that IL-5 produced a rapid activation and tyrosine phosphorylation of SHPTP2 within 1 min. The tyrosine phosphorylated SHPTP2 was complexed with the adapter protein Grb2 in IL-5-stimulated eosinophils. Furthermore, SHPTP2 appeared to physically associate with beta common (betac) chain of the IL-5 receptor (IL-5betacR). The association of SHPTP2 with IL-5betacR was reconstituted using a synthetic phosphotyrosine-containing peptide, betac 605-624, encompassing tyrosine (Y)612. The binding to the phosphotyrosine-containing peptide increased the phosphatase activity of SHPTP2, whereas the same peptide with the phosphorylated Y612--> F mutation did not activate SHPTP2. Only SHPTP2 antisense oligonucleotides, but not sense SHPTP2, could inhibit tyrosine phosphorylation of microtubule-associated protein kinase, and reverse the eosinophil survival advantage provided by IL-5. Therefore, we conclude that the physical association of SHPTP2 with the phosphorylated betac receptor and Grb2 and its early activation are required for the coupling of the receptor to the Ras signaling pathway and for prevention of eosinophil death by IL-5. 相似文献
7.
WI Bensinger KS Schiffman L Holmberg FR Appelbaum R Maziarz P Montgomery E Ellis S Rivkin P Weiden K Lilleby S Rowley S Petersdorf JP Klarnet W Nichols A Hertler R McCroskey CH Weaver CD Buckner 《Canadian Metallurgical Quarterly》1997,19(12):1183-1189
The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens. 相似文献
8.
How senile plaques and neurofibrillary tangles are linked represents a major gap in our understanding of the pathophysiology of Alzheimer's disease. We characterized a hippocampal neuronal culture system in which tau undergoes maturation in vivo; rat neurons maintained in culture for more than 3 weeks replicated the splicing and phosphorylation changes that tau undergoes upon maturation in situ. Using this model system, we induced an Alzheimer-like neuritic dystrophy following the application of fibrillar beta-amyloid. The dystrophy consisted of focal distortions and swellings within the neurites and an altered phosphorylation of the adult tau isoforms. Fibrillar beta-amyloid induced the concomitant activation of MAP kinase and GSK3 beta. The aberrant activation of several signaling pathways may lead to the abnormal phosphorylation of tau and neuritic degeneration. 相似文献
9.
KS Min AR Khan MK Kwon YJ Jung Z Yun Y Kiso 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2005,80(8):909-915
The performance of a laboratory‐scale anaerobic acidogenic fermenter fed with a mixture of blended kitchen food‐waste and primary sludge from a sewage treatment plant was investigated for the production of volatile fatty acids (VFA). The operating variables for acidogenic fermentation were kitchen food‐waste content (10 and 25 wt %), hydraulic retention time (HRT: 1, 3 and 5 days), temperature (ambient: 18 ± 2 °C, and mesophilic: 35 ± 2 °C) and pH (varied from 5.2 to 6.7). The experimental results indicated that effluent VFA concentrations and VFA production rates were higher at ambient temperature than at mesophilic conditions. The net amount of VFA with 10 wt % food‐waste increased up to 920 mg dm?3 with an increase of HRT, but contrasting results (a decrease of 2610 mg dm?3) were found due to the conversion of VFA into biogas in the case of 25 wt % food‐waste, which increased significantly at HRT of 3–5 days. In terms of biogas composition (CO2 and CH4), the organic matter was converted into CO2 through the oxidative pathway by facultative species at low temperature while mesophilic temperature and optimum pH (6.3–7.8) played a pivotal role in increasing rate of conversion of VFA into biogas by methanogenesis. Rates of VFA production and their conversion are dependent on the food‐waste content in the mixture. Yet, the higher concentration of food‐waste (25% compared with 10%) did not produce VFA proportionally due to the increased rate of conversion of VFA into gaseous products. The maximum VFA production rate (0.318 g VFAproduced g?1 VSfed day?1) was achieved in the 10 wt % food‐waste at ambient temperature and at a 5‐day HRT. Copyright © 2005 Society of Chemical Industry 相似文献
10.
RM Bionta G Blewitt CB Bratton D Casper A Ciocio R Claus M Crouch ST Dye S Errede GW Foster W Gajewski KS Ganezer M Goldhaber TJ Haines TW Jones D Kielczewska WR Kropp JG Learned JM LoSecco J Matthews HS Park LR Price F Reines J Schulz S Seidel E Shumard D Sinclair HW Sobel JL Stone L Sulak R Svoboda G Thornton van der Velde JC C Wuest 《Canadian Metallurgical Quarterly》1987,36(1):30-36