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2.
Controlled release of lidocaine hydrochloride from the surfactant-doped hybrid xerogels. 总被引:2,自引:0,他引:2
We investigate the controlled release of lidocaine hydrochloride from the doped silica-based xerogels. In the xerogel preparation, tetraethoxysilane (TEOS), methyltriethoxysilane (MTES), and propyltriethoxysilane (PTES) are used as precursors, and a nonionic surfactant Igepal CO 720 is used as a dopant. The experimental results suggest that the release of lidocaine hydrochloride can be easily controlled by partially substituting TEOS with the organosilanes, and/or by adding the dopant. Adding the organosilane precursors lowers the release of both the drug and the surfactant in the order of TEOS, MTES/TEOS, and PTES/TEOS xerogels. The release from the PTES/TEOS xerogels is much lower than that from the other xerogels. The release of lidocaine hydrochloride is obviously suppressed by the addition of Igepal CO 720, while the release of Igepal CO 720 is slightly promoted by the addition of the drug. The overall release process is found to be diffusion-controlled, and the release behaviors can be well explained by considering the effects of the textual properties of the xerogels and the interactions among the drug, the surfactant, and the xerogel matrices. 相似文献
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4.
Blockade of LTB4-induced chemotaxis by bioactive molecules interfering with the BLT2-Gαi interaction
BLT2, a low-affinity leukotriene B4 (LTB4) receptor, is a member of the G-protein coupled receptor (GPCR) family and is involved in the pathogenesis of inflammatory diseases such as asthma. Despite its clinical implications, however, no pharmacological inhibitors are available. In the present study, we screened for small molecules that interfere with the interaction between the third intracellular loop region of BLT2 (BLT2iL3) and the Gαi3 protein subunit (Gαi3), using a high-throughput screening (HTS) assay with a library of 1040 FDA-approved drugs and bioactive compounds. We identified two small molecules—purpurin [1,2,4-trihydroxy-9,10-anthraquinone; IC50 = 1.6 μM for BLT2] and chloranil [tetrachloro-1,4-benzoquinone; IC50 = 0.42 μM for BLT2]—as specific BLT2-blocking agents. We found that blockade of the BLT2iL3-Gαi3 interaction by these small molecules inhibited the BLT2-downstream signaling cascade. For example, BLT2-signaling to phosphoinositide-3 kinase (PI3K)/Akt phosphorylation was completely abolished by these molecules. Furthermore, we observed that these small molecules blocked LTB4-induced chemotaxis by inhibiting the BLT2-PI3K/Akt-downstream, Rac1-reactive oxygen species-dependent pathway. Taken together, our results show that purpurin and chloranil interfere with the interaction between BLT2iL3 and Gαi3 and thus block the biological functions of BLT2 (e.g., chemotaxis). The present findings suggest a potential application of purpurin and chloranil as pharmacological therapeutic agents against BLT2-associated inflammatory human diseases. 相似文献
5.
Su Jin Park Su Jin Kim Yumie Rhee Ji Hyun Byun Seong Hwan Kim Myoung Hee Kim Eun Jig Lee Sung-Kil Lim 《Journal of bone and mineral research》2007,22(6):889-896
The FIGNL1 gene was proven to be a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). In this in vitro study, the AAA proteins inhibited osteoblast proliferation and stimulated osteoblast differentiation. We showed that FIGNL1 may play some regulatory role in osteoblastogenesis. INTRODUCTION: The fidgetin-like 1 (FIGNL1) gene encodes a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). Although the FIGNL1 protein localizes to both the nucleus and cytoplasm, the function of FIGNL1 remains unknown. In a previous study, we identified several genes that mediate the anabolic effects of basic fibroblast growth factor (bFGF) on bone by using microarray data. FIGNL1 was one of the genes that downregulated >2-fold in MC3T3-E1 cells after treatment with bFGF. Therefore, this study was aimed to identify and confirm the function of FIGNL1 on osteoblastogenesis. MATERIALS AND METHODS: We examined the effect of the FIGNL1 gene on proliferation, differentiation, and apoptosis in mouse osteoblast cells (MC3T3-E1 and mouse primary calvarial cells) using flow cytometry, RT-PCR, cell proliferation assay, and cell death assay. MC3T3-E1 cells and mouse calvarial cells were transfected with small interfering RNA (siRNA) directed against the FIGNL1 or nontargeting control siRNA and examined by cell proliferation and cell death assays. Also, FIGNL1 was fused to enhance green fluorescent protein (EGFP), and the EGFP-fused protein was transiently expressed in MC3T3-E1 cells. RESULTS: Reduced expression of FIGNL1 by bFGF and TGF-beta1 treatment was verified by RT-PCR analysis. Overexpression of FIGNL1 reduced the proliferation of MC3T3-E1 and calvarial cells, more than the mock transfected control cells did. In contrast, siFIGNL1 transfection significantly increased the proliferation of osteoblasts, whereas overexpression of FIGNL1 did not seem to alter apoptosis in osteoblasts. Meanwhile, overexpression of FIGNL1 enhanced the mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN) in osteoblasts. In contrast, siFIGNL1 decreased the expression of ALP and OCN. A pEGFP-FIGNL1 transfected into MCT3-E1 cells had an initially ubiquitous distribution and rapidly translocated to the nucleus 1 h after bFGF treatment. CONCLUSIONS: From these results, we proposed that FIGNL1, a subfamily member of the AAA family of proteins, might play some regulatory role in osteoblast proliferation and differentiation. Further analyses of FIGNL1 will be needed to better delineate the mechanisms contributing to the inhibition of proliferation and stimulation of osteoblast differentiation. 相似文献
6.
7.
Otitis media is a common childhood disease caused by multiple factors. Understanding the pathogenesis of otitis media is important in the diagnosis and management of it. The mode of therapy should be chosen depending on the type and stage of the disease. Treatment options available to an otolaryngologist include antibiotics, tympanocentesis, myringotomy and tympanostomy tube insertions, adenoidectomy with or without tonsillectomy, exploratory tympanotomy, atympanoplasty, and mastoidectomy. 相似文献
8.
Phospholipase C (PLC) isozymes are known to be regulated, in part, by heterotrimeric GTP-binding protein (G-protein) subunits, including Gα subunits of the Gq family and Gβγ subunits. New data show that PLC can also be regulated by a high molecular weight G-protein that doubles as a cellular transglutaminase. Furthermore, a soluble phosphatidylinositol transfer protein (PITP) has been implicated in sustaining the activity of PLC by delivering substrate to the plasma membrane. Such diverse regulatory mechanisms imply that the PLC isozymes are precisely controlled and have specific roles in generating second messengers in response to various external stimuli. 相似文献
9.
Kyung Cheon Kim Kwang Jin Rhee Hyun Dae Shin Young Mo Kim 《Knee surgery, sports traumatology, arthroscopy》2007,15(12):1478-1481
Calcific tendinitis is a common condition with characteristic clinical and radiological findings. Although we do not know
which condition initiated the pathologic cascade, we present a rare case of calcific tendinitis of the long head of the biceps
brachii at its origin, associated with a SLAP lesion. The calcium deposit was removed and the SLAP lesion was repaired with
a suture anchor arthroscopically. 相似文献
10.
Rhee SH 《Biomaterials》2004,25(7-8):1167-1175
Effect of poly(epsilon-caprolactone) (PCL) content on the bioactivity and mechanical properties of PCL/silica hybrid was investigated. The PCL/silica hybrids with different PCL contents were prepared through co-condensation reaction with triethoxysilane end capped PCL and tetraethyl orthosilicate. The higher the PCL content in the hybrid, the lower the apatite-forming rate and showed polymer-like ductile-tough fracture behavior. On the contrary, the lower the PCL content in the hybrid, the higher the apatite-forming rate and showed ceramic-like hard-brittle fracture behavior. At the intermediate PCL content, the apatite-forming rate and its mechanical properties showed also intermediate behaviors. The highest tensile strength and Young's modulus could be obtained at intermediate PCL content and they were around 20 and 600 MPa, respectively, while the strain at failure was around 50%. This new kind of hybrid material is likely to have the potential to be used as a bone repairing material because of its apatite-forming ability and the mechanical properties comparable to human cancellous bone. 相似文献