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111.
A novel preparative method for hexaprofen, which is a potent antiinflammatory agent, is described. Friedel-Crafts reaction of cyclohexylbenzene with ethyl α-chloro-α-(methylthio) acetate1 and α-chloro-α-(methylthio) acetonitrile2 afforded ethyl 2-(methylthio)-2-(4-cyclohexylphenyl) acetate7 and 2-methylthio-2-(4-cyclohexylphenyl) acetonitrile8, respectively. Compounds7 and8 were converted into the corresponding ethyl 2-methylthio-2-(4-cyclohexylphenyl) propionate9 and 2-methylthio-2-(4-cyclohexylphenyl) propionitrile10 by methylation with sodium hydride and methyl iodide. Hexaprofen13 was prepared by hydrolysis of ethyl 2-(4-cyclohexylphenyl) propionate11 and of 2-(4-cyclohexylphenyl) propionitrile12 followed by desulfurization of compounds9 and10. 相似文献
112.
Glutamate excitotoxicity, which is mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA receptors, directly contributes to the neuronal cell loss associated with both acute insults and chronic neurodegenerative disorders. Conjugated linoleic acid (CLA) is a group of dienoic derivatives of linoleic acid shown to have anticarcinogenic and antioxidative activities. To evaluate the effect of a mixture of CLA isomers (cis-9, trans-11 and cis-10, trans-12 octadecadienoic acids) on glutamate- and NMDA-induced excitotoxicity, primary cultures of rat cortical neurons were treated for 15 min with 300 microM glutamate or NMDA in the presence of various concentrations of CLA. After the exposure, cell cultures were maintained at 37 degrees C for 18 h in minimum essential medium supplemented with glucose. Neuronal injury was measured by a colorimetric cell proliferation assay, and a qualitative assessment was made by phase-contrast microscopy. CLA inhibited glutamate- and NMDA-induced neuronal cell death in a concentration-dependent fashion with the most effective dose for neuroprotection being 500 microM. These results demonstrate that a mixture of CLA isomers exhibits protective action against glutamate- and NMDA-induced excitotoxicity. 相似文献
113.
Abstract: We made an artificial skin comprised of a stratified layer of keratinocytes and a dermal matrix with a type I collagen containing fibroblasts. In this work, we showed keratinocyte behavior under primary culture, gel contractions varying with concentration of collagen solution, and cell growth plots in the collagen gel. The optimum behavior of dermal equivalent could be obtained using 3.0 mg/ml collagen solution and attached gel culture. The attached gel culture had a jumping effect of growth factor on cell growth at the lag phase. To develop the artificial skin, 1× 105 cells/cm2 of keratinocytes were cultured on the dermal equivalent at air-liquid interface. Finally, to overcome the problem that artificial skin of collagen gel was torn easily during suturing of grafting, we prepared histocompatible collagen mesh and attached the mesh to the bottom of the gel. Cultured artificial skins were successfully grafted onto rats. 相似文献
114.
115.
Sequential production and activation of matrix-metalloproteinase-9 (MMP-9) with breast cancer progression 总被引:10,自引:0,他引:10
Sun Young Rha Joo Hang Kim Jae Kyung Roh Kyong Sik Lee Jin Sik Min Byung Soo Kim Hyun Cheol Chung 《Breast cancer research and treatment》1997,43(2):175-181
The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical pointin tumor invasion and metastasis. We measured theactivity of MMP-9 from 28 normal, 12 benignand 126 breast cancer tissues using gelatin zymographywith an image analysis system. ProMMP-9 was expressedin 17.5% of the cancer patients compared to2.5% in 40 non-cancerous tissues (p=0.014).The mature form of MMP-9 (82 kD) wasexpressed only in T2–T4 stages. During the earlyphase of breast cancer (DCIS and T1 stage)progression, only production of proMMP-9 increased. However, asthe cancer grew or invaded skin (T2–T4), orwith lymphovascular permeation, both production and activation ofMMP-9 increased. In conclusion, proMMP-9 production was themain cause of increased MMP-9 activity during theearly phase, while both production and activation increasedin the late phase of breast cancer. 相似文献
116.
Purpose: To investigate the relationships between the axonal sprouting and target neurotization by central neurons after nerve heterocon-nection. Methods: Unilateral (right) vagal-hypoglossal nerve anastomosis (VHA) was performed in adult cats. Following 3-315 days postoperation (dpo), quantitative analyses and ultrastructural changes in the proximal portion of the vagal-hypoglossal heteroconnected nerve as well as the time course of neuronal regeneration were studied. Along with this, horseradish peroxidase (HRP) retrograde tracing technique was used to label the neurons of dorsal motor vagal nucleus (DMV) and nucleus ambiguus (NA) to ascertain if target neurotization was established. Results: The contralateral (left) intact vagus nerve proximal to the level of ansa cervicalis showed an average of 33 +/- 1 myelinated and 74 +/- 4 unmyelinated axons in 727 &mgr;m(2) sectional area of the nerve. In the heteroconnected nerve at the corresponding level just proximal to the anastomosis site, there was a marked increase in the number of small axons sprouting from the unmyelinated nerve fibers between 18 and 25 dpo. The number of these axonal sprouts appeared to decline at 32 dpo but its increase of 131 % was sustained until the late regeneration stage at 315 dpo when compared with the contralateral nerve serving as a control. The mean number of myelinated axons per area unit (727 &mgr;m(2)) was reduced to 18 at 3 dpo but was immediately restored to the normal range at 7 dpo. The retrograde labelling of neurons in both the DMV and NA was first detected at 22 dpo and was progressively increased peaking by about 67 dpo. Conclusions: We conclude that compared with the unmyelinated axons, the myelinated axons may acquire a superior interaction with the new target. Furthermore, the postoperative neurotization of tongue muscles may initiate and facilitate the retraction of the redundant axonal sprouts. 相似文献
117.
Myositis ossificans originating from the chest wall is extremely rare. We report a case of myositis ossificans occurring in a young woman with progressive painful swelling in the chest wall. Preoperative examination suggested a malignant neoplasm originating from soft tissue. Although rare, myositis ossificans is one of the potential causes of painful swelling in the chest wall, and can be mistaken for a malignant neoplasm. 相似文献
118.
119.
Amphiphilic amino acid copolymers as stabilizers for the preparation of nanocrystal dispersion 总被引:2,自引:0,他引:2
Jonghwi Lee Soo-Jeong Lee Ji-Yeun Choi Ji Youn Yoo Cheol-Hee Ahn 《European journal of pharmaceutical sciences》2005,24(5):441-449
The recent advance of particle size engineering in nanometer ranges has widened the formulation opportunities of relatively water-insoluble drugs. However, the ‘nanoformulation’ suffers from a lack of systematic understanding about the requirements of polymeric stabilizers. Furthermore, the polymers that can be used for the preparation of nanocrystals are so limited that finding a proper stabilizer for a given formulation is often difficult. In this study, amino acid copolymers whose properties can systematically be tailored are developed, and their morphological and compositional effects are investigated. Copolymers containing lysine (K) as their hydrophilic segments, and phenylalanine (F) or leucine (L) as their hydrophobic segments successfully produce stable nanocrystals (200–300 nm) in water, while copolymers of K and alanine (A) could not generate nanosized particles. Not the morphology but the hydrophobicity of copolymers seems to be a critical parameter in the preparation of drug nanocrystals by wet comminution. The effective stabilization performance of copolymers requires the hydrophobic moiety content to be higher than 15 mol%. Comminution for only 5 min is long enough for nanocrystal preparation, and the crystallinity of drug is found intact after the processing. 相似文献
120.
Ahwon Lee Sung-Hak Lee Chan Kwon Jung Gyungsin Park Kyo Young Lee Hyun Joo Choi Ki Ouk Min Tae Jung Kim Eun Jung Lee Youn Soo Lee 《Pathology, research and practice》2018,214(5):713-719
Targeted application of next-generation sequencing (NGS) technology allows detection of specific mutations that can provide treatment opportunities for cancer patients. We evaluated the applicability of the Ion AmpliSeq Cancer Hotspot Panel V2 (CHV2) using formalin-fixed, paraffin-embedded (FFPE) tissue of clinical specimens.Thirty-five FFPE tumour samples with known mutational status were collected from four different hospitals and sequenced with CHV2 using an Ion Chef System and Ion S5 XL system. Out of 35 cases, seven were sequenced with Oncomine focus Assay Panel for comparison. For the limit of detection test, we used an FFPE reference standard, a cell line that included an engineered 50% EGFR T790?M in an RKO cell line background. Coverage analysis results including number of mapped reads, on target percent, mean depth, and uniformity were not different according to hospitals. Sensitivity for mutation detection down to 3% was demonstrated. NGS results showed 100% concordance with the results from single molecular pathology tests Assay in 30 cases with 24 known positive mutations and 14 known negative mutations, and another NGS panel of the Oncomine focus in seven cases.The CHV2 NGS test for solid tumours using Ion chef system and S5 XL system in clinical molecular pathology laboratories for analysis of solid tumours could be routinely used and could replace some single molecular pathology tests after a stringent and thorough validation process. 相似文献