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排序方式: 共有398条查询结果,搜索用时 218 毫秒
121.
Cherney RJ Mo R Meyer DT Hardman KD Liu RQ Covington MB Qian M Wasserman ZR Christ DD Trzaskos JM Newton RC Decicco CP 《Journal of medicinal chemistry》2004,47(12):2981-2983
In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (MMP-2 IC(50) = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structure of 26 in MMP-13 confirms the key hydrogen bonds and prime side binding in the active site. 相似文献
122.
Adenocarcinoma arising in association with gastric heterotopic pancreas: A case report and review of the literature 总被引:11,自引:0,他引:11
We report a case of adenocarcinoma arising in a focus of heterotopic pancreas, occurring in the stomach of a 52-year-old man. The patient presented with gastric outlet obstruction. Radiographic studies revealed thickening of the gastric wall, but endoscopy failed to reveal a mucosal abnormality. A 50% distal gastrectomy was performed, along with vagotomy. Microscopic examination revealed extensive involvement of the muscularis propria of the distal stomach by heterotopic pancreas. The ectopic pancreas had a microscopic appearance consistent with Heinrich's class III, in which the majority of the heterotopic pancreas was characterized by cystically dilated duct structures. Occasional islets were present. Intimately associated with the cystically dilated ducts was a prominent number of small infiltrating ducts lined by columnar or cuboidal cells with enlarged hyperchromatic nuclei containing prominent nucleoli. These were consistent with a well-differentiated invasive adenocarcinoma. Despite multiple sectioning, no connection between the adenocarcinoma and the overlying gastric mucosa was seen. Adenocarcinoma arising within ectopic pancreas is a rare occurrence with fewer than 30 well-documented cases reported in the world literature to our knowledge. 相似文献
123.
The streptococcal cell wall model of arthritis in Lewis rats consists of an acute, non-T-cell-dependent initiation phase, followed by a remission and then a chronic, inflammatory T-cell-dependent phase. In this report, we define pertinent changes in the cognate and noncognate immune system of the Lewis rats during various phases of the disease. We examined changes in the population size of various cell types using lineage-specific markers in three different tissues (blood, spleen, and lymph nodes) over 28 days. Our results indicate that the T cell and monocyte populations were significantly altered in PG-PS-treated rats and the activation status of these cells parallel initiation, remission, and chronic phases of joint inflammation. Activation of B cells also increases in certain tissues in the chronic phase of the disease. In summary, our results confirm the involvement of both innate and cognate immunity in the development of arthritis and demonstrate that monocytes, in addition to T cells, play a substantive role in the induction and maintenance of the inflammatory process in this rat model. 相似文献
124.
125.
Victor Garcia-Montoto Sylvain Verdier David C. Dayton Ofei Mante Carine Arnaudguilhem Jan H. Christensen Brice Bouyssiere 《RSC advances》2021,11(43):26732
Renewable feedstocks, such as lignocelulosic fast pyrolysis oils and both vegetable oil and animal fats, are becoming a viable alternative to petroleum for producing high-quality renewable transportation fuels. However, the presence of phosphorus-containing compounds, mainly from phospholipids, in these renewable feedstocks is known to poison and deactivate hydrotreating catalysts during fuel production. In this work, gel permeation chromatography (GPC) combined with inductively coupled plasma high-resolution mass spectrometry (ICP-HRMS) was used to analyze feedstocks including unprocessed soybean oil, animal fat, and pyrolysis oils from red oak and milorganite to identify phosphorus species. The results have shown the presence of a wide range of different phosphorous compounds among all the samples analysed in this work. The GPC-ICP-HRMS analyses of a vegetable oil and two animal fats have shown different fingerprints based on the molecular weight of each of the samples, highlighting the structural differences among their corresponding phosphorus-containing compounds. While the presence of low-molecular-weight species, such as phospholipids, was expected, several high-molecular-weight species (MW > 10 000 Da) have been found, suggesting that high-molecular-weight micelles or liposomes might have been formed due to the high concentration of phospholipids in these samples. Results obtained through the hydroxylation of a mix of phospholipids (asolectin) and its posterior GPC-ICP-HRMS agree with this hypothesis. With respect to the lignocellulosic catalytic fast pyrolysis oil samples, the GPC-ICP-HRMS results obtained suggest that either aggregation or polymerization reactions might have occurred during the pyrolysis process, yielding phosphorus-containing compounds with an approximate molecular weight above 91 000 kDa. In addition, an aggregation phenomenom has been observed for those phosphorus species present within the fast pyrolysis oils after being stored for 3 months, especially for those pyrolysis oils contaning pre-processed feedstocks, such as milorganite.Renewable feedstocks, such as lignocelulosic fast pyrolysis oils and both vegetable oil and animal fats, are becoming a viable alternative to petroleum for producing high-quality renewable transportation fuels. 相似文献
126.
Ryan C. Gessner Ariel D. Hanson Steven Feingold Avery T. Cashion Ana Corcimaru Bryant T. Wu Christopher R. Mullins Stephen R. Aylward Lola M. Reid Paul A. Dayton 《Biomaterials》2013
A method of 3D functional ultrasound imaging has been developed to enable non-destructive assessment of extracellular matrix scaffolds that have been prepared by decellularization protocols and are intended for recellularization to create organoids. A major challenge in organ decellularization is retaining patent micro-vascular structures crucial for nutrient access and functionality of organoids. The imaging method described here provides statistical distributions of flow rates throughout the tissue volumes, 3D vessel network architecture visualization, characterization of microvessel volumes and sizes, and delineation of matrix from vascular circuits. The imaging protocol was tested on matrix scaffolds that are tissue-specific, but not species-specific, matrix extracts, prepared by a process that preserved >98% of the collagens, collagen-associated matrix components, and matrix-bound growth factors and cytokines. Image-derived data are discussed with respect to assessment of scaffolds followed by proof-of-concept studies in organoid establishment using Hep3B, a human hepatoblast-like cell line. Histology showed that the cells attached to scaffolds with patent vasculature within minutes, achieved engraftment at near 100%, expressed liver-specific functions within 24 h, and yielded evidence of proliferation and increasing differentiation of cells throughout the two weeks of culture studies. This imaging method should prove valuable in analyses of such matrix scaffolds. 相似文献
127.
Cherry C. Chen Paul S. Sheeran Shih-Ying Wu Oluyemi O. Olumolade Paul A. Dayton Elisa E. Konofagou 《Journal of controlled release》2013
Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood–brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Passive cavitation detection was used in the attempt to establish a correlation between the amount of dextran delivered in the brain and the acoustic emission recorded during sonication. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of an FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, suggesting that contrast agent-dependent acoustic emission monitoring was needed. A more homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FUS-induced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature. 相似文献
128.
Mr. Kenneth R. Larsen PhD John G. Moore MD Merril T. Dayton MD Zhong Yu MD 《Digestive diseases and sciences》1993,38(8):1435-1440
Circadian rhythms exist in several gastric parameters affecting ulcerogenesis. This study investigated possible circadian rhythmicity in observed aspirin (ASA)-induced gastric lesions in the rat. In five experiments 183 rats were studied at 14 time points over a 24-hr period. Rats were adapted for three weeks on a 12-hr light schedule, fasted 18 hr, then given oral acidified ASA. One hour later, the rats were sacrificed, the stomachs were removed, stretched flat, photographed, scanned, and measured for percent area of gross lesions in the gastric corpus by computer planimetry. Cosinor rhythmometric analysis showed a significant (P<0.001) rhythm. Mean of rhythm (MESOR) was 5.60±0.25% of total corpus. Amplitude was 25.80±6.07% of MESOR. Peak time (acrophase) was 1909±0101 hr after lights on. Thus, gastric vulnerability to ASA injury exhibited circadian rhythmicity with peak injury during the dark period in this species. 相似文献
129.
Cohen Z Senagore AJ Dayton MT Koruda MJ Beck DE Wolff BG Fleshner PR Thirlby RC Ludwig KA Larach SW Weiss EG Bauer JJ Holmdahl L 《Diseases of the colon and rectum》2005,48(6):1130-1139
INTRODUCTION Postoperative abdominal adhesions are associated with significant morbidity and mortality, placing a substantial burden on healthcare systems worldwide. Development of a bioresorbable membrane containing up to 23 percent glycerol and chemically modified sodium hyaluronate/carboxymethylcellulose offers ease of handling and has been shown to provide significant postoperative adhesion prevention in animals. This study was designed to assess the safety of glycerol hyaluronate/carboxymethylcellulose and to evaluate its efficacy in reducing the incidence, extent, and severity of postoperative adhesion development in surgical patients.METHODS Twelve centers enrolled 120 patients with ulcerative colitis or familial polyposis who were scheduled for a restorative proctocolectomy and ileal pouch-anal anastomosis with diverting loop ileostomy. Before surgical closure, patients were randomized to no antiadhesion treatment (control) or treatment with glycerol hyaluronate/carboxymethylcellulose membrane under the midline incision. At ileostomy closure, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision.RESULTS Data were analyzed using the intent-to-treat population. Treatment with glycerol hyaluronate/carboxymethylcellulose resulted in 19 of 58 patients (33 percent) with no adhesions compared with 6 of 60 adhesion-free patients (10 percent) in the no treatment control group (P = 0.002). The mean extent of postoperative adhesions to the midline incision was significantly lower among patients treated with glycerol hyaluronate/carboxymethylcellulose compared with patients in the control group (P < 0.001). The severity of postoperative adhesions to the midline incision was significantly less with glycerol hyaluronate/carboxymethylcellulose than with control (P < 0.001). Adverse events were similar between treatment and no treatment control groups with the exception of abscess and incisional wound complications were more frequently observed with glycerol hyaluronate/carboxymethylcellulose.CONCLUSIONS Glycerol hyaluronate/carboxymethylcellulose was shown to effectively reduce adhesions to the midline incision and adhesions between the omentum and small bowel after abdominal surgery. Safety profiles for the treatment and no treatment control groups were similar with the exception of more infection complications associated with glycerol hyaluronate/carboxymethylcellulose use. Animal models did not predict these complications.Supported in full by grants from Genzyme Corporation, Cambridge, Massachusetts.Lena Holmdahl, M.D., Ph.D. is an employee of Genzyme Corporation. 相似文献
130.
Kym PR Iyengar R Souers AJ Lynch JK Judd AS Gao J Freeman J Mulhern M Zhao G Vasudevan A Wodka D Blackburn C Brown J Che JL Cullis C Lai SJ LaMarche MJ Marsilje T Roses J Sells T Geddes B Govek E Patane M Fry D Dayton BD Brodjian S Falls D Brune M Bush E Shapiro R Knourek-Segel V Fey T McDowell C Reinhart GA Preusser LC Marsh K Hernandez L Sham HL Collins CA 《Journal of medicinal chemistry》2005,48(19):5888-5891
4-(1-Benzo[1,3]dioxol-5-ylmethylpiperidine-4-ylmethyl)-6-chlorochromen-2-one (7) is a potent, orally bioavailable melanin concentrating hormone receptor 1 (MCHr1) antagonist that causes dose-dependent weight loss in diet-induced obese mice. Further evaluation of 7 in an anesthetized dog model of cardiovascular safety revealed adverse hemodynamic effects at a plasma concentration comparable to the minimally effective therapeutic concentration. These results highlight the need for scrutiny of the cardiovascular safety profile of MCHr1 antagonists. 相似文献