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51.
Background and purpose:
We investigated the effects of a synthetic flavonol, 3′,4′-dihydroxyflavonol (DiOHF) on the expression of monocyte chemoattractant protein-1 (MCP-1) in rat vascular smooth muscle cells.Experimental approach:
MCP-1 expression was assessed by quantitative real-time PCR and protein phosphorylation by immunoprecipitation and Western blots.Key results:
DiOHF (1–30 µmol·L−1) concentration-dependently reduced MCP-1 expression in both quiescent cells and cells stimulated with platelet-derived growth factor (PDGF) or interleukin 1-β. The effect of DiOHF was associated with a suppression of focal adhesion kinase (FAK)-mediated signalling. In vitro kinase assays demonstrated that DiOHF is a potent inhibitor of FAK kinase activity (EC50= 2.4 µmol·L−1). Expression of FAK-related non-kinase reduced basal MCP-1 expression, but not that induced by PDGF or interleukin 1-β. DiOHF also inhibited autophosphorylation of PDGF receptors. The PDGF receptor inhibitor AG-1296 potently suppressed basal and PDGF-induced MCP-1 expression. Inhibition of extracellular signal-regulated kinase activation by DiOHF, either directly or indirectly, may also be involved in its effects on MCP-1 expression. DiOHF had no inhibitory effect on either p38 or nuclear factor-κB activation. Moreover, DiOHF inhibited smooth muscle cell spreading (a FAK-mediated response) and proliferation.Conclusions and implications:
This is the first report on a flavonoid compound (DiOHF) that is a potent FAK inhibitor. DiOHF also inhibits PDGF receptor autophosphorylation. These effects underlie the inhibitory action of DiOHF on MCP-1 expression in smooth muscle cells. Our results suggest that DiOHF might be a useful tool for dissection of the (patho)physiological roles of FAK signalling.British Journal of Pharmacology (2009) 157, 597–606; doi:10.1111/j.1476-5381.2009.00199.x; published online 9 April 2009 相似文献52.
Laparoscopic partial posterior (Toupet) fundoplication improves esophageal bolus propagation on scintigraphy 总被引:1,自引:0,他引:1
Wykypiel H Hugl B Gadenstaetter M Bonatti H Bodner J Wetscher GJ 《Surgical endoscopy》2008,22(8):1845-1851
BACKGROUND: Impaired esophageal clearance is important in the pathogenesis of gastroesophageal reflux disease (GERD). It is unknown whether esophageal clearance improves following antireflux surgery. The aim of this study was to investigate the effect of laparoscopic Nissen fundoplication (NF), laparoscopic partial posterior (Toupet) fundoplication (PPF) or medical therapy on esophageal clearance. METHODS: This was a prospective nonrandomized crossover study. Sixty patients were evaluated with endoscopy, esophageal manometry, radionuclide scanning of esophageal emptying, and assessment of symptoms prior to surgery or medical therapy and 6 months after treatment. In 20 GERD patients with normal esophageal peristalsis an NF was performed, in 20 patients with impaired esophageal peristalsis a PPF was chosen, and 20 patients received proton-pump inhibitor (PPI) treatment. RESULTS: On endoscopy, esophagitis had resolved in all patients after surgery; two patients with medical therapy still had esophagitis. On manometry, a significant improvement of lower esophageal sphincter competence was seen in both surgical groups. LES relaxation was complete after PPF, but incomplete after NF. Esophageal peristalsis did not improve after medical therapy, was significantly improved after PPF, but had worsened after NF. On scintigraphic esophageal emptying for solid meals, there was no improvement after medical therapy but a significant improvement after PPF. A significant deterioration of esophageal emptying was observed after NF. There was a strong correlation between scintigraphic and manometric evaluation of peristalsis preoperatively (r(s) = -0.87, p < 0.05) and postoperatively (r(s) = -0.82, p < 0.05). There was no change in dysphagia after medical therapy and after NF but a significant improvement after PPF. Globus sensation was significantly improved after PPF but did not change after medical therapy or NF. Postprandial bloating and inability to belch were significantly more common after NF than after PPF. CONCLUSION: Laparoscopic partial posterior (Toupet) fundoplication can restore a preoperatively defective esophageal bolus propagation on scintigraphy with the same antireflux effect as the laparoscopic Nissen fundoplication, but with lower side-effects. 相似文献
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We measured red blood cell iron incorporation (RBC-inc) in 13 human milk-fed premature infants (birthweight 1037 +/- 289 g, gestational age 27 +/- 2 wk, weight at start of study 1571 +/- 426 g) who were receiving full tube-feedings of human milk fortified with a commercial human milk fortifier (FortHM). The relative RBC-inc of supplemental iron (2 mg/kg/d of ferrous sulfate) was assessed using 57Fe sulfate mixed directly into a 24-h volume of FortHM, and 54Fe sulfate given as a bolus between two FortHM feedings the next day. RBC-inc was similar between the two methods of supplemental iron administration (4.7 +/- 2.5% vs 4.6 +/- 1.5%, respectively). Although these values are lower than RBC-inc expected from iron native to human milk, the relatively large amount of iron in the supplements contributed most of the iron incorporated into RBC by the infants. There was a significant positive correlation between the reticulocyte count and RBC-inc. As the high nutrient (especially calcium) content of the FortHM did not interfere with iron utilization, adding iron directly to FortHM, or incorporating it into commercial fortifiers, may be a practical method to provide iron to premature infants. 相似文献
55.
OBJECTIVE: The purpose of this study was to assess the clinical and economic impact of the introduction of inhaled corticosteroid therapy for asthma in a cohort of children 12 years and younger who were North Carolina Medicaid enrollees.
METHODS: The North Carolina Medicaid claims database was used to retrieve clinical and economic variables for the purpose of this study. The case group, which was comprised of 84 children who started corticosteroid inhaler therapy between March 1994 and March 1995, was followed up for 1 year before and 1 year after the start of the therapy. The control group was comprised of 72 children with similar severity of asthma who remained on any other therapy other than corticosteroids for a continuous 2-year period. Paired t-tests were used to compare differences, and multiple regression analysis was used to adjust for potential confounders.
RESULTS: There was a 58% reduction in hospital visits, and a 19% reduction in physician visits in the case group after initiation of inhaled corticosteroids. In the control group, an increase of 34% in the number of outpatient visits occurred in the second year. All the decreases and increases were statistically significant. Children with regular patterns of inhaled corticosteroid refills were found to be significantly lower costing for Medicaid. However, after adjusting for potential confounders, no significant change in health care costs per asthmatic child occurred as a result of the introduction of inhaled corticosteroid therapy.
CONCLUSION: Overall, the study found that introduction of inhaled corticosteroids in a cohort of asthmatic children enrolled in Medicaid was beneficial to Medicaid because it brought about dramatic decreases in health care utilization without additionally increasing costs. 相似文献
METHODS: The North Carolina Medicaid claims database was used to retrieve clinical and economic variables for the purpose of this study. The case group, which was comprised of 84 children who started corticosteroid inhaler therapy between March 1994 and March 1995, was followed up for 1 year before and 1 year after the start of the therapy. The control group was comprised of 72 children with similar severity of asthma who remained on any other therapy other than corticosteroids for a continuous 2-year period. Paired t-tests were used to compare differences, and multiple regression analysis was used to adjust for potential confounders.
RESULTS: There was a 58% reduction in hospital visits, and a 19% reduction in physician visits in the case group after initiation of inhaled corticosteroids. In the control group, an increase of 34% in the number of outpatient visits occurred in the second year. All the decreases and increases were statistically significant. Children with regular patterns of inhaled corticosteroid refills were found to be significantly lower costing for Medicaid. However, after adjusting for potential confounders, no significant change in health care costs per asthmatic child occurred as a result of the introduction of inhaled corticosteroid therapy.
CONCLUSION: Overall, the study found that introduction of inhaled corticosteroids in a cohort of asthmatic children enrolled in Medicaid was beneficial to Medicaid because it brought about dramatic decreases in health care utilization without additionally increasing costs. 相似文献
56.
Laparoscopic Nissen fundoplication is an effective treatment for gastroesophageal reflux disease. 总被引:30,自引:4,他引:26 下载免费PDF全文
R A Hinder C J Filipi G Wetscher P Neary T R DeMeester G Perdikis 《Annals of surgery》1994,220(4):472-483
OBJECTIVE: The open Nissen fundoplication is effective therapy for gastroesophageal reflux disease. In this study, the outcomes in 198 patients treated with the laparoscopic Nissen fundoplication was evaluated for up to 32 months after surgery to ascertain whether similar positive results could be obtained. SUMMARY BACKGROUND DATA: To ensure surgical success, patients were required to have mechanically defective sphincters on manometry and increased esophageal acid exposure on 24-hour pH monitoring. The patients either had severe complications of gastroesophageal reflux disease or had failed medical therapy. These requirements have been found to be necessary to ensure a successful surgical outcome. METHODS: The disease was complicated by ulceration (46), stricture (25) and Barrett's esophagus (33). Patients underwent standard Nissen fundoplications identical in every detail to open procedures except that the procedures were carried out by the laparoscopic route. RESULTS: Perioperative complications included gastric or esophageal perforation (3), pneumothorax (2), bleeding (2), breakdown of crural repair (2) and periesophageal abscess (1). The only mortality occurred from a duodenal perforation. Six patients required conversion to the open procedure. The median hospital stay was 3 days. One hundred patients were observed for follow-up for 6 to 32 months (median 12 months), with outcomes similar to the open Nissen fundoplication. Further surgery was required for two patients who had recurrent gastroesophageal reflux and one who developed an esophageal stricture. Ninety-seven percent are satisfied with their decision to have the operation. CONCLUSIONS: The laparoscopic Nissen fundoplication can be carried out safely and effectively with similar positive results to the open procedure and with all of the advantages of the minimally invasive approach. 相似文献
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JH Raphael JL Southall TV Gnanadurai GJ Treharne GD Kitas 《BMC musculoskeletal disorders》2002,3(1):17-8