29 research outputs found
Smoothelin in vascular smooth muscle cells
Get PDFSmoothelin-A and -B have only been found in fully differentiated contractile smooth muscle cells. They are increasingly used to monitor the smooth muscle cell differentiation process to a contractile or synthetic phenotype. Vascular-specific smoothelin-B is the first smooth muscle cell marker that disappears when vascular tissues are compromised, for example, in atherosclerosis or restenosis. Recently obtained data show that smoothelin deficiency results in a considerable loss of contractile potential and hence in impaired smooth muscle function and suggest that smoothelins are part of the contractile apparatus
Wnt/frizzled signalling modulates the migration and differentiation of immortalized cardiac fibroblasts
Get PDFThe Wnt/frizzled (Fzd) signal transduction cascade has been implicated in the proliferation, differentiation, and migration of many cell types, but the role of this pathway in cardiac fibroblast differentiation is not known. Our lab previously showed an up-regulation of Fzd-1 and -2 expression in myofibroblasts after myocardial infarction (MI), indicating a potential role for the Fzd receptor in fibroblast-myofibroblast differentiation. The present study was performed to further define the role of specific Wnt and Fzd proteins in the proliferation, migration, and differentiation of cardiac fibroblasts. Because primary fibroblasts become senescent after a few passages and are difficult to transfect, we immortalized rat cardiac fibroblasts with telomerase [cardiac fibroblasts immortalized with telomerase (CFIT)]. Proliferation of CFIT was not significantly influenced by Wnt/Fzd signalling. The migration, however, was attenuated by all Wnt/Fzd combinations tested. Also, specific Wnt/Fzd combinations modulated the expression of the following myofibroblast markers: collagen I alpha 1, collagen III, fibronectin and its splice variants, and alpha-smooth muscle actin. The results indicate that myofibroblast migration and differentiation, but not proliferation, can be modulated by interventions in Wnt/Fzd signalling. Therefore, Wnt/Fzd signalling may serve as a novel therapeutic target to ameliorate wound healing after MI
Research on Readers' Advisory Services in American Public Libraries
No full text本研究採用網路問卷調查法，以美國公共圖書館從事讀者諮詢顧問服務之106位館員為研究對象，藉由其對此項服務之認知，探討美國公共圖書館讀者諮詢顧問服務施行之範圍與內涵，瞭解其對讀者諮詢顧問服務的定義、功能、訓練目標等方面之看法，及其對美國公共圖書館施行讀者諮詢顧問服務所遭遇的困難與障礙，與讀者諮詢顧問服務未來發展方向之看法。研究者依據研究結果，針對本次問卷調查之填答者所服務之美國公共圖書館、未來國內規劃提供讀者諮詢顧問服務之公共圖書館以及國內圖書資訊學教育與圖書資訊學相關組織提出數項建議。This research investigated the scope and contents of readers' advisory services in American public libraries. Specifically, it explored librarians' perspective on the following issues: definition, function, and training objectives of readers' advisory services; the problems and challenges librarians face; their opinions on future developments in readers' advisory services. The data collection was carried out by an online questionnaire and the participants included 106 librarians who provided readers' advisory services in American public libraries. Through literature reviews and research results, the author provides suggestions for readers' advisory services in Taiwan's public libraries to consider. The author also provides suggestions for American public libraries that participated in this research, Taiwan's public libraries that intend to provide readers' advisory services in the future, and Library and Information Science related majors in the educational realm
Endothelial activation markers and their key regulators after restrictive bariatric surgery
Get PDFOBJECTIVE: Increased plasma levels of endothelial activation markers in obese subjects reflect the positive association between cardiovascular diseases and obesity. The pro-inflammatory state associated with obesity is thought to play a major role in endothelial cell activation in severely obese individuals. Previous studies demonstrated that long-term weight loss after bariatric surgery is accompanied by a decreased proinflammatory state. However, little is known about the long-term effects of bariatric surgery on endothelial cell activation. RESEARCH METHODS AND PROCEDURES: Plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble endothelial selectin (sE-selectin), and soluble vascular cell adhesion molecule-1 (sVCAM-1), all markers of endothelial cell activation, and of their regulators adiponectin and resistin were measured at different time-points postoperatively in 26 consecutive patients who underwent restrictive surgery, with a follow-up of 2 years. RESULTS: During the first 6 months after bariatric surgery, sE-selectin levels decreased. Despite substantial weight loss, sICAM-1 and sVCAM-1 plasma levels did not decrease significantly. After 24 months, sICAM-1 levels were significantly decreased, whereas sE-selectin levels were further decreased. However, sVCAM-1 levels remained elevated. Adiponectin levels did not change significantly during the first 6 months after bariatric surgery, whereas resistin levels increased. After 24 months, adiponectin levels were similar to normal-weight controls, but resistin levels remained high. DISCUSSION: Reductions in plasma levels of different markers of endothelial activation after bariatric surgery show different temporal patterns, suggesting that distinct mechanisms are involved in their regulation. Although not all endothelial activation markers normalize after bariatric surgery, our findings suggest that bariatric surgery can reduce endothelial activation in the long term. AD - Department of General Surgery, P.O. Box 616, 6200 MD Maastricht, The Netherlands. [email protected]
Novel evidence for chronic exposure to endotoxin in human nonalcoholic steatohepatitis.
Get PDFBACKGROUND: Endotoxin is hypothesized to play an important role in the activation of inflammatory pathways associated with nonalcoholic steatohepatitis (NASH). However, demonstration of hepatic endotoxin exposure is challenging due to the inaccessibility of the portal circulation. Furthermore, reliable measurement of the relatively low endotoxin levels in plasma of patients with liver disease and subsequent interpretation remain difficult. GOALS: In this study, we used the EndoCab assay that measures endogenous antibodies to the core region of endotoxin to estimate hepatic endotoxin exposure over time. STUDY: IgG levels against endotoxin were measured in peripheral plasma obtained from 21 severely obese patients with NASH and 9 severely obese patients with healthy livers. RESULTS: Plasma IgG levels against endotoxin were significantly elevated in patients with NASH compared with patients with healthy livers (48+/-63 GMU/mL vs. 10+/-13 GMU/mL). Moreover, these IgG levels progressively increased with NASH grade (grade 1 29+/-37; grade 2 58+/-51; grade 3 84+/-132 GMU/mL, P<0.05). There was no relation between plasma IgG levels and NASH stage. CONCLUSIONS: Plasma IgG levels against endotoxin were found to be increased in biopsy-proven human NASH and increased with aggravated inflammation in NASH, suggesting a relationship between chronic endotoxin exposure and the severity of human NASH
Regulation and characteristics of vascular smooth muscle cell phenotypic diversity
Get PDFVascular smooth muscle cells can perform both contractile and synthetic functions, which are associated with and characterised by changes in morphology, proliferation and migration rates, and the expression of different marker proteins. The resulting phenotypic diversity of smooth muscle cells appears to be a function of innate genetic programmes and environmental cues, which include biochemical factors, extracellular matrix components, and physical factors such as stretch and shear stress. Because of the diversity among smooth muscle cells, blood vessels attain the flexibility that is necessary to perform efficiently under different physiological and pathological conditions. In this review, we discuss recent literature demonstrating the extent and nature of smooth muscle cell diversity in the vascular wall and address the factors that affect smooth muscle cell phenotype
Endoscopic duodenal-jejunal bypass liner rapidly improves type 2 diabetes.
Get PDFBariatric procedures excluding the proximal small intestine improve glycemic control in type 2 diabetes within days. To gain insight into the mediators involved, we investigated factors regulating glucose homeostasis in patients with type 2 diabetes treated with the novel endoscopic duodenal-jejunal bypass liner (DJBL). Seventeen obese patients (BMI 30-50 kg/m(2)) with type 2 diabetes received the DJBL for 24 weeks. Body weight and type 2 diabetes parameters, including HbA(1c) and plasma levels of glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon, were analyzed after a standard meal before, during, and 1 week after DJBL treatment. At 24 weeks after implantation, patients had lost 12.7 +/- 1.3 kg (p <0.01), while HbA(1c) had improved from 8.4 +/- 0.2 to 7.0 +/- 0.2 % (p <0.01). Both fasting glucose levels and the postprandial glucose response were decreased at 1 week after implantation and remained decreased at 24 weeks (baseline vs. week 1 vs. week 24: 11.6 +/- 0.5 vs. 9.0 +/- 0.5 vs. 8.6 +/- 0.5 mmol/L and 1,999 +/- 85 vs. 1,536 +/- 51 vs. 1,538 +/- 72 mmol/L/min, both p <0.01). In parallel, the glucagon response decreased (23,762 +/- 4,732 vs. 15,989 +/- 3,193 vs. 13,1207 +/- 1,946 pg/mL/min, p <0.05) and the GLP-1 response increased (4,440 +/- 249 vs. 6,407 +/- 480 vs. 6,008 +/- 429 pmol/L/min, p <0.01). The GIP response was decreased at week 24 (baseline-115,272 +/- 10,971 vs. week 24-88,499 +/- 10,971 pg/mL/min, p <0.05). Insulin levels did not change significantly. Glycemic control was still improved 1 week after explantation. The data indicate DJBL to be a promising treatment for obesity and type 2 diabetes, causing rapid improvement of glycemic control paralleled by changes in gut hormones
Short-term overfeeding induces insulin resistance in weight-stable patients after bariatric surgery
Get PDFBACKGROUND: Short time overfeeding of rats rapidly leads to insulin resistance (IR). A study with healthy human volunteers, which we suggest are less susceptible for developing IR after short time overfeeding, did not show these effects on IR. Therefore a study population of weight-stable, former morbidly obese subjects (BMI 31.3 kg/m2), which were treated with bariatric surgery approximately 3 years ago was selected. METHODS: Eleven subjects were submitted to a 7-day overfeeding study, resulting in a 53% increase in caloric intake (1,227 +/- 394.4 to 1,879.2 +/- 298.4 kcal/day). During normal diet and after overfeeding, insulin sensitivity was measured using steady state plasma glucose (SSPG) levels. At these time points, BMI and waist/hip ratio together with plasma levels of inflammatory markers (CRP, AGP, LBP, and TNF-alpha receptors) and plasma leptin values were also measured. RESULTS: SSPG levels after overfeeding increased from 8.2 +/- 3.2 to 10.6 +/- 2.6 mmol/l (P < 0.05), indicating decreased insulin sensitivity after overfeeding. Fasting plasma insulin, glucose, circulating levels of inflammatory markers, BMI, and waist/hip ratio remained unchanged. CONCLUSIONS: This study shows that overfeeding in a group of weight-stable, former morbidly obese subjects 3 years after bariatric surgery results in decreased insulin sensitivity. The mechanisms behind decreased insulin sensitivity induced by overfeeding are poorly understood, but the present results reveal that a unique human model is available to study these mechanisms, leading to a better understanding of the pathophysiology of IR
Small intestinal alterations in severely obese hyperglycemic subjects
Get PDFDe laatste jaren is er een toenemende belangstelling voor de rol van de dunne darm in de pathofysiologie van type 2 diabetes. Deze rol wordt benadrukt door de snelle verbetering van diabetes die optreedt na gastric bypass chirurgie en na plaatsing van de zogenaamde endobarrier, een teflon koker, in de proximale dunne darm. Bovendien laat de werkzaamheid van agonisten van het darmhormoon glp-1 (dpp-4-remmers) zien dat de darm een belangrijk targetorgaan is voor de medicamenteuze behandeling van type 2 diabetes
