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1.
Ioannis Smyrnias Stephen P. Gray Darlington O. Okonko Greta Sawyer Anna Zoccarato Norman Catibog Begoña López Arantxa González Susana Ravassa Javier Díez Ajay M. Shah 《Journal of the American College of Cardiology》2019,73(14):1795-1806
Background
The mitochondrial unfolded protein response (UPRmt) is activated when misfolded proteins accumulate within mitochondria and leads to increased expression of mitochondrial chaperones and proteases to maintain protein quality and mitochondrial function. Cardiac mitochondria are essential for contractile function and regulation of cell viability, while mitochondrial dysfunction characterizes heart failure. The role of the UPRmt in the heart is unclear.Objectives
The purpose of this study was to: 1) identify conditions that activate the UPRmt in the heart; and 2) study the relationship among the UPRmt, mitochondrial function, and cardiac contractile function.Methods
Cultured cardiac myocytes were subjected to different stresses in vitro. Mice were subjected to chronic pressure overload. Tissues and blood biomarkers were studied in patients with aortic stenosis.Results
Diverse neurohumoral or mitochondrial stresses transiently induced the UPRmt in cultured cardiomyocytes. The UPRmt was also induced in the hearts of mice subjected to chronic hemodynamic overload. Boosting the UPRmt with nicotinamide riboside (which augments NAD+ pools) in cardiomyocytes in vitro or hearts in vivo significantly mitigated the reductions in mitochondrial oxygen consumption induced by these stresses. In mice subjected to pressure overload, nicotinamide riboside reduced cardiomyocyte death and contractile dysfunction. Myocardial tissue from patients with aortic stenosis also showed evidence of UPRmt activation, which correlated with reduced tissue cardiomyocyte death and fibrosis and lower plasma levels of biomarkers of cardiac damage (high-sensitivity troponin T) and dysfunction (N-terminal pro–B-type natriuretic peptide).Conclusions
These results identify the induction of the UPRmt in the mammalian (including human) heart exposed to pathological stresses. Enhancement of the UPRmt ameliorates mitochondrial and contractile dysfunction, suggesting that it may serve an important protective role in the stressed heart. 相似文献2.
T. McLaughlin F. Abbasi C. Lamendola G. Yee S. Carter S.W. Cushman 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(1):62-68
Background and Aims
Overweight and obesity increase risk for diabetes and cardiovascular disease, largely through development of insulin resistance. Benefits of dietary weight loss are documented for obese individuals with insulin resistance. Similar benefits have not been shown in overweight individuals. We sought to quantify whether dietary weight loss improves metabolic risk profile in overweight insulin-resistant individuals, and evaluated potential mediators between weight loss and metabolic response.Methods and Results
Healthy volunteers with BMI 25–29.9 kg/m2 underwent detailed metabolic phenotyping including insulin-mediated-glucose disposal, fasting/daylong glucose, insulin, triglycerides, FFA, and cholesterol. Subcutaneous fat biopsies were performed for measurement of adipose cell size. After 14 weeks of hypocaloric diet and 2 weeks of weight maintenance, cardiometabolic measures and biopsies were repeated. Changes in weight, % body fat, waist circumference, adipose cell size and FFA were evaluated as predictors of change in insulin resistance.Weight loss (4.3 kg) yielded significant improvements in insulin resistance and all cardiovascular risk markers except glucose, HDL-C, and LDL-C. Improvement in insulin sensitivity was greater among those with <2 vs >2 cardiovascular risk factors at baseline. Decrease in adipose cell size and waist circumference, but not weight or body fat, independently predicted improvement in insulin resistance.Conclusions
Weight loss yields metabolic health benefits in insulin-resistant overweight adults, even in the absence of classic cardiovascular risk factors. Weight loss-related improvement in insulin sensitivity may be mediated through changes in adipose cell size and/or central distribution of body fat. The insulin-resistant subgroup of overweight individuals should be identified and targeted for dietary weight loss.Clinical trials identifier
NCT00186459. 相似文献3.
Mousa Alharbi Nicholas Giacomantonio Lindsey Carter John Sapp Martin Gardner Chris J. Gray Amir M. AbdelWahab Ratika Parkash 《The Canadian journal of cardiology》2019,35(4):382-388
Background
Cardiac rehabilitation (CR) intervention programs are currently not part of management in patients with atrial fibrillation (AF). We sought to determine the effect of CR compared with a specialized AF clinic (AFC) and usual care on outcomes in patients with AF.Methods
This was a single-centre retrospective cohort study that was carried out using 3 databases: the Hearts in Motion database (2010-2014), prospectively collected data in an AFC (2011-2014), and a retrospective chart review for patients in usual care (2009-2012). Three care pathways were compared: (1) CR; (2) AFC; and (3) usual specialist-based care. The main outcome was AF-related emergency department visits and cardiovascular hospitalizations.Results
Of 566 patients with newly diagnosed AF, 133 (23.5%) patients underwent CR, 197 patients (34.8%) attended the AFC, whereas the remaining 236 (41.7%) were followed in a usual specialist-based care clinic. At 1 year, AF-related emergency department visits and cardiovascular hospitalization rates occurred in 7.5% in the CR group, 16.8% in the AFC group, and 29.2% in usual care. After a propensity matched analysis, usual care was associated with the highest rate of the main outcome (odds ratio, 4.91; 95% confidence interval, 2.09-11.53) compared with CR, as did the AFC compared with CR (odds ratio, 2.75; 95% confidence interval, 1.14-6.6).Conclusions
Among patients with AF, CR was associated with a lower risk of AF-related outcomes. These findings support further study of the use of CR in the management of these patients to determine the optimal model of care for AF patients. 相似文献4.
V. Provost V. Lamantia S. Bissonnette Y. Cyr M. Faraj 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(5):504-512
Background and aims
Higher fiber intake is associated with increased insulin sensitivity (IS) and reduced glucose-induced insulin secretion (GIIS) during isocaloric-diets; however, its role in hypocaloric-diets is unclear. We examined whether increased fiber intake predicts the amelioration in IS and GIIS following a hypocaloric-diet.Methods and results
This is a post-hoc analysis of 55 adult subjects (BMI > 27 kg/m2) who completed a 6-month hypocaloric-diet (?500 kcal/day). Dietary intake was assessed using 3-day food records at baseline and post-intervention. We evaluated glucose-induced insulin and C-peptide secretions as AUC of plasma insulin and C-peptide during intravenous-glucose-tolerance tests (IVGTT) and IS via hyperinsulinemic-euglycemic clamps. Data analysis employed regression models and 2-way RM ANOVAs. Post-intervention % change in fiber intake was associated positively with ISclamp (r = 0.30) and negatively with % change in total (r = ?0.37) and 2nd phase GIISIVGTT (r = ?0.44) but not C-peptide secretion. It remained associated with lower 2nd phase GIISIVGTT after adjustment for sex and % changes in BMI and energy-intake, independently of other macronutrients. Subjects who increased fiber intake (to 28.7 ± 9.0 g/day) had a greater decrease in 2nd phase GIISIVGTT, not C-peptide secretion, independently of sex or changes in adiposity or energy-intake compared to subjects who decreased intake (to 20.0 ± 6.8 g/day).Conclusion
Higher fiber intake is an independent predictor of reduced 2nd phase glucose-induced hyperinsulinemia after a hypocaloric-diet. It was not associated with plasma C-peptide, suggesting a role in faster insulin clearance rather reduced insulin secretion. Promoting high-fiber intake may increase the effectiveness of hypocaloric-diets in preventing type 2 diabetes.Registration
ISRCTN14476404, BioMedCentral.com.Clinical trial registration
This trial was registered at BioMed Central as ISRCTN14476404, on July 28th, 2017. 相似文献5.
Hong Chee Chew Arjun Iyer Mark Connellan Sarah Scheuer Jeanette Villanueva Ling Gao Mark Hicks Michelle Harkness Claudio Soto Andrew Dinale Priya Nair Alasdair Watson Emily Granger Paul Jansz Kavitha Muthiah Andrew Jabbour Eugene Kotlyar Anne Keogh Kumud Dhital 《Journal of the American College of Cardiology》2019,73(12):1447-1459
Background
Transplantation of hearts retrieved from donation after circulatory death (DCD) donors is an evolving clinical practice.Objectives
The purpose of this study is to provide an update on the authors’ Australian clinical program and discuss lessons learned since performing the world’s first series of distantly procured DCD heart transplants.Methods
The authors report their experience of 23 DCD heart transplants from 45 DCD donor referrals since 2014. Donor details were collected using electronic donor records (Donate Life, Australia) and all recipient details were collected from clinical notes and electronic databases at St. Vincent’s Hospital.Results
Hearts were retrieved from 33 of 45 DCD donors. A total of 12 donors did not progress to circulatory arrest within the pre-specified timeframe. Eight hearts failed to meet viability criteria during normothermic machine perfusion, and 2 hearts were declined due to machine malfunction. A total of 23 hearts were transplanted between July 2014 and April 2018. All recipients had successful implantation, with mechanical circulatory support utilized in 9 cases. One case requiring extracorporeal membrane oxygenation subsequently died on the sixth post-operative day, representing a mortality of 4.4% over 4 years with a total follow-up period of 15,500 days for the entire cohort. All surviving recipients had normal cardiac function on echocardiogram and no evidence of acute rejection on discharge. All surviving patients remain in New York Heart Association functional class I with normal biventricular function.Conclusions
DCD heart transplant outcomes are excellent. Despite a higher requirement for mechanical circulatory support for delayed graft function, primarily in recipients with ventricular assist device support, overall survival and rejection episodes are comparable to outcomes from contemporary brain-dead donors. 相似文献6.
Mateusz K. Hołda Jorge D. Zhingre Sanchez Michael G. Bateman Paul A. Iaizzo 《JACC: Cardiovascular Interventions》2019,12(2):169-178
Objectives
The authors aimed to comprehensively detail the right atrioventricular valve functional leaflet anatomies.Background
The rapid development of both surgical and percutaneous repair techniques for tricuspid regurgitation has renewed interest in variations in the morphology of the right atrioventricular valve.Methods
The functioning right atrioventricular valves of 40 reanimated human hearts were imaged using Visible Heart methodologies. Hearts were then perfusion-fixed and dissected, uniquely allowing for the comparative assessments of functional versus fixed valve anatomies from the same set of donor hearts.Results
The right atrioventricular valves have “3-leaflet” configurations in 57.5% and “4-leaflet” configurations in the remaining hearts. For 4-leaflet valves, extra leaflets were commonly observed in the most inferior regions of the annuli. No difference in valve perimeters between 2 valve types were observed (112.2 vs. 117.1 mm; p = 0.14). In 3-leaflet valves, septal, mural, and superior leaflets occupied 32.2 ± 6.5%, 15.9 ± 5.5%, and 25.5 ± 6.2% of the annulus, respectively, whereas in the 4-leaflet arrangements, these values were 27.0 ± 5.8% (septal), 12.0 ± 4.5% (inferior), 13.7 ± 9.4% (mural), and 19.8 ± 6.1% (superior). The muroseptal/inferoseptal commissures were usually located in the cavotricuspid regions, whereas the inferomural and superomural commissures were in the right atrial appendage vestibule area.Conclusions
The right atrioventricular valve has 4 functional leaflets in more than 40% of cases. The authors found that the inferomural region is the most variable area of the valve and believe that anatomic variation is an important consideration for planned interventions. 相似文献7.
Yide Cao Shuai He Zhonghao Tao Wen Chen Yueyue Xu Peisheng Liu Rui Wang Jianfeng Wu Liangpeng Li Xin Chen 《The Canadian journal of cardiology》2019,35(4):490-500
Background
The IκB kinase (IKK) complex has been found to have critical functions in cancer and the immune system. In particular, IKKα, which is a member of the IKK complex, has been shown to influence the inflammatory response and malignant diseases. However, the role of IKKα in macrophages after myocardial infarction (MI) remains largely unknown.Methods
Sham or MI operations were performed on macrophage-specific IKKɑ knockout (mIKKɑ?/?) mice and IKKɑflox/flox littermates. We ligated the left anterior descending coronary artery of the MI group and observed the results at 3, 7, and 30 days after MI.Results
We discovered more severe cardiac dysfunction with reduced angiogenesis, fibrosis, and collagen deposition in mIKKɑ?/? than in IKKɑflox/flox. In addition, we also observed that macrophages in mIKKɑ?/? were easier to polarize to the M1 phenotype and expressed more proinflammatory factors than IKKɑflox/flox. Mechanistically, IKKα deficiency in macrophages inhibited the alternative nuclear factor-κB/RelB pathway and enhanced the MEK1/2/ERK1/2 pathway.Conclusions
Overall, our data identified IKKɑ in the heart as a novel mediator that protected the heart from a severe inflammatory response and attenuated ventricular remodelling after MI by negatively regulating macrophage polarization to the M1 phenotype. Therefore, IKKα may serve as a potential therapeutic target for treatment after MI. 相似文献8.
Jay J. Idrees Fabio Bagante Faiz Gani Brad F. Rosinski Qinyu Chen Katiuscha Merath Mary Dillhoff Jordan Cloyd Timothy M. Pawlik 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2019,21(4):456-464
Background
The objective of the current study was to compare outcomes among patients combined colon (CR) and liver resection (LR) for the treatment of simultaneous colorectal liver metastasis (CRLM) versus patients undergoing two-stage CR and LR.Methods
Patients undergoing surgery for CRLM between 2004 and 2014 were identified using the Nationwide Inpatient Sample (NIS). Propensity-score matching was used to compare patients undergoing CR + LR with patients undergoing two-stage CR and LR.Results
Among 83,410 patients, CR + LR was performed in 5659 (6.7%), stage C + LR was performed in 5659 (6.7%), while isolated CR and LR was performed in 70,177 (84.0%) and 7574 (9.3%) patients, respectively. The number of patients undergoing CR + LR increased from 423 in 2004 to 580 in 2014 (Δ = +37%). Patients undergoing CR + LR had lower postoperative morbidity (CR + LR vs. two-staged CR and LR: 38.5% vs. 61.2%), shorter LOS (median LOS: 8 days [IQR: 7–12] vs. 14 days [IQR: 10–21]), and lower postoperative mortality (3.1% vs. 5.9%) versus patients undergoing two-stage CR and LR. Compared with patients undergoing two-staged CR and LR, median hospital costs were $13,093 lower for patients undergoing CR + LR (median costs: $36,775 [IQR: 26,416–54,245] vs. $23,682 [IQR: 16,299–32,996]).Conclusion
CR + LR was increasingly performed for treatment of CRLM. Compared with two-staged CR and LR, CR + LR was associated with improved outcomes and lower costs. 相似文献9.
Troy Francis Nader Kabboul Valeria Rac Nicholas Mitsakakis Petros Pechlivanoglou Joanna Bielecki David Alter Murray Krahn 《The Canadian journal of cardiology》2019,35(3):352-364
Background
The clinical effectiveness of cardiac rehabilitation (CR) on health-related quality of life (HRQOL) is an area that has not been consistently explored. The objective of this systematic review was to evaluate the effectiveness of providing any core component of CR on HRQOL domains.Methods
We performed a meta-analysis and meta-regression of randomized controlled trials (RCTs) on the core components of CR. RCTs included adult patients with diagnosed coronary artery disease via angiography, myocardial infarction, angina, or who had undergone coronary revascularization. The Cochrane Library, MEDLINE, EMBASE, CINAHL, SCI-EXPANDED, Psych INFO, and Web of Science were searched from inception to April 27, 2017. Outcomes included overall, physical, emotional, and social HRQOL. Outcomes were reported as standardized mean change (SMC) with 95% confidence intervals (CIs). Effect size changes of 0.2, 0.5, and 0.8 SD units reflect a small, moderate, and large effect, respectively.Results
Forty-nine reports of 41 RCTs with 11,747 patients were included. Summary effect sizes were: overall HRQOL SMC, 0.28 (95% CI, 0.05-0.50), physical HRQOL SMC, 0.47 (95% CI, 0.13-0.81), emotional HRQOL SMC, 0.37 (95% CI, ?0.02 to 0.77), and social HRQOL SMC, 0.13 (95% CI, ?0.06 to 0.32). Meta-regression revealed type of CR intervention and year of publication as positive statistically significant treatment effect modifiers.Conclusions
Receiving CR was shown to improve HRQOL, with exercise-, nonexercise-, and psychological-based interventions playing a vital role. Although these improvements in HRQOL were modest they still reflect an incremental benefit compared with receiving usual care. 相似文献10.
Ahmed AlBadri C. Noel Bairey Merz B. Delia Johnson Janet Wei Puja K. Mehta Galen Cook-Wiens Steven E. Reis Sheryl F. Kelsey Vera Bittner George Sopko Leslee J. Shaw Carl J. Pepine Bina Ahmed 《Journal of the American College of Cardiology》2019,73(6):684-693
Background
Currently as many as one-half of women with suspected myocardial ischemia have no obstructive coronary artery disease (CAD), and abnormal coronary reactivity (CR) is commonly found.Objectives
The authors prospectively investigated CR and longer-term adverse cardiovascular outcomes in women with and with no obstructive CAD in the National Heart, Lung, and Blood Institute–sponsored WISE (Women’s Ischemia Syndrome Evaluation) study.Methods
Women (n = 224) with signs and symptoms of ischemia underwent CR testing. Coronary flow reserve and coronary blood flow were obtained to test microvascular function, whereas epicardial CR was tested by coronary dilation response to intracoronary (IC) acetylcholine and IC nitroglycerin. All-cause mortality, major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, stroke, and heart failure), and angina hospitalizations served as clinical outcomes over a median follow-up of 9.7 years.Results
The authors identified 129 events during the follow-up period. Low coronary flow reserve was a predictor of increased MACE rate (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.01 to 1.12; p = 0.021), whereas low coronary blood flow was associated with increased risk of mortality (HR: 1.12; 95% CI: 1.01 to 1.24; p = 0.038) and MACE (HR: 1.11; 95% CI: 1.03 to 1.20; p = 0.006) after adjusting for cardiovascular risk factors. In addition, a decrease in cross-sectional area in response to IC acetylcholine was associated with higher hazard of angina hospitalization (HR: 1.05; 95% CI: 1.02 to 1.07; p < 0.0001). There was no association between epicardial IC-nitroglycerin dilation and outcomes.Conclusions
On longer-term follow-up, impaired microvascular function predicts adverse cardiovascular outcomes in women with signs and symptoms of ischemia. Evaluation of CR abnormality can identify those at higher risk of adverse outcomes in the absence of significant CAD. (Women's Ischemia Syndrome Evaluation [WISE]; NCT00000554) 相似文献11.
R.C. Bonadonna A. Giaccari R. Buzzetti G. Aimaretti D. Cucinotta A. Avogaro G. Perseghin M. Larosa G.B. Bolli C.G. Fanelli 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(5):496-503
Background and aims
Fostering patient's self-managing of basal insulin therapy could improve glucose control, by removing patient's and physician's barriers to basal insulin initiation, titration and glucose monitoring. The Italian Titration Approaches Study (ITAS) aims at demonstrating non-inferiority (<0.3% margin) in efficacy of glucose control (change in glycated hemoglobin [HbA1c] after 24 weeks) by the same titration algorithm of insulin glargine 300 U/mL (Gla-300), managed by the (nurse assisted) patient versus the physician, in insulin naïve patients with Type 2 Diabetes Mellitus (T2DM), uncontrolled with previous treatments.Methods and results
ITAS is a phase IV, 24-week, national, multicenter, open label, randomized (1:1) parallel group study. 458 patients were enrolled, 359 randomized, and 339 completed the study, in 46 Italian centers. Baseline characteristics and previous medications of the ITT population (N = 355) are reported. Mean ± SD age, T2DM duration, HbA1c, FPG and BMI were 64.0 ± 9.8 years, 11.6 ± 7.6 years, 8.79 ± 0.65%, 170.9 ± 42.3 mg/dL, and 30.3 ± 5.6 kg/m2, respectively. Vascular and metabolic disorders were most frequent (73.8% and 58.3%, respectively). More than 90% of patients were on metformin.Conclusion
ITAS is the first study to compare two different managers (nurse-assisted patient vs physician) of the same titration algorithm of Gla-300 in insulin naïve patients with T2DM in unsatisfactory glucose control. This study might provide novel evidence on the efficacy/effectiveness of patient-managed titration algorithm of Gla-300 in a pragmatic setting and may reduce barriers to basal insulin initiation and its titration. 相似文献12.
Timothy R.G. Cartlidge Mhairi K. Doris Stephanie L. Sellers Tania A. Pawade Audrey C. White Renzo Pessotto Jacek Kwiecinski Alison Fletcher Carlos Alcaide Christophe Lucatelli Cameron Densem James H.F. Rudd Edwin J.R. van Beek Adriana Tavares Renu Virmani Daniel Berman Jonathon A. Leipsic David E. Newby Marc R. Dweck 《Journal of the American College of Cardiology》2019,73(10):1107-1119
Background
Bioprosthetic aortic valve degeneration is increasingly common, often unheralded, and can have catastrophic consequences.Objectives
The authors sought to assess whether 18F-fluoride positron emission tomography (PET)-computed tomography (CT) can detect bioprosthetic aortic valve degeneration and predict valve dysfunction.Methods
Explanted degenerate bioprosthetic valves were examined ex vivo. Patients with bioprosthetic aortic valves were recruited into 2 cohorts with and without prosthetic valve dysfunction and underwent in vivo contrast-enhanced CT angiography, 18F-fluoride PET, and serial echocardiography during 2 years of follow-up.Results
All ex vivo, degenerate bioprosthetic valves displayed 18F-fluoride PET uptake that colocalized with tissue degeneration on histology. In 71 patients without known bioprosthesis dysfunction, 14 had abnormal leaflet pathology on CT, and 24 demonstrated 18F-fluoride PET uptake (target-to-background ratio 1.55 [interquartile range (IQR): 1.44 to 1.88]). Patients with increased 18F-fluoride uptake exhibited more rapid deterioration in valve function compared with those without (annualized change in peak transvalvular velocity 0.30 [IQR: 0.13 to 0.61] vs. 0.01 [IQR: ?0.05 to 0.16] ms?1/year; p < 0.001). Indeed 18F-fluoride uptake correlated with deterioration in all the conventional echocardiographic measures of valve function assessed (e.g., change in peak velocity, r = 0.72; p < 0.001). Each of the 10 patients who developed new overt bioprosthesis dysfunction during follow-up had evidence of 18F-fluoride uptake at baseline (target-to-background ratio 1.89 [IQR: 1.46 to 2.59]). On multivariable analysis, 18F-fluoride uptake was the only independent predictor of future bioprosthetic dysfunction.Conclusions
18F-fluoride PET-CT identifies subclinical bioprosthetic valve degeneration, providing powerful prediction of subsequent valvular dysfunction and highlighting patients at risk of valve failure. This technique holds major promise in the diagnosis of valvular degeneration and the surveillance of patients with bioprosthetic valves. (18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome [18F-FAABULOUS]; NCT02304276) 相似文献13.
Tomoharu Yokooji Takahiro Fukushima Koh Hamura Naoki Ninomiya Ryo Ohashi Takanori Taogoshi Hiroaki Matsuo 《Allergology international》2019,68(2):247-253
Background
Aspirin enhances food allergy symptoms by increasing absorption of ingested allergens. The objective of this study is to elucidate the role of aspirin in facilitating intestinal absorption of the wheat allergen, gliadin, in rats.Methods
Plasma concentrations of gliadin were determined after oral administration by gavage or administration into a closed intestinal loop in rats. We used an in situ intestinal re-circulating perfusion experiment to examine the effect of pepsin on aspirin-facilitated gliadin absorption. Fluorescein isothiocyanate (FITC)-labeled dextran-40 (FD-40) was used as a marker of non-specific absorption. The molecular size of gliadin and its allergenicity in plasma were examined using immunoblot analysis and intradermal reaction tests with Evans blue dye (EBD) extravasation, respectively.Results
Aspirin increased plasma concentrations of gliadin after oral administration but had no effect in the closed intestinal loop study. An in situ intestinal re-circulating perfusion study showed that FITC-labeled gliadin was absorbed similarly to FD-40. Aspirin increased absorption of both intact and pepsin-digested gliadin, with a more significant effect on absorption of pepsin-treated gliadin. Immunoblotting showed that most gliadin was absorbed in intact form. When the gliadin fraction was extracted from rat plasma after gavage and injected intradermally into gliadin-sensitized rats, EBD extravasation was observed at injection sites in a gliadin dose-dependent manner.Conclusions
Aspirin increased the absorption of intact and pepsin-digested gliadin via the paracellular pathway, maintaining their allergenicity. Moreover, the effect of aspirin on gliadin absorption was enhanced by modification and digestion of gliadin in the stomach. 相似文献14.
M.H. Schernthaner-Reiter B.K. Itariu M. Krebs M. Promintzer-Schifferl T.M. Stulnig A. Tura C.H. Anderwald M. Clodi B. Ludvik G. Pacini A. Luger G. Vila 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(4):334-342
Background and aims
Growth differentiation factor 15 (GDF15) is a strong predictor of cardiovascular morbidity and mortality found to be both marker and target of impaired glucose metabolism. GDF15 increases following glucose administration and is up-regulated in obesity and diabetes. We investigate here the relationship between GDF15 and beta cell function.Methods and results
In this cross-sectional study we evaluated GDF15 concentrations in 160 obese subjects (BMI 35–63 kg/m2, age 39.4 ± 18.6 years, m/f 38/122) who underwent a 75 g oral glucose tolerance test (OGTT). Based on the OGTT results, the cohort was divided into two groups: 1) normal fasting glucose and normal glucose tolerance (n = 80), 2) impaired fasting glucose, impaired glucose tolerance or type 2 diabetes (n = 80). The relationship of GDF15 to fasting and OGTT-based dynamic insulin sensitivity and insulin secretion parameters was evaluated.GDF15 was higher in the prediabetes and diabetes groups and correlated with HbA1c, glucose, insulin as well as baseline and dynamic indices of insulin sensitivity and estimated beta cell function. Multiple regression analysis revealed that age, waist-to-height ratio, glomerular filtration rate and prehepatic beta cell function, but not the grade of impairment of glucose metabolism, were independent predictors of GDF15. Subgroup analysis showed that of all parameters of glucose metabolism only C-peptide, fasting prehepatic beta cell function and insulinogenic index remained significantly related to GDF15 in both groups.Conclusion
We conclude that in patients with severe obesity, GDF15 strongly relates to beta cell function and should be further investigated as a potential therapeutic target and biomarker guiding treatment options. 相似文献15.
Objectives
This study aimed to explore double-negative T (DNT) cell cytotoxicity to pancreatic cancer and the effect of the Fas (CD95, APO-1)/FasL (CD178) signaling pathway on this process.Methods
DNT cells from the peripheral blood of healthy volunteers were expanded in vitro. The inhibitory effect of DNT cells on pancreatic cancer cells was investigated using a CCK-8 assay and nude mouse tumor model. A mechanistic study was performed using pathway blocking assays.Results
DNT cells were amplified in vitro with >90% purity, and the growth of pancreatic cancer in vitro was significantly inhibited by DNT cells. After coculture with DNT cells, Fas, caspase-8 and cleaved caspase-8 showed increased expression in pancreatic cancer cells. When blocking agent decoy receptor 3 (DcR3) was added, the antitumor effect of DNT cells and the expression of Fas, caspase-8 and cleaved caspase-8 were reduced in pancreatic cancer cells. In the nude mouse tumor model, the tumor volume and weight were lower in the DNT cell group and gemcitabine group than in the blank control group. Additionally, the expression of Fas, caspase-8 and cleaved caspase-8 was higher in the DNT cell group than in the blank control group. Moreover, DNT cells promoted apoptosis in cancer cells and animal model tissues.Conclusion
DNT cells inhibited the growth of pancreatic cancer, and the Fas/FasL signaling pathway was involved in this process. 相似文献16.
Yongzhi Zhai Lu Gan Sai Huang Qinrui Xing Xuan Zhou Lili Wang Cong Feng Li Chen Tanshi Li 《Pancreatology》2019,19(1):158-162
Objectives
To study the therapeutic effect of early peripancreatic lavage of ulinastatin on severe acute pancreatitis(SAP).Methods
Sixteen pigs were divided into 4 groups: model(SAP), saline lavage(SL), ulinastatin lavage(UL), intravenous ulinastatin(IU). UL and SL group were given peripancreatic lavage of ulinastatin by ultrasound-guided perirenal catheterization and IU group was intravenously instilled with ulinastatin. The multi-organ functions and the inflammatory factors were observed.Results
UL group has the best therapeutic effect. The changes of multi-organ functions and the inflammatory factors were compared with SAP group as follows. In time window of treatment: amylase (p?<?0.01), lipase (p?<?0.01), ALT (p?>?0.05), AST (p?<?0.05), CR (p?<?0.01), UR (p?<?0.01), IL-6 (p?<?0.01), IL-10 (p?<?0.01). In post-treatment phase: amylase (p?<?0.01), lipase (p?<?0.01), ALT (p?<?0.01), AST (p?<?0.01), CR (p?<?0.05), UR (p?>?0.05), IL-6 (p?<?0.01), IL-10 (p?<?0.01).Conclusions
Early peripancreatic lavage of ulinastatin in SAP could effectively improve the multi-organ functions and inflammatory response. 相似文献17.
Liu S Li Y Lin T Fan X Liang Y Heemann U 《Diabetes research and clinical practice》2011,91(2):177-182
Background
This study was to investigate the effects of human insulin and insulin glargine on proliferation of T24 human bladder cancer cells and the implication of the PI3K/Akt and MEK/ERK1/2 pathways.Methods
After exposure to insulin or glargine at the indicated concentrations for certain time courses, in the absence or presence of inhibitor for MEK (PD98059) or PI3K (LY294002), T24 cell proliferation was evaluated by CCK-8 assay. Phosphorylation of Akt and ERK1/2 was analyzed by Western blot.Results
Insulin and glargine similarly induced phosphorylation of Akt and slight increases in T24 cell proliferation at 10-100 IU/L. LY294002 remarkably reduced T24 cell proliferation in all groups. However, in the presence of LY294002, cell growth was still promoted by insulin and glargine relative to LY294002-treated group. Accordingly, LY294002 profoundly reduced protein levels of pAkt, while insulin and glargine increased pAkt in T24 cells pretreated with LY294002 as compared with cells treated with LY294002 alone. PD98059 reduced pERK while enhanced T24 cell proliferation. Insulin and glargine increased pERK at 15, 30, 60 min, not at 24 h.Conclusions
High dose human insulin and insulin glargine similarly promoted T24 bladder cancer cell proliferation via PI3K-independent activation of Akt. 相似文献18.
19.
Background
Remote ischemic postconditioning (RIPostC) could reduce myocardial ischemia/reperfusion injury markedly. However, the mechanism of the protective signal transfer of RIPostC to the heart remains unclear. In this study, we hypothesize that macrophage migration inhibitory factor (MIF) plays an important role in the cardioprotection conferred by RIPostC.Methods
RIPostC was induced by 4 cycles of 5 min ischemia/5 min reperfusion on the lower limbs of rats immediately after myocardial reperfusion. The plasma level of MIF was compared between the RIPostC and reperfusion injury groups. (S,R)-3-(4-hydroxy -phenyl)-4,5–dihydro-5-isoxazoleacetic acid methyl ester (ISO-1) was used as a potent inhibitor of MIF. 2-methoxyestradiol (2ME2), an inhibitor of HIF-1α (hypoxia-inducible factor-1α)，was used as a tool to inhibit the role of HIF-1α.Results
We found that a significant elevation in the level of plasma MIF occurred when RIPostC was carried out; this elevation could be blocked by femoral occlusion. The cardiac MIF level decreased significantly after RIPostC stimulus compared with the ischemia/reperfusion (IR) group (P < 0.01). In addition, inhibition of MIF by ISO-1 could induce the loss of cardioprotection and aggravate the apoptosis of the heart in RIPostC. RIPostC confers protection against myocardial IR injury via the MIF-AMPK signaling pathway. Finally, inhibition of HIF-1α may result in the reduction of plasma MIF in RIPostC.Conclusions
MIF plays an important role in RIPostC through the humoral pathway in a HIF-1α?dependent manner, which could activate the cardiac AMP-activated protein kinase (AMPK) pathway to confer powerful cardioprotection. 相似文献20.
E.P.B. Dopona V.F. Rocha L.N.S. Furukawa I.B. Oliveira J.C. Heimann 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(3):301-305