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《Gastrointestinal endoscopy》2019,89(6):1141-1149
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BackgroundAntibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis.ObjectivesThe authors aimed to generate and characterize immunoglobulin (Ig)G monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants.MethodsThe authors created hybridomas from an unimmunized low-density lipoprotein (LDL) receptor-deficient (Ldlr?/?) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization.ResultsLO9 reacted well with native LDL bound to immobilized matrix components and less well to oxidized LDL. LO9 binding to immobilized native LDL was not neutralized by fluid-phase native LDL, indicating an adhesion-dependent epitope. The authors localized the epitope to a 20 amino-acid peptide sequence (P5) in the globular amino-terminus of apolipoprotein B. LO9 reacted with antigen in mouse atherosclerosis and in both human stable and ruptured coronary atherosclerosis. Furthermore, in vivo near-infrared fluorescence molecular tomographic imaging, and ex vivo confocal microscopy showed that intravenously injected LO9 localized beneath endothelium of the aortic arch in Ldlr?/? mice, in the vicinity of macrophages.ConclusionsThe authors believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis.  相似文献   

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Background and aimsTo evaluate the effects of a high-fat diet during post-weaning growth on intermediate metabolism and retroperitoneal adipose tissue, in adult male rats exposed to adequate or deficient zinc intake during prenatal and postnatal life.Methods and resultsFemale Wistar rats were fed low- or control-zinc diets from pregnancy to offspring weaning. Male offspring born from control mothers were fed either control or high-fat, control-zinc diets for 60 days. Male offspring born from zinc deficient mothers were fed either low-zinc or high-fat, low-zinc diets for 60 days. At 74 days of life, oral glucose tolerance test was performed. In 81-day-old offspring, blood pressure, lipid profile, plasmatic lipid peroxidation and serum adiponectin level were determined. In retroperitoneal adipose tissue, we evaluated oxidative stress, morphology and adipocytokines mRNA expression. Low-zinc diet induced adipocytes hypertrophy, increased oxidative stress, and decreased adiponectin mRNA expression in adipose tissue. Low-zinc diet increased systolic blood pressure, triglyceridemia, plasmatic lipid peroxidation and glycemia at 3 h after glucose overload. Animals fed high-fat or high-fat, low-zinc diets showed adipocytes hypertrophy, decreased adiponectin mRNA expression, and increased leptin mRNA expression and oxidative stress in adipose tissue. They also exhibited decreased serum adiponectin levels, increased triglyceridemia, plasmatic lipid peroxidation and area under the oral glucose tolerance curve. High-fat, low-zinc diet induced greater alterations in adipocyte hypertrophy, leptin mRNA expression and glucose tolerance test than high-fat diet.ConclusionZinc deficiency since early stages of intrauterine life could increase susceptibility to metabolic alterations induced by high-fat diets during postnatal life.  相似文献   

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BackgroundAlthough cardiac magnetic resonance (CMR) is considered the gold standard for myocardial fibrosis detection, cardiac computed tomography (CCT) is emerging as a promising alternative.ObjectivesThe purpose of this study was to assess feasibility and diagnostic accuracy of a comprehensive functional and anatomical evaluation with CCT as compared with CMR in patients with newly diagnosed left ventricular dysfunction (LVD).MethodsA total of 128 consecutive patients with newly diagnosed LVD were screened. Based on the exclusion criteria, 28 cases were excluded. CCT was performed within 10 days from CMR. Biventricular volumes and ejection fraction, and presence and pattern of delayed enhancement (DE), were determined, along with evaluation of coronary arteries among patients undergoing invasive angiography in the 6 months after CCT.ResultsSix cases were excluded because of claustrophobia at CMR. Among the 94 patients who formed the study population, the concordance between CCT and CMR in suggesting the cause of the LVD was high (94.7%, 89/94 patients) in the overall population and was 100% for identifying ischemic cardiomyopathy. The CCT diagnostic rate for DE assessment was also high (96.7%, 1,544/1,598 territories) and similar to that of CMR (97.4%; P = 0.345, CCT vs CMR). Moreover, CCT showed high diagnostic accuracy in the detection of DE (94.8%, 95% CI: 93.6%-95.8%) in a territory-based analysis. Biventricular volumes and function parameters as measured by CCT and CMR were similar, without significant differences with the exception of a modest difference in RV volume. CCT was confirmed to be accurate for assessing arterial coronary circulation. The mean radiation exposure of the whole CCT was 7.78 ± 2.53 mSv (0.84 ± 0.24 mSv for DE).ConclusionsCCT performed with low-dose whole-heart coverage scanner and high-concentration contrast agent appears an effective noninvasive tool for a comprehensive assessment of patients with newly diagnosed LVD.  相似文献   

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《Pancreatology》2020,20(7):1550-1557
BackgroundThe refusal of blood transfusions compels surgeons to face ethical and clinical issues. A single-institution experience with a dedicated perioperative blood management protocol was reviewed to assess feasibility and short-term outcomes of true bloodless pancreatic surgery.MethodsThe institutional database was reviewed to identify patients who refused transfusion and were scheduled for elective pancreatic surgery from 2010 through 2018. A protocol to optimize the hemoglobin values by administration of drugs stimulating erythropoiesis was systematically used.ResultsPerioperative outcomes of 32 Jehovah’s Witnesses patients were included. Median age was 67 years (range, 31–77). Nineteen (59.4%) patients were treated with preoperative erythropoietin. Twenty-four (75%) patients underwent pylorus-preserving pancreaticoduodenectomy, 4 (12.5%) distal pancreatectomy (DP) with splenectomy, 3 (9.4%) spleen-preserving DP, and 1 (3.1%) total pancreatectomy. Median estimated blood loss and surgical duration were 400 mL (range, 100–1000) and 470 min (range, 290–595), respectively. Median preoperative hemoglobin was 13.9 g/dL (range, 11.7–15.8) while median postoperative nadir hemoglobin was 10.5 g/dL (range, 7.1–14.1). The most common histological diagnosis (n = 15, 46.9%) was pancreatic ductal adenocarcinoma. Clavien-Dindo grade I-II complications occurred in fourteen (43.8%) patients while one (3.1%) patient had a Clavien-Dindo grade IIIa complication wich was an abdominal collection that required percutaneous drainage. Six (18.8%) patients presented biochemical leak or postoperative pancreatic fistula grade B. Median hospital stay was 16 days (range, 8–54) with no patient requiring transfusion or re-operation and no 90-day mortality.ConclusionsA multidisciplinary approach and specific perioperative management allowed performing pancreatic resections in patients who refused transfusion with good short-term outcomes.  相似文献   

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Background & AimsEosinophilic esophagitis (EoE) is a chronic, immune-mediated disease for which there is currently no pharmacologic therapy approved by the U.S. Food and Drug Administration.MethodsIn this double-blind, placebo-controlled, phase 3 trial, patients 11–55 years of age with EoE and dysphagia were randomized 2:1 to receive budesonide oral suspension (BOS) 2.0 mg twice daily or placebo for 12 weeks at academic or community care practices. Co-primary endpoints were the proportion of stringent histologic responders (≤6 eosinophils/high-power field) or dysphagia symptom responders (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] score) over 12 weeks. Changes in DSQ score (key secondary endpoint) and EoE Endoscopic Reference Score (EREFS) (secondary endpoint) from baseline to week 12, and safety parameters were examined.ResultsOverall, 318 patients (BOS, n = 213; placebo, n = 105) were randomized and received ≥1 dose of study treatment. More BOS-treated than placebo-treated patients achieved a stringent histologic response (53.5% vs 1.0%; Δ53% [95% confidence interval (CI), 43.8%–59.5%]; P < .001) or symptom response (52.6% vs 39.1%; Δ13% [95% CI, 1.6%–24.3%]; P = .024) over 12 weeks. BOS-treated patients also had greater improvements in least-squares mean DSQ scores and EREFS over 12 weeks than placebo-treated patients: DSQ, –13.0 (SEM 1.2) vs –9.1 (SEM 1.5) (Δ–3.9 [95% CI, –7.1 to –0.8]; P = .015); EREFS, –4.0 (SEM 0.3) vs –2.2 (SEM 0.4) (Δ–1.8 [95% CI, –2.6 to –1.1]; P < .001). BOS was well tolerated; most adverse events were mild or moderate in severity.ConclusionsIn patients with EoE, BOS 2.0 mg twice daily was superior to placebo in improving histologic, symptomatic, and endoscopic outcomes over 12 weeks. BOS 2.0 mg twice daily was well tolerated. ClinicalTrials.gov number: NCT02605837.  相似文献   

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