227 research outputs found
Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD:an individual patient data meta-analysis
Non-invasive markers of liver fibrosis: adjuncts or alternatives to liver biopsy?
Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care
Clinical and translational implications of the caveolin gene family: lessons from mouse models and human genetic disorders.
Here we review the clinical and translational implications of the caveolin gene family for understanding the pathogenesis of human diseases, including breast and prostate cancers, pulmonary hypertension, cardiomyopathy, diabetes, and muscular dystrophy. Detailed phenotypic analysis of caveolin knockout mice has served to highlight the crucial role of a caveolin deficiency in the pathogenesis of many human disease processes. Mutations in the human caveolin genes are associated with a number of established genetic disorders (such as breast cancer, lipodystrophy, muscular dystrophy, and cardiomyopathy), making the caveolins important and novel targets for drug development. The implementation of new strategies for caveolin replacement therapy-including caveolin mimetic peptides-is ongoing
Detection and alterations of acetylcarnitine (AC) in human liver by 1H MRS at 3T after supplementation with L-carnitine
Purpose: Acetylcarnitine can be assessed in vivo using proton MRS (1H-MRS) with long TEs and this has been previously applied successfully in muscle. The aim of this study was to evaluate a 1H-MRS technique for liver acetylcarnitine quantification in healthy humans before and after L-carnitine supplementation.
Method: Baseline acetylcarnitine levels were quantified using a STEAM sequence with prolonged TE in 15 healthy adults. Using STEAM with four different TEs was evaluated in phantoms. To assess reproducibility of the measurements, five of the participants had repeated 1H-MRS without receiving L-carnitine supplementation. To determine if liver acetylcarnitine could be changed after L-carnitine supplementation, acetylcarnitine was quantified 2 h after intravenous L-carnitine supplementation (50 mg/kg body weight) in the other 10 participants. Hepatic lipids were also quantified from the 1H-MRS spectra.
Results: There was good separation between the acetylcarnitine and fat in the phantoms using TE = 100 ms. Hepatic acetylcarnitine levels were reproducible (coefficient of reproducibility = 0.049%) and there was a significant (p
Conclusion: Our results demonstrate that our 1H-MRS technique could be used to measure acetylcarnitine in the liver and detect changes following intravenous supplementation in healthy adults despite the presence of lipids. Our techniques should be explored further in the study of fatty liver disease, where acetylcarnitine is suggested to be altered due to hepatic inflexibilities
Clinical utility of MRI biomarkers for identifying NASH patients’ high risk of progression: A multi-center pooled data and meta-analysis
Transcriptional evidence for the "Reverse Warburg Effect" in human breast cancer tumor stroma and metastasis: Similarities with oxidative stress, inflammation, Alzheimer's disease, and "Neuron-Glia Metabolic Coupling"
Caveolin-1
(-/-) null stromal cells are a novel genetic model for cancer-associated
fibroblasts and myofibroblasts. Here, we used an unbiased informatics
analysis of transcriptional gene profiling to show that Cav-1 (-/-)
bone-marrow derived stromal cells bear a striking resemblance to the
activated tumor stroma of human breast cancers. More specifically, the
transcriptional profiles of Cav-1 (-/-) stromal cells were most closely
related to the primary tumor stroma of breast cancer patients that had
undergone lymph-node (LN) metastasis. This is consistent with previous
morphological data demonstrating that a loss of stromal Cav-1 protein (by
immuno-histochemical staining in the fibroblast compartment) is
significantly associated with increased LN-metastasis. We also provide
evidence that the tumor stroma of human breast cancers shows a
transcriptional shift towards oxidative stress, DNA damage/repair,
inflammation, hypoxia, and aerobic glycolysis, consistent with the "Reverse
Warburg Effect". Finally, the tumor stroma of "metastasis-prone" breast
cancer patients was most closely related to the transcriptional profiles
derived from the brains of patients with Alzheimer's disease. This suggests
that certain fundamental biological processes are common to both an activated
tumor stroma and neuro-degenerative stress. These processes may include oxidative
stress, NO over-production (peroxynitrite formation), inflammation, hypoxia, and
mitochondrial dysfunction, which are thought to occur in Alzheimer's disease
pathology. Thus, a loss of Cav-1 expression in cancer-associated myofibroblasts
may be a protein biomarker for oxidative stress, aerobic glycolysis, and
inflammation, driving the "Reverse
Warburg Effect" in the tumor micro-environment
and cancer cell metastasis
Emergent percutaneous cardiopulmonary bypass in patients having cardiovascular collapse in the cardiac catheterization laboratory
Percutaneous cardiopulmonary bypass (PCB) was instituted in 30 initially stable patients who developed either cardiac arrest refractory to resuscitation (n = 7) or cardiogenic shock (mean arterial blood pressure <50 mm Hg unresponsive to fluid resuscitation or vasopressors) (n = 23) after a cathetertzation laboratory complication. Events leading to collapse included abrupt closure during percutaneous transluminal coronary angioplasty (PTCA) (n = 22), complications from diagnostic cardiac catheterization (n = 6), left ventricular perforation during mural valvuloplasty (n = 1), and right ventricular perforation during pericardiocentesis (n = 1). PCB was initiated within 20 minutes of cardiovascular collapse in 83% of patients (arrest: 21 +/- 13 minutes [range 10 to 50]; and shock: 17 +/- 6 minutes [range 10 to 30]). Mean arterial blood pressure increased on PCB from 0 to 56 mm Hg in patients with cardiac arrest and from 37 to 63 mm Hg in those with cardiogenic shock at mean PCB flow rates of 2.5 to 5.0 liters/min. Subsequent therapy on PCB included emergent cardiac surgery (n = 14), PTCA (n = 13) and medical therapy (n = 3). Six patients (20%) survived to hospital discharge (3 with cardiac surgery, 2 with PTCA, and 1 with medical therapy). All 7 patients with refractory cardiac arrest died despite further interventions on PCB, whereas 6 of 23 (26%) with cardiogenic shock survived to hospital discharge. Thus, in response to cardiovascular collapse in the catheterization laboratory, PCB does not salvage patients who do not regain a stable cardiac rhythm. PCB can stabilize patients who develop cardiogenic shock for further interventions which are lifesaving in only a minority of patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31621/1/0000554.pd
PYY plays a key role in the resolution of diabetes following bariatric surgery in humans.
BACKGROUND: Bariatric surgery leads to early and long-lasting remission of type 2 diabetes (T2D). However, the mechanisms behind this phenomenon remain unclear. Among several factors, gut hormones are thought to be crucial mediators of this effect. Unlike GLP-1, the role of the hormone peptide tyrosine tyrosine (PYY) in bariatric surgery in humans has been limited to appetite regulation and its impact on pancreatic islet secretory function and glucose metabolism remains under-studied. METHODS: Changes in PYY concentrations were examined in obese patients after bariatric surgery and compared to healthy controls. Human pancreatic islet function was tested upon treatment with sera from patients before and after the surgery, in presence or absence of PYY. Alterations in intra-islet PYY release and insulin secretion were analysed after stimulation with short chain fatty acids (SCFAs), bile acids and the cytokine IL-22. FINDINGS: We demonstrate that PYY is a key effector of the early recovery of impaired glucose-mediated insulin and glucagon secretion in bariatric surgery. We establish that the short chain fatty acid propionate and bile acids, which are elevated after surgery, can trigger PYY release not only from enteroendocrine cells but also from human pancreatic islets. In addition, we identify IL-22 as a new factor which is modulated by bariatric surgery in humans and which directly regulates PYY expression and release. INTERPRETATION: This study shows that some major metabolic benefits of bariatric surgery can be emulated ex vivo. Our findings are expected to have a direct impact on the development of new non-surgical therapy for T2D correction
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