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Douleur et stéatopathie hépatiques, des manifestations systémiques sous estimées de la BPCO / Pain and Fatty liver disease, underestimated systemic manifestations of COPDViglino, Damien 14 September 2018 (has links)
La bronchopneumopathie chronique obstructive (BPCO) est une des maladies chroniques les plus fréquentes et constitue une des premières causes de mortalité dans le monde avec un impact sociétal majeur et des couts de santé considérables. La BPCO est aujourd’hui considérée comme une maladie multi-systémique dont le pronostic est lié en grande partie à ses comorbidités et à la survenue d’exacerbations. Les exacerbations qui vont ponctuer l’évolution de la BPCO précipitent le déclin de la fonction respiratoire et favorisent la décompensation des comorbidités et la survenue d’événements cardiovasculaires comme des infarctus du myocarde ou des accidents vasculaires cérébraux. La prise en charge moderne de la BPCO est basée sur la mise en place d’un soin intégré incluant la prise en charge des comorbidités et une meilleure détection et gestion des exacerbations.Dans ce travail de thèse nous abordons l’atteinte hépatique (stéatopathie hépatique non alcoolique - NAFLD) dans la BPCO comme une comorbidité sous-estimée (publication 1) alors qu’elle a probablement des implications pronostiques importantes (publication 2). La BPCO s'accompagne également de symptômes non respiratoires tel que des douleurs, dont les variations et localisations sont peu connues pendant et après l'exacerbation (publication 3). Le traitement de ces douleurs par des opiacés pourrait avoir un effet spécifiquement délétère dans cette population (publication 5). Les enjeux de réforme du système de santé avec une optimisation cout-efficacité incitent à développer et valider de nouvelles méthodes de prise en charge ambulatoire des exacerbations (publication 6).Dans une première partie de la thèse nous explorons les liens épidémiologiques entre BPCO et NAFLD. Nous explorerons également les conséquences d’une telle association sur le devenir cardiovasculaire des patients à moyen terme. Dans une deuxième partie, nous cherchons à définir les caractéristiques des douleurs avant et après exacerbation au cours de la BPCO, le lien entre douleur, anxiété et dépression chez ces patients et la sécurité d'emploi des morphiniques dans cette population fragile. Dans une dernière partie, nous aborderons la stratification du risque lié à une exacerbation de BPCO, et la possibilité d’une prise en charge ambulatoire extrahospitalière pour les exacerbations de sévérité modérée. / Chronic Obstructive Pulmonary Disease (COPD) is one of the most common chronic diseases and is one of the leading causes of death in the world with major societal impact and considerable health costs. COPD is now considered a multi-systemic disease whose prognosis is largely related to its comorbidities and the occurrence of exacerbations. The exacerbations that punctuate the evolution of COPD precipitate the decline of respiratory function and promote the decompensation of comorbidities and the occurrence of cardiovascular events such as myocardial infarction or cerebrovascular accidents. The modern management of COPD is based on the implementation of integrated care including the management of comorbidities and better detection and management of exacerbations.In this thesis we address liver injury (non-alcoholic fatty liver disease - NAFLD) in COPD as an underestimated comorbidity (publication 1), although it probably has important prognostic implications (publication 2). COPD is also associated with non-respiratory symptoms such as pain, the variations and locations of which are poorly known during and after exacerbation (publication 3). Treatment of this pain with opiates may have a specifically deleterious effect in this population (publication 5). The challenges of health system reform with cost-effectiveness optimization encourage the development and validation of new methods of outpatient management of exacerbations (publication 6).In a first part of the thesis we explore the epidemiological links between COPD and NAFLD. We will also explore the consequences of such an association on the cardiovascular outcome of patients in the medium term. In a second part, we seek to define the characteristics of pain before and after exacerbation during COPD, the link between pain, anxiety and depression in these patients and the safety of opioids in this fragile population. In the last part, we will discuss the stratification of the risk linked to an exacerbation of COPD, and the possibility of outpatient care for exacerbations of moderate severity.
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Hepatic NAD salvage pathway is enhanced in mice on a high-fat dietPenke, Melanie, Larsen, Per S., Schuster, Susanne, Dall, Morten, Jensen, Benjamin A.H., Gorski, Theresa, Meusel, Andrej, Richter, Sandy, Vienberg, Sara G., Treebak, Jonas T., Kiess, Wieland, Garten, Antje 02 March 2020 (has links)
Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme for NAD salvage and the abundance of Nampt has been shown to be altered in non-alcoholic fatty liver disease. It is, however, unknown how hepatic Nampt is regulated in response to accumulation of lipids in the liver of mice fed a high-fat diet (HFD). HFD mice gained more weight, stored more hepatic lipids and had an impaired glucose tolerance compared with control mice. NAD levels as well as Nampt mRNA expression, protein abundance and activity were significantly increased in HFD mice. Enhanced NAD levels were associated with deacetylation of p53 and Nfκb indicating increased activation of Sirt1. Despite impaired glucose tolerance and increased hepatic lipid levels in HFD mice, NAD metabolism was significantly enhanced. Thus, improved NAD metabolism may be a compensatory mechanism to protect against negative impact of hepatic lipid accumulation.
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Non-Invasive Assessment of Hepatic Steatosis in Patients with NAFLD Using Controlled Attenuation Parameter and 1H-MR SpectroscopyKarlas, Thomas, Wiegand, Johannes January 2014 (has links)
Introduction: Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease
(NAFLD). 1H-Magnetic resonance spectroscopy (1H-MRS) and the ultrasound-based controlled attenuation parameter (CAP)
correlate with biopsy proven steatosis, but have not been correlated with each other so far. We therefore performed a headto-
head comparison between both methods.
Methods: Fifty patients with biopsy-proven NAFLD and 15 healthy volunteers were evaluated with 1H-MRS and transient
elastography (TE) including CAP. Steatosis was defined according to the percentage of affected hepatocytes: S1 5-33%, S2
34–66%, S3 $67%.
Results: Steatosis grade in patients with NAFLD was S1 36%, S2 40% and S3 24%. CAP and 1H-MRS significantly correlated
with histopathology and showed comparable accuracy for the detection of hepatic steatosis: areas under the receiveroperating
characteristics curves were 0.93 vs. 0.88 for steatosis $S1 and 0.94 vs. 0.88 for $S2, respectively. Boot-strapping
analysis revealed a CAP cut-off of 300 dB/m for detection of S2-3 steatosis, while retaining the lower cut-off of 215 dB/m for
the definition of healthy individuals. Direct comparison between CAP and 1H-MRS revealed only modest correlation (total
cohort: r = 0.63 [0.44, 0.76]; NAFLD cases: r = 0.56 [0.32, 0.74]). For detection of F2–4 fibrosis TE had sensitivity and specificity
of 100% and 98.1% at a cut-off value of 8.85 kPa.
Conclusion: Our data suggest a comparable diagnostic value of CAP and 1H-MRS for hepatic steatosis quantification.
Combined with the simultaneous TE fibrosis assessment, CAP represents an efficient method for non-invasive
characterization of NAFLD. Limited correlation between CAP and 1H-MRS may be explained by different technical aspects,
anthropometry, and presence of advanced liver fibrosis.
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INTELLIGENT HEALTHCARE DATA ANALYTICS COUPLED WITH SENSOR ASSESSMENT FOR NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)Ridhi Deo (12480750) 29 April 2022 (has links)
<p>This research was conducted to develop and evaluate a screening tool for Hepatic Steatosis (or fatty liver) detection using machine learning based models. The developed models are intended to be used as a potential clinical decision support tool for identifying patients with Non-Alcoholic Fatty Liver Disease (NAFLD). Two versions of a HS prediction tool are discussed in Paper 1, Objectives 1A, and 1B, respectively.</p>
<p>Explainability analysis of the developed models is also a major component of this work, discussed in Paper 2. Models from Paper 1 are analyzed further for interpretability and the results are then compared with current clinical literature. Insights from the explainability analysis are used to identify best models that follow the clinical literature logically. Most contributing features within each model are also identified in this work.</p>
<p>Another aspect of NAFLD management is related to the chronic exposure to heavy metals in the environment (such as: Arsenic, Lead, Cadmium etc.). The heavy metal exposure component is explored in two ways in this dissertation. In paper 3, another version of the ML-based screening tool is explored by including heavy metal exposure data. The results from the model (with heavy metal data) are then compared with models that exclude the heavy metal exposure data. The results and their implications are discussed in paper 3.</p>
<p>Arsenic is a major hepatotoxin and the chronic exposure can lead to severe liver injury. In Paper 4, a commercially available Arsenic detection kit was examined for Arsenic detection in water at a household level. The kit was evaluated following a short experimental plan and the obtained results are discussed. Finally, the obtained images were quantified digitally using a customized image analysis and pattern recognition algorithm. The methods used for quantification and the obtained results are also discussed.</p>
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The Association Between Non-Alcoholic Fatty Liver Disease and Atrial Fibrillation: A Meta-AnalysisWijarnpreecha, Karn, Boonpheng, Boonphiphop, Thongprayoon, Charat, Jaruvongvanich, Veeravich, Ungprasert, Patompong 01 October 2017 (has links)
The association between non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) has been suggested by recent epidemiological studies although the results were inconsistent. This meta-analysis was conducted to summarize all available data. Methods A comprehensive literature review was conducted using MEDLINE and EMBASE database through May 2017 to identify all studies that reported the risk of AF among patients with NAFLD versus those without NAFLD. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. Results Of 1009 studies, 5 studies (two cross-sectional studies and three cohort studies) with 238,129 participants met the eligibility criteria and were included in the meta-analysis. The risk of AF in patients with NAFLD was significantly higher than subjects without NAFLD with the pooled risks ratio of 2.06 (95% confidence interval, 1.10–3.85). The statistical heterogeneity was high with an I2 of 78%, which was the major limitation of this meta-analysis. Conclusions A significantly increased risk of AF among patients with NAFLD was demonstrated in this study.
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Regulation of Metabolism by Hepatic OXPHOS: A DissertationAkie, Thomas E. 02 October 2015 (has links)
Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent issue in the modern world, predisposing patients to serious pathology such as cirrhosis and hepatocellular carcinoma. Mitochondrial dysfunction, and in particular, diminished hepatic oxidative phosphorylation (OXPHOS) capacity, have been observed in NAFLD livers, which may participate in NAFLD pathogenesis.
To examine the role of OXPHOS in NAFLD, we generated a model of enhanced hepatic OXPHOS using mice with liver-specific transgenic expression of LRPPRC, a protein which activates mitochondrial transcription and augments OXPHOS capacity. When challenged with high-fat feeding, mice with enhanced hepatic OXPHOS were protected from the development of liver steatosis and inflammation, critical components in the pathogenesis of NAFLD. This protection corresponded to increased liver and whole-body insulin sensitivity. Moreover, mice with enhanced hepatic OXPHOS have increased availability of oxidized NAD+, which promotes complete fatty acid oxidation in hepatocytes.
Interestingly, mice with enhanced hepatic OXPHOS were also protected from obesogenic effects of long-term high-fat feeding. Consistent with this, enhanced hepatic OXPHOS increased energy expenditure and adipose tissue oxidative gene expression, suggesting a communication between the liver and adipose tissue to promote thermogenesis. Examination of pro-thermogenic molecules revealed altered bile acid composition in livers and serum of LRPPRC transgenic mice. These mice had increased expression of bile acid synthetic enzymes, genes which are induced by NAD+ dependent deacetylase SIRT1 activation of the transcriptional co-regulator PGC-1a. These findings suggest that enhanced hepatic OXPHOS transcriptionally regulates bile acid synthesis and dictates whole-body energy expenditure, culminating in protection from obesity.
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Lipoxin-A4 in the rabbit model of atherosclerosis and liver steatosisSingh, Jaskamal Kaur 21 February 2019 (has links)
BACKGROUND: Obesity is a global health problem that is associated with wide range of diseases, including atherosclerosis and Nonalcoholic fatty liver (NAFL) disease. Hepatic inflammation can cause cirrhosis, hepatic decompensation (liver failure) and cancer. Recent research now looks at the chronic systemic effects and inter-organ communication between atherosclerosis potentially promoting the development of NAFL. The resolution of inflammation is regulated naturally in the body by specialized pro-resolving mediators (SPMs). Immunoresolvents like ⍹6-derived Lipoxin A4 are suggested as a therapeutic strategy to overcome chronic inflammation and disease. In this study we investigated the therapeutic potential of Lipoxin A4 (LXA4) in cholesterol fed rabbit model of hypercholesterolemia, with atherosclerotic plaques and confined vascular endothelial injury and its effect on the progression of NAFL.
OBJECTIVE: This is a continuation of studies pioneered in the Hamilton lab and an extension of the recent study by Taylor et. al in 201811 linking aortic plaque and liver disease. We will now investigate the therapeutic potential of Lipoxin A4 on lipid-rich atherosclerotic plaques in cholesterol fed rabbits and its effect on the progression of NAFL to NASH.
METHODS: In vivo magnetic resonance imaging (MRI) measured aortic atherosclerotic inflammation (with plaque Gd-enhancement), plaque size (vessel wall area), and composition, within rabbits fed normal chow or a 1% cholesterol-enriched diet. Biomarkers in the blood were monitored in the rabbits, with follow-up by histology, which included Masson’s trichrome staining. Light Microscopy was used for liver imaging. Ex vivo MRI, T1W imaging was used to quantify VWA (vessel wall area), with Image J programming.
RESULTS: Cholesterol-fed rabbits with and without aortic injury developed hypercholesterolemia, NAFL, and atherosclerotic plaques in the aorta. Elevated plasma gamma-glutamyl transferase (GGT; p =0.014) and the ratio of liver enzymes aspartate and alanine aminotransferases (AST/ALT; p = 0.033) confirmed the progression of steatosis to non-alcoholic steatohepatitis (NASH). Histological images showed less fibrosis in those rabbits fed 1% CHOL diet with injury treated with LipoxinA4, when compared to 1% CHOL diet and injury alone. The plasma biomarkers showed a decrease in cholesterol (79%) and triglycerides (49.9%) in those rabbits given LXA4 therapy. The LXA4 treated 1% CHOL diet with injury group showed a marked decrease in the aorta vessel wall area when compared to the 1% CHOL diet with injury, without treatment; as seen in ex vivo, MRI T1W imaging.
CONCLUSION: Lipoxin implementation in cholesterol fed rabbits that have localized regions of highly inflamed aortic atherosclerotic plaques, may contribute to the attenuation on the progression of NAFL to NASH as seen in histology and plasma biomarkers including; cholesterol and triglycerides. Lipoxin as a therapeutic has an effect on treating atherosclerotic plaques and attenuating atherosclerosis progression.
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Detection of histological features in liver biopsy images to help identify Non-Alcoholic Fatty Liver DiseaseSethunath, Deepak 26 April 2018 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / This thesis explores a minimally invasive approach of diagnosing Non-Alcoholic Fatty Liver disease (NAFLD) on mice and humans which can be useful for pathologists while performing their diagnosis. NAFLD is a spectrum of diseases going from least severe to most severe – steatosis, steatohepatitis, fibrosis and finally cirrhosis. This disease primarily results from fat deposition in the liver which is unrelated to alcohol or viral causes. In general, it affects individuals having a combination of at least three of the five metabolic syndromes namely, obesity, hypertension, diabetes, hypertriglyceridemia, and hyperlipidemia. Given how common these metabolic syndromes have become, the rate of NAFLD has increased dramatically over the years affecting about three-quarters of all obese individuals including many children, making it one of the most common diseases in United States. Our study focuses on building various computational models which help identify different histological features in a liver biopsy image, thereby analyzing if a person is affected by NAFLD or not. Here, we develop and validate the performance of automated classifiers built using image processing and machine learning methods for detection of macro- and microsteatosis, lobular and portal inflammation and also categorize different types fibrosis in murine and human fatty liver disease and study the correlation of automated quantification of macrosteatosis, lobular and portal inflammation, and fibrosis (amount of collagen) with expert pathologist’s semi-quantitative grades. Our research for macrosteatosis and microsteatosis prediction shows the model’s precision and sensitivity as 94.2%, 95% for macrosteatosis and 79.2%, 77% for microsteatosis. Our models detect lobular and portal inflammation(s) with a precision, sensitivity of 79.6%, 77.1% for lobular inflammation and 86%, 90.4% for portal inflammation. We also present the first study on identification of the six different types of fibrosis having a precision of 85.6% for normal fibrosis and >70% for portal fibrosis, periportal fibrosis, pericellular fibrosis, bridging fibrosis and cirrhosis. We have also quantified the amount of collagen in a liver biopsy and compared it to the pathologist semi-quantitative fibrosis grade.
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Studies on the Anti-obesity Effects of Major Isoflavones in the Hot Water Extract of Pueraria Flowers / 葛の花熱水抽出物の主要イソフラボン類の抗肥満作用に関する研究Kamiya, Tomoyasu 23 January 2014 (has links)
京都大学 / 0048 / 新制・論文博士 / 博士(農学) / 乙第12807号 / 論農博第2792号 / 新制||農||1020(附属図書館) / 学位論文||H26||N4810(農学部図書室) / 80851 / (主査)教授 河田 照雄, 教授 金本 龍平, 教授 谷 史人 / 学位規則第4条第2項該当 / Doctor of Agricultural Science / Kyoto University / DFAM
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Leptin improves fatty liver independently of insulin sensitization and appetite suppression in hepatocyte-specific Pten-deficient mice with insulin hypersensitivity / インスリン感受性亢進を示す肝細胞特異的Pten欠損マウスを用いたインスリン感受性改善および食欲抑制非依存性のレプチンによる脂肪肝改善作用の検討Kataoka, Sachiko 25 May 2015 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19171号 / 医博第4013号 / 新制||医||1010(附属図書館) / 32163 / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 柳田 素子, 教授 横出 正之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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