NASH Case Study

Table 2 shows some of the chemical mediators involved in Mr X’s inflammatory process, causing it to become more severe and uncontrolled, resulting in a further decline in his clinical presentation.

Towards the end of his medical training in the early 1980s, Gokhan Hotamisligil was working on a unique tumor case on a patient and found they were comprised primarily of fat cells. The fatty tumors were due to a rare condition, Proteus Syndrome. Working in the field of metabolic regulation Hotamisligil began to explore the underlying pathways for insulin resistance. In his dissertation he discovered that the fat tissue of obese animals and humans were capable of producing inflammatory mediators. His research helped shape the current view of fat tissue as a “discrete, active organ in its own right, continuously exchanging messages with the rest of the body by way of the bloodstream.” By early 2002 Hotamisligil and his laboratory made

s symptoms, supported by x-rays and biopsies of the small and large intestine. Tumor necrosis factor alpha, TNFa, a protein released when the immune system is activated, is a major catalyst in the inflammatory process and is believed to play a major role in the pathogenesis of the disease.

* It is thought that the microbes regulate the expression of the gut protein fasting-induced adipocyte protein (FIAF). This protein is an inhibitor of lipoprotein lipase (LPL).

Cirrhosis is the eighth leading cause of death in the United States and the thirteenth leading cause of death worldwide.1 Cirrhosis is the irreversible fibrosis of the liver characterized by hepatic architectural distortion secondary to fibrous tissue and the formation of regenerative nodules.2 These anatomical changes cause hepatic vascular resistance and an increase in blood flow leading to portal hypertension. Porto-systemic collaterals develop in order to overcome the increased portal pressure gradient.3 Nitric oxide, an endogenous vasodilator is also released in effort to overcome portal pressure with the expense of causing systemic vasodilation and a decrease in blood pressure. As a result, a marked activation of neurohumoral vasoactive factors occurs in an effort to maintain an effective arterial blood pressure. Hypervolemia, increased cardiac index, decreased systemic vascular resistance, and systemic hypotension are manifestations of portal hypertension.3 Chronic hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholism, nonalcoholic steatohepatitis (NASH), and non-alcoholic fatty liver disease (NAFLD) are all major causes of cirrhosis.

It goes without saying; Steve Nash is the best player in Phoenix Suns’ history. Not only was he the Suns’ best player during his tenure, he was also one of the best players in the entire NBA.

Journalism, like many other industries, is going through significant changes because of technology. This is why conventions like NASH 79 are important for young journalists to attend in order to gain a stronger understanding of integrating these changes in their work. Below I have outlined my potential learning outcomes and reasons for wanting to attend the NASH 79 conference.

Inflamed tissues from Ulcerative Colitis (UC) patients show increased oxidative and nitrosative damage, leading to accumulation of mutations and dysplastic progression27,28. Infiltrating leukocytes from these patients have increased ROS production in basal conditions and in response to different ligands29. Since TLR4 mediates ROS production in leukocytes22, it is easy to speculate that immune cells drive pro-tumorigenic effects of TLR4. However, bone marrow-transfer experiments in our lab demonstrate that non-immune TLR4 participates in development of neoplasia8. Furthermore, we have shown that epithelial TLR4 activation predisposes to colitis and CAC6. To understand the role of epithelial TLR4 in neoplasia, our research has focused on the

As a widely used analgesic and antipyretic agent, acetaminophen (APAP) overdose induced hepatotoxicity is one of the most common causes of acute liver failure in the USA and in most Western European countries [1]. Although a number of studies have forced on the influences of N-acetyl-p-benzoquinone imine (NAPQI), a highly reactive metabolite of APAP that depletes hepatic glutathione, and increases in oxidative stress during APAP toxicity [2], other mechanisms such as immune response also raise the susceptibility in the early stages of APAP-induced liver injury [3]. Accumulating evidence demonstrates a critical role of inflammatory cytokine released in early liver damage after APAP intoxication [4, 5]. Kupffer cells (KCs), the liver resident macrophages, are major sources of reactive oxygen species (ROS) and inflammatory

Medical researchers are in wide agreement that a process called “inflammation” underlies most of the chronic diseases of the Western world. While the inflammatory response helps the body to heal itself and fight off infections from bacteria and viruses, when the condition is present in large amounts over long periods of time, cancer, diabetes, heart disease, and arthritis often result. Chronic inflammation is the body’s self-protective response to environmental threats such as saturated fats, processed foods, a sedentary lifestyle, smoking, and stress.

Several possible mechanisms through which the changes in gut microbiota can influence the pathophysiology of metabolic syndrome have been proposed. Dysbiosis of the gut microbiota due to triggers such us a high fat diet can alter the distribution gut junction proteins leading to the translocation of the colonic contents such as LPS to the blood. This increased gut permeability and leakage of contents referred to as Endotoxemia contributes to low grade inflammation. In gut dysbiosis the gut microbiota become more efficient at energy extraction and the SCFA produced may act as signaling molecules and stimulate a cascade od signaling that increases fat storage and energy production. Gut microbiota regulates expression of fasting induced adipose factor (FIFA) proteins which suppress expression of LPL thus fat storage is

Evaluator continued to cover completing job applications with Ms. Nash. Evaluator explained to Ms. Nash that employers use job application forms as a screening tool to decide who they will interview. Evaluator explained to Ms. Nash, she can influence whether or not she eventually gets hired by how she fills out the form. Ms. Nash stated that she has difficulties completing job applications. Evaluator and Ms. Nash complete a sample application. They also discussed the importance of keeping identification current and available such as state ID and social security card. Ms. Nash and Evaluator also practice on her learning her social security number for employment purpose.

Tumour necrosis factor (TNF) is responsible for the disruption of the tight junction between endothelial cells which results in an increased permeability to plasma proteins and fluid, which worsens fluid accumulation in the alveoli further impairing gas exchanged (Bersten & Soni, 2009:709). TNF comprises of two different molecules, firstly TNFa which leads to programmed cell death in target cells, and when combined with IL-1 which acts on the central nervous system causing lethargy (Marieb, 2004). TNFB stimulates granulocyte activity and B cell proliferation which shows an increase in neutrophil count (Jean- Baptise, 2007:63).

The World Gastroenterology Organization (WGO) has recently declared NALFD as most common cause of liver disease. Obesity is an increasing problem not only in the UK but worldwide. An estimated 26% of the adults in the UK are considered to be obese 1, 2. Obesity induced metabolic syndrome may lead to NAFLD, which can progress to Nonalcoholic Steatohepatitis (NASH), and in turn to advanced fibrosis and an increased risk of Hepatocellular Carcinoma (HCC) 2, 3.

Our previous data suggests that extracellular vesicles (EVs) released from stressed steatotic hepatocytes are chemotactic toward macrophages (6), therefore, we next looked at circulating EVs in all four groups of mice. As predicted there was an increase in circulating EVs in mice fed the FFC diet in comparison to chow-fed mice (Fig. 7A). FFC-fed mice treated with FTY720 (treated group) had lower circulating EVs than the FFC-fed saline injected (control group) mice, though the circulating EVs in this group (FFC-FTY) remained higher than the chow-fed FTY treated group (Fig. 7A). This reduction in EVs is likely due to a reduction in liver injury in the FFC-fed FTY treated group, though we cannot exclude a direct effect of FTY720 on release of EVs by steatotic hepatocytes. Furthermore, though EVs were lower in the treated group (FFC-FTY), the EV S1P content and C16:0 ceramide content were not lower (Fig. 7B). This supports our hypothesis that EV S1P acts as a chemoattractant to macrophages via S1P receptor activation on macrophages; and that FTY720 administration to mice impairs the recruitment of proinflammatory monocyte-derived macrophages to the