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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are common indications for ICU admission and mechanical ventilation. ALI/ARDS also consumes significant health care resources and is a common cause of death in ICU patients. Obesity produces changes in respiratory system physiology that could affect outcomes for ALI/ARDS patients and their response to treatment. Additionally, the biochemical alterations seen in obese patients, such as increased inflammation and altered metabolism, could affect the risk of developing ALI/ARDS in patients with another risk factor (eg, sepsis). The few studies that have examined the influence of obesity on the outcomes from ALI/ARDS are inconclusive. Furthermore, observed results could be biased by disparities in provided care.
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PMID:Obesity and acute lung injury. 1970 48

Obese patients with sepsis have higher morbidity and mortality rates than normal weight subjects. One crucial factor is the disease-associated disturbed energy balance. Ghrelin is an orexigenic peptide, mainly produced in the stomach. Leptin is an adipose-tissue derived peptide, circulating as free (fl) and receptor-bound protein (bl) acting antagonistically to ghrelin's effects on food intake. In the present study we tested the weight dependent influence of an intravenous (i.v.) ghrelin injection on leptin levels as well as hepatic protein expression in healthy and endotoxemic rats. Male Lewis rats were randomly divided into four diet-induced obese and four normal weight groups. Application of either ghrelin or NaCl was followed by a bolus injection of LPS or NaCl. Blood was collected at five time points (up to 24 h) to measure fl and bl by radioimmunoassay. Furthermore, hepatic leptin, leptin receptor and ghrelin expression were investigated immunohistochemically. Results revealed a late shift from high elevated fl to significantly enhanced levels of bl in ghrelin treated obese animals. Both fl and bl levels remained unaffected in lean rats. The findings suggest that an increased body weight of the treated animals is associated with altered hormone levels after therapeutic interventions with ghrelin.
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PMID:Ghrelin treatment increases receptor-bound leptin in healthy and endotoxemic obese Lewis rats. 1987 93

Coronary artery disease is a primary co-morbidity in metabolic diseases such as metabolic syndrome, diabetes and obesity. One contributing risk factor for coronary artery disease is low high-density lipoprotein-cholesterol (HDLc). Several factors influence steady-state HDLc levels, including diet, genetics and environment. Perhaps more important to coronary artery disease is factors that attribute to the dynamics of reverse cholesterol transport, storage, and excretion of excess cholesterol. HDLc biogenesis, clearance and innate ability to serve as a cholesterol acceptor and transporter all contribute to HDLc's function as a negative regulator of cardiovascular disease. With the recent failure of torcetrapid, focus is being placed on HDLc biology and its role in various metabolic diseases. Low HDLc levels are often associated with an increased state of background inflammation. Recently, several syndromes with clear pro-inflammatory components have been shown to be inversely correlated with low HDLc levels in the absence of obesity, diabetes and metabolic syndrome. Early studies with HDLc during the acute-phase response suggest that HDLc is substantially physically modified during acute infection and sepsis, and recent studies show that HDLc is physically modified by chronic pro-inflammatory disease. In this review, several of these connections are described and cytokine signalling related to HDLc is examined.
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PMID:Regulation of high-density lipoprotein by inflammatory cytokines: establishing links between immune dysfunction and cardiovascular disease. 2004 97

Atherosclerosis with its complications like heart attack and stroke, is the most frequent cause of death in the industrialized countries. Oxidized low-density lipoproteins (LDL) play a major role in the pathogenesis of atherosclerosis. Inhibition of cholesterol synthesis by statins has several protective effects but is not sufficient to prevent the uptake of oxidized LDL and the development of atherosclerotic plaques. For this reason a selective pharmacological inhibition of the uptake of oxidized LDL (oxLDL) in endothelial cells is an interesting therapeutic approach. An important novel target molecule is the endothelial lectin-like oxLDL receptor LOX-1. This receptor is able to take up both minimally and highly oxidized LDL. In addition it mediates endothelial phagocytosis of aged and apoptotic cells and plays a role in thrombocyte adhesion and in the interaction between bacterial proteins and endothelial cells in sepsis. LOX-1 is induced by proinflammatory cytokines, oxLDL, angiotensin II, endothelin-1 and arterial hypertension. LOX-1 increases endothelial dysfunction and atherosclerosis by endothelial uptake of oxLDL. This is the reason why LOX-1 has been considered as a novel link between hypertension and atherosclerosis. Transgenic overexpression of the LOX-1 receptor and high-fat diet induces intramyocardial vascular disease and endothelial dysfunction in resistance arteries. In contrast, genetic deletion of the LOX-1 gene reduces the development of atherosclerotic plaques. In the clinical context LOX-1 has been detected in the early phase of endothelial dysfunction and atherosclerosis in arteries of patients with coronary heart disease. Several novel data support a role of LOX-1 in the endothelial dysfunction in diabetic vascular and renal disease, hypercholesterolemia, obesity and preeclampsia. This makes the LOX-1 receptor a novel and interesting target molecule in endothelial dysfunction and atherosclerosis.
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PMID:[LOX-1 receptor as a novel target in endothelial dysfunction and atherosclerosis]. 2014 62

Obesity is on the advance in western industrialised countries and is therefore increasingly relevant also to intensive care medicine. In contrast to the common prejudice that obese patients probably have a higher ICU mortality than lean patients, convincing meta-analyses have revealed that this is not the case. Nevertheless, obese ICU patients are challenging. Especially mechanic ventilation has to be addressed: besides obesity-related anatomical problems that may complicate intubation, obstructive sleep apnoea, obesity hypoventilation syndrome and increased intra-abdominal pressure are of major relevance concerning ventilation, weaning and successful extubation. Also the risk of infections is increased in obese ICU patients, although this does not seem to increase the risk of sepsis. Nevertheless, the interplay of obesity and sepsis is a fascinating field in that adipous tissue is not just a passive reservoir of energy but an active endocrine and immunomodulating organ. However, the way of how adipokines interact with inflammation and coagulation in sepsis has yet to be clarified.
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PMID:Mortality, morbidity and special issues of obese ICU patients. 2036 11

Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure.
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PMID:Role of carnitine in disease. 2039 44

Visfatin (NAMPT formerly known as PBEF1) is an adipokine that is strongly expressed in visceral fat and has caused much debate among researchers, regarding its involvement in glucose homeostasis and insulin resistance. It was initially isolated from bone marrow cells, and its involvement in inflammatory procedures such as sepsis and acute lung inflammation is now evident. Several studies have also reported an association of plasma visfatin levels with obesity. We undertook an evaluation of the involvement of the NAMPT gene in the development of type 2 diabetes (T2DM) in the Greek population. We studied 178 patients with T2DM and 177 controls that were matched for sex, age and body mass index. We genotyped three tagging SNPs selected from the HapMap II CEPH European population as reference for the Greek population. These three SNPs tag another 12 SNPs over the entire NAMPT gene with a mean r(2) of 0.92. No indications of association with disease status were found with any of the tested variants or the inferred haplotypes. Results were also negative when the quantitative traits of weight and BMI were tested. Although our study covers common variants across the NAMPT gene, the possible involvement of rare variants in T2DM etiology cannot be ruled out and will require the investigation of very large numbers of cases and controls.
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PMID:Genetic variation in the visfatin (PBEF1/NAMPT) gene and type 2 diabetes in the Greek population. 2045 5

The adipose-derived hormone leptin is well known for its contribution to energy metabolism and satiety signaling in the hypothalamus. Previous studies suggested that obesity is an independent risk factor for sepsis morbidity and mortality, and it is associated with elevated baseline levels of circulating leptin in normal, nonseptic patients. In mouse endotoxemia and cecal ligation puncture models of sepsis, we observed elevated levels of leptin and soluble leptin receptor (sLR). Exogenously administered leptin increased mortality in endotoxemia and cecal ligation puncture models and was associated with increased expression of adhesion and coagulation molecules, macrophage infiltration into the liver and kidney, and endothelial barrier dysfunction. Conversely, longform leptin receptor-deficient mice were protected from sepsis morbidity and mortality and had less endothelial dysfunction. Furthermore, an in vitro study revealed that leptin-induced endothelial dysfunction is likely mediated, at least in part, by monocytes. Moreover, administration of an sLR conferred a survival benefit. Human septic patients have increased circulating sLR concentrations, which were correlated with disease severity indices. Together, these data support a pathogenic role for leptin signaling during sepsis.
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PMID:Leptin exacerbates sepsis-mediated morbidity and mortality. 2051 46

Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine, the effect of which on arresting random immune cell movement was recognized several decades ago. Despite its historic name, MIF also has a direct chemokine-like function and promotes cell recruitment. Multiple clinical studies have indicated the utility of MIF as a biomarker for different diseases that have an inflammatory component; these include systemic infections and sepsis, autoimmune diseases, cancer, and metabolic disorders such as type 2 diabetes and obesity. The identification of functional promoter polymorphisms in the MIF gene (MIF) and their association with the susceptibility or severity of different diseases has not only served to validate MIF's role in disease development but also opened the possibility of using MIF genotype information to better predict risk and outcome. In this article, we review the clinical data of MIF and discuss its potential as a biomarker for different disease applications.
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PMID:Macrophage migration inhibitory factor (MIF): a promising biomarker. 2052 Aug 54

The relationship between patient cross-sectional area and both volume CT dose index (CTDI) and dose length product was explored for abdominal CT in vivo, using a 16 multidetector row CT (MDCT) scanner with automatic exposure control. During a year-long retrospective survey of patients with MDCT for symptoms of abdominal sepsis, cross-sectional areas were estimated using customised ellipses at the level of the middle of vertebra L3. The relationship between cross-sectional area and the exposure parameters was explored. Scans were performed using a LightSpeed 16 (GE Healthcare Medical Systems, Milwaukee, WI) operated with tube current modulation. From a survey of 94 patients it was found that the CTDI increased with the increase in patient cross-sectional area. The relationship was logarithmic rather than linear, with a least-squares fit to the data (R(2) = 0.80). For abdominal CT the cross-sectional area gave a measure of patient size based on the region of the body to be exposed. Exposure parameters increased with increasing cross-sectional area and the greater radiation exposure of larger patients was partly a consequence of their size. Given increasing obesity levels we believe that cross-sectional area and scan length should be added to future dose surveys, allowing patient size to be considered as a factor of relevance when examining population doses.
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PMID:The in vivo relationship between cross-sectional area and CT dose index in abdominal multidetector CT with automatic exposure control. 2053 Aug 59


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