Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pathophysiological alterations of liver sinusoidal endothelial cells (LSECs) impact liver and metabolism. LSEC fenestrations are pores facilitating lipoproteins and macromolecule transfer between blood and hepatocytes. The Gram negative bacterium Pseudomonas aeruginosa is one of the most common opportunistic nosocomial pathogens, especially in post-liver transplant recipients. Gram negative bacterial endotoxin (lipopolysaccharide, LPS) and the P. aeruginosa toxin, pyocyanin, have marked effects on LSECs, including loss of porosity (defenestration). Currently proposed mechanisms for sepsis-hyperlipidaemia, an important response to Gram negative bacterial sepsis, include tissue lipoprotein-lipase inhibition and increased hepatic triglyceride production. Owing to the well-substantiated role of LSECs in liver-allograft rejection and hyperlipidaemia, we propose defenestration of the LSEC is an additional cellular mechanism for sepsis-hyperlipidaemia, including pseudomonal sepsis post-liver transplantation.
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PMID:Pseudomonas aeruginosa and the hyperlipidaemia of sepsis. 2000 39

The Gram-negative bacterium Pseudomonas aeruginosa is one of the most common opportunistic pathogens, especially after liver transplantation. Pathophysiological alterations of liver sinusoidal endothelial cells (LSECs) have far-reaching repercussions on the liver and on metabolism. LSECs are perforated with fenestrations, pores that facilitate the transfer of lipoproteins and macromolecules between blood and hepatocytes. Gram-negative bacterial endotoxin (lipopolysaccharide, LPS) and the P. aeruginosa toxin, pyocyanin, have marked effects on LSECs. Initial loss of LSEC porosity (defenestration) induced by P. aeruginosa pyocyanin and LPS may confer subsequent immune tolerance to circulating bacterial antigens and toxins. This review collates the known immune responses of the liver to Gram-negative bacterial toxins, with a focus on LSECs. Hyperlipidemia is an important response to Gram-negative bacterial sepsis. The mechanisms proposed for sepsis-associated hyperlipidemia include tissue lipoprotein lipase inhibition and upregulated hepatic triglyceride production. In this review, we propose defenestration of the LSECs by bacterial toxins as an additional mechanism for the hyperlipidemia of sepsis. Given the role of LSECs in hyperlipidemia and liver allograft rejection, LSEC changes induced by P. aeruginosa toxins including LPS and pyocyanin may have significant clinical implications.
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PMID:Pathogenesis of the hyperlipidemia of Gram-negative bacterial sepsis may involve pathomorphological changes in liver sinusoidal endothelial cells. 2060 8

Extensively burned patients often suffer from sepsis, a complication that enhances postburn hypermetabolism and contributes to increased incidence of multiple organ failure, morbidity and mortality. Despite the clinical importance of burn sepsis, the molecular and cellular mechanisms of such infection-related metabolic derangements and organ dysfunction are still largely unknown. We recently found that upon endoplasmic reticulum (ER) stress, the white adipose tissue (WAT) interacts with the liver via inflammatory and metabolic signals leading to profound hepatic alterations, including hepatocyte apoptosis and hepatic fatty infiltration. We therefore hypothesized that burn plus infection causes an increase in lipolysis of WAT after major burn, partially through induction of ER stress, contributing to hyperlipidemia and profound hepatic lipid infiltration. We used a two-hit rat model of 60% total body surface area scald burn, followed by intraperitoneal (IP) injection of Pseudomonas Aeruginosa-derived lipopolysaccharide (LPS) 3 d postburn. One day later, animals were euthanized and liver and epididymal WAT (EWAT) samples were collected for gene expression, protein analysis and histological study of inflammasome activation, ER stress, apoptosis and lipid metabolism. Our results showed that burn plus LPS profoundly increased lipolysis in WAT associated with significantly increased hepatic lipid infiltration. Burn plus LPS augmented ER stress by upregulating CHOP and activating ATF6, inducing NLRP3 inflammasome activation and leading to increased apoptosis and lipolysis in WAT with a distinct enzymatic mechanism related to inhibition of AMPK signaling. In conclusion, burn sepsis causes profound alterations in WAT and liver that are associated with changes in organ function and structure.
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PMID:Alternative Mechanism for White Adipose Tissue Lipolysis after Thermal Injury. 2673 77

A 79-year-old man with liver failure, hypertension and hyperlipidemia presented with a 1.5-month history of progressive nasal crusting and pain on the inside of the nose, advancing into a necrotic columella and philtrum. On rigid endoscopy, debris extended to middle and inferior turbinate to midway posteriorly. Initial culture swabs and CT were negative. The patient underwent endoscopic biopsy of the lesion, with histopathological findings revealing abundant acute inflammation and minute fragments of atypical squamous epithelium, favouring reactive atypia. Non-invasive fungal hyphae were identified. Bacterial cultures revealed Staphylococcus epidermidis, Corynebacterium accolens, Curvularia species and Pseudomonas putida A current literature search failed to find other published cases of P. putida nasal infections. P. putida is generally difficult to isolate on swab culture as the surrounding tissue is necrosed; this case highlights the importance of reconsidering bacterial infection and obtaining a tissue biopsy in the case of non-healing necrotic-appearing tissue with negative culture swab and CT without evidence of mass.
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PMID:Bacteria-induced nasal necrosis with negative cultures. 3281 33