The histopathology and ultrastructure of steatitis affecting common dab Limanda limanda. (1/12)

This study presents a new description, based on histopathological and ultrastructural studies, of a disease affecting the common dab Limanda limanda (L.). The condition can be recognised by the presence of multiple orange or yellow lesions in the pterygophorial region of the fish. The principal histopathological features are necrosis of fat cells, extensive macrophage infiltration leading to the formation of granulomatous structures, and the accumulation of lipopigment by lipid peroxidation. Based on this description, the condition has been diagnosed as steatitis. Although pathology associated with lipid peroxidation is the dominant characteristic of the lesions examined, it is proposed that this process is secondary to necrosis of the adipose tissue. The aetiology is discussed in the light of these observations. In addition, the first record of this condition affecting long rough dab Hippoglossoides platessoides (Fabricius) is made.  (+info)

P-selectin glycoprotein ligand-1 (rPSGL-Ig)-mediated blockade of CD62 selectin molecules protects rat steatotic liver grafts from ischemia/reperfusion injury. (2/12)

We examined the effects of early blockade of CD62 selectin-mediated adhesive interactions in steatotic rat liver models of ex vivo cold ischemia followed by reperfusion or transplantation by administration of P-selectin glycoprotein ligand-1 (rPSGL-Ig). In the model of cold ischemia/reperfusion, livers pretreated ex vivo with rPSGL-Ig at harvesting from obese Zucker rats showed significantly decreased portal resistance, increased bile production, and diminished hepatic endothelial neutrophil infiltration, as compared with untreated controls. Pretreatment of fatty livers with rPSGL-Ig prior to transplantation extended the survival of lean Zucker rat recipients from 40% to 90%. This effect correlated with significantly improved liver function, depressed neutrophil activity, and decreased histologic features of hepatocyte injury. Intragraft expression of CD62 P-selectin was similar in both recipient groups. rPSGL-Ig treatment decreased intragraft infiltration by CD3/CD25 cells, diminished expression of pro-inflammatory TNFalpha, IL-6, iNOS, IL-2 and IFN-gamma, without significantly affecting mRNA levels coding for anti-inflammatory IL-4. Thus, rPSGL-Ig blockade of CD62-mediated adhesive interactions protects against severe ischemia/reperfusion injury suffered otherwise by steatotic rat livers. These findings document the potential utility of rPSGL-Ig in increasing the transplant donor pool through modulation of marginal steatotic livers.  (+info)

Evaluation of abnormal liver function tests. (3/12)

Interpretation of abnormalities in liver function tests is a common problem faced by clinicians. This has become more common with the introduction of automated routine laboratory testing. Not all persons with one or more abnormalities in these tests actually have liver disease. The various biochemical tests, their pathophysiology, and an approach to the interpretation of abnormal liver function tests are discussed in this review.  (+info)

Anemia, myopathy, and pansteatitis in vitamin E-deficient captive marmosets (Callithrix spp.). (4/12)

Five young adult pet marmosets (Callithrix spp.) were presented with weight loss (5/5); fecal retention (3/5); diarrhea (2/5); impaired locomotion (3/5); anemia (4/4); hypoproteinemia or hypoalbuminemia (3/4); elevations of creatine phosphokinase, lactic dehydrogenase, and alanine aminotransferase (3/4); and renal failure with hypercholesterolemia (2/4). All anemic marmosets had low serum vitamin E levels. The anemia responded to vitamin E and selenium therapy in two marmosets. One of the five marmosets died before presentation, and two others died despite therapy. The two marmosets necropsied had degenerative myopathy, pyogranulomatous pansteatitis, and increased erythrophagocytosis and hemosiderosis. The striated muscle and adipose tissue of both marmosets were negative for coxsackievirus ribonucleic acid by in situ hybridization. These findings suggest that vitamin E deficiency may be involved in the development of anemia, myopathy, and steatitis in callitrichids; however, in some marmosets, underlying diseases such as chronic colitis may have influenced the development of anemia and impaired vitamin E status.  (+info)

The ins and outs of mitochondrial dysfunction in NASH. (5/12)

Rich diet and lack of exercise are causing a surge in obesity, insulin resistance and steatosis, which can evolve into steatohepatitis. Steatosis and nonalcoholic steatohepatitis (NASH) can also be induced by drugs such as amiodarone, tamoxifen and some antiretroviral drugs. There is growing evidence that mitochondrial dysfunction, and more specifically respiratory chain deficiency, plays a role in the pathophysiology of NASH whatever its initial cause. In contrast, the B-oxidation of fatty acids can be either increased (as in insulin resistance-associated NASH) or decreased (as in drug-induced NASH). However, in both circumstances, the generation of reactive oxygen species (ROS) by the damaged respiratory chain is augmented, as components of this chain are over-reduced by electrons, which then abnormally react with oxygen to form increased amounts of ROS. Concomitantly, ROS oxidize fat deposits to release lipid peroxidation products that have detrimental effects on hepatocytes and other hepatic cells. In hepatocytes, ROS and lipid peroxidation products further impair the respiratory chain, either directly or indirectly through oxidative damage to the mitochondrial genome. This, in turn, leads to the generation of more ROS and a vicious cycle ensues. Mitochondrial dysfunction can also lead to apoptosis or necrosis depending on the energy status of the cell. ROS and lipid peroxidation products also activate stellate cells, thus resulting in fibrosis. Finally, ROS and lipid peroxidation increase the generation of several cytokines (TNF-alpha, TGF-B, Fas ligand) that play sundry roles in the pathogenesis of NASH. Recent investigations have shown that some genetic polymorphisms can significantly increase the risk of steatohepatitis and that several drugs can prevent or even reverse NASH. For the next decade, reducing the incidence of NASH will be a major challenge for hepatologists.  (+info)

Hepatocellular toxicosis associated with the alternate administration of carprofen and meloxicam in a siberian husky. (6/12)

A 4-year-old female Siberian Husky was diagnosed with pyogranulomatous steatitis at the site of a recurrence of left anal sac rupture (day 1). Carprofen and orbifloxacin were given for 13 days without improvement. A single dose of meloxicam was administered prior to surgical resection of the anal sac, and based on elevated liver enzyme activity, liver supportive therapy was initiated. The dog received carprofen and orbifloxacin orally on the evening of day 14. The dog became anorectic the following morning, and began vomiting. Despite supportive therapy, the dog was unresponsive to treatment and died on day 16. Postmortem examination revealed severe vacuolar change and acute necrosis of hepatocytes consistent with carprofen and meloxicam induced-toxicosis.  (+info)

The proinflammatory phenotype of PECAM-1-deficient mice results in atherogenic diet-induced steatohepatitis. (7/12)

The severity of nonalcoholic steatohepatitis (NASH) is determined by environmental and genetic factors, the latter of which are incompletely characterized. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kDa transmembrane glycoprotein expressed on blood and vascular cells. In the present study, we provide data for the novel finding that genetic deficiency of PECAM-1 potentiates the development and progression of NASH. We found that the rate of development and severity of diet-induced NASH are markedly enhanced in PECAM-1-deficient [knockout (KO)] mice relative to wild-type (WT) mice, as measured by histological and biochemical evaluation. Livers from KO mice exhibited typical histological features of NASH, including macrovesicular fat accumulation, hepatocyte injury with infiltration of inflammatory cells, fibrosis, and heightened oxidative stress. Alanine aminotransferase, a marker for liver injury, was also significantly higher in KO compared with WT mice. Consistent with a role for PECAM-1 as a suppressor of proinflammatory cytokines, plasma levels of inflammatory cytokines, including TNF-alpha and monocyte chemoattractant protein-1 (MCP-1), were also significantly higher in KO compared with WT mice. These findings are the first to show that the PECAM-1-deficient mouse develops progressive nonalcoholic fatty liver disease (NAFLD), supporting a role for PECAM-1 as a negative regulator of NAFLD progression. Future examination of recently identified PECAM-1 allelic isoforms in humans as potential risk factors for developing NASH may be warranted.  (+info)

Cytomegalovirus infection of adipose tissues induces steatitis in adult mice. (8/12)

Young adult mice infected with MCMV were shown to develop inflammatory lesions in the peripancreatic and salivary gland adipose tissues. MCMV replication was detected by immunoperoxidase staining and electron microscopy in adipocytes, fibroblasts, endothelial cells and pericytes in brown and white adipose tissues. More infected cells were detected in C3H mice than in BALB/c, BALB.B, BALB.K or C57BL/6 mice. Peripancreatic steatitis consisted of a monocytic infiltrate surrounding focal necrosis of adipocytes, the severity of which was influenced by the route of inoculation, virus dose, and genetic susceptibility to disseminated MCMV-disease. C57BL/6 mice showed the greatest susceptibility with severe coalescing focal inflammation around areas of coagulative necrosis. Salivary gland adipose tissues exhibited lymphocytic steatitis, which was reduced in Nu/Nu mice.  (+info)

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