Abstract
Omega-3 polyunsaturated fatty acids such as alpha-linolenic acid (ALA) and eicosapentaenoic acid reduce the risk of ischemic heart disease; however, the efficacy of these compounds in the setting of inherited cardiomyopathy has not been well studied. Investigators used UM-X7.1 hamsters to determine if administration of ALA has an effect on the development of inherited cardiomyopathy. The UM-X7.1 strain has a deletion of the delta-sarcoglycan gene, a structural glycoprotein found in the cell membranes of cardiac and skeletal muscles. The delta-sarcoglycan-null phenotype results in altered contacts between adjacent cells and the extracellular matrix, detachment of the basal membrane, and abnormal intracellular signaling. Compared with UM-X7.1 hamsters fed a standard diet, hamsters fed an ALA-enriched diet exhibited markedly reduced histopathologic and ultrastructural lesions in cardiac muscle, including marked reduction in myofiber loss, reduced fibrosis, and preservation of plamsalemmal and mitochondrial membrane integrity. The hamsters also had improved hemodynamic measurements and increased lifespan. This study indicates that dietary supplementation with ALA may improve cardiac function in some forms of inherited cardiomyopathy.
Fiaccavento R, Carotenuto F, Minieri M, et al. Alpha-linolenic acid-enriched diet prevents myocardial damage and expands longevity in cardiomyopathic hamsters. Am J Pathol
This report describes an outbreak of hepatotoxicosis in horses following ingestion of fall panicum (Panicum dichotomiflorum). Fourteen horses showed signs of liver disease within a few days after being fed hay from a new shipment. Histopathologic lesions in the liver included single cell necrosis and apoptosis, hepatocyte swelling and vacuolation, irregularly clumped chromatin, minimal to moderate fibrosis, and bile duct hyperplasia. A few horses also had lymphocytic hepatitis and megalocytosis. Bile crystals were not observed. Ultrastructural changes included micro- and macrovesicular lipid vacuoles and proliferation of smooth endoplasmic reticulum. A feeding trial confirmed that the source of the toxin was fall panicum. Interestingly, photosensitization was not noted in either the natural or experimental cases, but this may have been due to lack of sun exposure in both settings. Fall panicum is abundant in some regions, but hepatotoxicosis has not been previously reported in horses. The authors speculate on possible explanations for the occurrence and rapidity of signs in this outbreak.
Johnson AL, Divers TJ, Freckleton ML, McKenzie HC, Mitchell E, Cullen JM, McDonough SP. Fall panicum (Panicum dichotomiflorum) hepatotoxicosis in horses and sheep. J Vet Intern Med
The concept of cancer stem cells in solid tumors has received considerable attention in recent years. Investigators have now identified a human colon cancer-initiating cell (CC-IC). Primary human colon cancer cells were implanted under the renal capsule of NOD/SCID mice. CC-ICs were positive for CD133, whereas CD133-negative cells were unable to initiate tumor growth in mice. Xenograft tumors were positive for cytokeratin-20 and expressed mucin antigens, carcinoembryonic antigen, and p53 similarly to the parent tumors. Limiting dilution experiments indicated that there is one CC-IC in 5.7×104 unfractionated tumor cells and one CC-IC in 262 CD133+ cells. This study provides evidence in support of the presence of cancer stem cells in colon cancer. Because stem cells are thought to be responsible for initiating and sustaining neoplastic growth, identification of this small population within the bulk of the tumor is important for a better understanding of cancer biology and therapeutic interventions.
O'Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature
The ability to survey large areas of luminal surfaces in the gastrointestinal tract and coronary arteries would be a remarkable step forward in diagnostic testing. The authors of this study performed comprehensive volumetric microscopy with fiber-optic imaging, termed optical frequency-domain imaging (OFDI). Using specialized catheters with rotating optical cores, they visualized the esophagus and coronary arteries of swine and obtained 3-dimensional images of the tissue microstructure. A 4.5 cm segment of the esophageal lumen was visualized in 5.8 minutes, which enabled microscopic evaluation of 2 mm in depth along that length. Similarly, swine coronary arteries were visualized by injecting small amounts of saline to temporarily clear blood from the immediate vicinity. Comparison of the OFDI images with postmortem histologic samples of the same regions demonstrated remarkable similarities. The authors state that this technique could “bridge the gap between noninvasive radiologic techniques, which provide wide-field imaging but lack sufficient resolution for cellular diagnosis, and point-sampling approaches such as excisional biopsy.” Veterinary pathologists could play a leading role in advancing this technology for the biomedical community.
Yun SH, Tearney GJ, Vakoc BJ. Comprehensive volumetric optical microscopy in vivo. Nat Med
The mechanism by which antigen presenting cells and lymphocytes leave inflamed skin and migrate to afferent lymphatics is unknown. In this report investigators show that inflammatory cytokines in the dermis stimulate changes in dermal lymphatic endothelial cells which allow leukocyte transmigration. Using a mouse model of oxazolone-induced hypersensitivity, the authors found that tumor necrosis factors alpha and beta stimulate rapid up-regulation of leukocyte adhesion molecules ICAM-1 and VCAM-1 on the endothelium of lymphatic vessels draining the inflamed skin. Administration of neutralizing antibodies to ICAM-1 and VCAM-1 blocked the migration of CD11+ dendritic cells into the lymphatics. Furthermore, the authors identified numerous chemokines that participate in this process. The adhesion molecules ICAM-1 and VCAM-1 were previously thought to be exclusive to leukocyte migration in blood vessels.
Johnson LA, Clasper S, Holt AP, Lalor PF, Baban D, Jackson DG. An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium. J Exp Med