Ursolic acid induces allograft inflammatory factor-1 expression via a nitric oxide-related mechanism and increases neovascularization

Ursolic acid (UA), a triterpenoid compound found in plants, is used in the human diet and in medicinal herbs and possesses a wide range of biological benefits including antioxidative, anti-inflammatory, and anticarcinogenic effects. Endothelial expression of allograft inflammatory factor-1 (AIF-1) mediates vasculogenesis, and nitric oxide (NO) produced by endothelial NO (eNOS) represents a mechanism of vascular protection. It is unclear whether UA affects the neovascularization mediated by AIF-1 and eNOS expression. This study investigated the effects and mechanisms of UA on angiogenesis in vivo in hind limb ischemic animal models and in vitro in human coronary artery endothelial cells (HCECs). This study explored the impact of UA on endothelial cell (EC) activities in vitro in HCECs, vascular neovasculogenesis in vivo in a mouse hind limb ischemia model, and the possible role of AIF-1 in vasculogenesis. The results demonstrate that UA enhances collateral blood flow recovery through induction of neovascularization in a hind limb ischemia mouse model. In vitro data showed that UA increases tube formation and migration capacities in human endothelial cells, and exposing HCECs to UA increased AIF-1 expression through a NO-related mechanism. Moreover, UA administration increased capillary density and eNOS and AIF-1 expression in ischemic muscle. These findings suggest that UA may be a potential therapeutic agent in the induction of neovascularization and provide a novel mechanistic insight into the potential effects of UA on ischemic vascular diseases.     

Pharmacokinetics of Oxytetracycline in Nile Tilapia Oreodromis niloticus Challenged with Streptococcus iniae and Vibrio vulnificus

Tissue depletion studies of antibacterials are an important part of data packages required to obtain a label from the U.S. Food and Drug Administration (FDA) in the United States for use of therapeutants in food fishes. Currently, withdrawal tima are set based on results of such studies obtained from healthy animals. Bacterial infection can lead to dramatic physiological changes in affected fish. In this investigation, the impact of bacterial infection on depletion kinetics of oxytetracycline (OTC) was examined in tilapia Oreochromis niloticus challenged with Streptococcus iniae (a model Gram positive bacterium) or Vibrio vulnificus (a model Gram negative bacterium). An additional group of fish injected with Brain Heart Infusion (BHI) broth was included as a non-infectious stimulus. Although some differences in elimination kinetics of OTC were observed between treated fish and non-treated controls, OTC was rapidly eliminated from tilapia in all groups. In all cases, mean concentration of OTC was below the current 2.0 ppm (μg/g) FDA tolerance for OTC in the edible portion (muscle plus skin) after day 3 postdosing.     

Infection of Tilapia Oreochromis sp. by Vibrio vulnificus in Freshwater and Low-salinity Environments

The first isolation of Vibrio vulnificus in southern Taiwan from hybrid tilapia Oreochromis sp. raised in freshwater and brackish water environments is documented in this report. The infection was only found in fish in ponds where the salinity was less than 10 ppt. Tilapia raised in water of higher salinities in the same region were not affected. Grossly visible signs of infection included dark coloration, lethargy, and external hemorrhage and ulceration of the skin. The most prominent internal signs of infection included splenomegaly and severe hemorrhagic lesions in the liver. Septicemia was documented in moribund fish. All bacterial isolates from moribund fish were tested by polymerase chain reaction, using V. vulnificus hemolysin/cytolysin gene‐specific primers. Sequence data from the 16S ribosomal RNA gene suggest that these isolates were V. vulnificus. The isolates were indole and mannitol positive, characteristics shared by human clinical isolates and isolates from freshwater European eel, Anguilla anguilla. The isolates from tilapia were unique in that they were negative for ornithine decarboxylase and citrate.