Simvastatin Reduces Lipopolysaccharides-Accelerated Cerebral Ischemic Injury via Inhibition of Nuclear Factor-kappa B Activity

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusion-evoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-1β in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-κB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IκB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.     

Subungual Soft Tissue Chondroma with Nail Deformity in a Child

Soft tissue chondroma is a rare benign tumor of the cartilage. It occurs commonly in distal extremities of middle‐aged patients. It is usually asymptomatic and grows slowly, making early diagnosis difficult. We report a 10‐year‐old patient with a 1‐year history of a subungual soft tissue chondroma on her left fifth finger. The lesion arose from nail bed and distal nail matrix, resulting in nail dystrophy. Magnetic resonance imaging revealed a soft tissue tumor in the subungual region and soft tissue chondroma was diagnosed, based on histopathologic findings. Dermatologists should consider soft tissue chondroma in the differential diagnosis of subungual tumors of children.     

A robust method for assessing chemically induced mutagenic effects in the oral cavity of transgenic Big Blue® rats

The Big Blue® (BB) in vivo mutation assay uses transgenic rodents to measure treatment‐induced mutations in virtually any tissue. The BB assay can be conducted in rats or mice and is ideal for investigating tissue‐specific mutagenic mode of action of tumor induction. Some tissues such as oral mucosa have not been thoroughly studied. Due to the small quantity and cartilaginous nature of oral cavity tissues, development of special prosection and DNA isolation methods was required to permit robust analysis of mutations in these tissues. Improved surgical methods permitted collection of adequate and reproducible quantities of tissue (～45 mg gingiva/buccal and ～30 mg gingiva/palate). Optimized DNA isolation methods included use of liquid nitrogen pulverization, homogenization, nuclei pelleting, digestion, and phenol/chloroform extraction, to yield sufficient quantities of DNA from these tissues. In preliminary optimization work, mutant frequency (MF) in tongue and gingiva was increased in rats exposed to the promutagen, benzo[a]pyrene, and the direct mutagen, N‐ethyl‐N‐nitrosourea. The oral cavity carcinogen, 4‐nitroquinoline‐1‐oxide (4‐NQO; 10 ppm in drinking water; 28 days), was qualified as a positive control for mutagenesis in oral tissues since it caused significant increases in cII MFs in gingiva/palate (50.2‐fold) and gingiva/buccal tissues (21.3‐fold), but not in liver or bone marrow (0.9‐ and 1.4‐fold, respectively). These results are consistent with the observation that 4‐NQO primarily induces tumors in oral cavity. Results also demonstrate the utility of the BB rat mutation assay and optimized methods for investigation of oral cavity mutagenicity, and by extension, analysis of other small and cartilaginous tissues. Environ. Mol. Mutagen. 56:629–636, 2015. © 2015 Wiley Periodicals, Inc.