Nrf2 is essential to antioxidant response element (ARE)-mediated host defense. Sulforaphane (SFN) is a phytochemical antioxidant known to affect multiple cellular targets including Nrf2-ARE pathway in chemoprevention. However, the role of SFN in non-malignant airway disorders remain unclear. To test if pre-activation of Nrf2-ARE signaling protects lungs from oxidantinduced acute injury, wild-type (Nrf2 +/+) and Nrf2-deficient (Nrf2 −/−) mice were given SFN orally or as standardized broccoli sprout extract diet (SBE) before hyperoxia or air exposure. Hyperoxiainduced pulmonary injury and oxidation indices were significantly reduced by SFN or SBE in Nrf2 +/+ mice but not in Nrf2 −/− mice. SFN upregulated a large cluster of basal lung genes that are

Abstract. Diarrhea and unexpected death were encountered in a group of young Syrian hamsters (Mesocricetus auratus) used for hyperlipoproteinemia and atherosclerosis research. The animals were fed an atherogenic diet containing 18% saturated fat and 0.366% cholesterol. Mortality began 45 days after hamsters were placed on this atherogenic diet. The atherogenic studies were aborted at 74 days because of high mortality. Toxigenic Clostridium dzjicile was isolated from animals found dead or euthanatized because of illness. Signs observed were unexpected death and acute liquid diarrhea. Characteristic pathologic changes were necrosis and hemorrhage of the intestinal mucosa with acute inflammation. Hepatic lipidosis was a consistent finding presumed to be associated with the consumption of the atherogenic diet. The study was repeated by placing 23 hamsters on the atherogenic diet and 10 hamsters on the control diet. In animals fed the atherogenic diet, the average time to mortality differed between studies, but clinical signs, gross and histologic lesions, culture findings, and toxin results in both atherogenic diet groups were similar. C. dzfiile was not isolated from the feeds. No antibiotics were found in the atherogenic diet. The results from these studies suggest that hamsters fed an atherogenic diet have increased susceptibility to disease caused by C. dzflcile as compared with hamsters fed a normal fat and cholesterol diet.

Tramadol is an opioid-like analgesic with relatively mild side effects. Because it is inexpensive and is not classified as a controlled substance by the US federal government, the authors wanted to evaluate its applicability as a practical and effective analgesic in male Sprague Dawley rats. They measured the efficacy of four dosages (4, 12.5, 25 or 50 mg tramadol per kg body weight) and three routes of administration (per os (p.o.) in a flavored gelatin cube, subcutaneous (s.c.) or intraperitoneal (i.p.)) using the hot-plate test and the tail-flick test, which were carried out 1 week apart. Rats that were dosed p.o. were given flavored gelatin cubes without tramadol on the 2 d before testing to help them become acclimated to the gelatin, in an effort to increase the likelihood that they would consume the gelatin on the testing day. Results from the hot-plate and tail-flick tests for rats that were given tramadol p.o. were similar before and after administration, regardless of tramadol dosage, suggesting that this route of administration was not effective. The s.c. route of administration was effective at dosages of 25 mg and 50 mg tramadol per kg body weight, although these dosages also resulted in sedation and skin lesions. The i.p. route of administration was also effective at dosages of 12.5 mg, 25 mg and 50 mg tramadol per kg body weight, though sedation was observed at dosages of 25 mg and 50 mg per kg body weight. Intraperitoneal administration of 12.5 mg tramadol per kg body weight had no notable side effects, and the authors plan to further study this dosage and route of administration in a rodent surgical model of pain.

In this study, the authors evaluated the analgesic efficacy of tramadol (an opioid-like analgesic), carprofen (a nonsteroidal anti-inflammatory drug) and a combination of both drugs (multimodal therapy) in a rat laparotomy model. The authors randomly assigned rats to undergo either surgery (abdominal laparotomy with visceral manipulation and anesthesia) or anesthesia only. Rats in each group were treated with tramadol (12.5 mg per kg body weight), carprofen (5 mg per kg body weight), a combination of tramadol and carprofen (12.5 mg per kg body weight and 5 mg per kg body weight, respectively) or saline (anesthesia control group only; 5 mg per kg body weight). The authors administered analgesia 10 min before anesthesia, 4 h after surgery or (for the rats that received anesthesia only) anesthesia and 24 h after surgery or anesthesia. They measured locomotor activity, running wheel activity, feed and water consumption, body weight and fecal corticosterone concentration of each animal before and after surgery. Clinical observations were made after surgery or anesthesia to evaluate signs of pain and distress. The authors found that carprofen, tramadol and a combination of carprofen and tramadol were all acceptable analgesia regimens for a rat laparotomy model.

Over the last decade, interest in the role of the microbiome in health and disease has increased. The use of germ-free animals and depletion of the microbial flora using antimicrobials are 2 methods commonly used to study the microbiome in laboratory mice. Germ-free mice are born, raised, and studied in isolators in the absence of any known microbes; however, the equipment, supplies, and training required for the use of these mice can be costly and time-consuming. The use of antibiotics to decrease the microbial flora does not require special equipment, can be used for any mouse strain, and is relatively inexpensive; however, mice treated in this manner still retain microbes and they do not live in a germ-free environment. One commonly used antibiotic cocktail regimen uses ampicillin, neomycin, metronidazole, and vancomycin in the drinking water for 2 to 4 wk. We found that the palatability of this mixture is low, resulting in weight loss and leading to removal of mice from the study. The addition of sucralose to the medicated water and making wet food (mash) with the medicated water improved intake; however, the low palatability still resulted in a high number of mice requiring removal. The current study evaluated a new combination of antibiotics designed to reduce the gut microbiota while maintaining body weights. C57BL/6NCrl mice were placed on one of the following drinking water regimens: ampicillin/neomycin/metronidazole/vancomycin water (n = 16), enrofloxacin/ampicillin water (n = 12), or standard reverse osmosis deionized water (RODI) (n = 11). During an 8 day regimen, mice were weighed and water consumption was measured. Feces were collected before and after 8 d of treatment. Quantitative real-time PCR (real-time qPCR) for 16S bacterial ribosome was performed on each sample, and values were compared among groups. The combination of enrofloxacin and ampicillin improved water intake, together with a greater reduction in gut flora.