Effects of Buprenorphine, Chlorhexidine, and Low-level Laser Therapy on Wound Healing in Mice.

Systemic buprenorphine and topical antiseptics such as chlorhexidine are frequently used in research animals to aid in pain control and to reduce infection, respectively. These therapeutics are controversial, especially when used in wound healing studies, due to conflicting data suggesting that they delay wound healing. Low-level laser therapy (LLLT) has been used to aid in wound healing without exerting the systemic effects of therapies such as buprenorphine. We conducted 2 studies to investigate the effects of these common treatment modalities on the rate of wound healing in mice. The first study used models of punch biopsy and dermal abrasion to assess whether buprenorphine HCl or 0.12% chlorhexidine delayed wound healing. The second study investigated the effects of sustained-released buprenorphine, 0.05% chlorhexidine, and LLLT on excisional wound healing. The rate of wound healing was assessed by obtaining photographs on days 0, 2, 4, 7, and 9 for the punch biopsy model in study 1, days 0, 1, 2, 4, 6, 8, 11, and 13 for the dermal abrasion model in study 1, and days 0, 3, 6, and 10 for the mice in study 2. Image J software was used to analyze the photographed wounds to determine the wound area. When comparing the wound area on the above days to the original wound area, no significant differences in healing were observed for any of the treatment groups at any time period for either study. Given the results of these studies, we believe that systemic buprenorphine, topical chlorhexidine, and LLLT can be used without impairing or delaying wound healing in mice.

NTP/NIEHS Global Contributions to Toxicologic Pathology.

National Toxicology Program (NTP) pathologists are engaged in important initiatives that have significant global impact. These initiatives build on its leadership in pathology peer review and publications in the areas of toxicologic pathology, clinical pathology, and laboratory animal medicine. Over the past decade, NTP/National Institute of Environmental Health Sciences research initiatives have focused on cancer and noncancer hazard identification, with the goal of understanding cellular and molecular mechanisms of disease. New initiatives of significant global impact include the web-based nonneoplastic lesion atlas and an NTP partnership with international scientists to investigate molecular mechanisms at the whole genome level, which will be used to inform potential mechanisms of environmental exposures in human cancers. Also, we are dedicated to contributing to pathology and toxicology organizations through service on executive committees and editorial boards, participating in international projects and symposiums, and providing training for future leaders in toxicologic pathology. Herein, we provide highlights of our global contributions.

Impact of Environmental Enrichment Devices on NTP In Vivo Studies.

The goal of this study was to determine whether the use of nesting material or polycarbonate shelters as enrichment devices would have an impact on end points commonly measured during the conduct of the National Toxicology Program (NTP) 13-week studies. The study design was consistent with the NTP 13-week toxicity studies. Harlan Sprague-Dawley (HSD) rats and their offspring and B6C3F1/N mice were assigned to control (unenriched) and enriched experimental groups. Body weight, food and water consumption, behavioral observations, fecal content, clinical pathology, gross pathology, organ weights, and histopathology were evaluated. Enriched male mice and male and female rats exhibited decreased feed intake without a subsequent decrease in body weight; this may have been the result of the nesting material reducing the effect of cold stress, thereby allowing for more efficient use of feed. There were statistical differences in some hematological parameters; however, these were not considered physiologically relevant since all values were within the normal range. Gross pathology and histopathological findings were background changes and were not considered enrichment-related. Nesting material and shelters were used frequently and consistently and allowed animals to display species-typical behavior. There was no significant impact on commonly measured end points in HSD rats and B6C3F1/N mice given enrichment devices.

Effects of buprenorphine, meloxicam, and flunixin meglumine as postoperative analgesia in mice.

C57BL/6NCrl male mice (n = 60; age, 6 to 7 wk) underwent partial hepatectomy or no surgery and were given 1 of 3 analgesics pre- and postoperatively. Food and water consumption, body weight, running wheel activity, locomotor activity, and serum corticosterone concentrations were measured before and after surgery. Mice that were surgically manipulated weighed significantly less on days 1 through 3 after surgery than did mice not manipulated surgically. On the day of surgery, the surgery groups consumed significantly less feed (-1.5±0.35 g) than did nonsurgery groups. There were no differences in water consumption on any day between surgery and nonsurgery groups or among the 3 analgesic groups. For running wheel activity, significant decreases in the surgery groups were seen at day 1 after surgery compared with baseline. Surgery groups that received buprenorphine and meloxicam returned to baseline activity levels on day 2 after surgery. Open-field testing revealed no significant differences in locomotor activity in any groups; however, posttreatment locomotor activity in the buprenorphine nonsurgery group was increased compared with baseline, and posttreatment locomotor activity in the flunixin meglumine surgery group was decreased compared with baseline. Serum corticosterone concentrations were within normal limits regardless of treatment in all groups. Comparison of the overall results indicated that meloxicam and buprenorphine, at the dose given, appear to be suitable postoperative analgesics for partial hepatectomy in mice. Flunixin meglumine at the given dosage (2.5 mg/kg) may not provide adequate analgesia for partial hepatectomy.

Analgesic effects of tramadol, carprofen or multimodal analgesia in rats undergoing ventral laparotomy.

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.

Evaluation of dosages and routes of administration of tramadol analgesia in rats using hot-plate and tail-flick tests.

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.

Commentary: update on animal models for NTP studies.

Based on recommendations of participants at the National Toxicology Program (NTP) workshop "Animal Models for the NTP Cancer Bioassay: Strains and Stocks-Should We Switch?" some modifications to the NTP rodent cancer bioassay were made. The B6C3F1 remains the mouse model used in the cancer bioassay. The use of multiple strains of mice will be explored through a new branch within the NTP, the Host Susceptibility Branch. Several rat models were evaluated; the Harlan Sprague Dawley rat is currently being used in the NTP studies.

Metastatic uterine adenocarcinoma in an 8-year-old gilt.

An 8-y-old gilt was evaluated after the onset of hemorrhagic perineal discharge. Uterine adenocarcinoma with metastases to the lungs and regional lymph nodes was diagnosed at necropsy. Tumor cells lacked expression of estrogen receptor alpha and progesterone receptor. This case represents the first reported uterine adenocarcinoma in a research pig and the first swine uterine neoplasia in which steroid hormone receptor expression was evaluated.

NTP workshop: animal models for the NTP rodent cancer bioassay: stocks and strains--should we switch?

The National Toxicology Program (NTP) hosted a workshop, "Animal Models for the NTP Rodent Cancer Bioassay: Strains and Stocks--Should We Switch?" on June 16-17, 2005, at the National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, North Carolina. The workshop's objectives were to determine (1) whether the currently used models, the F344/N rat and B6C3F1/N mouse, continue to be appropriate to identify substances that may pose a carcinogenic hazard for humans and (2) whether the NTP should consider conducting cancer bioassays using multiple strains of rats and/or mice to better capture the range of genetic variability. Workshop participants advised the NTP to discontinue using the current F344/N strain due to the recent issues with fertility, seizure activity, and chylothorax and provided several options on how the program should approach identifying and selecting a new rat model. Participants believed that the B6C3F1/N mouse is still appropriate for use by the NTP, but suggested the NTP take steps to better understand and address increases in background rates of liver tumors in this strain. Finally, the participants supported the NTP exploring the use of the multiple strain approach, although they raised many questions concerning data interpretation and feasibility. This article also outlines the NTP's next steps in pursuing the workshop recommendations.

The laboratory animal boards study group: A multifaceted tool for preparation for the American College for Laboratory Medicine board examination.

Preparation for the specialty board examination for the American College of Laboratory Animal Medicine (ACLAM) is an intensive process that is facilitated by geographic regions where many people studying for the exam are located in close proximity. However, many people work at institutions that are distant from these 'study centers'. Approximately 10 y ago, the Laboratory Animal Boards Study Group (LABSG) online journal club was established to provide a forum for journal review for examination preparation. Over the years, the mission of this group has expanded to include practice examinations and practicals, questions from common resources, and summaries and questions from common laboratory animal science journals. These study aids are beneficial for those preparing for the ACLAM certification examination. They are also beneficial for those preparing for the technician and manager certification examinations offered by the American Association for Laboratory Animal Science (AALAS). This article is intended to be an introduction to the variety of study aids available through the LABSG online journal review club and the LABSG web page (www.labsg.org). It also provides details on the demographics of participants and an exploration of how this resource enhances examination preparation.