Faculty Bibliography

Murine fur mites are reported to exist in over one-third of research institutions and can be problematic to eliminate. Current treatment strategies can be labor-intensive, toxic, and may confound research studies. The ideal method would be technically simple, safe, effective, and relatively inexpensive. When we found that mice from a noncommercial vendor were infested with Myocoptes musculinus, the animals were treated topically with Cydectin pour-on (containing moxidectin 0.5%) at 0.5 [corrected] mg/kg. After one treatment, mites were eradicated from all infested mice. No toxic effects or clinical signs of illness were observed in the mice. To the authors' knowledge, this is the first report of topical moxidectin as a treatment for murine acariasis

Mouse parvovirus (MPV) has been increasingly prevalent in laboratory animal facilities, and the source of infection often can be difficult to determine. After 4 years of sporadic MPV detected in our sentinel mice and continual failure to identify index cases in colony mice, we developed a regimen to house newly arrived vendor mice in large sterile cages with a high stocking density. Some of these mice were retained in isolation after the remaining mice were deployed as sentinels. After detecting MPV seropositive sentinel mice 4 weeks after introduction to the mouse colonies in one facility, the remaining naive mice that had been previously housed with those sentinels also tested positive for MPV, despite never having been exposed to colony mice. These results suggest that commercially bred mice intended for use as sentinels may, in fact, arrive at animal facilities already infected with MPV. Depending upon numerous factors, including the health surveillance methods used, it is possible that a low prevalence of MPV may exist undetected at rodent vendors

A high frequency of struvite urolithiasis, hydronephrosis, and other urinary tract lesions developed in a group of Lewis rats inoculated intracranially with lymphocytic choriomeningitis virus (LCMV). Initially, clinically ill rats were referred to necropsy: 30 rats over 3 years. These rats had high frequency of urolithiasis (8/30, 27%), hydronephrosis (12/30, 40%), cystitis (9/30, 30%), transitional cell carcinoma (4/30, 13%), and pyelonephritis (19/30, 63%). Lesions were more common in LCMV-inoculated rats. After this trend was noted, all rats on this protocol were necropsied as part of a cohort study (n = 144). Although the apparent frequency of disease was lower due to increased sampling, there still was a high number of urolithiasis (9/144, 6%) and hydronephrosis (40/144, 28%) cases. All cases of urolithiasis developed in rats inoculated with LCMV (9/44, 20%), as did most cases of hydronephrosis (31/44, 70%). Although sham-injected and uninoculated control rats also had high frequency of hydronephrosis (6/57 [11%] and 3/43 [7%], respectively), LCMV-inoculated rats had a significantly higher frequency of disease than did sham inoculated (P < 0.0001) and uninoculated (P < 0.0001) controls. These results suggest that Lewis rats may be predisposed to developing lesions of the urinary tract, and that intracranial inoculation of rats with LCMV augments this tendency, leading to formation of struvite calculi and associated urinary tract disease

OBJECTIVE: To better understand HIV-1 sexual transmission risk, we have studied the susceptibility of HIV-2-exposed, uninfected (EU) female pig-tailed macaques to intravaginal (IVAG) re-challenge with the homologous HIV-2 strain, followed by heterologous SHIV89.6p. METHODS: Nine female macaques, previously protected by a post-exposure prophylaxis (PEP) regimen, along with one mock-treated EU animal, were re-exposed to HIV-2 by the IVAG route approximately 1.5 years later. A single follow-up challenge was performed approximately 1 year later with SHIV89.6p to assess susceptibility of chronic HIV-2-infected animals to further re-infection and pathogenic effects with a heterologous virus, somewhat mimicking HIV-1. RESULTS: Eight of ten macaques (80%) became infected systemically with HIV-2, and plasma or cervicovaginal vRNA levels did not appreciably differ from prior historic non-PEP control macaques. Interestingly, all eight HIV-2-infected females were susceptible to SHIV89.6p infection by either intravenous (n = 4) or IVAG exposure (n = 4) after one inoculation. Plasma vRNA levels in these groups were controlled by week 8 and there were no decrease in CD4+ T cells > 50%. The remaining two HIV-2 EU macaques, inoculated intrarectally with SHIV89.6p, were unable to control virus replication and succumbed to disease by week 25 or week 61. CONCLUSIONS: Our findings demonstrate that successful PEP regimens to prevent an initial infection do not have any lasting protective effects. The observed lack of cross-protection against SHIV89.6p transmission among chronic HIV-2-infected macaques provides modeling support for limited epidemiologic data indicating that human HIV-2 infection does not protect against HIV-1 infection, but may serve to alter overt clinical outcome

The pinworm Syphacia muris was eradicated from rats after treatment with fenbendazole-medicated chow (150 ppm) and without environmental decontamination for > 54 months. However, this regimen was successful only when the treatment was delivered and efficacy monitoring was done by personnel of the institutional animal resources program. The same pinworm elimination program failed 7 to 24 months after the cessation of treatment in a satellite colony in which animal care, including provision of medicated diet and sample collection for efficacy monitoring, was provided by research personnel. A failure to uniformly deliver adequate therapeutic doses or reinoculation of rats with pinworm eggs from the contaminated environment could not be excluded as causes of the failure. However, there were risk factors, and animal care practices unique to the satellite colony that may have facilitated the re-emergence of pinworms. These risk factors included hand-washing of cages, storage of contact bedding in areas that were not vermin-proof, and animal care provided by personnel having contact with rodents of pet-store origin

PURPOSE: Nitric oxide (NO) is important in regulation of platelet aggregation, endothelial function, and intravascular thrombosis. The purposes of this study were to assess the effect of thrombolysis on endothelial function in a porcine model of deep venous thrombosis (DVT) and to evaluate the effect of NO precursor l-arginine on endothelial function after thrombolytic therapy. METHODS: DVT was created in bilateral iliac veins by deploying a self-expanding stent-graft that incorporated an intraluminal stenosis, from a groin approach. Five pigs underwent sham operation. After 7 days of DVT, animals were randomized to three groups: saline pulse-spray (saline group, n = 5), thrombolytic pulse-spray with tissue plasminogen activator (alteplase, 8 mg; t-PA group, n = 5), and thrombolytic pulse-spray plus intravenous l-arginine (20 mmol/L; arginine group, n = 5). At 2 weeks iliac vein patency was evaluated at venography and intravascular ultrasound scanning. NO level was determined with a chemiluminescent assay of the nitrite and nitrate metabolites (NO(x)). Thrombogenicity was evaluated with radiolabeled platelet and fibrin deposition. Veins were harvested and evaluated with light microscopy and scanning electron microscopy. Endothelial function was evaluated with organ chamber analysis. RESULTS: All iliac veins remained patent at 2 weeks. The luminal areas in the sham, saline, t-PA, and arginine groups were 53 +/- 23 mm(2), 14 +/- 11 mm(2), 34 +/- 19 mm(2), and 42 +/- 21 mm(2), respectively. No difference in endothelial cell structure was observed between the three treatment groups at light microscopy or scanning electron microscopy. Although no difference in fibrin deposition was noted among the three treatment groups, decreased platelet deposition occurred in the arginine group compared with the saline or t-PA groups (P <.05). The arginine group showed greater endothelial-dependent relaxation compared with the t-PA or saline groups (73% +/- 23% vs 49% +/- 18% and 32% +/- 21%; P <.05). Local NO(x) level in the arginine group was correspondingly higher compared with the saline or t-PA groups (1.8 +/- 0.3 micromol/L vs 0.3 +/- 0.05 micromol/L and 0.2 +/- 0.04 micromol/L; P <.05). CONCLUSIONS: NO precursor l-arginine supplementation enhances NO production at sites of venous thrombosis. Moreover, l-arginine preserves endothelial vasoreactivity and reduces platelet deposition after thrombolysis in iliac DVT. These data suggest that l-arginine may preserve endothelial function after thrombolysis and may reduce the likelihood of postthrombotic syndrome

Mouse hepatitis virus (MHV) infection in immunocompetent mice is typically self limiting, and transmission is short lived. With the recent surge in the development of genetically engineered mutant mice with alterations in immune system components, however, MHV clearance may be disrupted. We report confirmed persistent transmission of MHV from tumor necrosis factor (TNF) knockout mice, B6.129S1-Tnftm1Lj (TNF -/-), to nude and immunocompetent sentinel mice over a period of five months. Infection with MHV was confirmed in nude sentinel mice by use of reverse transcriptase-polymerase chain reaction (RT-PCR) detection of viral RNA in ascending colon and feces. The RT-PCR-analyzed specimens recovered from sentinel animals were sequenced, and 92% homology to the N region of the MHV strain S genome was documented. In addition, immunocompetent mice had evidence of seroconversion to MHV infection and RT-PCR-positive fecal and ascending colon specimens after only 24 h of direct contact with the TNF -/- mice. To the authors' knowledge, this is the first reported experimental evidence that MHV transmission can occur for several months, from persistently infected mice to sentinel mice, over a short-term exposure period

An adult male cynomolgous macaque (Macaca fascicularis) died suddenly after anesthesia for a positron emission tomography scan. Bacteriologic culture of the mucopurulent secretions recovered from the endotracheal tube yielded heavy growth of Pseudomonas putida, a known endotoxin producer. Histologically, the lungs had severe, diffuse perivascular edema and neutrophils marginating to the endothelium. The sudden death and the pathologic findings were consistent with peracute endotoxic shock. Numerous environmental swab specimens of the surgical suite and equipment were submitted for bacteriologic culture, as were swab specimens of endotracheal secretions from a control animal; however, Pseudomonas putida was not isolated from any specimen. The animal in this report may have carried Pseudomonas putida as a commensal in the oropharynx, and the stress of anesthesia may have resulted in increased sensitivity to the endotoxin

PURPOSE: Pseudoaneurysm is a known complication of arteriovenous grafts in chronic hemodialysis and can result in graft disruption or thrombosis if left untreated. This study evaluated the safety and efficacy of endovascular repair with Wallgraft endoprosthesis (Boston Scientific, Inc, Watertown, Mass) in a porcine arteriovenous graft (AVG) pseudoaneurysm model. Materials and Methods: Bilateral groin AVG pseudoaneurysms (n = 18) were created with an oversized Dacron interposition graft within a polytetrafluoroethylene femoral AVG in nine domestic swine and allowed to mature 28 +/- 4 days (standard deviation). Transluminal placement of Wallgraft was performed to exclude the pseudoaneurysm from the AVG circulation. Hemodialysis was performed (400 mL/min x 1 hour, with intravenous heparin 30 units/kg) every 4 days for a total of 6 weeks via 15-gauge needles in the treated AVG pseudoaneurysm site. Arteriography and duplex ultrasound scan were performed to determine AVG patency and pseudoaneurysm flow. Histologic evaluation was performed to determine Wallgraft morphology. In vitro pulsatile flow chamber was used to determine maximal flow volume without peri-Wallgraft endoleak. RESULTS: All AVG pseudoaneurysms were successfully excluded with the Wallgrafts. Twelve AVG (67%) remained patent at the completion of the study. No Wallgraft migration occurred from hemodialysis. Transient peri-Wallgraft endoleak (<2 hours after hemodialysis) was present in 13 of 18 (72%) and four of 12 (33%) AVG pseudoaneurysms by weeks 1 and 6, respectively. With maintenance of an intraluminal pressure of 80, 100, 120, 140, and 160 mm Hg in the pulsatile flow chamber, the maximal flow rates without peri-Wallgraft endoleak were 625 +/- 120, 650 +/- 145, 620 +/- 95, 425 +/- 110, and 262 +/- 86 mL/min. Scanning electron microscopy showed a neointimal layer covered with thrombus on the Wallgraft surface. CONCLUSION: Endoluminal placement of Wallgraft endoprosthesis provides adequate structural support for continuous hemodialysis after AVG pseudoaneurysm exclusion. Transient blood flow in the pseudoaneurysm cavity may occur immediately after the hemodialysis, which may represent the effect of heparin used during hemodialysis. This study suggests Wallgraft is a safe and effective treatment for AVG pseudoaneurysm and permits continuous hemodialysis