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Species-dependent differences in relative incidence of spontaneous variations and malformations should be considered in the assessment of the translational value of reproductive and developmental safety assessments. The objective of this evaluation was to compare litter parameters and the frequency of external, visceral, and skeletal malformations and variations across species in the Sprague-Dawley rat, New Zealand White rabbit, and Göttingen minipig and to determine whether notable differences exist. Pregnant female rats (n = 824), rabbits (n = 540), and minipigs (n = 70) from vehicle control groups were included in the analysis, equating to 10,749 rat, 5,073 rabbit, and 378 pig fetuses collected at term by cesarean delivery. Preimplantation loss was more frequent than postimplantation loss in the rat and rabbit, whereas the opposite was observed in the minipig. Several external and visceral malformations and variations such as domed head, bent tail, abdominal edema, and anal atresia were observed in all 3 species. Visceral malformations of the heart and major blood vessels were remarkably more frequent in the minipig and rabbit, respectively; ventricular and atrium septum defects were observed in 1.9% and 2.1%, respectively, for the minipig fetuses, whereas they were observed in equal or less than 0.02% among the rat and rabbit fetuses evaluated in this study. Understanding species-dependent differences in spontaneous variations and malformations can be useful for the interpretation of embryo–fetal development study results. The current analysis identified relevant differences between commonly used species in reproductive toxicology with potential implications for data assessment.

The choroid plexus (CP) produces cerebrospinal fluid and has epithelial, interstitial, and vascular compartments. The CP is a potential site of toxicity, and recognizing the normal microanatomy in different animal models is important for the pathologist. In preclinical studies with beagle dog and New Zealand white rabbits, we observed variable numbers of adipocytes in the CP interstitium of control and xenobiotic-treated animals. The adipocytes were unilocular and consistent morphologically with white adipose tissue. There was a striking variability in the number of adipocytes; however, the presence of adipocytes was not associated with other microscopic findings that would suggest a pathologic process. The morphology of adipocytes was reminiscent of what is observed normally in the interstitium of other tissues like skeletal muscle, bone marrow, and the subcutis. Therefore, we propose that the interstitial adipocytes not be recorded as a finding in preclinical studies unless the adipocytes are altered spontaneously (ie, lipoma) or after xenobiotic treatment.

Clostridium septicum is the causative agent of histotoxic infections, including malignant edema and braxy (necrotizing abomasitis) in several animal species. The carcass of a 2-year–old, female New Zealand white rabbit with a history of acute depression and obtundation followed by death was received at the California Animal Health and Food Safety Laboratory System (San Bernardino, California) for necropsy and diagnostic workup. No gross lesions were detected at necropsy. Microscopically, there was moderate to severe, multifocal fibrinonecrotizing, transmural gastritis with numerous intralesional Gram-positive, sporulated rods, and disseminated thrombosis of the brain, lungs, heart, and liver, with occasional intravascular rods. The rods observed within the gastric wall and thrombi in the stomach and lung were positive for C. septicum by immunohistochemical staining. However, this microorganism was not isolated from stomach content. Clostridium septicum should be included in the list of possible etiologies of gastritis in rabbits.

The mechanics of adhesions at a local tissue level have not been extensively studied. This study compared microstrains and macrostrains in adhesions of immobilized and mobilized partially lacerated flexor digitorum profundus tendons in a New Zealand White rabbit model. At 2 weeks, 50 digits were randomized to either gross tensile testing or micromechanical assessment, in which the movement of fluorescently labelled cell nuclei, acting as dynamic markers, was visualized using real-time confocal microscopy. The structural stiffness and load at failure of immobilized adhesions were 140% and 160% of that of mobilized adhesions, respectively, and both differences were statistically significant. Micromechanically, different patterns of loading and failure were observed. Mobilized adhesions exhibited over a three-fold higher local strain, which was less uniformly distributed. Confocal microscopy provided an accurate measure of local strain. For the first time, it has been possible to visualize, define, and quantify local adhesion tissue mechanics. Mobilization appears to favour the formation of sites expressing increased local strain responses or those predisposed to heterogeneity and localized failure.

Background Biomechanical and histological properties of osteochondral transplantation have not been extensively examined. Hypothesis Osteochondral grafts have properties similar to native articular cartilage. Study Design Controlled laboratory study. Methods A 2.7 mm (diameter) × 4.0 mm (depth) osteochondral defect was created in 17 New Zealand white rabbit knees. An osteochondral graft, harvested from the contralateral knee, was transplanted into the defect. Eight rabbits were sacrificed each at 6 and 8 weeks. Results The 12-week grafts (1213.6 ± 309.0 N/mm) had significantly higher stiffness than the 6-week grafts (483.1 ± 229.1 N/mm; P< .001) and of normal cartilage (774.8 ± 117.1 N/mm; P< .003). Stiffness of the 6-week grafts was significantly lower than normal cartilage (P< .036). At all time points, full-thickness defects had significantly lower stiffness than normal cartilage (P< .001). Histologically, transplanted grafts scored significantly higher than the full-thickness defects (P< .001). The defects showed inconsistent, fibrocartilage healing. The grafts demonstrated cartilage viability, yet with a persistent cleft between the graft and host. Conclusions Osteochondral transplants undergo increased stiffness in the short term, with evidence of structurally intact grafts. Clinical Relevance Osteochondral transplantation may be a viable treatment option; however, long-term investigation on graft function is necessary.

Objective Clinical studies have shown both abnormal and normal mental and psychomotor development in patients with craniosynostosis. However, a number of confounding variables make study comparisons difficult. For these reasons, the present study describes early neuromotor development in an homogeneous rabbit model of craniosynostosis. Design Fifty-three newborn New Zealand white rabbit kits were used: 13 were wild-type, normal control rabbits; 23 had delayed-onset coronal suture synostosis (onset is approximately 57 to 74 days post conception); and 17 had early-onset coronal suture synostosis (onset is approximately 21 to 25 days post conception). All rabbits were observed individually and blindly in an open field, daily for 2 minutes, from birth through the first 14 days of life. The first day of emergence of 10 different mature behaviors and developmental events (in developmental order of appearance: falling, righting, cliff avoidance, first sign of fur, body elevation, head elevation, circling, dragging, eye opening, and hopping) was recorded for each kit. Daily activity levels (grid crossing), and body weights were also recorded. Results Significant group (p < .05) differences were observed in 9 of 11 measures. Both synostosed groups had significantly (p < .05) accelerated onset of behavior in 8 of 9 measures, compared with wild-type controls. The early-onset synostosis group had significantly (p < .05) accelerated onset in five of eight measures, compared with wild-type controls, and three of eight measures, compared with the delayed-onset synostosis group. Conclusions Synostotic rabbits showed precocious neuromotor development possibly through frontal lobe constrictions and altered brain activity from increased intracranial pressure, although primary genetic effects cannot be ruled out.

S-(1,2-dichlorovinyl)-L-cysteine (DCVC)-induced nephrotoxicity in vivo was investigated in New Zealand White rabbits. A primary emphasis in these studies was further characterization of DCVC-induced nephrotoxicity using a variety of serum and urinary analytes, including sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Additionally, the role of oxidative injury was assessed to address the dichotomy between reports indicating that such a mechanism is important in vivo and those indicating that such mechanisms do not contribute substantially to the mechanism of effects observed in vitro. Urine was collected prior to and at 8 and 24 hr after iv administration of DCVC. Serum was collected 15 min prior to and 24 hr after DCVC administration. Rabbits were euthanized 24 hr post-DCVC administration, and kidneys were fixed in formalin and further processed for light microscopic examination. DCVC (10 mg/kg, iv) induced a 45-50-fold increase in total urinary protein excretion, a 10-15-fold increase in urinary N-acetyl-β-D-glucosaminidase concentration, plus a marked glucosuria by 24 hr postadministration. Additionally, DCVC increased serum creatinine levels by about 2-fold, with a trend toward increased blood urea nitrogen. SDS-PAGE analysis of rabbit urine confirmed the clinical finding of marked proteinuria in DCVC-treated animals, which in contrast to previously reported data was due to the presence of both low and high molecular weight proteins. Antioxidants had no significant effect on DCVC-dependent renal injury, nor was there evidence for DCVC-induced lipid peroxidation, as measured by either thiobarbituric acid-reactive substances or a commercial assay for malondialdehyde and hydroxalkenals. These latter data are consistent with previously published in vitro evidence citing no major role for lipid peroxidation in DCVC-induced nephrotoxicity.

The ultimate success of any free flap transfer depends not only on the experience of the given surgical team, but also requires constant vigilance in the perioperative period to assure continued anastomotic patency. Clinical acumen remains the 'industry' standard, but adjunctive monitoring devices are important to reinforce these subjective evaluations. We routinely use laser Doppler flowmetry in spite of known drawbacks, including expense. On the other hand, we know that pulse oximetry is a possible and readily available alternative. The efficacy of these two monitoring systems was directly compared in a New Zealand white rabbit central artery and vein ear model. Arterial occlusion was immediately recognized by a precipitous drop in flow and oxygen saturation (SaO2). A rapid drop in flow after venous occlusion with a trend to zero was also noted with laser Doppler flowmetry. The SaO2 had a very slow but steady gradual decline, but values remained in the range of normoxemia for a prolonged time. Because a minimum threshold of SaO2 for predicting venous occlusion was elusive, the usefulness of pulse oximetry for monitoring microsurgical composite tissue transfers is limited.La réussite complète de toute greffe libre repose non seulement sur l’expérience de l’équipe chirurgicale mais aussi sur une vigilance constante en période périopératoire dans le but d’assurer la perméabilité anastomotique. L’acuité clinique demeure la norme dans «l’industrie » mais les dispositifs de surveillance d’appoint sont également importants pour préciser ces évaluations subjectives. Nous utilisons communément la fluxmétrie Doppler à laser malgré ses inconvénients connus, y compris son coût. D’autre part, nous savons que l’oxymétrie pulsée constitue une solution possible et accessible.L’efficacité de ces deux systèmes de surveillance a fait l’objet d’une comparaison directe réalisée sur une artère et une veine centrales d’oreille de lapin blanc de Nouvelle-Zélande. L’occlusion artérielle a été immédiatement décelée par une chute précipitée du débit d’oxygène et de la saturation du sang en oxygène (SaO

Background Optical coherence tomography (OCT) is a non-invasive, high-resolution imaging technology that is capable of delivering real-time, near histologic level images of tissues. Acute smoke inhalation causes airway edema, which leads to major morbidity and mortality, but the ability to assess airway injury in a clinical setting is limited. The purpose of this study is to assess the ability of OCT to detect and monitor progression of inhalation airway injury with minimally invasive techniques. Methods A ventilated New Zealand White rabbit smoke inhalation injury model using fumes from burnt unbleached cotton was employed to simulate acute smoke inhalation injury. A 1 mm diameter flexible fiberoptic OCT probe was introduced into the distal trachea to image airway mucosa and submucosa. Progression of injury edema was measured over 6 hours with OCT imaging using a prototype superluminescent diode OCT system we constructed in our laboratory. OCT tracheal images from the smoke inhalation injury animals were compared to control rabbit tracheas for quantitative tracheal mucosal thicknesses measurements. Results Results revealed significant airway mucosal thickening in the experimental group consistent with tracheal edema, which occurs as early as 30 minutes after smoke inhalation. Conclusion OCT is a valuable imaging modality capable of evaluating superficial airway pathology with high resolution in vivo after acute inhalation injury.

The present interest in malformations of the rabbit stems almost entirely from a chain of events that originated in the thalidomide disaster and expanded through a multiplicity of animal studies which, among other things, demonstrated that thalidomide consistently causes malformations in the rabbit embryo. Culmination of the chain was the acceptance of the rabbit as a suitable species for teratogenicity screening tests in the safety evaluation of new drugs (Table 1). It is now evident that, for drug evaluation studies, susceptibility of the test species to thalidomide is a somewhat doubtful recommendation. Thalidomide is unique and atypical so that a positive result obtained with it is not necessarily indicative that a species will be susceptible to teratogens that depend on quite different modes of action. Fortunately the rabbit (especiaIly the New Zealand White) possesses a number of basic characteristics that are an asset in teratology studies. Some of these characteristics, and the advantages that spring from them, are: domesticated and of moderate size (foetus 40 g, adult 3-4 kg)~easily visible defects, moderate drug need, ease of handling and maintenance, short gestation (32 days); prolonged oestrus and induced ovulation~pregnancy easily and accurately timed, artificial insemination possible

Summary1. Methods of concentrating soluble proteins are reported for aqueous extracts of cornea. These methods apparently do not denature the proteins. 2. These methods were applied to increase concentration of protein from aqueous extracts of bovine, swine, New Zealand White rabbit and mongrel rabbit corneas to a level which would permit ultracentrifugal analysis of these extracts. 3. Fundamental differences in number of protein fractions and particle size distribution were noted in these extracts. This suggests a species difference in soluble corneal proteins. 4. Differences were noted in sedimentation diagrams of extracts from New Zealand White rabbits and mongrel rabbits, suggesting differences in soluble corneal protein content of different strains of the same species.The authors wish to thank Lt. Col. L. J. Milch of the School of Aviation Medicine, Randolph Field, Texas for valuable advice and evaluation of this work.

A New Zealand White rabbit on which larvae of Hyalomma rufipes were fed died of theileriosis due to Theileria annulata 22 days after the larvae had fed. The larvae were direct progeny of an enorged female collected from trade cattle in the veterinary control post at Ibadan. The danger attending the feeding on rabbits of first progeny of ticks collected from cattle in countries where some tick-borne diseases are endemic is highlighted. The possibility of transovarial transmission of Theileria is discussed.