Deep subconjunctival injection of gentamicin for the treatment of bacterial conjunctivitis in macaques (Macaca mulatta and Macaca fascicularis).

Infectious conjunctivitis occurs in a number of domestic and laboratory animal species and is usually treated topically with eye drops or eye ointments, which must be administered several times a day and sometimes for a prolonged period of time. In aggressive nonhuman primates or other large laboratory animal species, this may require the use of anesthesia or physical restraint before each treatment, which can be stressful to the animals and demanding for personnel. The authors describe a technique for administering deep subconjunctival injections of an antibiotic to laboratory macaques for the treatment of conjunctivitis. Three cases of recurrent conjunctivitis in macaques that responded poorly to other treatment approaches were effectively treated using this technique. This approach is recommended for the treatment of conjunctivitis in macaques and other large animal species.

Novel pathologic findings associated with urinary retention in a mouse model of mucopolysaccharidosis type IIIB.

Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome type B) is a metabolic disorder with devastating clinical characteristics starting in early childhood and leading to premature death. A knockout mouse strain was developed that models this disease. Mice of the strain B6.129S6- Naglu(tm1Efn)/J are invaluable for investigating pathogenesis and possible treatment modalities. However, the mouse strain also exhibits some objectionable phenotypic features. One such feature, urinary retention, not only is atypical of human MPS IIIB but often leads to early termination of experiments due to animal welfare concerns. The aim of this study was to investigate abnormalities associated with the urinary retention. Necropsies were performed on 9-mo-old mice; urinalysis, hematology and blood chemistry parameters were evaluated, and urogenital specimens were microscopically examined. Histopathologic examinations of urinary tract specimens proved illuminating regarding pathology in the urinary tract. A large mononuclear cell infiltrate was discovered in mutant mice of both sexes, more pronounced in females compared with male mice. The infiltrate comprises of large rounded or polygonal cells with generous variably vacuolated, granular eosinophilic cytoplasm and small round vesicular nuclei. These cells were present throughout and expand the interstitium of the lower urinary tract. Either this results in extrinsic compression of the lumen of the urethra, eventually leading to obstructive uropathy, bladder hyperdistension, and urinary retention or possibly interferes with the neurogenic component of micturition needs to be further investigated. The novel finding of an unexpected mononuclear cell infiltrate in the urinary tract in the knockout mice B6.129S6- Naglu(tm1Efn)/J is reported.

Successful management of long-term general anesthesia in rabbits used as an animal model of human disease.

The rabbit represents a popular animal model for basic science research, but projects requiring anesthesia and endotracheal intubation represent a technical challenge because of the difficulty in accessing the animal's airway and sensitivity to common anesthetic agents. We hypothesized that transoral intubation under direct visualization with guidewire assistance would improve airway access success and reduce perioperative mortality in the rabbit. Of the 39 New Zealand White rabbits that had passive inhalation anesthesia and were intubated using wire-guided assistance under direct laryngeal visualization, 33 were intubated using a flexible wire after the rigid guide had resulted in airway injury in three of the first six rabbits. Animals were then maintained under general anesthesia during a 4- to 5-h procedure. At the completion of the procedure, animals were recovered from anesthesia and extubated. All 39 animals were successfully intubated, mostly on the first attempt. There were two animal deaths, both in the first six animals; one death was a direct result of laryngeal injury from the rigid wire guide initially used. One additional animal in the first six had pulmonary difficulty after an airway injury but recovered and was successfully used in the experiment. Two animals developed gastric distention during anesthesia, which was alleviated with placement of an orogastric tube without adverse sequelae. No animals developed problems with oxygenation during the experiment, but over half (52.8%) had end-tidal CO2 (ETCO2) above 45 mmHg at least once during the surgery, and 13 rabbits were above this level for longer than 1 h. An average of 18 min elapsed between withdrawal of anesthesia and the time when spontaneous respirations and chewing movements returned. Animals then could be safely extubated. There was no correlation between high perioperative ETCO2 and time to recovery from anesthesia (P = 0.18, r = 0.23).

Mouse model of Sanfilippo syndrome type B: relation of phenotypic features to background strain.

Sanfilippo syndrome type B or mucopolysaccharidosis type III B (MPS IIIB) is a lysosomal storage disorder that is inherited in autosomal recessive manner. It is characterized by systemic heparan sulfate accumulation in lysosomes due to deficiency of the enzyme alpha-N-acetylglucosaminidase (Naglu). Devastating clinical abnormalities with severe central nervous system involvement and somatic disease lead to premature death. A mouse model of Sanfilippo syndrome type B was created by targeted disruption of the gene encoding Naglu, providing a powerful tool for understanding pathogenesis and developing novel therapeutic strategies. However, the JAX GEMM Strain B6.129S6-Naglutm1Efn mouse, although showing biochemical similarities to humans with Sanfilippo syndrome, exhibits aging and behavioral differences. We observed idiosyncrasies, such as skeletal dysmorphism, hydrocephalus, ocular abnormalities, organomegaly, growth retardation, and anomalies of the integument, in our breeding colony of Naglu mutant mice and determined that several of them were at least partially related to the background strain C57BL/6. These background strain abnormalities, therefore, potentially mimic or overlap signs of the induced syndrome in our mice. Our observations may prove useful in studies of Naglu mutant mice. The necessity for distinguishing background anomalies from signs of the modeled disease is apparent.