Fertility after homologous prepubertal testis transplantation in the dog.

Canine models of hereditary human diseases are widely used throughout the biomedical community, particularly when no suitable rodent model exists. In several models, the homozygote dogs die prior to puberty, or have substantially reduced fertility. Prepubertal transplantation of the testes was used to propagate the genotype of a mutant dog that would not otherwise have survived until puberty. The transplant recipient remained fertile 7 years postoperatively. To begin determining the factors necessary for successful function in testis transplants, prepubertal dogs that were dog leukocyte antigen (DLA) identical and disparate were examined for fertility and compared to the original transplant recipient as well as unoperated and sham-operated dogs. Immunosuppression was maintained with cyclosporine (CyA) and prednisone in the immediate postoperative period and CyA alone thereafter. The DLA-identical dogs demonstrated initial acceptance of the transplant, whereas one of two underwent chronic rejection. Both DLA-disparate dogs had subacute rejection prior to sexual maturity. These results demonstrate that homologous transplantation of prepubertal testes can be an effective method to preserve genotype in DLA-identical dogs. This model may also be useful for studying testis development and immunobiology.

Anesthetic protocol: propofol use in Rhesus macaques (Macaca mulatta) during magnetic resonance imaging with stereotactic head frame application.

Magnetic resonance image (MRI) guidance is often necessary for accurate targeting for stereotactic intracranial surgery in animals used for experimental research studies. The magnetic field created by the MR imaging equipment, logistics of the use of stereotactic head frame in confined space and the need to limit movement of the subject during the imaging creates unique challenges. We demonstrate in this study the usefulness of intravenous propofol to anesthetize adult Rhesus monkeys to obtain high resolution 3D MR images immediately followed by conversion to inhalation anesthesia and stereotactic intracranial surgery with the head frame 'in situ.' There was minimal morbidity with achieving a high degree of precision for the stereotactic targeting.

Pig-tailed macaques infected with human immunodeficiency virus (HIV) type 2GB122 or simian/HIV89.6p express virus in semen during primary infection: new model for genital tract shedding and transmission.

Characterizing human immunodeficiency virus (HIV) expression in semen during primary infection remains essential to understanding the risk of sexual transmission. This investigation represents the first systematic evaluation of male genital tract shedding to use a nonhuman primate model, including the impact of exposure route and viral virulence. Male macaques were inoculated with either a chronic disease-causing virus (HIV-2(GB122); n=4 intravenous; n=4 intrarectal) or an acutely pathogenic simian/HIV strain (SHIV(89.6P); n=2 intravenous). All macaques were systemically infected, and seminal plasma virion-associated RNA (vRNA) levels were approximately 10-fold lower than those in blood. In HIV-2(GB122) infection, seminal virus was delayed by 1-2 weeks compared with that in blood. Intrarectal inoculation resulted in a shorter duration of seminal vRNA expression and intermittent seminal cell provirus. No delays, higher peaks ( approximately 50-fold), or longer durations in seminal virus expression were noted for SHIV(89.6P) infection. This novel model definitively establishes that virus dissemination results in early peak seminal levels and provides a basis for evaluating interventions targeting male genital tract expression.

Congenital bilateral ureteral stenosis and hydronephrosis in a neonatal puppy.

Three days after an uneventful parturition, a Brittany spaniel/beagle puppy (Canis familiaris) was nursing but not gaining weight as rapidly as were its littermates. Although its diet was supplemented, the puppy died 10 days after birth. The renal pelves were enlarged and filled with urine. Both ureters were thin throughout their length, and urine could not be expressed from either kidney into its respective ureter. The bladder contained no urine and was firmly embedded in the umbilicus. Histologically, both kidneys were hydronephrotic and contained hypoplastic collecting tubules. The diameter of the right (0.55 mm) and left (0.57 mm) ureters at the uteropelvic junction were narrower than those of an age-matched control of the same breed (1.03 mm and 1.02 mm) and were lined by hypoplastic urothelium. Trichrome staining of the ureters revealed excessive collagen and disorganized smooth muscle fibers; in contrast, the control had predominantly circular smooth muscle fibers and less fibrous tissue. Although neither blood nor aqueous humor could be evaluated for urea nitrogen, we suspect that the puppy died from uremia. The congenital bilateral ureteral stenosis and hydronephrosis of the described puppy is similar to a form of uteropelvic obstruction in humans.

Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2).

Postexposure prophylaxis (PEP) after intravaginal exposure to human immunodeficiency virus (HIV) was investigated using the HIV type 2 (HIV-2)/pig-tailed macaque transmission model. PEP for 28 days with the reverse transcriptase inhibitor (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA; tenofovir) was initiated 12 to 72 h following HIV-2 exposure. Systemic infection was not evident in the 12- and 36-h groups, as defined by plasma viremia, cell-associated provirus, antibody responses, and lymph node virus. Breakthrough infection in the 72-h group was detected at week 16 post-virus exposure. These results demonstrate for the first time using a vaginal transmission model that early intervention after high-risk sexual exposures may prevent infection.

Fenbendazole treatment without environmental decontamination eradicates Syphacia muris from all rats in a large, complex research institution.

Syphacia muris parasitism was eliminated from rats and voles by feeding fenbendazole-medicated chow (150 ppm) for five 7-day periods; treatment periods were separated by 7-day periods of feeding non-medicated chow, yielding atotal treatment course of 9 weeks. No other manipulations to facilitate eradication, including the use of filter tops, autoclaved cages, environmental decontamination, colony depopulation, breeding cessation, and research restriction, were done. The examination of 3143 cellophane-tape impressions of the anus and 160 cecal examinations from euthanized rats and voles during the treatment period and for 7 months afterwards confirmed the efficacy of treatment. Treatment was rapidly effective in voles. In rats, pinworm eggs persisted at high levels for 2 weeks after the start of treatment, but no eggs were found after 22 days.