Placental immunopathology and pregnancy failure in the FIV-infected cat.

Placental HIV infections frequently result in infected babies or miscarriage. Aberrant placental cytokine expression during HIV infections may facilitate transplacental viral transmission or pregnancy perturbation. The feline immunodeficiency virus (FIV)-infected cat is a model for HIV infections due to similarities in biology and clinical disease. The purpose of this study was to evaluate placental immunomodulator expression and reproductive outcome using the FIV-infected cat model. Kittens were cesarean delivered from FIV-B-2542-infected and control queens near term; placental and fetal tissues were collected. Real-time RT-PCR was used to measure expression of representative placental Th1 cytokines, interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma), a Th2 cytokine, IL-10, and chemokine receptor CXCR4. On average, control queens delivered 3.8 kittens/litter; 1 of 31 kittens (3.2%) was non-viable. FIV-infected queens produced 2.7 kittens/litter; 15 of 25 concepti (60%) were non-viable. FIV was detected in 14 of 15 placentas (93%) and 21 of 22 fetuses (95%) using PCR. Placental immunomodulator expression did not differ significantly when placentas from infected cats were compared to those of control cats. However, elevated expression of Th1 cytokines and increased Th1/Th2 ratios (IL-1beta/IL-10) occurred in placentas from resorptions. Therefore, increased placental Th1 cytokine expression was associated with pregnancy failure in the FIV-infected cat.

Failure to detect bovine immunodeficiency virus contamination of stud bull spermatozoa, blood leukocytes, or semen leukocytes in samples supplied by artificial insemination centers.

OBJECTIVE: To determine whether bovine immunodeficiency virus (BIV) infection could be detected in spermatozoa, blood leukocytes, or semen leukocytes from stud bulls in artificial insemination centers. ANIMALS: 30 bulls at 3 artificial insemination centers. PROCEDURE: Polymerase chain reaction testing that used 3 sets of primer pairs targeting pol and env regions of the BIV proviral genome was performed on DNA extracted from semen leukocytes, spermatozoa, and blood leukocytes from each bull. Southern blot analysis was performed to increase sensitivity of detection. Western blot analysis of plasma samples was used to detect antibodies against BIV. RESULTS: BIV provirus was not detected in DNA samples obtained from semen leukocytes, spermatozoa, or blood leukocytes, and antibodies against BIV were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: Contrary to our report of high point prevalence of BIV contamination of semen from a single artificial insemination center, bulls of the study reported here did not appear to be infected. Maximum risk of BIV infection in similar bulls was estimated at 10% with a confidence level of 95%.

Anaesthetic organ toxicity: is it really a problem?

The hepatotoxicity of halothane is now well known, but only became apparent after several years of use. The nephrotoxicity of methoxyflurane was not realized immediately, but once identified, led to its withdrawal from use. Therefore, when new agents that appear to offer significant advantages over established drugs become available, exhaustive testing and monitoring is necessary to ensure their safety. Sevoflurane, recently available in the UK and the USA but used for some time in Japan, has been subjected to considerable scrutiny.

Pharmacokinetics of potential anti-AIDS agents thiofoscarnet and foscarnet in the cat.

The pharmacokinetics of thiophosphonoformate (TPFA) and phosphonoformate (foscarnet, PFA) were studied in normal adult cats, a species susceptible to feline immunodeficiency virus (FIV) infection. Parent drugs and metabolites were quantitated by high-performance liquid chromatography (HPLC). TPFA had a mean terminal plasma half-life of 42 min, a total clearance of 4.58 ml/min/kg, and a renal clearance of 1.24 ml/min/kg (N = 4). TPFA underwent in vivo metabolism to PFA and thiophosphonic acid (TPA); the latter was inactive against HIV reverse transcriptase. The 6-h cumulative urinary excretion was 42.3% of the intravenous administered dose of TPFA, consisting of 23.5% unchanged TPFA, 13.8% PFA, and 5.0% TPA. In comparison, PFA had a mean (N = 5) terminal half-life of 172 min and a total clearance of 1.88 ml/min/kg, approximating its renal clearance. There was no evidence of PFA metabolism. Oral doses of TPFA were administered either in enteric-coated capsules or in solution by gavage. The mean oral bioavailability of encapsulated TPFA and PFA was 22 and 8%, respectively. When given by gavage, TPFA had a higher mean bioavailability (33%), but with a greater variability. Based on the 6-h cumulative urinary excretion of TPFA, the mean oral bioavailability of TPFA was 44%, similar to that based on plasma data. The TPFA appears to be superior to PFA because of its greater oral bioavailability and its ability to deliver an active metabolite, PFA, to the systemic circulation after oral dosing.

Early events in the immunopathogenesis of feline retrovirus infections.

Feline leukemia virus and feline immunodeficiency virus (FIV) are lymphotropic retroviruses that cause a wide range of diseases in domestic cats. Although it is known that both viruses are capable of infecting T lymphocytes and that infected cats are lymphopenic, it was not known how infection with either virus might alter specific lymphocyte subpopulations. Using a panel of monoclonal antibodies to feline lymphocyte subpopulations, we examined, by use of flow cytometric analysis, lymphocyte changes in cats naturally infected with FeLV or FIV and explored the early stages in the immunopathogenesis of experimentally induced infection with these viruses. Both groups of naturally infected cats had T-cell lymphopenia. In the FIV-infected cats, the T-cell decrease was principally attributable to loss of CD4+ cells, whereas CD8+ and B-cell numbers remained normal. This led to inversion of the CD4+ to CD8+ ratio in these cats. In contrast, the T-cell lymphopenia in FeLV-infected cats resulted from decrease in CD4+ and CD8+ cells, which led to a CD4+ to CD8+ ratio within normal limits. Experimentally induced infection with these 2 viruses supported these findings. Infection with FIV induced early (10 weeks after infection), chronic inversion of the CD4+ to CD8+ ratio. In contrast, infection with FeLV did not alter CD4+ to CD8+ ratio in the first 20 weeks after infection.

Jimson weed seed toxicity in cattle.

A subacute experiment was undertaken for 14 days. The results obtained from these studies suggest that: 1) unless a highly Jimson weed seed contaminated feed is ingested (greater than 0.09% of body weight) or force fed, death should be a rare consequence of Jimson weed seed contamination; 2) Jimson weed seed toxicity in cattle as a result of feed contamination appears a self-limiting problem (rumen atony and anorexia prevent further intoxication until the blood levels of alkaloids are reduced to allow normal ruminant intestinal function); 3) cattle may exhibit signs of atropine toxicity at contamination levels of 881 seed/kg of feed or higher; 4) rumen fluid from heifers fed diet containing 4,408 Jimson weed seed had the greatest VFA concentration change from day 0 to 7; 5) in vitro fermentation of diets resulted in no difference in IVDMD values, but VFA concentration values tended to increase with increased concentrations of Jimson weed seed in the diet.

Host-parasite relationships of Zygocotyle lunata (Trematoda) in the domestic chick.

Domestic chicks were infected with Zygocotyle lunata to determine gross and histopathological effects on the caecal tissues, to observe the method of feeding by worms and to examine the effects of crowding on the growth and development of the worm. Caecal weights and dimensions were significantly reduced in infected chicks. Caecal debris, abundant in control chicks, stained positive for proteins, polysaccharides, acid mucopolysaccharides and neutral fats. Caecal debris was rarely seen in infected chicks. The lumen of the intestinal caeca of the worms contained acellular material which showed protease activity and stained positive for proteins, polysaccharides and acid mucopolysaccharides. Histopathological effects of the infection showed a disruption of the architecture of host caecal mucosa, worm to worm attachment, tissue plugs in the worm acetabulum, and an engorgement of host mucosal tissue with erythrocytes. Stunting due to worm crowding was very evident and by 2 weeks post-infection, worms from single-worm infections were sexually mature and more than twice the length of immature flukes obtained from chicks infected with 100-500 cysts.

In vivo and in vitro excystation of Zygocotyle lunata (Trematoda) metacercariae and histochemical observations on the cyst.

Encysted metacercariae of Zygocotyle lunata (Trematoda) excyst within 2 hr postexposure in the lower ileum of the domestic chick. Optimal in vitro excystation of this species occurs following pretreatment of the cyst for 15 min in 1% acidified pepsin, treatment in 0.02 M sodium dithionite (a reductant) for 1 to 2 min and then 2 hr treatment in an excystation medium containing 1% sodium glycocholate plus 1% trypsin in Earle's BSS adjusted to pH 8.8 with tris and maintained at 41 C. The cyst of this species is a dome-shaped hemisphere containing an inner and outer wall. The outer wall contains mainly acid mucopolysaccharides, whereas the inner wall is mainly proteinaceous. The cyst contains a ventral lid which only was visualized during excystation.