Antiviral therapy in cats progressively infected with feline leukaemia virus: lessons from a series of 18 consecutive cases from Australia.

BACKGROUND: It is doubtful that any of the treatments proposed for feline leukaemia virus (FeLV) infection are effective, despite the entity being described 60 years ago. METHODS: Eighteen pet cats with progressive FeLV infections were recruited in Australia. One or more antiviral drugs were trialled in 16 cats, while two FeLV-infected cats were not handleable and served as untreated controls. Six cats were administered RetroMAD1™ only (0.5 mg/kg orally twice daily), a commercially available recombinant chimeric protein with proposed antiretroviral activity. Three cats were administered the integrase inhibitor raltegravir only (10-15 mg/kg orally twice daily), a drug used as a component of highly effective antiretroviral therapy for human immunodeficiency virus (HIV-1) infection. Three cats were administered RetroMAD1™ and raltegravir concurrently, and four cats were administered raltegravir and the reverse transcriptase inhibitor zidovudine (AZT, 5 mg/kg orally twice daily) concurrently. FeLV RNA and p27 antigen loads were measured at two timepoints (T1-2 months and T3-5 months) during therapy and compared to baseline (pretreatment) levels, to assess the response to therapy using linear modelling. The median survival time (MST) of the cats from commencement of FeLV treatment to death was also determined and compared between treatments. RESULTS: The MST for the 16 FeLV-positive cats which received antiviral therapy was 634 days, while the MST from FeLV diagnosis to death for the two untreated control cats was 780 days. In cats treated with RetroMAD1™, FeLV viral load decreased from T0 to T1-2 months (median viral load reduced from 1339 × 106 to 705 × 106 copies/mL plasma; P = 0.012), but MST was reduced compared to cats not given RetroMAD1™ (426 days vs 1006 days; P = 0.049). Cats treated with raltegravir and AZT had no significant changes in FeLV viral load over time, but p27 antigen load was decreased from T0 to T3-5 months in cats treated with raltegravir (median p27 antigen level reduced from 50.2% to 42.7%; P = 0.005). All other results were not significantly affected by the treatment provided. Importantly, statistically significant and substantial associations were found between age at FeLV diagnosis and survival time (P = 0.046, R2 = 18.6) and between FeLV viral load at T0 and survival time (P = 0.004, R2 = 44.4). Younger cats, and cats with higher levels of pretreatment FeLV RNA, had reduced survival times. Cats treated with RetroMAD1™ were typically younger (median age 2.0 vs 8.0 years), likely explaining the observed reduction in MST. A significant association was found between FeLV viral load and p27 antigen load at T0 (P = 0.015, R2 = 32.9). CONCLUSIONS: Results from this small case series do not provide convincing support for the use of RetroMAD1™, raltegravir or AZT, alone or in combination, for the treatment of cats progressively infected with FeLV. The changes observed were biologically insignificant. Age and FeLV viral load at diagnosis are useful prognostic markers, and p27 antigen concentration can be used to predict viral load. Larger field trials should be performed examining antiretroviral therapy in FeLV-positive cats with progressive infections, preferably using three or more drugs from at least two classes, as is standard with human antiretroviral therapy. Future studies would be easier in countries with a higher prevalence of FeLV infections than Australia.

The bovine cumulus proteome is influenced by maturation condition and maturational competence of the oocyte.

In vitro maturation (IVM) of oocytes has still a negative impact on the developmental competence of oocytes. Therefore, this study analysed the cumulus proteome of individual cumulus-oocyte complexes (COCs) with and without maturational competence, matured under in vivo or in vitro conditions (n = 5 per group). A novel, ultrasensitive mass spectrometry (MS) based protein profiling approach, using label-free quantification, was applied. The detected cumulus proteome included 2226 quantifiable proteins and was highly influenced by the maturation condition (479 differentially expressed proteins) as well as maturational competence of the corresponding oocyte (424 differentially expressed proteins). Enrichment analysis showed an overrepresentation of the complement and coagulation cascades (CCC), ECM-receptor interaction and steroid biosynthesis in cumulus of COCs that matured successfully under in vivo conditions. Verification of the origin of CCC proteins was achieved through detection of C3 secretion into the maturation medium, with significantly increasing concentrations from 12 (48.4 ng/ml) to 24 hours (68 ng/ml: p < 0.001). In relation, concentrations in follicular fluid, reflecting the in vivo situation, were >100x higher. In summary, this study identified important pathways that are impaired in IVM cumulus, as well as potential markers of the maturational competence of oocytes.

The benefits of exercise in individuals with traumatic brain injury: a retrospective study.

OBJECTIVE: This study examined the benefits of exercise. DESIGN: A retrospective study. SETTING: A community-based sample. PARTICIPANTS: A sample of 240 individuals with traumatic brain injury (TBI) (64 exercisers and 176 nonexercisers) and 139 individuals without a disability (66 exercisers and 73 nonexercisers). MAIN OUTCOME MEASURES: Scales measuring disability and handicap. RESULTS: It was found that the TBI exercisers were less depressed than nonexercising individuals with TBI, TBI exercisers reported fewer symptoms, and their self-reported health status was better than the nonexercising individuals with TBI. There were no differences between the two groups of individuals with TBI on measures of disability and handicap. CONCLUSIONS: The findings suggest that exercise improves mood and aspects of health status but does affect aspects of disability and handicap.