Repeated cisplatin treatments inhibit gastrointestinal motility and induces baroreflex changes and mechanical hyperalgesia in rats.

Cisplatin is a chemotherapy agent known for its neurotoxicity. We evaluated the effect of cisplatin on the gastric emptying (GE), gastrointestinal (GI) transit of liquid, baroreflex function, thermal, and mechanical withdrawal latencies in rats. Cisplatin increased the GE of liquid with doses ≥ 2 mg.kg(-1) by 59.7-77.4%. This GE delay was not present two weeks after the treatment with five doses of cisplatin at 1 mg.kg(-1). Cisplatin also enhanced baroreflex gain possibly by increasing sympathetic activity. Our results demonstrated that cisplatin (2-10 mg.kg(-1)) causes autonomic neuropathy with GI and baroreflex changes and mechanical but not thermal hyperalgesia in rats.

Immunological and pathological responses of red deer resistant or susceptible genotypes, to experimental challenge with Mycobacterium avium subsp. paratuberculosis.

This study aimed to monitor the clinical, immunological and pathological changes in red deer for 49 weeks after experimental oral challenge with Mycobacterium avium subsp. paratuberculosis (MAP) and to assess the heritability of resistance in the offspring of two red stags. Eighteen young deer, which were bred from unselected hinds and sired by two stags resistant (R) or susceptible (S) to paratuberculosis, were challenged with MAP and monitored for 49 weeks. Biopsy samples of the jejunal lymph node were collected at Weeks 4 and 13 and at necropsy after euthanasia of clinically affected animals or when electively killed at Week 49. Three animals (two S and one R) developed clinical disease and were euthanised. The nine S offspring had significantly more severe lesions than the nine R offspring (Mantel-Haenszel Chi-square P=0.017). The average Lesion Severity Score (LSS) of R offspring was 5.9 (mild), and 7/9 had no or very mild lesions. In contrast, the LSS of S offspring averaged 11.7 (severe), and 7/9 had severe lesions. Most of the resistant, but not the susceptible, animals showed evidence of resolving lesions and a reduction in the number of MAP between 13 and 49 weeks after challenge. One R offspring appeared to completely cure itself, and progressed from mild culture-positive paratuberculosis lesions at Week 13 to having no signs of disease or infection 36 weeks later. This study showed significant heritable resistance/susceptibility to paratuberculosis and key differences in immunological responses in the first 3 months after challenge, indicating different paths to relative success or failure to control MAP. In general, R deer had higher IFN-γ levels, low antibody titres and fewer MAP, while S deer had lower IFN-γ levels, higher antibody and more MAP.

Age susceptibility of red deer (Cervus elaphus) to paratuberculosis.

The aim of this study was to measure the relative susceptibility of three age classes of red deer (Cervus elaphus) to the various manifestations of infection and disease states due to Mycobacterium avium subsp. paratuberculosis (MAP) after experimental oral challenge. Three groups of seronegative female deer (30 three-month-old weaners, 20 fifteen-month-old yearlings and 20 adults) received four oral doses of approximately 10(9) colony forming units (cfu) of a bovine strain of MAP. They were monitored for 50 weeks by weighing, blood sampling for immunological assays, skin testing and faecal culturing. Clinically affected animals were promptly euthanised and the remaining deer were killed at the end of the study. Necropsies were carried out and samples of intestine and associated lymph nodes were taken for culture and histopathology from all deer. Ten weaners developed clinical paratuberculosis and were euthanased 20-28 weeks post-challenge (pc). No clinical cases occurred in the yearlings or adults. All 10 clinically affected weaners had severe gross and histopathological lesions typical of paratuberculosis (Johne's disease). At slaughter, gross lesions were seen in the jejunal lymph nodes of 8/17 weaners, 2/19 yearlings, and 0/20 adults. MAP was cultured from samples of the intestine and/or lymph nodes from all 10 clinical cases and from 16/17 weaners, 19/19 yearlings and 18/20 adult hinds at slaughter. Lesion Severity Scores of deer slaughtered 50 weeks pc averaged 4.9, 3.5 and 1.1 for the weaner, yearling and adult groups, respectively. At some time over the course of the trial, 24/28 weaners were antibody positive and immediately prior to slaughter, 13/17 weaners, 15/19 yearlings and 3/20 hinds were antibody positive. There is a strong age-related resistance against clinical disease and subclinical disease, but not to infection with MAP, after heavy oral challenge.