SummaryThe stroma as a crucial target in rat mammary gland carcinogenesis

Studies reveal that surface waters worldwide are contaminated with hormonally active agents, many released from sewage treatment plants. Another potential source of aquatic hormonal contamination is livestock feedlot effluent. In this study, we assessed whether feedlot effluent contaminates watercourses by measuring a) total androgenic [methyltrienolone (R1881) equivalents] and estrogenic (17β-estradiol equivalents) activity using the A-SCREEN and E-SCREEN bioassays and b) concentrations of anabolic agents via gas chromatography-mass spectroscopy and enzyme-based immunoassays. Water samples were collected over 3 years from up to six sites [all confluent with the Elkhorn River, Nebraska, USA: a feedlot retention pond (site 1), a site downstream from site 1 (site 2), a stream with intermediate livestock impact (site 3), and three sites with no observable livestock impact (sites 4-6)] and two sources of tap water. In 1999, samples from site 1 contained 9.6 pM R1881 equivalents and 1.7 pM 17β-estradiol equivalents. Site 2 samples had estrogen levels similar to those in site 1 samples but lower androgen levels (3.8 pM R1881 equivalents). Androgen levels in site 3 samples were similar to those in site 2 samples, whereas estrogen levels decreased to 0.7 pM 17β-estradiol equivalents. At site 6, androgen levels were approximately half those found at site 3, and estrogen levels were comparable with those at site 3. Sampling in later years was limited to fewer sites because of drought and lack of permission to access one site. Instrumental analysis revealed estrone but no significant levels of resorcylic acid lactones or trenbolone metabolites. Tap water was devoid of hormonal activity. We conclude that feedlot effluents contain sufficient levels of hormonally active agents to warrant further investigation of possible effects on aquatic ecosystem health. Key words: agricultural runoff, anabolic steroid hormones, aquatic ecosystem health, A-SCREEN, concentrated animal feeding operations (CAFOs), environmental androgens, environmental estrogens, E-SCREEN, personal care products, pharmaceuticals.

There is mounting evidence that the stroma plays a crucial role in mammary gland carcinogenesis. Here, we report that mammary gland stroma from mature and multiparous rats prevents neoplastic development and encourages normal ductal growth of grafted epithelial cancer cells. Fifty thousand epithelial cancer cells were injected into the cleared fat pads of virgin hosts at 24, 52, 80, and 150 days of age and of hosts that had undergone two cycles of pregnancy, lactation, and involution. Six months after inoculation, tumor incidence was 75%, 100%, 50%, and 18.2% in 24-, 52-, 80-, and 150-day-old virgin rats, respectively, and 0% in the twice-parous animals. Most remarkably, these neoplastic cells appeared to form normal ducts in all hosts-Ha-ras-1 mutation served as a marker to identify the tumor origin of the outgrowths. The tumor development pattern suggests a parallel to the phenomenon of age- and reproductive state-dependent susceptibility and resistance to chemical carcinogens. As susceptibility to carcinogenesis decreases, the ability of the stroma to reprogram neoplastic epithelial cells increases. Thus, the neoplastic phenotype is context-dependent, and it therefore offers the intriguing possibility that the process of carcinogenesis is amenable to normalization or cure once the mechanisms of stroma-mediated normalization are elucidated and manipulated.

Background: Thrombocytopenia in dogs is common in critical care medicine, but availability of fresh platelet concentrates in veterinary medicine can be limiting. Lyophilized platelets have long shelf-lives and can be easily transported, stored, and administered in various settings. Objective: To evaluate the efficacy and safety of a novel trehalose-stabilized canine lyophilized platelet product in thrombocytopenic dogs with clinically-evident bleeding. Animals: Eighty-eight dogs with platelet counts <50 × 10 3 /μL and a standardized bleeding assessment tool (DOGiBAT) score ≥2. Methods: Multicenter, randomized, non-blinded, non-inferiority clinical trial comparing dimethyl sulfoxide (DMSO)-stabilized cryopreserved platelet concentrates (CPP) with trehalose-stabilized lyophilized platelets (LP) for control of bleeding in thrombocytopenic dogs. Dogs were randomized to receive 3 × 10 9 platelets/kg of LP or CPP. Primary outcome measures were change in DOGiBAT score, platelet count, need for additional red cell transfusion and all-cause mortality.

SF and PF in dogs spontaneously breathing room air have good correlation, suggesting that SF may be a useful, noninvasive surrogate for PF when assessing oxygenation in canine patients. Further studies are warranted to confirm and validate this relationship in spontaneously breathing and mechanically ventilated dogs on varying levels of FiO2 and to assess the ability of SF to predict outcome.