-The objectives of the work described in this paper were: (i) to study the outcome of challenging ewes with Mannheimia haemolytica, at different sites of their teats, (ii) to compare the effects of two different isolates of the organism and (iii) to describe the features of the resulting lesions. Thirty-two ewes were used in the study and allocated into one of two groups (A or B, n = 16); they were challenged with one of two isolates of M. haemolytica, respectively, strain ES26L of known pathogenicity or strain VSM08L from the teat duct of a healthy ewe. Each group was further divided into four equal subgroups: the ewes in the A1/B1 subgroups were intramammarily challenged; one teat of the ewes in the A2/B2 subgroups was immersed into a broth-culture of the organisms; one teat of the ewes in the A3/B3 subgroups was inoculated 2 mm-deep, whilst one teat of the ewes in the A4/B4 subgroups was inoculated 6 mm-deep. The animals were monitored clinically, bacteriologically and cytologically before and after challenge; one animal in each subgroup was euthanised 2, 4, 7 and 11 days after challenge. All ewes in the A1/B1 subgroups developed clinical mastitis, whilst of the other animals, only one ewe in each of the A4/B4 subgroups did. Neither of the two strains used was associated with more positive bacteriological or CMT results; the A2/B2 subgroups were associated with less positive results than the A3/B3 and A4/B4 subgroups. In some ewes of the A2/B2 subgroups, mild leucocytic infiltration in the teat was evident; in the ewes of the A3/B3 subgroups, leucocytic infiltration (neutrophils, lymphocytes, plasma cells) was seen, as well as a lymphoid hyperplasia at the border between the teat duct and teat cistern; in ewes of the A4/B4 subgroups, intense subepithelial leucocytic infiltration was the salient feature. No differences were found in the severity of lesions between the two strains used or the three treatments carried out. Although strain VSM08L had been isolated from the teat duct of a healthy ewe, it caused mastitis when inoculated intramammarily; although strain ES26L is of known pathogenicity for the mammary gland, it did not cause clinical mastitis when deposited 2 mm-deep into the teat. These findings point to a protective role of the teat of ewes, which appear to limit bacterial penetration from the teat duct or cistern to the mammary gland. The lymphoid tissue, at the border between the teat duct -teat cistern, may play a significant protective role.

In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn’t assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure. Groups of Sprague Dawley (CD-SD) rats (20 males and 20 females) will be treated with mixtures of pesticides or mixtures of pesticides together with FAs and common consumer product chemicals in 0.0, 0.25 × acceptable daily intake (ADI)/tolerable daily intake (TDI), ADI/TDI and 5 × ADI/TDI doses for 104 weeks. All animals will be examined every day for signs of morbidity and mortality. Clinical chemistry hematological parameters, serum hormone levels, biomarkers of oxidative stress, cardiotoxicity, genotoxicity, urinalysis and echocardiographic tests will be assessed periodically at 6 month intervals. At 3-month intervals, ophthalmological examination, test for sensory reactivity to different types of stimuli, together with assessment of learning abilities and memory performance of the adult and ageing animals will be conducted. After 24 months, animals will be necropsied, and internal organs will be histopathologically examined. If the hypothesis of an increased risk or a new hazard not currently identified from cumulative exposure to multiple chemicals was observed, this will provide further information to public authorities and research communities supporting the need of replacing current single-compound risk assessment by a more robust cumulative risk assessment paradigm.

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BackgroundNicotinamide adenine dinucleotide (NAD+) and its phosphorylated form (NADP+) are key molecules in ubiquitous bioenergetic and cellular signaling pathways, regulating cellular metabolism and homeostasis. Thus, supplementation with NAD+ and NADP+ precursors emerged as a promising strategy to gain many and multifaceted health benefits. In this proof-of-concept study, we sought to investigate whether chronic nicotinamide riboside administration (an NAD+ precursor) affects exercise performance.MethodsEighteen Wistar rats were equally divided in two groups that received either saline vehicle or nicotinamide riboside at a dose of 300 mg/kg body weight/day for 21 days via gavage. At the end of the 21-day administration protocol, both groups performed an incremental swimming performance test.ResultsThe nicotinamide riboside group showed a tendency towards worse physical performance by 35 % compared to the control group at the final 10 % load (94 ± 53 s for the nicotinamide riboside group and 145 ± 59 s for the control group; P = 0.071).ConclusionOur results do not confirm the previously reported ergogenic effect of nicotinamide riboside. The potentially negative effect of nicotinamide riboside administration on physical performance may be attributed to the pleiotropic metabolic and redox properties of NAD+ and NADP+.Electronic supplementary materialThe online version of this article (doi:10.1186/s12970-016-0143-x) contains supplementary material, which is available to authorized users.

-In order to study the effects of sheep teat disorders on the protection of the mammary gland, we used a Mannheimia haemolytica isolate, which did not cause clinical mastitis when deposited into intact teats. In the first experiment, this was deposited into the duct of teats with orf (Group A, n = 5) or papilloma (Group B, n = 3). In the second, teats were chapped and then, the organism was deposited into the duct (Group C, n = 7) or on the skin (Group D, n = 4). Ewes with healthy teats were controls (Group E, deposition into duct, n = 5; Group F, deposition on skin, n = 2). The ewes in Groups A, B or C developed clinical mastitis 5 h later, whilst the ewes in Group D developed it 2 d later; no control ewe developed clinical mastitis. In ewes with teat lesions, the organism was isolated from secretion samples and the California Mastitis Test became positive 5 h after challenge; neutrophils and lymphocytes were seen in Giemsa-stained secretion films from Group A or B ewes, whilst macrophages, neutrophils and lymphocytes in films from Group C or D ewes; neutrophils were predominating in films from Group E or F ewes. Inside the teats of Group A, B, C or D ewes, folds, hyperaemia and mucosal thickness were seen; histologically, subepithelial leucocytic infiltration was seen. In Group A or B ewes, no evidence of lymphoid tissue at the teat duct-cistern border was found. In Group C or D ewes, intense erosion and ulceration of the teat skin and conspicuous lymphoid tissue at the teat duct-cistern border, were evident; lesions characteristic of haemorrhagic mastitis were in the mammary parenchyma. In control ewes, subepithelial leucocytic infiltration in the teat duct and lymphoid tissue as above, were evident. We postulate that teat lesions can be predisposing factor to mastitis, by adversely affecting defences and speeding the process of infection and making it more severe. mastitis / sheep / teat / predisposing factor / orf