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    Protothecosis in four dogs in New Zealand.
    (Taylor and Francis Group, 2023-09-04) Price PSA; Klobukowska HJ; Castillo-Alcala F; Foxwell JA; Orbell GMB; Brown S; Irving AC
    CASE HISTORIES: Medical records of four dogs diagnosed with protothecosis in New Zealand were reviewed. The dogs were aged between 4 and 9 years and three of the four dogs were female. Breeds were one Labrador, one Miniature Schnauzer and two crossbreeds. The reasons for initial veterinary evaluation were a cough and opaque appearance of the right eye (Case 1), diarrhoea (Cases 2 and 3), and cutaneous disease (Case 4). CLINICAL FINDINGS: The ocular signs were characterised by panuveitis, retinal detachment and secondary glaucoma. Gastrointestinal signs included chronic haemorrhagic diarrhoea due to colitis. Three cases had disseminated infection and developed both bilateral, blinding, ocular disease and chronic gastrointestinal disease. Cutaneous signs consisted of draining fistulae over the olecranon, multifocal cutaneous nodules, and ulceration and tracts of the foot pads. Disseminated protothecosis was confirmed by histopathology of biopsied ocular tissues in Cases 1 and 2 and by gastrointestinal biopsies in Case 3. Prototheca spp. were also identified in cytological specimens from Cases 1 and 4 and recovered by culture in Cases 2 and 4. Cutaneous protothecosis was diagnosed in Case 4 initially by cytology and histopathology of skin lesions, and Prototheca zopfii was confirmed by PCR of cultured organisms. TREATMENT AND OUTCOME: Prior to diagnosis of protothecosis, a variety of treatments were prescribed to treat the gastrointestinal and ocular signs. After diagnosis, only Cases 2 and 4 received medication aimed at treating the protothecal infection, which was itraconazole in both cases. Following the progression of clinical signs and concerns about quality of life, all four dogs were euthanised. DIAGNOSIS: Disseminated protothecosis in three dogs, cutaneous protothecosis in one dog. CLINICAL RELEVANCE: Canine protothecosis is rarely reported, despite the ubiquity of the causal algae, and the disease usually carries an extremely grave prognosis when infection is generalised. In New Zealand, protothecosis should be considered as a differential diagnosis in dogs with panuveitis, chorioretinitis or retinal detachment, colitis, or nodular, ulcerative or fistulating cutaneous lesions.
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    Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis
    (y Elsevier Inc on behalf of the American Academy of Allergy, Asthma & Immunology, 4/01/2018) Frei R; Ferstl R; Roduit C; Ziegler M; Schiavi E; Barcik W; Rodriguez-Perez N; Wirz OF; Wawrzyniak M; Pugin B; Nehrbass D; Jutel M; Smolinska S; Konieczna P; Bieli C; Loeliger S; Waser M; Pershagen G; Riedler J; Depner M; Schaub B; Genuneit J; Renz H; Pekkanen J; Karvonen AM; Dalphin J-C; van Hage M; Doekes G; Akdis M; Braun-Fahrländer C; Akdis CA; von Mutius E; O'Mahony L; Lauener RP; Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study group; Protection Against Allergy Study in Rural Environments (PASTURE)/Mechanisms of Early Protective Exposures on Allergy Development (EFRAIM) study group
    BACKGROUND: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. OBJECTIVE: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. METHODS: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. RESULTS: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells. CONCLUSIONS: In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.
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    Identification of biomarkers of colitis to monitor effects of dietary omega-3 polyunsaturated fatty acids in the interleukin-10 gene-deficient mouse model of inflammatory bowel diseases : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Manawatū, New Zealand
    (Massey University, 2016) Berger, Nadja
    Inflammatory bowel diseases (IBD) are characterised by chronic inflammation of the gastrointestinal tract including the colon (colitis). Increased dietary intake of salmon, which is rich in eicosapentaenoic acid (EPA), was well tolerated by IBD patients, leading to a perceived decrease in symptoms. However, better knowledge of the mechanisms by which EPA-rich diets affect IBD severity, and appropriate biomarkers for assessing these effects, are needed for potential targeted nutritional interventions. This dissertation aimed to determine the temporal effects (early (9 weeks of age) vs. established (12 weeks)) of a diet containing 3.7% EPA, and the dose-dependent effects (15% to 45%) of a salmon diet at 12 weeks of age, on the severity of colitis. Molecular responses in colon and/or liver of the interleukin-10 gene-deficient (Il10-/-) mouse model of IBD and healthy mice were assessed. Caecum digesta, urine and blood were mined to identify biomarkers (microbiota, metabolites and genes) of these responses. The EPA diet reduced the severity of colitis only in 12-week-old Il10-/- mice. This response was associated with changes in gene expression associated with lymphocyte function, eicosanoid signalling and peroxisome proliferator-activated receptor gamma signalling. The blood immune cell gene expression profile did not correlate with reduced colitis in these mice, but the urine metabolite profile was related to changes in colonic tryptophan metabolism. The effects of the salmon diets on colitis were dose-dependent in 12-week-old Il10-/- mice. The intermediate amount of salmon (30%) reduced the severity of colitis and lymphocyte-related gene expression, while enhancing genes in metabolic pathways. Tryptophan metabolism was not affected in these mice, but the urinary metabolite profile correlated with effects on hepatic tocopherol metabolism, as shown by reduced abundance of gamma-carboxyethylhydroxychroman glucoside. The abundances of V. akkermansia, Eubacterium spp., and an unclassified Rikenellaceae were further affected in these mice. This is the first report describing molecular responses in the colon and liver of Il10-/- mice fed a salmon diet associated with reduced colitis. Ultimately these responses could be validated for use in humans, and potentially enable management of IBD with diet.
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    The effects of dietary eicosapentaenoic acid and arachidonic acid on gene expression changes in a mouse model of human inflammatory bowel diseases : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Palmerston North, New Zealand
    (Massey University, 2010) Knoch, Bianca
    Nutrigenomics studies the genome-wide influence of nutrients to understand the association between nutrition and human health. Studies in animal models and humans have demonstrated that dietary n-3 polyunsaturated fatty acids (PUFA) from fish oil may be beneficial in inflammatory bowel diseases (IBD). This thesis aimed to test the hypothesis that dietary n-3 PUFA eicosapentaenoic acid (EPA) reduced and n-6 PUFA arachidonic acid (AA) increased colitis in the interleukin- 10 gene-deficient (Il10–/–) mouse model of IBD, and that these PUFA altered the intestinal bacteria community during colitis development using genome-wide expression and bacterial profiling. Using a combined transcriptomic and proteomic approach, the time-course study defined the onset and progression of colitis in Il10–/– mice. Histopathology, transcript and protein changes before and after colitis onset involved in innate and adaptive immune responses suggested delayed remodelling processes in colitic Il10–/– mice and 11 weeks of age as suitable time point to study the effects of dietary PUFA on colitis development. Comparing the transcriptome and proteome profiles associated with colon inflammation of mice fed with the AIN-76A or oleic acid (OA) diet showed that OA was an appropriate control for unsaturated fatty acids in multi-omic studies. The PUFA intervention study indicated that dietary EPA-induced lipid oxidation might have a potential anti-inflammatory effect on inflamed colon tissue partially mediated through activation of peroxisome proliferator-activated receptor alpha (PPARα). Unexpectedly, dietary AA decreased the expression of inflammatory and stress colonic genes in Il10–/– mice. Altered intestinal bacteria community observed in Il10–/– mice before and after colitis onset was associated with the lack of IL10 protein led to changes in intestinal metabolic and signalling processes. Interestingly, dietary EPA and AA seemed to change intestinal bacteria profiles during colitis development. The role of PPARα in the colon was further examined in a concluding study which identified vanin1 as a likely new PPARα-target gene which may also be involved in lipid metabolism. These findings using a state-of-the-art approach combining transcriptomics, proteomics and physiology provide a basis for future research on molecular mechanisms underlying the effects of dietary PUFA, and might contribute to the development of fortified foods that improve intestinal health and wellness.