Sionagh Smith | University of Edinburgh (original) (raw)
Papers by Sionagh Smith
Toxicology, 2012
a b s t r a c t Organophosphorus (OP) insecticide self-poisoning is responsible for about one-qua... more a b s t r a c t Organophosphorus (OP) insecticide self-poisoning is responsible for about one-quarter of global suicides. Treatment focuses on the fact that OP compounds inhibit acetylcholinesterase (AChE); however, AChE-reactivating drugs do not benefit poisoned humans. We therefore studied the role of solvent coformulants in OP toxicity in a novel minipig model of agricultural OP poisoning. Gottingen minipigs were orally poisoned with clinically relevant doses of agricultural emulsifiable concentrate (EC) dimethoate, dimethoate active ingredient (AI) alone, or solvents. Cardiorespiratory physiology and neuromuscular (NMJ) function, blood AChE activity, and arterial lactate concentration were monitored for 12 h to assess poisoning severity. Poisoning with agricultural dimethoate EC40, but not saline, caused respiratory arrest within 30 min, severe distributive shock and NMJ dysfunction, that was similar to human poisoning. Mean arterial lactate rose to 15.6 [SD 2.8] mM in poisoned pigs compared to 1.4 [0.4] in controls. Moderate toxicity resulted from poisoning with dimethoate AI alone, or the major solvent cyclohexanone. Combining dimethoate with cyclohexanone reproduced severe poisoning characteristic of agricultural dimethoate EC poisoning. A formulation without cyclohexanone showed less mammalian toxicity. These results indicate that solvents play a crucial role in dimethoate toxicity. Regulatory assessment of pesticide toxicity should include solvents as well as the AIs which currently dominate the assessment. Reformulation of OP insecticides to ensure that the agricultural product has lower mammalian toxicity could result in fewer deaths after suicidal ingestion and rapidly reduce global suicide rates.
The Veterinary Journal, 2012
Equine periodontal disease (EPD) is a common and painful condition, the aetiology and pathology o... more Equine periodontal disease (EPD) is a common and painful condition, the aetiology and pathology of which are poorly understood. To characterise the histopathological lesions associated with EPD, the skulls of 22 horses were assessed grossly for the presence of periodontal disease, and a standard set of interdental tissues taken from each for histopathological examination.
Journal of Veterinary Internal Medicine, 2007
Background: This investigation was prompted by the referral of increasing numbers of young Texel ... more Background: This investigation was prompted by the referral of increasing numbers of young Texel and Beltex rams with ataxia and weakness, or wobbler syndrome.
Journal of Small Animal Practice, 2013
A seven-year-old, ovariohysterectomised female dwarf lop rabbit (Oryctolagus cuniculus) was refer... more A seven-year-old, ovariohysterectomised female dwarf lop rabbit (Oryctolagus cuniculus) was referred with severe swelling and erythema of the mucocutaneous junctions of the lips, nares and vulva. Bilateral, severe periocular dermatitis was also present. Heavy pure growths of a member of the Staphylococcus intermedius group were cultured from nasal and aural swabs and skin biopsies. Other possible differential diagnoses were eliminated by standard tests. The clinical features and histopathological characteristics of the biopsies were most consistent with mucocutaneous pyoderma, a dermatosis previously reported in dogs but not in rabbits. Treatment of the bacterial infection with oral marbofloxacin and topical ofloxacin eye drops together with supportive therapy resulted in resolution of the lesions. To the authors' knowledge, this is the first report of mucocutaneous bacterial pyoderma, similar to mucocutaneous pyoderma of dogs, in a rabbit.
Veterinary Immunology and Immunopathology, 2015
The expression patterns of secreted (MUC2 and MUC5AC) and membrane-tethered (MUC1, MUC4, MUC12 an... more The expression patterns of secreted (MUC2 and MUC5AC) and membrane-tethered (MUC1, MUC4, MUC12 and MUC13) mucins were monitored in healthy pigs and pigs challenged orally with Lawsonia intracellularis. These results showed that the regulation of mucin gene expression is distinctive along the GI tract of the healthy pig, and may reflect an association between the function of the mucin subtypes and different physiological demands at various sites. We identified a specific depletion of secreted MUC2 from goblet cells in infected pigs that correlated with the increased level of intracellular bacteria in crypt cells. We concluded that L. intracellularis may influence MUC2 production, thereby altering the mucus barrier and enabling cellular invasion.
Veterinary research, 2014
Lawsonia intracellularis is an obligate intracellular bacterium, responsible for the disease comp... more Lawsonia intracellularis is an obligate intracellular bacterium, responsible for the disease complex known as proliferative enteropathy (PE). L. intracellularis is associated with intestinal crypt epithelial cell proliferation but the mechanisms responsible are yet to be defined. Microarray analysis was used to investigate the host-pathogen interaction in experimentally infected pigs to identify pathways that may be involved. Ileal samples originating from twenty-eight weaner pigs experimentally challenged with a pure culture of L. intracellularis (strain LR189/5/83) were subjected to microarray analysis. Microarray transcriptional signatures were validated using immunohistochemistry and quantitative real time PCR of selected genes at various time points post challenge. At peak of infection (14 days post challenge) 86% of altered transcripts were down regulated, particularly those involved in maintenance of mucosal integrity and regulation of cell transport. Among the up-regulated t...
Veterinary Immunology and Immunopathology, 2014
Neospora caninum is recognized as a major cause of reproductive losses worldwide but its pathogen... more Neospora caninum is recognized as a major cause of reproductive losses worldwide but its pathogenesis is not completely understood. Immune mediated placental pathology has been reported as being responsible for compromising pregnancy probably due to the adverse effects of exacerbated Th1 type response at the maternal-foetal interface. Different clinical outcomes are known to occur following experimental infections of cattle at different stages of gestation, with foetal death being the most common finding during early gestation, and the birth of live congenitally infected calves following infection later in gestation.
Veterinary Research, 2014
Infection with Neospora caninum stimulates host cell-mediated immune responses, which may be resp... more Infection with Neospora caninum stimulates host cell-mediated immune responses, which may be responsible for placental damage leading to bovine abortion. The aim of this study was to compare immune responses in the bovine placenta, following experimental infection in different stages of pregnancy. Placentomes were examined by immunohistochemistry and inflammation in early gestation was generally moderate to severe, particularly in the placentas carrying non-viable foetuses, whereas it was milder in later stages, mainly characterised by the presence of CD3 + , CD4 + and γδ T-cells. This distinctive cellular immune response may explain the milder clinical outcome observed when animals are infected in later gestation.
Toxicology, 2012
a b s t r a c t Organophosphorus (OP) insecticide self-poisoning is responsible for about one-qua... more a b s t r a c t Organophosphorus (OP) insecticide self-poisoning is responsible for about one-quarter of global suicides. Treatment focuses on the fact that OP compounds inhibit acetylcholinesterase (AChE); however, AChE-reactivating drugs do not benefit poisoned humans. We therefore studied the role of solvent coformulants in OP toxicity in a novel minipig model of agricultural OP poisoning. Gottingen minipigs were orally poisoned with clinically relevant doses of agricultural emulsifiable concentrate (EC) dimethoate, dimethoate active ingredient (AI) alone, or solvents. Cardiorespiratory physiology and neuromuscular (NMJ) function, blood AChE activity, and arterial lactate concentration were monitored for 12 h to assess poisoning severity. Poisoning with agricultural dimethoate EC40, but not saline, caused respiratory arrest within 30 min, severe distributive shock and NMJ dysfunction, that was similar to human poisoning. Mean arterial lactate rose to 15.6 [SD 2.8] mM in poisoned pigs compared to 1.4 [0.4] in controls. Moderate toxicity resulted from poisoning with dimethoate AI alone, or the major solvent cyclohexanone. Combining dimethoate with cyclohexanone reproduced severe poisoning characteristic of agricultural dimethoate EC poisoning. A formulation without cyclohexanone showed less mammalian toxicity. These results indicate that solvents play a crucial role in dimethoate toxicity. Regulatory assessment of pesticide toxicity should include solvents as well as the AIs which currently dominate the assessment. Reformulation of OP insecticides to ensure that the agricultural product has lower mammalian toxicity could result in fewer deaths after suicidal ingestion and rapidly reduce global suicide rates.
The Veterinary Journal, 2012
Equine periodontal disease (EPD) is a common and painful condition, the aetiology and pathology o... more Equine periodontal disease (EPD) is a common and painful condition, the aetiology and pathology of which are poorly understood. To characterise the histopathological lesions associated with EPD, the skulls of 22 horses were assessed grossly for the presence of periodontal disease, and a standard set of interdental tissues taken from each for histopathological examination.
Journal of Veterinary Internal Medicine, 2007
Background: This investigation was prompted by the referral of increasing numbers of young Texel ... more Background: This investigation was prompted by the referral of increasing numbers of young Texel and Beltex rams with ataxia and weakness, or wobbler syndrome.
Journal of Small Animal Practice, 2013
A seven-year-old, ovariohysterectomised female dwarf lop rabbit (Oryctolagus cuniculus) was refer... more A seven-year-old, ovariohysterectomised female dwarf lop rabbit (Oryctolagus cuniculus) was referred with severe swelling and erythema of the mucocutaneous junctions of the lips, nares and vulva. Bilateral, severe periocular dermatitis was also present. Heavy pure growths of a member of the Staphylococcus intermedius group were cultured from nasal and aural swabs and skin biopsies. Other possible differential diagnoses were eliminated by standard tests. The clinical features and histopathological characteristics of the biopsies were most consistent with mucocutaneous pyoderma, a dermatosis previously reported in dogs but not in rabbits. Treatment of the bacterial infection with oral marbofloxacin and topical ofloxacin eye drops together with supportive therapy resulted in resolution of the lesions. To the authors' knowledge, this is the first report of mucocutaneous bacterial pyoderma, similar to mucocutaneous pyoderma of dogs, in a rabbit.
Veterinary Immunology and Immunopathology, 2015
The expression patterns of secreted (MUC2 and MUC5AC) and membrane-tethered (MUC1, MUC4, MUC12 an... more The expression patterns of secreted (MUC2 and MUC5AC) and membrane-tethered (MUC1, MUC4, MUC12 and MUC13) mucins were monitored in healthy pigs and pigs challenged orally with Lawsonia intracellularis. These results showed that the regulation of mucin gene expression is distinctive along the GI tract of the healthy pig, and may reflect an association between the function of the mucin subtypes and different physiological demands at various sites. We identified a specific depletion of secreted MUC2 from goblet cells in infected pigs that correlated with the increased level of intracellular bacteria in crypt cells. We concluded that L. intracellularis may influence MUC2 production, thereby altering the mucus barrier and enabling cellular invasion.
Veterinary research, 2014
Lawsonia intracellularis is an obligate intracellular bacterium, responsible for the disease comp... more Lawsonia intracellularis is an obligate intracellular bacterium, responsible for the disease complex known as proliferative enteropathy (PE). L. intracellularis is associated with intestinal crypt epithelial cell proliferation but the mechanisms responsible are yet to be defined. Microarray analysis was used to investigate the host-pathogen interaction in experimentally infected pigs to identify pathways that may be involved. Ileal samples originating from twenty-eight weaner pigs experimentally challenged with a pure culture of L. intracellularis (strain LR189/5/83) were subjected to microarray analysis. Microarray transcriptional signatures were validated using immunohistochemistry and quantitative real time PCR of selected genes at various time points post challenge. At peak of infection (14 days post challenge) 86% of altered transcripts were down regulated, particularly those involved in maintenance of mucosal integrity and regulation of cell transport. Among the up-regulated t...
Veterinary Immunology and Immunopathology, 2014
Neospora caninum is recognized as a major cause of reproductive losses worldwide but its pathogen... more Neospora caninum is recognized as a major cause of reproductive losses worldwide but its pathogenesis is not completely understood. Immune mediated placental pathology has been reported as being responsible for compromising pregnancy probably due to the adverse effects of exacerbated Th1 type response at the maternal-foetal interface. Different clinical outcomes are known to occur following experimental infections of cattle at different stages of gestation, with foetal death being the most common finding during early gestation, and the birth of live congenitally infected calves following infection later in gestation.
Veterinary Research, 2014
Infection with Neospora caninum stimulates host cell-mediated immune responses, which may be resp... more Infection with Neospora caninum stimulates host cell-mediated immune responses, which may be responsible for placental damage leading to bovine abortion. The aim of this study was to compare immune responses in the bovine placenta, following experimental infection in different stages of pregnancy. Placentomes were examined by immunohistochemistry and inflammation in early gestation was generally moderate to severe, particularly in the placentas carrying non-viable foetuses, whereas it was milder in later stages, mainly characterised by the presence of CD3 + , CD4 + and γδ T-cells. This distinctive cellular immune response may explain the milder clinical outcome observed when animals are infected in later gestation.