Resumo: A oclusão e a reperfusão das artérias esplâncnicas provoca alterações locais e sistêmicas derivadas principalmente da liberação de substâncias citotóxicas e da interação entre neutrófilos e células endoteliais. Buscando-se estudar os efeitos da pentoxifilina e da n-acetilcisteína em lesões provocadas em um modelo de isquemia e reperfusão (I/R), 60 ratos foram divididos em 6 grupos: SAL/CONT (salina/controle): animais submetidos à cirurgia, mas não à I/R, tratados com solução fisiológica; SAL/ISQ (salina/isquemia): animais submetidos à oclusão da artéria celíaca (AC), artéria mesentérica cranial (AMCr) e artéria mesentérica caudal (AMCa) durante 30 minutos, seguidos de 120 minutos de reperfusão, tratados com solução fisiológica; PTX/CONT: animais submetidos à cirurgia, mas não à I/R, tratados com pentoxifilina; PTX/ISQ: animais submetidos à I/R, tratados com pentoxifilina; NAC/CONT: animais submetidos à cirurgia, mas não à I/R, tratados com n-acetilcisteína; NAC/ISQ: animais submetidos à I/R, tratados com n-acetilcisteína. Os parâmetros avaliados foram pressão arterial média (PAM) carótida, pressão venosa jugular, fluxo sangüíneo na aorta e na AMCr, temperatura esofágica, hematócrito, hemogasometria, histologia intestinal, dosagem de espécies reativas ao ácido tiobarbitúrico (TBARS) em duodeno, jejuno e íleo e de malondialdeído (MDA) plasmático e do íleo. Nos grupos submetidos à I/R, a PAM teve queda significativa após 120 minutos de reperfusão; a pressão venosa não mostrou alterações no decorrer do experimento; houve queda do fluxo sangüíneo na aorta após os 30 minutos de isquemia, com queda mais acentuada ao final do período de reperfusão; o fluxo sangüíneo na AMCr diminuiu significativamente após 120 minutos de reperfusão, porém, em menor grau no grupo NAC/ISQ; a freqüência... (Resumo completo, clicar acesso eletrônico abaixo). / Abstract: Splanchnic artery occlusion and reperfusion result in local and remote tissue destruction caused by toxic factors released into the circulation and by neutrophil-endothelial cell interactions. In order to evaluate the effects of pentoxifylline (PTX) and n-acetilcysteine (NAC) on ischemia/reperfusion model (I/R), sixty rats were allocated into six groups: 1) SAL/CONT: Sham operation + saline; 2) SALI/ISQ: 30 min celiac, cranial and caudal mesenteric arteries occlusion + 120 min reperfusion + saline; 3) PTX/CONT: Sham operation + PTX (50 mg/kg); 4) PTX/ISQ: I/R + PTX; 5) NAC/SAL: Sham operation + NAC (430 mg/kg) and 6) NAC/ISQ: I/R + NAC. In all groups above mean arterial blood pressure (MABP), vein pressure, aorta and cranial mesenteric artery blood flow, heart rate, esophagus temperature, hematocrit, blood gas determination, histology, thiobarbituric acid reaction species (TBARS) and malondialdehyde (MDA) levels were determined. In I/R groups, MABP decreased significantly 120 minutes after reperfusion (p<0,05); as no difference in vein pressure were observed. Aorta blood flow decreased 30 minutes after ischemia, decreasing dramatically following restoration of blood flow. Cranial mesenteric artery blood flow decreased significantly after reperfusion, although the fall in NAC/ISQ group was attenuated. During the assays, heart rate was reduced, temperature decreased progressively and metabolic acidosis took place. Pentoxiffyline prevented histopathologic signs of injury in duodenum, jejunum and ileum, as well as n-acetilcysteine prevented ileum histopathologic signs of injury. I/R caused TBARS increase in NAC group jejunum and saline group ileum, but no difference was observed in plasmatic and ileal MDA. The present study allowed concluding that PTX was more efficient in preventing histophatologic injury than NAC, but neither PTX nor NAC... (Complete abstract, click electronic address below). / Orientador: Carlos Alberto Hussni / Coorientador: Winston Bonetti Yoshida / Mestre

Made available in DSpace on 2014-06-11T19:30:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-05-26Bitstream added on 2014-06-13T18:40:28Z : No. of bitstreams: 1 goncalvesjunior_i_dr_botfm.pdf: 14978707 bytes, checksum: bc384bf4e8557c0376c390efbcb98d16 (MD5) / Universidade Estadual Paulista (UNESP) / O uso de diferentes inibidores selectivos da COX-2 em vários estudos mostraram resultados conflitantes, relacionados principalmente a uma elevada taxa de deiscências nas suturas intestinal.Basedo na hipótese de que o uso de um antibiótico de largo espectro pode reduzir a carga bacteriana no sítio de lesão e, inversamente, reduzir a migração celular de PMNLs, o objetivo deste estudo foi determinar os efeitos do Paracoxibe, uma droga inibidora da COX- 2,disponível comercialmente, associada ou não ao Imipenem na cicatrização de anastomoses no ileo ecólon de ratos. Trezentos e sessenta e oito ratos brancos Wistar foram submetidos a laparotomia, a transecção do cólon esquerdo e do íleo terminalreanastomose randomizados para receber paracoxibe (0,66 mg / Kg), imipenem (30mg/Kg) ou solução salina (controles) por via intramuscular por 4 dias. Os ratos foram distribuídos em quatro grupos de 92 ratos: Grupo 1 (controle), grupo 2 (Paracoxib), grupo 3 (Imipenem) e grupo 4 (paracoxib / imipenem) Os animais em cada grupo foram sacrificados após 4,7,14 e 21 dias, sendo as anastomoses avaliadas por meio de medidas de força de ruptura e pelo exame histológico do processo de cicatrização. Doze animais do grupo paracoxibe (13%) e oito do grupo paracoxibe / Imipenem (8,7%) foram a óbito no 5° e 7° dia de pós operatóriopor deiscências da anastomose ileal. A força de ruptura nos ratos tratados com paracoxibe foi significativamente menor do que no grupo controle no 7°, 14° e 21° dias de pósoperatório das anastomoses do íleo (87,6 g, 184,3 g e 212,5 g<127,8 g, 243,6 g e 251G , P = 0,026) e no 4°,7°,14° e 21° dias de pós operatório as anastomoses de cólon (139,3 g, 170,4 g, 202,9 g e 299,9 g<203,3 g, 254,3 g, 364,2 g e 401g, p = 0,026). Não houve diferenças significativas entre os grupos paracoxibe, imipenem e paracoxib / imipenem. A tendência de aumento da força de... / The use of different selective COX-2 inhibitors in several studies showed conflicting results, related mostly from a high rate of dehiscence’s on intestinal sutures. Based on the hypothesis that the use of a broad spectrum antibiotic can decrease the bacterial load at the injured site and conversely reduce PMNLs cell migration, the aim of this study was to determine the effects of a new commercially available COX-2 inhibitor Paracoxib, associated or not to Imipenem on the healing of ileal and colonic anastomosis in rats. Three hundred and sixty eight white Wistar rats underwent laparotomy, ileal and left colon transection and reanastomosis and randomized to receive paracoxib (0,66 mg/Kg ), imipenem ( 30mg/Kg) or saline solution ( controls ) by intramuscular injections for 4 days. The rats were distributed in four groups of 92 rats: group1 (control); group 2 ( Paracoxib); group 3 ( Imipenem ) and group 4 (paracoxib/imipenem). Animals in each group were killed after 4,7,14 and 21 days, and the anastomosis evaluated by means of breaking strength measures and by histological examination of the healing process. Twelve animals in paracoxibe group (13% ) and eight on paracoxib/Imipenem group ( 8,7% ) died on on days 5 and 7 related to ileal anastomotic dehiscences. Breaking strength in rats treated with paracoxib was significantly lower than in the control group in post-operative day 7, 14 and 21 in ileal anastomoses ( 87,6g, 184,3g and 212,5g < 127,8g, 243,6g and 251g, p=0.026 ) and on days 4,7,14 and 21 in colonic anastomoses ( 139,3g, 170,4g, 202,9g and 299,9g < 203,3g, 254,3g, 364,2g and 401g, p=0.026 ). There were no significant diferences between imipenem, paracoxib and paracoxib/imipenem treated animals. A tendency of increased breaking strength were observed in paracoxib/imipenem group when compared to imipenem and paracoxib groups. The breaking strength increased progressivelly ... (Complete abstract click electronic access below)

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-03-29T14:52:20Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_BARBARA COSTA PAULINO_Agosto2016.OFICIAL.pdf: 2162827 bytes, checksum: e76b8cfadd5a941840853d352a5bc159 (MD5) / Made available in DSpace on 2017-03-29T14:52:20Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_BARBARA COSTA PAULINO_Agosto2016.OFICIAL.pdf: 2162827 bytes, checksum: e76b8cfadd5a941840853d352a5bc159 (MD5) Previous issue date: 2016-05-20 / CNPQ / A dieta ocidentalizada, rica em lipídeos, açúcar, sódio e alimentos processados e ultra processados tem sido apontada como um dos mais relevantes fatores associados ao excesso de peso/obesidade, comorbidades e distúrbios fisio-metabólicos observados em estudos epidemiológicos e experimentais em animais. O objetivo do presente estudo foi investigar os efeitos do soro de leite de cabra sobre o estado nutricional, microbiota, histologia intestinal e parâmetros bioquímicos de ratas e filhotes alimentados com dieta ocidentalizada. Foram utilizados 8 machos e 24 fêmeas da linhagem Wistar (da colônia do Departamento de Nutrição da Universidade Federal de Pernambuco) para o acasalamento dos animais. Ratas gestantes foram divididas em quatro grupos experimentais de acordo com a dieta: Controle ou Ocidentalizada e a suplementação ou não com soro de leite de cabra. Evolução ponderal e consumo alimentar das ratas seguiram por todo experimento. Ao desmame, as ratas e metade da prole de machos de cada ninhada foram eutanasiados para análise dos parâmetros bioquímicos, histologia intestinal, micro-organismos fecais. Metade dos filhotes foi submetida aos mesmos acompanhamentos e eutanasiados aos 45 dias de vida. A suplementação com soro de leite de cabra modificou poucos parâmetros nas ratas com exceção da alteração da quantidade de lactobacilos totais, que nos grupos controles com solução salina apresentaram uma média de 7,34±0,08 log.UFC/g-1 e 6,43±0,31 log.UFC/g-1 e no suplementado 7,79±0,30 log.UFC/g-1 e 6,94±0,45 log.UFC/g-1 para ratas com dieta ocidentalizada e padrão, respectivamente. Nos filhotes, a suplementação com soro de leite de cabra promoveu redução no ganho de peso e dos depósitos de gordura abdominal, alteração bioquímica, aumentou em 15% a contagem de lactobacilos e em 13% as enterobactérias. Além disso, minimizou o desgaste de células intestinais, limitando o processo inflamatório observado nos alimentados com dieta ocidentalizada. Dessa forma, pode-se sugerir que o soro de leite teve potencial efeito na microbiota fecal e morfologia intestinal, e que esses efeitos parecem depender da idade e do período de suplementação. / The westernized diet rich in fat, sugar, sodium and processed foods and processed ultra has been identified as one of the most important factors associated with overweight / obesity, comorbidities, and physiological and metabolic disorders observed in epidemiological and experimental studies in animals. The aim of this study was to investigate the effects of serum of goat milk on the nutritional status, microbiota, intestinal histology and biochemical parameters of rats and offispring fed westernized diet. Were used 8 male and 24 female Wistar (the colony of the Department of Nutrition at the Federal University of Pernambuco) for mating of animals. Pregnant rats were divided into four groups according to the diet: control or Westernized and supplemented or not with serum from goat milk. weight gain and food consumption of rats followed throughout the experiment. At weaning, rats, half male offspring in each litter were sacrificed for analysis of biochemical parameters, intestinal histology, faecal micro-organisms. Half of the pups was subjected to the same accompaniments and euthanized at 45 days of life. Supplementation with goat whey modified few parameters in rats with the exception of changing the amount of total lactobacilli that in control groups with saline had a mean of 7,34 ± 0,08 log.UFC/g-1 and 6, 43 ± 0,31 log.UFC/g1 and supplemented 7,79±0,30 log.UFC/g-1 and 6,94 ± 0,45 log.UFC/g-1 to rats with westernized diet and standard, respectively. In puppies, supplementation with goat whey promoted reduction of 200% in weight gain and deposits of abdominal fat, biochemical change, increased by 15% to lactobacillus count and 13% enterobacteria. In addition, minimized wear of intestinal cells by limiting the inflammatory process observed in fed westernized diet. Thus, it can be suggested that the whey had potential effect on fecal microbiota and intestinal morphology, and that these effects appear to depend on the age and supplementation period.

Made available in DSpace on 2014-07-29T15:13:44Z (GMT). No. of bitstreams: 1 Tese2011_Luciana_Bradstetter.pdf: 2039765 bytes, checksum: fc789f9ab9e7cf36309b7d69f8c21304 (MD5) Previous issue date: 201-11-18 / Mechanic obstruction of blood vessels that irrigate the intestine leads to ischemia and intense reduction of oxygenation and tissue perfusion. If oxygenated blood flow returns abruptly to tissues before cellular death reperfusion injury occurs; this can be initiated by several mechanisms resulting in inflammatory response. Intestinal ischemia/reperfusion (I/R) injury has been widely associated to cell necrosis, although another distinct biochemical and morphological type of cell death, called apoptosis, is involved. Such conditions are mediated by signaling molecules in cellular surface, which lead to long term changes in gene expression. In the majority of cells, MAP (Mitogen Activated Protein) kinases (MAPK), which are part of a group of cytoplasmic enzymes, will transmit mitogenic and cell differentiation signs. Three MAPK that have been identified in mammalian cells participate in the signaling pathway: ERK, p38 and JNK. Activated p38 and JNK are usually related to apoptosis, while activated ERK 1/2 (P44/42) have a protection function inhibiting apoptosis. With the purpose of minimizing reperfusion injury after liver transplant, Carolina Rinse Solution (CRS) was designed by North Carolina University, USA. Although this solution has been used in horses to attenuate I/R injury in horse intestine, little is known about the eventual tissue protection mechanism. The present study aimed to investigate the effects of topical and intraluminal CRS in I/R injury, and the activation profile of p38 and ERK 1/2 MAPK, in rabbit jejunum. Fifteen New Zealand rabbits were allocated to three groups: Sham-operated (A), Ischemia and reperfusion (B) and CRS (C). Groups B and C were subjected to one hour of jejunal ischemia and two hours of reperfusion. In group C, ten minutes prior to reperfusion, the bowel lumen was filled with CRS, and the segment was immersed in CRS until reperfusion onset. Changes such as degeneration, necrosis, edema, hemorrhage, PMN infiltration and margination were not significantly different between groups B and C, showing that topical and intraluminal CRS did not attenuate deleterious effects of I/R in small intestinal of rabbits. I/R stimulated the phosphorylation of p44/42 MAPK and p38 MAPK pathways in some layers of jejunum. Progressive activation of p44/42 MAPK was chiefly localized to the crypts of Lieberkühn, circular and longitudinal muscle layers, whereas p38 MAPK was prominently activated in myenteric plexus and both muscle layers. All layers that did respond to I/R insult with activation increase of ERK 1/2 and p38, in all groups, showed low baseline phosphorylation levels as compared to those that did not react to the insult. The results of this work indicate that topical and intraluminal CRS does not interfere in ERK 1/2 and p38 activation profile in rabbit jejunum subjected to I/R. / A obstrução mecânica de vasos sanguíneos que irrigam o intestino leva à isquemia, com redução na oxigenação e perfusão teciduais. Se o fluxo sanguíneo oxigenado retorna aos tecidos bruscamente antes da morte celular, ocorre a chamada injúria de reperfusão, a qual pode ser iniciada por vários mecanismos, levando a uma resposta inflamatória. A injúria de isquemia e reperfusão (I/R) tem sido amplamente associada à necrose celular, apesar de um tipo bioquímico e morfológico distinto de morte celular, chamada de apoptose, também esteja envolvida. Tais processos são mediados por moléculas de sinalização na superfície das células, as quais levam a mudanças na expressão dos genes. Na maioria das células, as MAP (Mitogen Activated Protein) quinases (MAPK), as quais são parte de um grupo de enzimas citoplasmáticas, transmitem os sinais mitogênicos e de diferenciação. Três MAPK que foram identificadas em células de mamíferos participam do mecanismo de sinalização: ERK, p38 e JNK. As MAPK p38 e JNK ativadas normalmente estão associadas à apoptose, enquanto ERK 1/2 (P44/42) ativada tem função de inibição da apoptose. Com o propósito de minimizar a injúria de reperfusão após o transplante de fígado, a solução de Carolina Rinse (CRS) foi desenvolvida pela Universidade da Carolina do Norte nos EUA. Essa solução tem sido utilizada para minimizar os efeitos da I/R em intestino de eqüinos, mas pouco se sabe do seu possível mecanismo de ação protetora. O presente estudo objetivou investigar os efeitos do uso tópico e intraluminal da CRS na injúria de I/R e no perfil de ativação das MAPK p38 e ERK 1/2 no jejuno de coelhos. Quinze coelhos da raça Nova Zelândia foram alocados em três grupos: Instrumentado (A), Isquemia e reperfusão (B) e CRS (C). Os grupos B e C foram submetidos a uma hora de isquemia e duas horas de reperfusão de jejuno. No grupo C, dez minutos antes da reperfusão, o lumen do segmento foi preenchido com CRS e o mesmo foi imerso em CRS até o início da reperfusão. Mudanças como degeneração, necrose, edema, hemorragia, infiltrado e marginação de PMN não foram significativamente diferentes entre os grupos B e C, o que mostra que o uso tópico e intraluminal da CRS não atenuou os efeitos deletérios da I/R no intestino delgado de coelhos. A I/R estimulou a fosforilação das MAPK p44/42 e p38 em algumas camadas do jejuno. A ativação progressiva de p44/42 ocorreu principalmente nas criptas de Lieberkühn e nas camadas musculares circular e longitudinal, enquanto a MAPK p38 foi ativada principalmente no plexo mioentérico e em ambas as camadas musculares. Todas as camadas que responderam ao insulto da I/R com aumento da ativação de ERK 1/2 e p38, em todos os grupos, apresentaram baixos níveis basais de fosforilação, quando comparados àquelas que não responderam ao insulto. Os resultados desse estudo indicam que o uso tópico e intraluminal da CRS não interfere no perfil de ativação de ERK 1/2 e p38 no jejuno de coelhos submetidos à I/R.

Introdução: O dióxido de titânio (TiO2) é um corante encontrado na forma de partículas em diversos produtos industrializados. Muitos estudos, a maioria envolvendo o trato respiratório, alertam sobre os efeitos prejudiciais advindos da exposição ao TiO2. Embora partículas da dieta, tais como o TiO2, sejam ingeridas diariamente, ainda existem poucos estudos investigando seus efeitos sobre o trato gastrointestinal. Objetivos: O objetivo principal desse trabalho é investigar a ação de nano (NP) e micropartículas (MP) de TiO2 sobre a resposta inflamatória no intestino delgado de camundongos. Material e Métodos: Camundongos Bl 57/6 foram divididos em 2 grupos experimentais, os quais receberam NP TiO2 (66 nm) ou MP TiO2 (260 nm) a uma dose de 100 mg/Kg/dia, e um grupo controle, o qual recebeu água destilada. O tratamento foi administrado por gavagem, durante 10 dias, uma vez ao dia. Ao final, o intestino delgado foi coletado para a análise de citocinas (IL-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, TNFa, IFNg e TGFb) por ELISA e quantificação de células T CD4+, T CD8+, células dendríticas e natural killers por imunohistoquímica. Resultados: Os resultados demonstram maior concentração de citocinas IL-12, TNFa, IFNg, IL-4, IL-23 e TGFb, e células T CD4+ nos grupos que receberam TiO2. O aumento de citocinas foi mais importante no íleo, onde há maior concentração de células M, as quais representam a principal via de captação de partículas no intestino. Conclusão: As partículas de TiO2 provocaram uma resposta pró-inflamatória, predominantemente do tipo Th1, no intestino delgado dos camundongos, especialmente no íleo. Esses dados representam uma evidência in vivo do potencial inflamatório de partículas de TiO2 sobre o trato gastrointestinal / Introduction: Titanium dioxide (TiO2) is a white pigment widely found as micro and nano-sized particles added to food, drugs, cosmetics, etc. Studies involving the pulmonary tract warn about adverse effects resulting from exposure to TiO2, emphasizing its inflammatory potential. Although the gastrointestinal tract is considerably exposed to TiO2 particles at daily basis there are few information regarding its adverse effects on intestine. Objectives: We aimed to investigate the effects of TiO2 nanoparticles (NP) and microparticles (MP) on inflammatory response in the small intestine of mice. Methods: Bl 57/6 mice received suspensions containing TiO2 (100 mg/Kg/day) as TiO2 NP (66 nm), or TiO2 MP (260 nm) by gavage for 10 days, once a day; control group received only distilled water. At the end of the treatment, the small intestine were extracted for assessment of cytokines (IL-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, TNFa, IFNg e TGFb) by ELISA and quantification of inflammatory cells (T CD4+, T CD8+, dendritic cells, and natural killer) by immunohistochemistry. Results: We found increased levels of T CD4+ cells and cytokines (IL-12, TNFa, IFNg, IL-4, IL-23, and TGFb) on groups receiving TiO2 when compared to control group. Cytokines production was more important on the ileum, local presenting greater concentration of M cells, which represent the main pathway of particles uptake on gut. Conclusion: Our findings indicate that TiO2 particles induce a Th1 mediated inflammatory response on small bowel in mice. These results represent an in vivo evidence of the inflammatory potential of TiO2 particles on the gastrointestinal tract

This study evaluated the changes in body composition, glycogen tissue reserves, visceral organ growth, and small intestine morphology in the young pig. A total of 96 crossbred pigs were euthanized at birth (pre-suckle), days 1, 2, 3, 5, 7, 14 postpartum, weaning at day 21, and days 1, 2, 3, 5, 7, 14, 28, and 42 post-weaning. Body composition of the pig had increasing dry matter and fat, decreasing ash, calcium and phosphorus, and relatively static protein percentage over the course of the study. Liver and muscle glycogen was greatest at birth. Following birth and weaning there was a distinct decrease in the amount of liver glycogen, while there was only a clear decrease in muscle glycogen at birth. Absolute measures of the visceral organs increased in a variety of manners (linear, quadratic and/or cubic); relative measures of visceral organs responded in different manners to increasing age. In the suckling period, villous height, villous height:crypt depth ratio, and goblet cell count was greater than in the post-weaning period. Crypt depth continued to increase through the entire study. Villi measurements of the middle and distal portion of the small intestine taken via scanning electron microscope, revealed different responses to increasing age, but numerically, villi width increased, villi density, enterocyte width, and microvilli density decreased, and microvilli diameter was relatively static. Villi, on average, increased the absorptive area of the small intestine 18 fold and microvilli increased the surface area on average 400 fold. This study provided a vast amount of biometric information on the development of the young pig from birth to 42 d post weaning.

As one of the most common medications, it is reasonable to assume that the adverse effects from nonsteroidal anti-inflammatory drugs (NSAIDs) are well understood. While this is the case for NSAID-induced gastropathy, NSAID-induced enteropathy is often clinically overlooked and has a pathogenesis that is incompletely understood. The goal of this study was to determine how alterations in the microbiota impact NSAID-induced intestinal injury. Initial studies explore how gastric acid secretion suppression substantially decreases Bifidobacteria in the small intestine, and emphasize how replenishment of these bacteria results in an amelioration of NSAID-induced enteropathy. Follow-up studies involved pretreating rats with specific bacteria that have conferred protection in other models of small intestinal injury. We examined the role that acetate may play in reducing the damage by evaluating bacteria that had an acetate production gene knocked out via homologous recombination. Protection levels were similar between wildtype and knockout bacteria, and it did not appear that acetate had a key role in damage reduction. Moreover, we found that changes in intestinal damage were dependent not only on the strain of bacteria used but also on the NSAID administered. None of the bacterial pretreatments tested protected against indomethacin- or diclofenac-induced small intestinal injury, and pretreatment with one specific bacterial strain resulted in a significant worsening of damage. To gain further insight as to the potential role of the microbiota in exacerbation of injury, we conducted studies using single antibiotics and antibiotic cocktails. No single antibiotic treatment conferred protection against naproxen-induced small intestinal injury, but an antibiotic cocktail decreased damage scores by ~46%. Furthermore we explored the effects of L-lactic acid supplementation of drinking water but this was unable to reduce naproxen-induced intestinal damage. Collectively, the work presented in this thesis provides novel insights on the relationship between alterations in the microbiota and susceptibility to NSAID-induced enteropathy. / Dissertation / Doctor of Philosophy (Medical Science)

yes / Background: Oral administration of purified omega-3 (ω-3) PUFAs is associated with changes to the fecal microbiome. However, it is not known whether this effect is associated with increased PUFA concentrations in the gut. Objectives: We investigated the luminal bioavailability of oral ω-3 PUFAs (daily dose 1 g EPA and 1g DHA free fatty acid equivalents as triglycerides in soft-gel capsules, twice daily) and changes to the gut microbiome, in the ileum. Methods: Ileostomy fluid (IF) and blood were obtained at baseline, after first capsule dosing (median 2 h), and at a similar time after final dosing on day 28, in 11 individuals (median age 63 y) with a temporary ileostomy. Fatty acids were measured by LC–tandem MS. The ileal microbiome was characterized by 16S rRNA PCR and Illumina sequencing. Results: There was a mean 6.0 ± 9.8-fold and 6.6 ± 9.6-fold increase in ileal EPA and DHA concentrations (primary outcome), respectively, at 28 d, which was associated with increased RBC ω-3 PUFA content (P ≤ 0.05). The first oral dose did not increase the ileal ω-3 PUFA concentration except in 4 individuals, who displayed high luminal EPA and DHA concentrations, which reduced to concentrations similar to the overall study population at day 28, suggesting physiological adaptation. Bacteroides, Clostridium, and Streptococcus were abundant bacterial genera in the ileum. Ileal microbiome variability over time and between individuals was large, with no consistent change associated with acute ω-3 PUFA dosing. However, high concentrations of EPA and DHA in IF on day 28 were associated with higher abundance of Bacteroides (r2 > 0.86, P < 0.05) and reduced abundance of other genera, including Actinomyces (r2 > 0.94, P < 0.05). Conclusions: Oral administration of ω-3 PUFAs leads to increased luminal ω-3 PUFA concentrations and changes to the microbiome, in the ileum of individuals with a temporary ileostomy.

The use of computed tomography in patients with gastrointestinal disease is increasing. However, the triple-phase computed tomographic angiographic appearance of the canine small intestine and the effects that phase of contrast enhancement and plane of reconstruction have on the appearance of the small intestine have not been fully evaluated. The purposes of this study were to investigate these effects on the appearance of the small intestinal wall. The minimal and maximal small intestinal diameter, wall thickness, number of wall layers identified, and degree of mucosal enhancement were recorded. The plane of reconstruction did not have any significant effects on wall thickness, diameter, degree of mucosal enhancement, or number of wall layers identified. There was a positive association between body weight and intestinal diameter. The arterial phase demonstrated the greatest mucosal enhancement and number of wall layers identified. The transverse plane was subjectively the most useful for evaluation of the small intestines.

The F-strain of Mycoplasma gallisepticum (FMG) is commonly used in vaccination programs to displace infections by more virulent natural or wild type Mycoplasma gallisepticum strains. However, a better understanding of the mechanisms responsible for altered egg production (EP) and egg quality in commercial layers infected with FMG is important, as these alterations can cause economic loss to the United States layer industry. This study was designed to examine potential mechanism(s) responsible for alterations in EP and egg quality by FMG-inoculation. The effects of FMG on production parameters and physiological characteristics of commercial laying hens were evaluated. In isolation units, 12 wk FMG inoculation delayed onset of lay approximately one wk, decreased overall EP, and decreased EP 34 wk post-inoculation. A 12 wk FMG inoculation also resulted in a higher incidence of fatty liver hemorrhagic syndrome, ovarian follicular regression, and decreased isthmal and vaginal proportions of the reproductive tract. Ovarian regression may be related to retarded production (liver), transport (blood), and/or uptake (ovary) of yolk particles. Changes in blood characteristics (i.e. lipid composition) with FMG colonization of the liver may become manifest through changes in egg constituents. As evidenced through changes in the relative weights of various reproductive organs, colonization of these organs by FMG, in addition to the liver, may also be a cause of the effects observed on EP. Increases in hematocrit, serum triglycerides, and plasma protein between 8 and 10 wk post FMG-inoculation, suggest that the initial weeks of EP are stressful. Post-peak decreases in these same variables suggest a more chronic inhibition on lipid and protein synthesis in the liver. Decreased blood lipid concentration may be directly responsible for the reductions in yolk lipid, cholesterol, and fatty acid deposition in 12 wk FMG-inoculated hens. Dual adverse effects in the caged layer facility on feed conversion and egg mass were realized in 22 wk FMG-inoculated birds. In contrast, a 12 wk FMG inoculation delayed onset of lay without a loss in total EP or egg mass. Therefore, inoculation with FMG at 12 wk is more practical and cost effective. Higher degrees of physiological stress experienced by hens in a caged layer facility may exacerbate the effects of FMG inoculation seen in the isolation units. These data demonstrate that alterations in performance and egg characteristics of commercial layers inoculated with FMG at either 12 or 22 wk of age and housed in either isolation units or caged layer facilities are related to mutual functional disturbances in the blood, liver, ovary, and oviduct without concomitant intestinal changes.