Orientador: Gervásio Henrique Bechara / Banca: Hélio José Montassier / Banca: Osvaldo Augusto Brasil Esteves Sant'Anna / Resumo: No hospedeiro bovino o nível de resistência ao carrapato Rhipicephalus (Boophilus) microplus varia de acordo com a raça sendo os fenótipos contrastantes herdáveis. O presente trabalho explora esses fenótipos a fim de estabelecer os perfis das respostas imunes, humoral e inflamatória, correlacionados com resistência em raça zebuína (Nelore) e susceptibilidade em raça taurina (HPB). Os animais foram expostos a infestação natural pelo R.(B.) microplus e amostras de soros foram coletadas em pontos estratégicos da cinética das infestações. Os níveis de imunoglobulinas totais (IgG1 e IgG2), bem como os de anticorpos IgG1, IgG2 e IgE anti-extrato de ovo, anti-extrato de larva não alimentada e anti-saliva foram determinados. Elementos da resposta inflamatória, como as principais proteínas de fase aguda e óxido nítrico, também foram dosados. Os resultados obtidos mostram que as infestações muito intensas, em hospedeiros suscetíveis, são capazes de modular os níveis séricos de IgG1 e IgG2 total, diminuindo-os significativamente em relação aos níveis observados durantes infestações menores. Também modulam negativamente a produção de todos os anticorpos específicos IgG1 e IgG2 avaliados a nível sistêmico. Bovinos susceptíveis ao carrapato produzem níveis mais altos de anticorpos IgE para todos os antígenos. O fenótipo susceptivel de infestação se diferencia pela maior freqüência do alótipo de IgG?2a, herdado por herança Mendeliana co-dominante. Animais suscetíveis, quando infestados, produzem níveis mais altos da proteína de fase aguda a1- glicoproteína ácida, de padrão anti-inflamatório, enquanto que animais resistentes produziram relativamente mais proteínas de fase aguda pró-inflamatórias, haptoglobina e amilóide sérica A. Em ambas as raças não houve diferença nos níveis de transferrina e óxido nítrico sistêmico, porém a produção de ambos é influenciada pelos níveis de infestação. / Abstract: In bovine hosts resistance to the cattle tick, Rhipicephalus (Boophilus) microplus, varies according to the breed, being the phenotypes of infestations inherited. The present work exploits these contrasting phenotypes in order to determine the profile of the humoral, inflammatory and acute phase responses that are correlated with resistance seen in a zebuine breed (Nelore) and susceptibility seen in a taurine breed (Holstein). Bovines were exposed to natural infestations with R.(B.) microplus and they presented, as expected, different levels of infestation that also varied in intensity according to the season of the year. Samples of sera were collected at strategic points during the kinetics of different cycles of infestations. The levels of total serum IgG1 and IgG2 immunoglobulins, as well as those of IgG1, IgG2 and IgE anti-egg extracts, anti-unfed larvae extracts and anti-saliva antibodies were measured. Components of the inflammatory response, nitric oxide, as well as acute phase proteins, were also measured. The results show that very intense infestations in ticksusceptible bovines modulate the serum levels of IgG1 and IgG2, which are significantly diminished relative to those observed during less intense infestations. Intense infestations also modulate the production of all specific IgG1 and IgG2 antibodies. Susceptible animals produced more specific IgE, suggesting that this isotype does not participate in resistance against ticks. The susceptible cattle also have a higher frequency of IgG?2a , which are encoded by Mendelian co-dominant alleles. When infested susceptible animals produced higher levels of the anti-inflammatory acute phase protein, a1-acid glycoprotein, whereas resistant animals produced relatively higher levels of the pro-inflammatory proteins, haptoglobin and serum amyloide A. / Mestre

Neste trabalho foram estudados os perfis renal, hepático, energético, hormonal e de proteínas de fase aguda (proteinograma) para avaliar possíveis interações com o desempenho reprodutivo em bovinos. Para isso, foram delineados três experimentos. No experimento 1 o objetivo foi verificar se a inseminação artificial (IA) causa alterações nos perfis renal, hepático, energético, hormonal e de proteínas de fase aguda e estudar as relações entre esses perfis e a hemodinâmica uterina. Foram utilizadas amostras de sangue de vacas Nelore que foram inseminadas (GIA, n=9) ou não (GC, n=9). As amostras foram coletadas 30 horas antes da IA, 4, 24, 48 e 168 horas após a IA. No experimento 2 o objetivo foi estudar os efeitos da qualidade do sêmen sobre o perfil hepático e proteinograma, e estudar a relação dos perfis renal, hepático, energético, hormonal e proteinograma sobre a vascularização uterina. Foram utilizadas amostras sanguíneas de 362 vacas, que foram divididas em três grupos experimentais de acordo com a qualidade do sêmen: Boa (n=121), Média (n=121) e Regular (n=120). As amostras foram coletadas 30 horas antes da IA, 4 e 24 horas após a IA. Por fim, o experimento 3 é um estudo retrospectivo, realizado com o objetivo de comparar os perfis renal, hepático, energético, hormonal, e proteínas de fase aguda entre animais prenhes e vazios após a IA, e verificar se há relação entre a hemodinâmica uterina e a fertilidade. Neste experimento, os animais foram divididos em dois grupos experimentais de acordo com o resultado da IA (prenhe, n=76 X vazia, n=45). Em todos os experimentos, nos mesmos momentos da coleta de sangue, foram realizadas avaliações ultrassonográficas do útero no modo color Doppler e espectral. As amostras dos experimentos 1, 2 e 3 foram submetidas à quantificação das proteínas de fase aguda e dos componentes metabólicos utilizando analisador bioquímico automático (RX Daytona) e à dosagem hormonal, pela técnica de radioimunoensaio. Os dados foram analisados pelo PROC MIXED (SAS, versão 9.2, 2010). Foram consideradas diferenças estatísticas quando P<0,05. No experimento 1, os grupos não diferiram quanto aos perfis renal, hepático, energético, hormonal e proteinograma, no entanto, o RI apresentou correlações positivas com AST e BHB e correlação negativa com estradiol. O estradiol também foi correlacionado com EV, entretanto essa correlação foi positiva. No experimento 2, os animais inseminados com sêmen B, M ou R apresentaram concentrações semelhantes das variáveis do perfil hepático e proteínograma. O RI foi correlacionado positivamente com colesterol, HDL, LDL, e progesterona, e negativamente com glicose, estradiol, albumina e proteína total. Já o EV apresentou correlações negativas com ureia, GGT e cortisol. No experimento 3, os grupos Vazio e Prenhe foram semelhantes quanto aos perfis renal, hepático, energético, hormonal, proteiograma e hemodinâmica uterina. Sendo assim, conclui-se que o processo da IA e a qualidade do sêmen utilizado não causam alterações sistêmicas, bem como a fertilidade não pode ser explicada por estas alterações. Adicionalmente, a hemodinâmica uterina é correlacionada com diversos parâmetros, no entanto, o padrão vascular do útero não mostrou relação com a fertilidade / In this study, were evaluated kidney, liver, energy, hormonal and acute phase proteins profiles to evaluate the possible interactions with the reproductive performance in cattle. For this, three experiments were designed. In experiment 1 the objective was to verify if artificial insemination (AI) causes changes in renal, liver, energetic, hormonal and acute phase proteins profiles and to study the relationship between these profiles and uterine hemodynamics. Blood samples from inseminated (GIA, n = 9) or non inseminated Nellore cows (CG, n = 9) were used. Samples were collected 30 hours before AI, 4, 24, 48 and 168 hours after AI. In experiment 2 the objective was to study the effects of semen quality on liver and protein profiles and study the relationship of renal, liver, energetic, hormonal and protein profiles on uterine vascularization. Blood samples of 362 cows were used, which were divided into three groups according to semen quality: Good (n = 121), medium (n = 121) and Regular (n = 1200. Samples were collected 30 hours before AI, 4 and 24 hours after AI. Finally, experiment 3 is a retrospective study, carried out in order to compare the renal, liver, energetic, hormonal, and acute phase proteins profiles between pregnant and non pregnant animals after AI, and check for relationship between uterine hemodynamics and fertility. In this experiment, animals were divided into two groups according to the result of AI (pregnant, n = 76 and non pregnant, n = 45). In all experiments, at the same time of blood sampling were performed sonographic evaluations of the uterus in color Doppler and spectral mode. The samples of experiments 1, 2 and 3 were subjected to quantification of acute phase proteins and metabolic components using automatic biochemical analyzer (RX Daytona) and to hormone dosage, by radioimmunoassay. Data were analyzed using PROC MIXED (SAS, version 9.2, 2010). Statistics differences were considered when P<0,05. In experiment 1, the groups did not differ about kidney, liver, energetic, hormonal and protein profiles, however, the RI showed positive correlations with AST and BHB and negative correlation with estradiol. Estradiol was also correlated with EV, however this correlation was positive. In experiment 2, the animals inseminated with semen B, M or R showed similar concentrations of the variables of liver and proteinogram profiles. The RI was positively correlated with cholesterol, HDL, LDL, and progesterone, and negatively with glucose, estradiol, albumin and total protein. EV showed negative correlations with urea, GGT and cortisol. In Experiment 3, the non pregnant and pregnant groups were similar about kidney, liver, energetic, hormonal, proteiogram profiles and uterine hemodynamics. Thus, in this study were not observed systemic changes caused by AI process and by quality of semen, and systemic differences did not notice is between non pregnant and pregnant animals. Additionally, uterine hemodynamic is correlated with various parameters, however, the vascular pattern of the uterus was not correlated with fertility

<p>In the present studies, aspects of some disease activity measures in rheumatoid arthritis (RA) have been investigated, including the effect of glucocorticoids on this activity. In RA, serum interleukin(IL)-6 levels were elevated and were shown to have a circadian rhythm, with peak levels in the morning, declining towards low or normal levels in the afternoon and evening. In contrast, serum levels of tumour necrosis factor(TNF) alpha were low and stable. In other connective tissue diseases, serum TNF alpha levels were elevated but without circadian variation, while IL-6 levels were low and stable. Nocturnal administration (at 2:00 a.m.) of low-dose prednisolone a few hours before the early morning peak of IL-6 was shown to be significantly more effective in reducing clinical symptoms of disease activity and serum IL-6 levels than the traditional morning administration (at 7:30 a.m.) of the same dose of prednisolone. Circulating monocytes are activated in RA, expressing receptors related to adhesion and phagocytosis. Treatment with glucocorticoids suppressed the expression of these receptors on monocytes, and this may be one mechanism of the beneficial effect of glucocorticoids in RA. Endogenous levels of cortisol seem to play a minor role in expression of monocyte receptors. The different acute phase markers used to assess disease activity in RA showed good corrrelations with each other and with serum IL-6 levels. There were especially strong corrrelations between C-reactive protein (CRP) and Serum amyloid protein A (SAA), and between fibrinogen and erythrocyte sedimentation rate (ESR). Fibrinogen and CRP showed stronger correlation than ESR with the Modified Health Assessment Questionnaire (MHAQ) score and with the neutrophil count. Four simple objective function tests were each compared with the HAQ score a with a radiological joint damage score (Larsen score). The objective function tests correlated with the MHAQ score, and each of these two methods of assessing physical disability correlated with pain, CRP and ESR. In addition, most of the objective function tests correlated significantly with radiological joint damage, while the MHAQ score did not.</p>

In the present studies, aspects of some disease activity measures in rheumatoid arthritis (RA) have been investigated, including the effect of glucocorticoids on this activity. In RA, serum interleukin(IL)-6 levels were elevated and were shown to have a circadian rhythm, with peak levels in the morning, declining towards low or normal levels in the afternoon and evening. In contrast, serum levels of tumour necrosis factor(TNF) alpha were low and stable. In other connective tissue diseases, serum TNF alpha levels were elevated but without circadian variation, while IL-6 levels were low and stable. Nocturnal administration (at 2:00 a.m.) of low-dose prednisolone a few hours before the early morning peak of IL-6 was shown to be significantly more effective in reducing clinical symptoms of disease activity and serum IL-6 levels than the traditional morning administration (at 7:30 a.m.) of the same dose of prednisolone. Circulating monocytes are activated in RA, expressing receptors related to adhesion and phagocytosis. Treatment with glucocorticoids suppressed the expression of these receptors on monocytes, and this may be one mechanism of the beneficial effect of glucocorticoids in RA. Endogenous levels of cortisol seem to play a minor role in expression of monocyte receptors. The different acute phase markers used to assess disease activity in RA showed good corrrelations with each other and with serum IL-6 levels. There were especially strong corrrelations between C-reactive protein (CRP) and Serum amyloid protein A (SAA), and between fibrinogen and erythrocyte sedimentation rate (ESR). Fibrinogen and CRP showed stronger correlation than ESR with the Modified Health Assessment Questionnaire (MHAQ) score and with the neutrophil count. Four simple objective function tests were each compared with the HAQ score a with a radiological joint damage score (Larsen score). The objective function tests correlated with the MHAQ score, and each of these two methods of assessing physical disability correlated with pain, CRP and ESR. In addition, most of the objective function tests correlated significantly with radiological joint damage, while the MHAQ score did not.

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Lipoprotein(a) (Lp(a)) consists of an LDL-like particle and the specific protein apo(a), which is very similar to plasminogen. Apo(a) contains repeated kringle structures and a serine protease domain, which cannot be activated by t-PA. Lp(a) is considered to be a predictor for atherosclerotic disease. It has been found incorporated in atherosclerotic plaques and inhibits in vitro fibrinolysis. Lp(a) was determined in 1527 randomly selected individuals participating in the Northern Sweden WHO-MONICA project. A weak but significant relation between Lp(a) and increasing age was found. Menopausal status was the strongest independent predictor of Lp(a) level in women. Fibrinogen was independently related to Lp(a) in both sexes. Only a minor fraction of Lp(a) variance could be explained for in a multiple regression model, which is in agreement with the contention that Lp(a) is highly genetically determined. Lp(a) was determined in 1571 patients investigated with coronary angiography because of suspected severe coronary artery disease (CAD). Patients with proven CAD at elective angiography had significantly higher Lp(a) than patients without significant CAD or healthy controls. Lp(a) was found to be an independent discriminator of CAD in both sexes. HLA-DR genotype 13 or 17 was found more frequently in 30 male patients with angiographic CAD at young age (&lt; 50 years) than in 30 age matched controls. These genotypes were common in patients with high Lp(a) levels, which indicates that Lp(a) may be related to immunological processes. The reaction of Lp(a) was investigated in 32 patients with acute myocardial infarction (AMI). Lp(a) increased during the first week, but the response was comparatively weak. Individual Lp(a) responses were heterogeneous and no correlations to infarct size or changes in the acute phase proteins were found. In a randomized cross-over study on 36 hypercholesterolaemic patients treated with simvastatin/placebo during 12+12 weeks Lp(a) did not change significantly, but patients with high Lp(a) levels at baseline tended to develop further increased Lp(a). To conclude, Lp(a) was found to be an independent predictor of angiographic CAD in both men and women. Lp(a) levels are primarily genetically determined and only a small fraction of Lp(a) variance could be explained by other factors in this study. Lp(a) may be related to HLA DR types and immunological processes involved in atherosclerotic disease. Lp(a) increased slightly during the first week of AMI, but was not related to changes in the acute-phase proteins. The effective LDL-lowering agent simvastatin did not influence Lp(a) significantly. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1993, härtill 5 uppsatser.</p> / digitalisering@umu

Thesis (Ph.D. in Cell and Developmental Biology) -- University of Colorado at Denver and Health Sciences Center, 2005. / Typescript. Includes bibliographical references (leaves 139-155).

Submitted by Socorro Pontes (socorrop@ufersa.edu.br) on 2017-04-27T13:18:30Z No. of bitstreams: 1 IsabellaOB_TESE.pdf: 902178 bytes, checksum: d42880aee64b712a238f040f4408a579 (MD5) / Approved for entry into archive by Vanessa Christiane (referencia@ufersa.edu.br) on 2017-05-02T15:22:15Z (GMT) No. of bitstreams: 1 IsabellaOB_TESE.pdf: 902178 bytes, checksum: d42880aee64b712a238f040f4408a579 (MD5) / Approved for entry into archive by Vanessa Christiane (referencia@ufersa.edu.br) on 2017-05-02T15:23:03Z (GMT) No. of bitstreams: 1 IsabellaOB_TESE.pdf: 902178 bytes, checksum: d42880aee64b712a238f040f4408a579 (MD5) / Made available in DSpace on 2017-05-02T15:23:13Z (GMT). No. of bitstreams: 1 IsabellaOB_TESE.pdf: 902178 bytes, checksum: d42880aee64b712a238f040f4408a579 (MD5) Previous issue date: 2016-10-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Acute phase proteins are glycoproteins produced by hepatocytes and released into the bloodstream in response to tissue damage resulting from acute inflammatory processes. Currently, they are considered biomarkers of inflammation or infection, compared with other variables such as hyperthermia, leukocytosis and neutrophilia, but in donkeys have not yet been analyzed. This study aimed to evaluate acute inflammatory response in donkeys submitted to ovariectomy by two different approaches. We randomly selected 18 adult females animals weighing on average 100 kg, which were divided into two groups: Group I, 9 animals were ovariectomized by laparotomy and group II, 9 animals by laparoscopy. After the surgeries were evaluated the following variables in whole blood: blood count, white blood cell count differential cell count, fibrinogen, haptoglobin, albumin, antitrypsin, alpha-1-acid glycoprotein, ceruloplasmin, transferrin, immunoglobulins A and G (acute phase proteins) . In the same time, the peritoneal fluid were measured: number of erythrocytes and leukocytes, cytological analysis differential (leukocytes and mesothelial cells), total protein, pH and acute phase proteins. All variables were analyzed before surgery, 12, 24, 48, 72 hours, 8 and 16 days after surgery. There was an increase (p <0.05) in the number of leukocytes with neutrophilia after surgery, regardless of the surgical serum and peritoneal procedure. Acute phase proteins had different behaviors in blood and peritoneal fluid. For the first time, we identified a P23.000kD protein in serum and peritoneal samples in donkeys. The interest on the role of acute phase proteins in the veterinary medicine, particularly in horses is growing, mainly aiming to use them as early markers of inflammation / Proteínas de fase aguda são glicoproteínas produzidas pelos hepatócitos e liberadas na corrente sanguínea em resposta a dano tecidual, decorrente de processos inflamatórios agudos. Atualmente, são consideradas biomarcadores da resposta inflamatória e infecciosa, quando comparada com outras variáveis como hipertermia, leucocitose e neutrofilia, porém em asininos ainda não foram bem analisadas. Objetivou-se avaliar resposta inflamatória aguda em asininos submetidos à ovariectomia por duas diferentes abordagens. Foram utilizados 18 animais, fêmeas adultas, pesando em média 100 kg, as quais foram divididas em dois grupos, de 09 animais cada, onde grupo I, foram ovariectomizadas por laparotomia e o grupo II por laparoscopia. Após as cirurgias foram avaliadas as seguintes variáveis no sangue total: hemograma, fibrinogênio, haptoglobina, albumina, antitripsina, alfa-1 glicoproteína ácida, ceruloplasmina, transferrina, imunoglobulinas A e G. Nos mesmos momentos, no líquido peritoneal, foram mensuradas: número de hemácias e leucócitos, análise citológica diferencial (leucócitos e células mesoteliais), proteínas totais, pH e proteínas de fase aguda. Todas as variáveis foram analisadas antes das cirurgias, 12, 24, 48, 72 horas, 8 e 16 dias após os procedimentos cirúrgicos. Houve um aumento (p<0,05) do número de leucócitos com neutrofilia após as cirurgias, independente do procedimento cirúrgico, no soro e líquido peritoneal. As proteínas de fase aguda tiveram comportamentos diferentes no sangue e líquido peritoneal. Neste trabalho identificamos, pela primeira vez, a proteína P23.000kD no soro e amostras peritoneais de asininos. O interesse sobre o papel das proteínas de fase aguda na medicina veterinária, em especial em equídeos vem crescendo, principalmente, visando utilizá-las como marcadores precoces do processo inflamatório / 2017-04-26

Submitted by ANNITA MORAIS GIRARDI null (annitamgirardi@gmail.com) on 2016-02-16T19:49:59Z No. of bitstreams: 1 Tese_Annita_Morais_Girardi.pdf: 19183057 bytes, checksum: cf7a9853bcc87aef37b3ca91a2afceea (MD5) / Approved for entry into archive by Sandra Manzano de Almeida (smanzano@marilia.unesp.br) on 2016-02-17T13:22:33Z (GMT) No. of bitstreams: 1 girardi_am_dr_jabo.pdf: 19183057 bytes, checksum: cf7a9853bcc87aef37b3ca91a2afceea (MD5) / Made available in DSpace on 2016-02-17T13:22:33Z (GMT). No. of bitstreams: 1 girardi_am_dr_jabo.pdf: 19183057 bytes, checksum: cf7a9853bcc87aef37b3ca91a2afceea (MD5) Previous issue date: 2016-01-26 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Este estudo avaliou o uso da termografia infravermelha e do exame radiológico digital como ferramentas de diagnóstico precoce da laminite em ovinos com acidose ruminal subaguda induzida experimentalmente e os efeitos da ingestão prolongada de alta proporção de alimento concentrado sobre as variáveis clínicas e laboratoriais. Foram utilizadas sete ovelhas adultas, com cânulas ruminais permanentes, que não tiveram prévio contato com alimento concentrado. Para a indução da acidose ruminal, incluiu-se ao volumoso, diariamente, 10% de alimento concentrado até atingir 80%, porcentagem mantida até completarem 19 semanas. A observação dos sinais de diarreia deu-se do quarto ao 22º dia e de laminite do quinto ao 24º dia. O fluido ruminal foi predominantemente líquido, de odor ácido e coloração amarelada. Observou-se elevação inicial nos valores da frequência cardíaca, tempo de sedimentação e flotação no fluido ruminal, plaquetas, neutrófilos segmentados, AST, FA, GGT, cálcio ionizado, magnésio, glicose, ureia, triglicérides e bilirrubinas indireta e total. No início do experimento, notou-se redução da frequência respiratória, linfocitopenia, monocitopenia, hipocalcemia, hipofosfatemia, hiponatremia, hipoproteinemia e hipocolesterolemia. A frequência de movimentos ruminais, o tempo de redução do azul de metileno, os níveis sanguíneos de creatinina, bilirrubina direta, lactato e CK foram reduzidos, enquanto as médias de temperatura, peso e escore corporal, eosinófilos, albumina, cloretos e potássio no sangue aumentaram durante todo o período de observação. Redução do pH ruminal ocorreu nos primeiros dias, a despeito de sua manutenção acima de 5,5 durante as 19 semanas de observação. Mecanismos compensatórios respiratórios e metabólicos, principalmente a acidificação da urina, mantiveram o pH sanguíneo dentro dos limites fisiológicos considerados para a espécie ovina. Dezesseis frações proteicas séricas foram separadas pela eletroforese, dentre elas oito proteínas identificadas pelos seus pesos moleculares, de funções desconhecidas. A maioria das proteínas de fase aguda e as imunoglobulinas identificadas no fracionamento eletroforético variaram durante o período de observação, sugerindo reação inflamatória. Nenhuma alteração macroscópica foi detectada à necropsia. A radiologia digital não permitiu a identificação de alterações podais decorrentes de laminite durante o período de avaliação. A termografia infravermelha detectou aumentos na temperatura da parede do casco mesmo sem a manifestação clínica de dor, indicando que esta técnica pode ser uma ferramenta útil para detectar laminite em ovinos numa fase precoce de evolução da doença. / This study evaluated the use of infrared termography and digital radiologic examination as early diagnostic tools for laminitis in sheep with experimentally induced subacute ruminal acidosis, and the effects of long-term ingestion of a high concentrate diet on clinical and laboratory variables. Seven adult ewes with permanent rumen cannula were used, which did not have any previous ingestion of concentrate feed. For the induction of ruminal acidosis, it was added to the roughage, 10% of concentrate feed until reach 80%, percentage held to the end of the 19-week experiment. Diarrhea signs were observed from fourth to 22nd day and laminitis from fifth to 24th day. Ruminal fluid was predominantly liquid, sour-smelling and yellowish. Initial increases of heart rate, sedimentation and flotation time, platelets, segmented neutrophils, AST, ALP, GGT, ionized calcium, magnesium, glucose, urea, triglycerides, indirect and total bilirubin were noted. At the beginning of the experiment, there was reduction of respiratory rate, lymphocytopenia, monocytopenia, hypocalcemia, hypophosphatemia, hyponatremia, hypoproteinemia, and hypocholesterolemia. Ruminal movement rate, methylene blue reduction time, creatinine, direct bilirubin, lactate and CK blood levels decreased, while body temperature, weight and score, eosinophils, albumin, chloride and potassium blood levels increase throughout the period. Ruminal pH reduction occurred within the first days, despite its maintenance above 5.5 during the 19 weeks. Respiratory and metabolic mechanisms, mainly urine acidification, remained the blood pH between physiologic limits for sheep. Sixteen protein fractions were separated by electrophoresis, among them eight proteins of unknown functions, identified by their molecular weights. Most acute phase proteins and the immunoglobulins identified in the electrophoretic fractionation varied throughout the observation period, suggesting inflammation. No macroscopic alteration was detected at necropsy. The digital radiology did not allow the identification of podal changes resulting from laminitis during the trial period. Infrared thermography has detected increases in the maximum temperature of the hoof wall, even without the clinical manifestation of pain, indicating that this technique can be an useful tool to detect laminitis in sheep at an early stage of the disease. / FAPESP: 2012/09111-7

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Trypanosomiasis is a disease of worldwide distribution which in Brazil is called "mal das cadeiras", owing the clinical signs shown by horses, which are the major species affected. The disease is caused by the protozoan Trypanosoma evansi, characterized by clinical signs such as weight loss, pale mucous membranes, swelling of the eyelid and vulva. Rabbits have been reported as a resistant species to T. evansi, however, is not yet known how immune aspects, such as innate immune and cholinergic system, behave in this species, not even as this inflammations pathways influence in rabbits's trypanotolerance. Thus, the aim of this study was to investigate the inflammatory response and cholinergic anti-inflammatory pathway and its relation to trypanotolerance in rabbits infected with T. evansi. For this, twelve female adult New Zealand rabbits, weighing 3.6 4.5 kg were used in this study. The animals were divided into two groups, a control group and an infected group, both with six animals. The rabbits belonging to the infected group received, intraperitoneally, 0.5 ml of rat blood containing 108 parasites per animal, while the control group received physiological solution by the same route. The experimental period reached 118 days. Blood was collected on days 0, 2, 7, 12, 27, 42, 57, 87, 102, and 118, for to determine the cholinesterases, and days 0, 5, 20, 35, 65, 95 and 118, for to evaluate blood count, total protein, serum proteinogram, immunoglobulins and acute phase proteins. There was an increase in the activity of butyrylcholinesterase (BChE), at 7th day PI, and in the activity of acetylcholinesterase (AChE), in 27th day PI. Furthermore, the infected group showed an increase in total protein and the fractions alpha, beta and gamma globulins along of experimental period. The reduction in albumin and hematocrit were observed in precise periods of experimental infection, as well as the increase in immunoglobulin G. Infection with T. evansi stimulated the production of acute phase proteins, such as C-reactive protein, haptoglobin, α-2 macroglobulin, being observed increase in immunoglobulin M (IgM) throughout the experimental period (118 days post-infection). From these results, it is concluded that the cholinergic pathway had influence the inflammatory response, through the action of AChE and BChE in the regulation of concentrations of acetylcholine, resulting in increased concentrations of cytokines and, consequently, in the production phase protein acute. The increase in IgM, associated with increased C-reactive protein and haptoglobin, suggests the involvement of these proteins in host defense against flagellated, with possible participation in trypanotolerance of rabbits infected with T. evansi. / A tripanossomose é uma enfermidade de distribuição mundial que, no Brasil, é denominada mal das cadeiras , em função dos sinais clínicos apresentados pelos equinos, principal espécie afetada. A doença é causada pelo protozoário Trypanosoma evansi, sendo caracterizada por sinais clínicos como perda de peso, mucosas pálidas, edema de pálpebra e vulva. Coelhos têm sido relatados como uma espécie resistente ao T. evansi, contudo, ainda não se sabe de que modo aspectos imunitários, como a imunidade inata e o sistema colinérgico, comportam-se nessa espécie, nem mesmo como essas vias da inflamação influenciam a tripanotolerância de coelhos. Assim, o objetivo deste trabalho foi investigar a resposta inflamatória e a via anti-inflamatória colinérgica e sua relação na tripanotolerância em coelhos infectados experimentalmente pelo T. evansi. Para tanto, foram utilizados 12 coelhos adultos, fêmeas, da raça Nova Zelândia, com peso corporal entre 3,6 a 4,5 Kg, divididos em dois grupos, um grupo controle e um grupo infectado, ambos com seis animais. Os coelhos pertencentes ao grupo infectado receberam, pela via intraperitoneal, 0,5 mL de sangue de rato contendo 108 tripanossomas por animal, enquanto que o grupo controle recebeu, pela mesma via, solução fisiológica. O período experimental foi de 118 dias, sendo o sangue coletado nos dias 0, 2, 7, 12, 27, 42, 57, 87, 102, e 118, para determinar as colinesterases, e nos dias 0, 5, 20, 35, 65, 95 e 118, para avaliar hemograma, proteínas totais, proteinograma sérico, imunoglobulinas e proteínas de fase aguda. Foi observado aumento na atividade da butirilcolinesterase (BChE) no 7° dia PI e da atividade da acetilcolinesterase (AChE) no 27° dia PI. Além disso, o grupo infectado apresentou aumento nas proteínas totais, bem como nas frações alfa, beta e gama globulinas ao longo do período experimental. A redução na albumina e no hematócrito foram observados em períodos pontuais da infecção experimental, bem como o aumento na imunoglobulina G. A infecção pelo T. evansi estimulou a produção de proteínas de fase aguda como a proteína C-reativa, haptoglobina, α-2 macroglobulina, sendo observado um aumento na imunoglobulina M (IgM) em todo o período experimental (118 dias pós-infecção). A partir desses resultados, conclui-se que a via colinérgica pode ter influência na resposta inflamatória, através da ação da BChE e AChE na regulação das concentrações de acetilcolina, acarretando em aumento nas concentrações de citocinas e, consequentemente, na produção de proteínas de fase aguda. A elevação na IgM, relacionada ao aumento da proteína C-reativa e haptoglobina, sugere o envolvimento dessas proteínas na defesa do hospedeiro contra o flagelado, e, possivelmente, na tripanotolerância de coelhos infectados com T. evansi.