Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / Derek A. Mosier / The bovine respiratory disease complex (BRDC) is a major concern for cattle producers in the United States and worldwide. One of the most costly and deadly components of BRDC is bovine pneumonic pasteurellosis (BPP) caused by Mannheimia haemolytica. The initial pulmonary inflammation associated with BPP is a characteristic serofibrinous exudation into the lung, which is believed to be induced by M. haemolytica virulence factors such as lipopolysaccharide (LPS) and leukotoxin (LKT) and host cytokines and chemokines such as tumor necrosis factor – α, interleukin – 1β, and interleukin – 8. However, these pulmonary changes often occur before virulence factors or cytokines are substantial components of the pulmonary microenvironment. Other proinflammatory molecules such as substance P (SP) may be involved in the pathogenesis of the peracute serofibrinous exudation of BPP. SP is an 11 amino acid long neuropeptide that is a neurotransmitter of pain that can be released from sensory nerves into tissues to cause neurogenic inflammation. Neurogenic inflammation is characterized by serofibrinous exudation and leukocyte activation. SP-like immunoreactivity was present in the airways, alveolar septa, macrophages, endothelium, and peribronchial nerves in both pneumonic and normal bovine lung; however, SP-like immunoreactivity was increased in pneumonic compared to normal bovine lung due to increased immunoreactivity in macrophages. SP and the combination of SP with histamine and LPS increased the permeability of a calf pulmonary arterial endothelial cell line to Evans blue dye labeled albumin by 12.34%, 13.57%, and 22.03%, respectively compared to a cell control. Similarly, SP and the combination of SP and histamine increased the monolayer permeability of a bovine adrenal gland capillary endothelium by 8.27% and 16.69% compared to a cell control. The increase in permeability was due to endothelial cell shape change and the formation of intercellular gaps rather than cell death. However, SP does not increase the surface expression of the β2 integrin CD18 (the M. haemolytica LKT receptor) on bovine neutrophils nor does it increase LKT-induced leukocytotoxicity of bovine peripheral blood leukocytes. These findings indicate that SP may be a contributor to BPP in association with other cytokines.

Master of Science / Department of Animal Sciences and Industry / Terry A. Houser / Nursery age pigs (n=198) were used to evaluate the difference in the occurrence of injection site abscesses between needle-free jet injection and conventional needle-and-syringe injection systems. Pigs were fed for 21 d prior to treatment administration to acclimate the pigs to the environment of the Kansas State University Segregated Early Weaning (SEW) unit. On d 21 each pig was injected with aluminum hydroxide adjuvant in the neck and ham with needle-free jet injection (Pulse Needle-Free Systems, Lenexa, KS) and conventional needle-and-syringe injection. Needle-free and conventional needle-and-syringe injections were randomly assigned to pig side yielding a total of 396 injections per treatment with a total of 792 injections sites. Immediately prior to injection, the external surface of the injection sites were contaminated with an inoculum of Arcanobacterium pyogenes, a bacterium commonly associated with livestock abscesses. The pigs were then fed for a period of 27 or 28 d. On d 27 or d 28 the pigs were humanely euthanized and sent to the Kansas State Veterinary Diagnostics Laboratory where necropsies were performed and the injection sites harvested for histopathological evaluation. The needle-free jet injection system was associated with more injection site abscesses than the conventional needle-and-syringe injection method for both neck (P=0.0625) and ham (P=0.0313) injection sites. Twelve abscesses were found at injection sites administered via needle-free jet injection method while only 1 abscess was found with the conventional needle-and-syringe injection method. 5 abscesses were found at the neck injection sites and 8 abscesses were found at ham injection sites. There were no significant differences seen in tissue granulation resulting from reaction to the adjuvant. In summary, the implementation of needle-free jet injection systems in market hog production will be beneficial to eliminate needles and needle fragments in meat products but, when in the presence of Arcanobacterium pyogenes, it may increase the occurrence of injection site abscesses in pork carcasses that will need to be trimmed in pork processing plants. Although more abscesses were associated with needle-free jet injection, their occurrence was observed at a very low rate given that all injection sites were intentionally contaminated prior to injection.

Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / David G. Renter / Bradley J. White / The objective of my research was to generate novel information concerning the epidemiology, diagnosis and prevention of bovine respiratory disease complex (BRDC), a common pre-weaning and post-weaning beef calf disease. To reach my objective, I conducted three prospective field trials within post-weaned calf populations, and one retrospective study of pre-weaned calves utilizing survey data. I evaluated differences in behavior, health and performance in calves receiving multiple component health programs. Calves in a minimally invasive program, which included primarily non-injectable products, displayed less aversion to initial product administration but experienced higher BRDC morbidity (P = 0.02) and poorer performance (P = 0.04) compared to calves in a more invasive (all injectable products) program. Secondly, in a study of Mannheimia haemolytica inoculated calves, I found that no parameter included in physical examinations, or common blood component evaluations could discern health from disease. However, disease recognition was aided by the measurement of the number of steps taken by a calf in a 24 hour period. None of the parameters that were evaluated predicted the severity of lung pathology. Thirdly, I conducted a study in post-weaned feeder calves that determined prevalence estimates for Mollicutes in general, and Mycoplasma bovis specifically, and their respective associations with health and performance. Nasal Mollicutes prevalence was high on arrival, and differences in calf performance were associated with (P < 0.01) nasal prevalence. More than half of the calves seroconverted to M. bovis; calves not seroconverting gained more weight (0.49 kg/head/day) during the study than those calves that did seroconvert (0.35 kg/head/day). Finally, I conducted a retrospective analysis of national U. S. cow-calf survey data to identify herd level management practices associated with pre-weaned calf BRDC. I found feeding antibiotics to pre-weaned calves, importing cattle, the number of outside visitors, economic purpose of the cow-calf operation, and breeding management of the herd were associated with herd-level pre-weaning BRDC rates. My research projects generated unique information concerning the epidemiology of important pathogens, differences among preventive health programs, objective BRDC diagnostic parameters, and pre-weaning BRDC risk factors. These research studies reinforce the complexity of BRDC and demonstrate the pathogen, animal and management factors affecting BRDC risk in pre- and post-weaned beef calves.

Master of Science / Department of Diagnostic Medicine/Pathobiology / Larry C. Hollis / Mark F. Spire / Two studies were undertaken to evaluate the use of Near Infrared Spectroscopy (NIRS) to determine arterial oxygen saturation (StO[subscript]2) in cattle with naturally-occurring Undifferentiated Bovine Respiratory Disease (UBRD) and experimentally-induced UBRD utilizing Mannheimia haemolytica. The first study was a natural infection model utilizing 679 beef heifers weighing approximately 227 kg (500 pounds) originating from a southeastern U.S. salebarn. Heifers were evaluated for UBRD upon feedlot arrival, at revaccination, at day 35 on feed, at re-implant time, and two weeks prior to shipment for slaughter. Animals deemed to have UBRD were treated for UBRD and data was collected for 5 days following treatment, while a comparable healthy cohort was also evaluated at the time of treatment. There was a trend for NIRS to be able to predict the incidence of subsequent UBRD when cattle were evaluated on arrival (p=0.0552). However, the ability to detect UBRD in clinically ill cattle was not significantly different (p>0.1690) when compared to healthy cohorts in this model. When carcass characteristics were evaluated at each time point, NIRS StO[subscript]2 values were able to differentiate between yield grades of animals with UBRD and healthy cohorts when evaluated at revaccination, day 35, re-implant, and pre-shipping (p<0.0199). NIRS tended to be able to differentiate yield grades at initial processing (p=0.0513). StO[subscript]2 was not a predictor of quality grade at any time point (p>0.1023), nor was there any correlation between lung lesions at slaughter and StO[subscript]2 (p>0.2292). The second study involved 12 head of 181 kg (400 pound) heifers which were subjected to an experimental challenge model of Mannheimia haemolytica. Animals were evaluated daily and StO[subscript]2 readings recorded 12 hours pre-inoculation, at inoculation, 6, 12 and 24 hours post inoculation and daily for the next 12 days. While NIRS could not definitively differentiate healthy cohort cattle from challenge cattle (p>0.0713), there were trends toward challenge cattle having lower StO[subscript]2 values than healthy controls. The authors conclude that while these studies did not provide conclusive evidence of the ability of NIRS to detect UBRD, further studies with a machine that is specifically calibrated and designed for use with cattle should be performed.

Master of Science / Department of Clinical Sciences / James D. Lillich / Objective: To assess the in vitro ability of a novel lipopolysaccharide binding compound (EVK063) to inhibit cytokine production in lipopolysaccharide-stimulated equine peripheral blood mononuclear cells Animals: Eight healthy horses were sources for mononuclear cells. Procedures: Replicate aliquots (concentrated at 4-5 million cells/mL) were stimulated with S. typhimurium lipopolysaccharide (LPS) (100ng/mL), treated with graded concentrations of EVK063, (0.01µM, 0.1µM, 1µM, 10µM), Polymyxin B (PMB) (10µM) and incubated at 37°C for 6 hours. Media and cell samples were collected and stored at -80°C for evaluation of Tumor necrosis factor (TNF) using an equine specific ELISA and Interleukin-6 (IL6) via qRT-PCR. NanoDrop confirmed RNA quantity and primer sets designed for equine IL6 and the housekeeping gene 18s were used. EVK063 toxicity was evaluated with propidium iodide staining as determined by flow cytometry. Data was normalized, expressed as percent inhibition of cytokine up-regulation by LPS, and statistically evaluated by analysis of variance. Statistical significance was set at P ≤ 0.05. Results: Samples incubated in media with 0% serum demonstrated the following results: 0.01µM and 0.1µM EVK063 maintained >90% cellular viability yet failed to significantly inhibit TNF production or IL6 expression. The 1µM and 10µM EVK063 concentrations exhibited 25% and 70% cell death respectfully and therefore an interpretation as to their efficacy to inhibit TNF production or IL6 expression could not be made. Samples incubated in media with 10% serum demonstrated the following results: 0.01µM, 0.1µM and 1µM concentrations of EVK063 maintained >90% cellular viability yet failed to inhibit TNF production or IL6 expression. The 10µM EVK063 concentration exhibited 35% cell death and therefore an interpretation as to the efficacy to inhibit TNF production or IL6 expression could not be made. In a whole blood preparation, all samples evaluated maintained >90% cellular viability. The 10µM EVK063 significantly reduced TNF production and IL6 expression. Conclusion: This in vitro study confirms the ability of EVK063 to inhibit TNF production and IL6 expression in LPS stimulated equine mononuclear cells with comparable results to PMB.

Master of Science / Department of Clinical Sciences / James D. Lillich / Objective - To compare the biomechanical characteristics of the currently recommended (CR) technique and a less invasive (LI) surgical approach for arthrodesis of the proximal interphalangeal joint (PIPJ). Additionally, to describe a technique for cartilage removal and disruption of the subchondral bone. Study design - Randomized paired limb design for biomechanical comparison. Cartilage removal and subchondral bone disruption was accomplished using an orthopedic drill bit. Sample Population – 76 cadaver limbs. Methods - Cadaver PIPJs were drilled using a 3.5mm, 4.5mm or 5.5mm drill bit. Articular surfaces were digitally photographed and analyzed. Other paired PIPJs were arthrodesed using either the CR or the LI surgical technique. Implants consisted of a 3-hole DCP and two 5.5mm transarticular screws. Constructs were tested to failure in dorso-palmar/plantar and latero-medial in single cycle 3-point bending. The maximum load and yield load was measured and composite stiffness was calculated and statistically compared. Results - The LI technique had significantly greater mean yield load (11.3 ± 2.8 kN vs. 7.68 ± 1.1 kN, P=0.008) and mean maximum load (13.5 ± 3.1 kN vs. 10.1 ± 1.94 kN, P= 0.02) under latero-medial bending. Under dorso-palmar/plantar bending there was no statistical difference between the surgical approaches (P=0.5). The 4.5mm drill bit removed 42% ± 7.3 of the cartilage and disrupted subchondral bone. The LI technique had a decreased surgical time (19 ± 3 min.) when compared with the CR (31 ± 3 min.) technique. Conclusion – The LI technique results in a stronger composite as measured in 3-point bending, loaded to failure. Clinical Relevance – The LI surgical technique may be considered for clinical cases requiring arthrodesis of the PIPJ as there is no reduction in composite strength.

Master of Science / Department of Diagnostic Medicine/Pathobiology / Roman Reddy R. Ganta / Ehrlichia chaffeensis is an emerging tick-borne rickettsial pathogen that causes infection in people and several vertebrate animals. One of the striking features of E. chaffeensis infection is the prolonged persistence in its vertebrate and tick hosts. The mechanism of persistent infection and the reasons for the host immune system failure to clear the infection are not well understood. One hypothesis is that differential gene expression serves as an important adaptive mechanism used by E. chaffeensis in support of its continued survival in both tick and vertebrate hosts. One way to test this hypothesis is by performing mutational analysis. However, the methods for introducing mutations in this pathogen have not yet been documented and are challenging, possibly due to its obligate, intraphagosomal growth requirement. Recently, a novel gene mutation method called ‘TargeTron Gene Knockout System’ that is based on the modified group II intron insertion strategy has been developed. This method appears to be effective in creating mutations in a wide range of gram positive and gram negative bacterial organisms. The group II intron can be programmed for insertion into virtually any desired DNA target with possibly high frequency and specificity. In this study, I focus on creating mutations in E. chaffeensis using the TargeTron gene knockout system. I prepared modified group II intron constructs retargeting for insertion into three E. chaffeensis genes: Ech_0126 (a transcriptionally silent gene), macrophage-specific expressed gene (p28-Omp 19, Ech_1143) and tick cell-specific expressed gene (p28-Omp 14, Ech_1136). In support of driving the expression of the modified group II introns in E. chaffeensis, the pathogen- specific high-expressing gene promoter (tuf) was inserted upstream to the transcription start site. In addition, a chloramphenicol acetyltransferase gene with E. chaffeensis rpsl promoter was introduced for use as a selection marker. The constructs were then evaluated by transforming into E. chaffeensis. Transformants with mutations, introduced in two of the three genes (Ech_0126 and Ech_1143), were identified by PCR and Southern blot methods. Although the mutants are detectable for up to 48 hours, establishment of stable transformants remains to be challenging. The outcomes of this project will have important implications in defining the pathogenesis of E. chaffeensis, particularly to assess the differences in the organism in tick and vertebrate hosts.

O objetivo do presente estudo foi avaliar os efeitos tóxicos da Senna occidentalis (So) sobre o sistema linfo-hematopoiético em ratos recém-desmamados ou expostos pré-natalmente. Avaliou-se nestes animais: o consumo de água e ração, o ganho de peso; parâmetros hematológicos, padrões histopatológicos, além da resposta imunológica específica e não específica. Inicialmente, o estudo foi realizado em ratos recém-desmamados, os quais foram expostos a diferentes concentrações de sementes de So na ração a saber: 1% (So1), 2% (So2) e 4% (So4) durante 14 dias ou que receberam So4 durante 28 dias. Os animais do grupo peer-feeding (PF) receberam a mesma quantidade de ração consumida pelos animais expostos a So4, porém isentas da planta. Após 14 dias de exposição, os resultados obtidos mostraram uma diminuição significante nos parâmetros de consumo de ração, de ganho de peso e da celularidade da medula óssea e do peso relativo no timo nos grupos So2 e So4 e um aumento no peso relativo do baço nos grupos So2 e So4. Entretanto, os animais dos grupos So4 e PF também apresentaram diminuição da celularidade da medula óssea. Na avaliação da resposta imune não especifica todos grupos expostos às sementes da planta, bem como o grupo PF, apresentaram redução na porcentagem de fagocitose por neutrófilos; porém, apenas o grupo So4 mostrou redução do burst basal por neutrófilos. O estudo morfológico do baço mostrou proliferação hematopoiética extramedular e aumento de megacariócitos multinucleados nos ratos do grupo So4. Apenas nos experimentos com animais do grupo So4 expostos por 28 dias, verificou-se similaridade entre resultados dos parâmetros acima descritos, além da ocorrência de anemia microcítica e hipocrômica. Num segundo momento avaliou-se as proles de ratas que receberam sementes de S. occidentalis a 4% na ração, do 6º ao 20º dia de gestação, assim como as proles das ratas do grupo peer-feeding (PF). Os filhotes provenientes de mães do grupo So4 e PF apresentaram um aumento do burst oxidativo e da fagocitose por neutrófilos. Os animais da prole do grupo PF apresentaram hemograma indicativo de anemia megaloblástica. Já no estudo morfológico do baço verificou-se hematopoiese extramedular nos filhotes das mães do grupo So4. Portanto, a presente pesquisa mostrou que a S. occidentalis pode comprometer alguns parâmetros do sistema imunológico de ratos expostos às sementes da planta durantes diferentes fases do desenvolvimento. Além disso, verificou-se que as sementes desta planta também promovem efeitos tóxicos sobre eritrócitos. A inclusão do grupo PF permitiu verificar que os efeitos observados não são decorrentes de possíveis alterações nutricionais promovidas pela redução do consumo de ração, mas sim relacionados ao efeito tóxico direto da S. occidentalis. / The aim of present study was to determinate the Senna occidentalis (So) toxic effects on lymphohematopoetic system in rats during the growth and pre-natal period. The effects were evaluated on the basis of food consumption, weight gain, hematological and immunological parameters, as well as histopathology analysis. Initially, the study was done in growing rats exposed to S. occidentalis seeds in different concentrations: 1% (So1), 2% (So2) and 4% (So4) in feed during 14 or 28 days. Peer feeding-group of rats (PF) was also evaluated; this group received the same amount of feed of those from So4-group, however, free of S. occidentalis seeds. S. occidentalis 14 days exposure decreased food consumption, weight gain, thymus relative organ weight and bone marrow cellularity and increased the spleen relative weight of rats from So2 and So4-group. However, So4- and PF- groups also presented a decreased bone marrow cellularity. All seed exposed-groups and also PF-group had a decrease on neutrophil phagocytosis percentage; however, only rats from So4-group had a decreased neutrophil basal burst. Spleen morphologic analysis indicated the presence of extramedular hematopoietic proliferation and increased multinucleated megakariocytes on So4-group. Similar results were found for all the parameters described after S. occidentalis exposure during 28 days. Furthermore, the rats of So-4 group presented microcytic and hypochromic anemia. On a second moment, rats offspring exposed to S. occidentalis at 4% in feed during the 6th to 20th gestational day and rats offspring of PF group were evaluated. The So4- and PF- rats offspring groups presented an increased neutrophil oxidative burst and phagocytosis, however PF-rats offspring group also had an altered complete blood count compatible with megaloblastic anemia. Moreover spleen morphologic analysis indicated the presence of extramedular hematopoiesis on So4 rats offspring group. Therefore, the present study showed that S. occidentalis can compromise some immunological parameters in rats exposed to seeds during different development periods. This exposure also promotes toxic effects on erythrocytes. The PF group allowed us to verify that the observed effects are related to direct S. occidentalis toxic effects and not due a possible nutritional alteration caused by the reduced feed ingestion.

Tanto no Brasil como em vários outros países, a Senna occidentalis é uma planta de interesse agropecuário, pois é encontrada em pastos ou como contaminante de cereais, podendo, causar intoxicação na criação animal. Além disto, vem sendo utilizada, empiricamente, na Medicina Humana, para o tratamento de várias afecções. Em estudo recente, verificou-se que frangos tratados com sementes de S. occidentalis apresentavam, além das lesões musculares, alterações em órgãos linfóides. Assim, o presente trabalho procurou verificar se as sementes de S. occidentalis poderiam produzir efeitos tóxicos nos órgãos linfóides de mamíferos, utilizando, para tal, ratos como modelo experimental. As sementes de S. occidentalis foram administradas, durante 14 dias, a ratos Wistar (150-200g), em diferentes concentrações de sementes desta planta na ração: 1% (So1), 2% (So2) e 4%(So4). Os animais do grupo peer-feeding (PF) receberam a mesma quantidade de ração consumida pelos animais tratados com So4, porém isentas da planta. Foram avaliados os seguintes parâmetros: consumo de água e ração e ganho de peso, avaliação hematológica e bioquímica, além da histopatologia, morfometria e de ensaios preconizados para o estudo da resposta imunológica não específica. Todos os ratos pertencentes aos diferentes grupos experimentais apresentaram diminuição no consumo de ração e água e no ganho de peso. A avaliação hematológica revelou anemia microcítica e hipocrômica nos animais que receberam 4% da planta. Além disso, todos os animais dos grupos So2 e So4 apresentaram depleção de células linfóides e redução da polpa branca do baço. Os ratos pertencentes ao grupo So4 apresentaram redução significante no peso relativo do timo e diminuição significante na região cortical e também no diâmetro dos folículos medulares deste órgão. Estes mesmos animais apresentaram diminuição da produção de água oxigenada e óxido nítrico. Em relação à resposta inflamatória, todos os animais dos grupos experimentais, apresentaram redução na evolução do edema inflamatório agudo e crônico. Assim, a presente pesquisa mostrou que, também em mamíferos, a S. occidentalis pode comprometer o sistema imunológico, haja vista as alterações encontradas no timo e baço dos ratos expostos à planta. Além disso, verificou-se que as sementes desta planta também promovem efeitos tóxicos sobre eritrócitos e alterações na resposta inflamatória. A inclusão do grupo PF permitiu verificar que os efeitos aqui encontrados não são devidos a possíveis alterações nutricionais promovidas pela queda do consumo de alimento e sim relacionados ao efeito tóxico direto da S. occidentalis. / Senna occidentalis is a weed which grows in pasture along fences and fields cultivated with cereals as corn and soybean and many reports have been showing intoxication with this plant in different animal species. The effects of daily administration of S. occidentalis seeds in different concentrations 1% (So1), 2 % (So2) and 4% (So4) in ration was investigated in rats. It was also evaluated the effects of rats that received the same amount of ration to those of So4-group, however free of S. occidentalis seeds, (PF-rats). The experimental period lasted 14 days and the effects were evaluated on the basis of food consumption, weight gain, hematological and biochemical parameters, inflammatory and immunological responses, as well as histopathology, relative organ weight and morphometric analysis. All experimental animals, showed significant decrease in ration and water consumption and body weight gain. The hematological parameters revealed microcytic and hypochromic anemia in those animals treated with the higher concentration S. occidentalis seeds. Morphometric analysis of the spleen from So2 and So4-animals displayed a significant decrease in the cortical thickness. The thymus from So4-rats showed reduction in the organ size, and the morphometry revealed thickness and reduction of the diameter of the follicles at the cortical area. The same animals presented reduction in hydrogen peroxide and nitric oxide production. In inflammatory response all experimental animals, showed significant decrease in the evolution of acute and chronic edema. These results showed that the alterations found in this present study are related to the poisonous effects of the S. occidentalis and not to the malnutrition.

Tanto no Brasil como em vários outros países, a Senna occidentalis é uma planta de interesse agropecuário, pois é encontrada em pastos ou como contaminante de cereais, podendo, causar intoxicação na criação animal. Além disto, vem sendo utilizada, empiricamente, na Medicina Humana, para o tratamento de várias afecções. Em estudo recente, verificou-se que frangos tratados com sementes de S. occidentalis apresentavam, além das lesões musculares, alterações em órgãos linfóides. Assim, o presente trabalho procurou verificar se as sementes de S. occidentalis poderiam produzir efeitos tóxicos nos órgãos linfóides de mamíferos, utilizando, para tal, ratos como modelo experimental. As sementes de S. occidentalis foram administradas, durante 14 dias, a ratos Wistar (150-200g), em diferentes concentrações de sementes desta planta na ração: 1% (So1), 2% (So2) e 4%(So4). Os animais do grupo peer-feeding (PF) receberam a mesma quantidade de ração consumida pelos animais tratados com So4, porém isentas da planta. Foram avaliados os seguintes parâmetros: consumo de água e ração e ganho de peso, avaliação hematológica e bioquímica, além da histopatologia, morfometria e de ensaios preconizados para o estudo da resposta imunológica não específica. Todos os ratos pertencentes aos diferentes grupos experimentais apresentaram diminuição no consumo de ração e água e no ganho de peso. A avaliação hematológica revelou anemia microcítica e hipocrômica nos animais que receberam 4% da planta. Além disso, todos os animais dos grupos So2 e So4 apresentaram depleção de células linfóides e redução da polpa branca do baço. Os ratos pertencentes ao grupo So4 apresentaram redução significante no peso relativo do timo e diminuição significante na região cortical e também no diâmetro dos folículos medulares deste órgão. Estes mesmos animais apresentaram diminuição da produção de água oxigenada e óxido nítrico. Em relação à resposta inflamatória, todos os animais dos grupos experimentais, apresentaram redução na evolução do edema inflamatório agudo e crônico. Assim, a presente pesquisa mostrou que, também em mamíferos, a S. occidentalis pode comprometer o sistema imunológico, haja vista as alterações encontradas no timo e baço dos ratos expostos à planta. Além disso, verificou-se que as sementes desta planta também promovem efeitos tóxicos sobre eritrócitos e alterações na resposta inflamatória. A inclusão do grupo PF permitiu verificar que os efeitos aqui encontrados não são devidos a possíveis alterações nutricionais promovidas pela queda do consumo de alimento e sim relacionados ao efeito tóxico direto da S. occidentalis. / Senna occidentalis is a weed which grows in pasture along fences and fields cultivated with cereals as corn and soybean and many reports have been showing intoxication with this plant in different animal species. The effects of daily administration of S. occidentalis seeds in different concentrations 1% (So1), 2 % (So2) and 4% (So4) in ration was investigated in rats. It was also evaluated the effects of rats that received the same amount of ration to those of So4-group, however free of S. occidentalis seeds, (PF-rats). The experimental period lasted 14 days and the effects were evaluated on the basis of food consumption, weight gain, hematological and biochemical parameters, inflammatory and immunological responses, as well as histopathology, relative organ weight and morphometric analysis. All experimental animals, showed significant decrease in ration and water consumption and body weight gain. The hematological parameters revealed microcytic and hypochromic anemia in those animals treated with the higher concentration S. occidentalis seeds. Morphometric analysis of the spleen from So2 and So4-animals displayed a significant decrease in the cortical thickness. The thymus from So4-rats showed reduction in the organ size, and the morphometry revealed thickness and reduction of the diameter of the follicles at the cortical area. The same animals presented reduction in hydrogen peroxide and nitric oxide production. In inflammatory response all experimental animals, showed significant decrease in the evolution of acute and chronic edema. These results showed that the alterations found in this present study are related to the poisonous effects of the S. occidentalis and not to the malnutrition.