Nicotine addiction continues to be a leading cause of preventable death worldwide. Despite the plethora of available treatments for smoking cessation, smoking relapse after attempts to quit remains high. It is possible that impairments in cognitive flexibility and underlying neurochemical circuits in nicotine addicts may foster maladaptive behaviors that affect individuals’ ability to refrain from taking drugs. Here we characterized the effects of spontaneous nicotine withdrawal on cognitive flexibility in mice using an operant strategy set-shifting task. Because frontostriatal circuits are critical for cognitive flexibility and brain-derived neurotrophic factor (BDNF) modulates glutamate plasticity, we also explored the effects of nicotine withdrawal on these neurochemical substrates. Adult male C57BL/6J mice were trained in an operant task that required the animals to switch from using a spatial response-driven strategy to a visual cue-based strategy to achieve rewards. Mice were exp / Psychology

In Drosophila melanogaster, the transcription factor Dorsal initiates dorsal-ventral (DV) patterning in the early embryo by activating or repressing genes, such as the transcription factors Twist and Snail, along the DV axis. Previous studies have shown that the microRNA gene miR-184 in the ventral portion of the embryos (the prospective mesoderm) at the early stages of Drosophila embryogenesis. In order to identify the tissue-specific enhancer that regulates miR-184 expression in the mesoderm, we generated transgenic fly lines and observed the expression of a reporter gene under the control of a potential cis-regulatory module (CRM). Our results show that this CRM is responsible for the regulation of miR-184 and furthermore, it is activated by Twist. / Biology

Primary sensory axons fail to regenerate into the spinal cord following dorsal root injury leading to permanent sensory deficits. Re-entry is prevented at the dorsal root entry zone (DREZ), the CNS-PNS interface. Current approaches for promoting DR regeneration across the DREZ have had some success, but sustained, long-distance regeneration, particularly of large-diameter myelinated axons, still remains a formidable challenge. Our lab has previously shown that induced expression of constitutively active B-RAF (kaBRAF) enhanced the regenerative competence of injured DRG neurons in adult mice. In this study, I investigated whether robust intraspinal regeneration can be achieved by selective expression of kaBRAF alone or in combination with deletion of the myelin-associated inhibitors or neuron-intrinsic growth suppressors (PTEN or SOCS3). To this end, I used LSL-kaBRAF: brn3a-CreERT2 transgenic mice in which kaBRAF can be induced selectively in sensory neurons. I have also bred LSL-kaBRAF: brn3a-CreERT2 mice with triple knock-out mice lacking Nogo, Mag and OMgp or mouse lines carrying floxed alleles of PTEN or SOCS3. Single, double, and triple conditional mice were subjected to cervical DR crush and AAV2-eGFP vectors were used to selectively label regenerating axons of large-diameter neurons. I compared the extent of regeneration at 3 weeks or 2 months after DR injury using conventional anatomical and behavioral analyses. I found that kaBRAF alone promoted axon regeneration across the DREZ but did not produce significant functional recovery by two months. Supplementary deletion of Nogo, MAG, and OMgp did not improve kaBRAF-induced regeneration. Deletion of PTEN or SOCS3 individually or in combination failed to promote axon regeneration across the DREZ. In marked contrast, simultaneous deletion of PTEN, but not SOCS3, dramatically enhanced kaBRAF-mediated regeneration enabling many more axons to penetrate the DREZ and grow deep into the spinal cord. This study shows that dual activation of BRAF-MEK-ERK and PI3K-Akt signaling is an effective strategy to stimulate robust intraspinal DR regeneration and may lead to recovery of sensory function after DR injury. / Biomedical Sciences

This dissertation characterizes the geometry, kinematics, and physical properties of insect internal structures that make up the respiratory and circulatory systems. This characterization is necessary to better understand how these systems function to transport fluids at the microscale, and ultimately, how we might computationally model this flow. Chapter 2 describes the geometry of the insect tracheal system, specifically testing if Murray's law applies to this system using three-dimensional imaging of tracheal tubes. Chapter 3 begins to characterize the physical properties of insect hemolymph, specifically the viscosity and density of hemolymph, using experimental measurements. Because insects are strongly affected by environmental temperature, this chapter also explores how hemolymph viscosity may be affected by temperature. Chapter 4 builds on the results of Chapter 3, exploring the effects of developmental responses to temperature on hemolymph viscosity and properties, as well as performance of the insect using experimental measurements. Finally, Chapter 5 presents a kinematic and structural characterization of the insect heart using a variety of imaging techniques and analyses. / Doctor of Philosophy / Insect physiology and morphology has long been studied by biologists and entomologists, with many of the basic features understood and characterized. The insect circulatory and respiratory systems differ greatly from those of many other organisms. Physically, these systems transport fluids through microscale environments which include a variety of pumps, networks, and other structures that facilitate flow. Functionally, the circulatory and respiratory systems are largely decoupled, unlike in vertebrates. The respiratory system transports air directly to deliver oxygen to tissues, whereas the circulatory system transports various nutrients and other chemicals via hemolymph. With these unique differences, investigation of these major biological transport systems in insects is essential to fully understand their structure and function. This dissertation addresses many of the basic structural and physical properties of the insect respiratory and circulatory systems that are still unknown, despite growing engineering analysis. First, I measured specific geometric features of the insect tracheal network and determined if Murray’s law applies to this system. Second, I quantified the viscosity of insect hemolymph, including in response to temperature. To expand upon this relationship further, I measured hemolymph viscosity, hemolymph composition, and insect performance after temperature acclimation during development. Last, I investigated the morphology and kinematics of the insect heart, using many methods of imaging and analysis to measure structural features of the heart wall, including during function. Hemolymph properties and heart morphology provide the physical basis of flow production within the circulatory system. Understanding flow production within the circulatory system, as well as design features of the respiratory system, are crucial in the construction of mathematical models of both hemolymph and air flow within the insect.

Rapid receptive field (RF) reorganization of somatosensory neurons in the rat dorsal horn was examined using extracellular single unit recording. Subcutaneous injection of lidocaine into RFs of dorsal horn neurons results in expansion of their RFs within minutes. The expanded RFs appear adjacent to or/and proximal to original RFs. Out of 63 neurons tested, 36 (58%) show RF reorganization. The data suggest that dorsal horn of spinal cord is one of the initial sites for RF reorganization. The neural mechanisms of this effect are not well understood. We propose that changes in biophysical properties (membrane conductance, length constant) of the neurons resulting from lidocaine injection contribute to RF reorganization. Iontophoretic application of glutamate onto dorsal horn neurons that show lidocaine induced RF's expansion were used to test the model. Application of glutamate produced reduction of reorganized RFs in 9 of 20 (45%) tested cells. Application of NBQX produced no effect on either original or expanded RFs indicate that RF shrinkage effects of glutamate involve NMDA receptors. The results are consistent with the prediction of the proposed model. Subcutaneous injection of capsaicin into tactile RFs of low threshold mechanoreceptive dorsal horn neurons produced no effect on the RF sizes that are consistent with other studies. Following the injection, the original RFs were completely silenced (46%) or remained responsive (54%).

A dor neuropática é uma condição debilitante causada por danos no sistema nervoso somatossensorial, como lesões dos nervos periféricos. As células do sistema imune, em particular os monócitos/macrófagos, desempenham um papel fundamental no desenvolvimento deste processo. Embora diversos estudos sugiram o envolvimento dessas células na medula espinal e gânglio da raiz dorsal (GRD) após a indução da neuropatia, a caracterização funcional e fenotípica, bem como a origem dessas células nesses órgãos, ainda não está esclarecida. Na medula espinal, estudos recentes têm demonstrado que apesar da massiva ativação e proliferação da micróglia residente, não há recrutamento de células mielóides para esse tecido após a indução da neuropatia, divergindo dos dados anteriormente descritos na literatura. Diante desses estudos controversos, iniciamos nosso trabalho demonstrando que possivelmente as células mielóides não são capazes de ultrapassar a barreira hematoencefálica e infiltrar na medula espinal após a indução da neuropatia periférica pelo modelo de SNI e assim, a ativação microglial ocorre de maneira independente do infiltrado dessas células neste tecido. No que se refere aos GRDs, trabalhos anteriores demonstram que há um aumento dos marcadores de ativação de macrófagos nesse tecido após a lesão periférica. Com isso, nós caracterizamos as subpopulações de monócitos/macrófagos presentes no GRD e identificamos, células CX3CR1+ e células CCR2+. De maneira interessante, ao isolarmos as células CX3CR1+ observamos que esse subtipo celular possa ser as principais células responsáveis pela produção dos mediadores inflamatórios no GRD após indução de SNI, enquanto as células CCR2+ parecem contribuir apenas de maneira parcial para a produção de IL-1? e TNF-? neste tecido, uma vez que a expressão desses mediadores não foi totalmente suprimida na ausência desse subtipo celular. Por fim, investigamos a origem desses subtipos de monócitos presentes no GRD. Por meio da parabiose entre animais wild type e GFP+, observamos que embora haja um pequeno aumento de células GFP+ no GRD de animais lesionados, essas células não são macrófagos. Corroborando com esses dados, ao realizarmos a parabiose de animais wild type com animais CX3CR1GFP/+CCR2RFP/+ não observamos presença de células CX3CR1 ou CCR2 no GRD após SNI. Em conjunto, nossos dados demonstram que existem duas subpopulações de monócitos no GRD, sendo uma delas residente e contribuindo de maneira efetiva para a produção dos mediadores inflamatórios locais e outra população de células CCR2+ que podem ter um papel mais relevante no sítio da lesão e assim, a exacerbação da inflamação local pode interferir indiretamente, na ativação das células presentes nos GRDs, bem como na produção dos mediadores inflamatórios no tecido, que vão contribuir para o desenvolvimento da dor neuropática. / Neuropathic pain is a debilitating disease due to severe damage to the nervous system, induced by peripheral nerve injury. The cells of the immune system, especially monocytes/macrophages, played a critical role in these process. Several projects have been suggested the role of these cells in the spinal cord and dorsal root ganglia (DRG) after neuropathic pain induction, but the functional and phenotypic characterization, as well as the source of cells, is still unclear. In the spinal cord, recent studies have shown that although massive activation and proliferation of the microglial occurred, there is no recruitment of myeloid cells to this tissue after the neuropathic pain induction, but this is contrary to previous findings in the literature. Based on this controversial studies, we first showed that myeloid cells are not able to overcome the blood-brain barrier and infiltrate in the spinal cord after the peripheral nerve injury by SNI model and thus, the microglial activation occurs independent of the infiltration of these cells in this tissue. With regard to DRGs, previous work has shown that there is an increase in the activation markers of macrophages after peripheral nerve injury.Thus, we characterized the subpopulations of monocytes/macrophages in the DRG and we identified CX3CR1+ and CCR2+ cells. Interestingly, when isolating the CX3CR1+ cells, we observed that this cell subtype may be the main cells responsible for the production of inflammatory mediators in the DRG after SNI induction, whereas CCR2+ cells appear to contribute only partially to the production of IL-1? and TNF-? in this tissue, since the expression of these mediators was not completely suppressed in the absence of this cellular subtype. Finally, we investigated the origin of these monocyte subtypes present in the DRG. Through parabiosis between wild type and GFP+ animals, we observed that although there is a small increase of GFP+ cells in the DRG of injured animals, these cells are not macrophages. Corroborating with these data, when performing the wild type parabiosis with CX3CR1GFP /+ CCR2RFP/+ animals, we did not observe the presence of CX3CR1 or CCR2 cells in the GRD after SNI. Finally, our data demonstrate that there are two subpopulations of monocytes in the DRG, one of them residing and contributing effectively to the production of local inflammatory mediators and another population of CCR2 cells that may have a more relevant role at the lesion site and thus, the exacerbation of local inflammation may indirectly interfere, in the activation of the cells present in the DRGs, as well as in the production of inflammatory mediators in the tissue, which will contribute to the development of neuropathic pain.

A miopatia dorsal cranial (MDC) acomete frangos de corte e é verificada a partir dos 33 dias de vida, quase exclusivamente nas linhas de abate e em diferentes matadourosfrigoríficos dos três estados do sul do Brasil, aonde vem causando prejuízos com condenações parciais e totais, gerando crescente preocupação, já que é um problema completamente desconhecido e faz parte de um alimento consumido em todo o mundo. O objetivo desta pesquisa foi fazer uma caracterização anatomopatológica da MDC, através da colheita e análise de dados relacionados ao problema em uma empresa avícola do sul do país. A caracterização foi realizada através de um estudo anatômico, avaliações macroscópicas e microscópicas do músculo envolvido e avaliação de outros músculos e vísceras de carcaças com lesão dorsal na busca de informações que pudessem indicar alguma etiologia conhecida. A colheita e análise de dados foi realizada em uma empresa com 0,5% ao mês de condenação por MDC. Pesquisou-se a idade de início da lesão nos frangos, a presença de possíveis problemas nutricionais e/ou miotóxicos e análise do banco de dados da condenação para alguns parâmetros zootécnicos. Pode-se verificar no estudo anatômico que na carcaça com MDC a vascularização local não estava evidente. A lesão macroscópica no músculo Anterior Latissimus Dorsi (ALD) foi 89% bilateral (de 110 carcaças avaliadas). A pele do local apresentou coloração amarelada, aumento de volume subcutâneo e ao corte, presença de fluido gelatinoso amarelo citrino e inodoro. Os músculos ALD lesionados apresentavam as superfícies inferiores e/ou superiores hemorrágicas, aumento da consistência, palidez e aderência aos músculos adjacentes e ao corte, aumento da espessura quando comparado a músculos sem alteração. Microscopicamente a lesão foi caracterizada como multifásica com presença de algumas fibras ainda viáveis, fibras em degeneração hialina, necrose flocular, outras em regeneração e extensa proliferação de tecido conjuntivo fibroso além de tecido fibro-adiposo. Tecido de granulação altamente vascularizado na periferia da lesão necrótica e envolvendo todo o músculo foi freqüentemente observado com grande quantidade de células inflamatórias mononucleares. Granulócitos foram verificados em alguns cortes do ALD macroscopicamente alterado. O ALD e demais músculos, sem lesão macroscópica, apresentaram lesões microscópicas de leves a muito intensas, sendo hialinização e necrose flocular as lesões predominantes em todos os outros músculos. Lesão microscópica foi encontrada tão cedo quanto 23 dias de vida. Nos corações, não foram encontradas alterações significativas. Nas moelas verificou-se picnose difusa nos miócitos. Os rins e as bursas de Fabricius apresentaram lesões, como severa necrose tubular e intensa depleção linfóide (>70%), respectivamente. Erros de dosagem do premix (vitamina E, selênio e ionóforos) na ração de frangos com MDC foram encontrados. Já sementes de Senna occidentalis não foram encontradas no alimento das mesmas. Machos, de linhagens pesadas, apresentando maiores médias de peso e idade ao abate apresentaram os maiores percentuais de condenação por MDC (P<0,01). Conclui-se que a MDC é multifásica, ocorrendo a partir de diferentes momentos de insulto e acomete com maior freqüência frangos pesados e de crescimento rápido. Deficiência de vitamina E e selênio ou níveis tóxicos de ionóforos podem estar contribuindo na indução desta “nova” miopatia. / “Miopatia dorsal cranial” (MDC) or dorsal cranial myopathy affects broiler chickens as early as their 33rd day of life, occurring almost exclusively on slaughter lines and in different slaughterhouses in the three southern states of Brazil where it has been causing economical losses, due to the resulting condemnation or downgrading of carcasses. It is cause for great concern as it is a completely unknown problem and chicken is an important food product consumed worldwide. The objective of this study was to conduct an anatomical and pathological characterization through the acquisition and analysis of data related to this problem in a poultry industry. This characterization was carried out through an anatomical study, histological evaluation of the damaged muscle and evaluation of other muscles and organs of carcasses presenting back injury, in the search for information that would reveal any known etiology. The data acquisition and analysis was carried out in a company with 0.5% of carcasses downgraded per month due to this disease. The age at which the lesion starts, the presence of possible nutritional and/or toxic myopathies, and the analysis of the condemnation database for some zootechnical parameters were carried out. It was found in an anatomical study that damaged muscle vascularization with MDC was not evident. Macroscopic lesions in the Anterior Latissimus Dorsi muscle (ALD) were 89% bilateral (in 110 carcasses evaluated). Skin on the lesion was yellowish, with a subcutaneous volume increase, and after cutting the skin was odorless with the presence of an edematous and gel-like yellow-citrine fluid. ALD muscle was hemorrhagic on the lower and/or upper surface, showing increased consistency and pallor and adherence to the adjacent muscles, and after cutting increased thickness was verified when compared to muscles without lesions. Microscopically the lesion was characterized as polyphasic with some viable muscle fibers, hyaline degenerated fibers, floccular necrosis, regenerating muscle fibers and extensive fibrosis and fibro-adipose tissue. Highly vascular granulation tissue at the border of the necrotic muscle was found with large amounts of inflammatory mononuclear cells. Some ALD macroscopically damaged muscle had granulocytes cells. ALD and other muscles, without macroscopic injury, showed from mild to intense microscopic lesions, fiber degeneration (hyaline) and floccular necrosis being the major lesions in the former muscles. Microscopic lesions were found as early as the 23rd day of life. There were no significant changes observed in the hearts, but there was a diffuse pyknosis of myocytes in the gizzards. The kidneys and the bursa of Fabricius had injuries such as severe tubular necrosis and severe lymphoid depletion (>70%), respectively. Errors in the mineral and vitamin dosage in the premix (vitamin E, selenium and ionophores) fed to the chickens with MDC were found. However, seeds of Senna occidentalis were not found in the feed. Males of heavy strains, having higher average weight and older age at slaughter had the highest percentage of downgrading due to MDC (P<0.01). Therefore, MDC is polyphasic and occurs at different times of insult, affecting most frequently heavy and fast-growing chickens. Deficiency of vitamin E/selenium or toxic levels of ionophores may be contributing to the induction of this recently observed type of myopathy.

Este trabalho teve como objetivo avaliar os efeitos sistêmicos, microcirculatórios assim como mudanças na expressão gênica renal, causados pela ação da noradrenalina, nitropussiato de sódio e levosimendan no tratamento do choque hemorrágico. Nesse estudo foi utilizado o modelo da câmara dorsal.Os animais foram sujeitos a choque hemorrágico e após, foram aleatoriamente divididos em quatro grupos. Os grupos foram: CTRL, recebeu apenas ringer lactato; NPS recebeu ringer lactato com nitroprussiato de sódio; NA recebeu ringer lactato com noradrenalina e LEV, recebeu ringer lactato com levosimendan. Foram avaliados parâmetros sistêmicos, assim como parâmetros microcirculatórios (comparados como percentual em relação ao momento basal). Além disso, foi avaliada a expressão gênica renal de eNOS, HIF-1&#945;, ICAM e caspase-3. O grupo NPS apresentou uma recuperação sustentada do diâmetro arteriolar ( 89 12 %) e DCF (125 114 %) ao final do tratamento. Houve recuperação da velocidade de hemácias nos grupos CTRL e NPS. Não houve diferença em relação ao número de leucócitos aderidos e/ou rolantes ao final do tratamento. A expressão gênica renal de eNOS e caspase-3 entre os grupos não apontou diferenças, entretanto houve diferença significativa na expressão renal de HIF- 1&#945; no grupo NA (0,65 0,08, UA) em relação ao grupo CTRL (0,44 0,06, UA) e LEV (0,45 0,06, UA). Todos os grupos tiveram uma maior expressão de ICAM (0,65 0,12; 0,7 0,12; 0,069 0,06; 0,65 0,12, UA) em relação ao grupo SHAM (0,50 0,05, UA). Ringer lactato puro ou associado com noradrenalina ou levosimendan não foram suficientes para recuperar e sustentar os parâmetros microvasculares. O tratamento com nitroprussiato de sódio foi o que apresentou os melhores resultados, com recuperação dos diâmetros arteriolar, da DCF e velocidade de hemácias. / This work aimed at evaluating the systemic and microcirculatory effects, as well as changes in renal gene expression elicited by noradrenalin, sodium nitroprusside and levosimendan associated to volume resuscitation in the treatment of hemorrhagic shock. The dorsal chamber model was used in this study. Animals were subjected to hemorrhagic shock and after that, were randomly distributed between four groups. Groups were: CTRL, received only lactated ringer's solution; NPS received lactated ringer's solution with sodium nitroprusside; NA received lactated ringer's solution with noradrenaline and LEV received lactated ringer's with levosimendan. Systemic and microcirculatory parameters were evaluated ( as percent change compared to baseline). Furthermore, renal genic expression of eNOS, HIF-1a and caspase-3 were also evaluated. NPS group presented a sustained recovery of arteriolar diameter ( 89 12 %) and FCD (125 114 %) at the end of the treatment. There was a red blood cell velocity recovery in CTRL and NPS groups. There was no difference regarding adhered or rolling leukocytes at the end of the treatment. eNOS and caspase-3 renal genic expression between groups showed no differences, however, there was a significant difference in renal genic expression of HIF-1&#945; in NA group (0,65 0,08, AU) compared to CTRL (0,44 0,06, AU) e LEV (0,45 0,06, AU). All groups had a higher expression of ICAM (0,65 0,12; 0,7 0,12; 0,069 0,06; 0,65 0,12, AU) compared to the SHAM group (0,50 0,05, AU). Ringer's lactate solution associated or not to noradrenaline or levosimendan were not enough to recover and sustain microvascular parameters. Treatment with sodium nitroprusside presented the best results, with sustained arteriolar diameter, FCD and RBCV recoveries.

Este trabalho teve como objetivo avaliar os efeitos sistêmicos, microcirculatórios assim como mudanças na expressão gênica renal, causados pela ação da noradrenalina, nitropussiato de sódio e levosimendan no tratamento do choque hemorrágico. Nesse estudo foi utilizado o modelo da câmara dorsal.Os animais foram sujeitos a choque hemorrágico e após, foram aleatoriamente divididos em quatro grupos. Os grupos foram: CTRL, recebeu apenas ringer lactato; NPS recebeu ringer lactato com nitroprussiato de sódio; NA recebeu ringer lactato com noradrenalina e LEV, recebeu ringer lactato com levosimendan. Foram avaliados parâmetros sistêmicos, assim como parâmetros microcirculatórios (comparados como percentual em relação ao momento basal). Além disso, foi avaliada a expressão gênica renal de eNOS, HIF-1&#945;, ICAM e caspase-3. O grupo NPS apresentou uma recuperação sustentada do diâmetro arteriolar ( 89 12 %) e DCF (125 114 %) ao final do tratamento. Houve recuperação da velocidade de hemácias nos grupos CTRL e NPS. Não houve diferença em relação ao número de leucócitos aderidos e/ou rolantes ao final do tratamento. A expressão gênica renal de eNOS e caspase-3 entre os grupos não apontou diferenças, entretanto houve diferença significativa na expressão renal de HIF- 1&#945; no grupo NA (0,65 0,08, UA) em relação ao grupo CTRL (0,44 0,06, UA) e LEV (0,45 0,06, UA). Todos os grupos tiveram uma maior expressão de ICAM (0,65 0,12; 0,7 0,12; 0,069 0,06; 0,65 0,12, UA) em relação ao grupo SHAM (0,50 0,05, UA). Ringer lactato puro ou associado com noradrenalina ou levosimendan não foram suficientes para recuperar e sustentar os parâmetros microvasculares. O tratamento com nitroprussiato de sódio foi o que apresentou os melhores resultados, com recuperação dos diâmetros arteriolar, da DCF e velocidade de hemácias. / This work aimed at evaluating the systemic and microcirculatory effects, as well as changes in renal gene expression elicited by noradrenalin, sodium nitroprusside and levosimendan associated to volume resuscitation in the treatment of hemorrhagic shock. The dorsal chamber model was used in this study. Animals were subjected to hemorrhagic shock and after that, were randomly distributed between four groups. Groups were: CTRL, received only lactated ringer's solution; NPS received lactated ringer's solution with sodium nitroprusside; NA received lactated ringer's solution with noradrenaline and LEV received lactated ringer's with levosimendan. Systemic and microcirculatory parameters were evaluated ( as percent change compared to baseline). Furthermore, renal genic expression of eNOS, HIF-1a and caspase-3 were also evaluated. NPS group presented a sustained recovery of arteriolar diameter ( 89 12 %) and FCD (125 114 %) at the end of the treatment. There was a red blood cell velocity recovery in CTRL and NPS groups. There was no difference regarding adhered or rolling leukocytes at the end of the treatment. eNOS and caspase-3 renal genic expression between groups showed no differences, however, there was a significant difference in renal genic expression of HIF-1&#945; in NA group (0,65 0,08, AU) compared to CTRL (0,44 0,06, AU) e LEV (0,45 0,06, AU). All groups had a higher expression of ICAM (0,65 0,12; 0,7 0,12; 0,069 0,06; 0,65 0,12, AU) compared to the SHAM group (0,50 0,05, AU). Ringer's lactate solution associated or not to noradrenaline or levosimendan were not enough to recover and sustain microvascular parameters. Treatment with sodium nitroprusside presented the best results, with sustained arteriolar diameter, FCD and RBCV recoveries.

A miopatia dorsal cranial (MDC) acomete frangos de corte e é verificada a partir dos 33 dias de vida, quase exclusivamente nas linhas de abate e em diferentes matadourosfrigoríficos dos três estados do sul do Brasil, aonde vem causando prejuízos com condenações parciais e totais, gerando crescente preocupação, já que é um problema completamente desconhecido e faz parte de um alimento consumido em todo o mundo. O objetivo desta pesquisa foi fazer uma caracterização anatomopatológica da MDC, através da colheita e análise de dados relacionados ao problema em uma empresa avícola do sul do país. A caracterização foi realizada através de um estudo anatômico, avaliações macroscópicas e microscópicas do músculo envolvido e avaliação de outros músculos e vísceras de carcaças com lesão dorsal na busca de informações que pudessem indicar alguma etiologia conhecida. A colheita e análise de dados foi realizada em uma empresa com 0,5% ao mês de condenação por MDC. Pesquisou-se a idade de início da lesão nos frangos, a presença de possíveis problemas nutricionais e/ou miotóxicos e análise do banco de dados da condenação para alguns parâmetros zootécnicos. Pode-se verificar no estudo anatômico que na carcaça com MDC a vascularização local não estava evidente. A lesão macroscópica no músculo Anterior Latissimus Dorsi (ALD) foi 89% bilateral (de 110 carcaças avaliadas). A pele do local apresentou coloração amarelada, aumento de volume subcutâneo e ao corte, presença de fluido gelatinoso amarelo citrino e inodoro. Os músculos ALD lesionados apresentavam as superfícies inferiores e/ou superiores hemorrágicas, aumento da consistência, palidez e aderência aos músculos adjacentes e ao corte, aumento da espessura quando comparado a músculos sem alteração. Microscopicamente a lesão foi caracterizada como multifásica com presença de algumas fibras ainda viáveis, fibras em degeneração hialina, necrose flocular, outras em regeneração e extensa proliferação de tecido conjuntivo fibroso além de tecido fibro-adiposo. Tecido de granulação altamente vascularizado na periferia da lesão necrótica e envolvendo todo o músculo foi freqüentemente observado com grande quantidade de células inflamatórias mononucleares. Granulócitos foram verificados em alguns cortes do ALD macroscopicamente alterado. O ALD e demais músculos, sem lesão macroscópica, apresentaram lesões microscópicas de leves a muito intensas, sendo hialinização e necrose flocular as lesões predominantes em todos os outros músculos. Lesão microscópica foi encontrada tão cedo quanto 23 dias de vida. Nos corações, não foram encontradas alterações significativas. Nas moelas verificou-se picnose difusa nos miócitos. Os rins e as bursas de Fabricius apresentaram lesões, como severa necrose tubular e intensa depleção linfóide (>70%), respectivamente. Erros de dosagem do premix (vitamina E, selênio e ionóforos) na ração de frangos com MDC foram encontrados. Já sementes de Senna occidentalis não foram encontradas no alimento das mesmas. Machos, de linhagens pesadas, apresentando maiores médias de peso e idade ao abate apresentaram os maiores percentuais de condenação por MDC (P<0,01). Conclui-se que a MDC é multifásica, ocorrendo a partir de diferentes momentos de insulto e acomete com maior freqüência frangos pesados e de crescimento rápido. Deficiência de vitamina E e selênio ou níveis tóxicos de ionóforos podem estar contribuindo na indução desta “nova” miopatia. / “Miopatia dorsal cranial” (MDC) or dorsal cranial myopathy affects broiler chickens as early as their 33rd day of life, occurring almost exclusively on slaughter lines and in different slaughterhouses in the three southern states of Brazil where it has been causing economical losses, due to the resulting condemnation or downgrading of carcasses. It is cause for great concern as it is a completely unknown problem and chicken is an important food product consumed worldwide. The objective of this study was to conduct an anatomical and pathological characterization through the acquisition and analysis of data related to this problem in a poultry industry. This characterization was carried out through an anatomical study, histological evaluation of the damaged muscle and evaluation of other muscles and organs of carcasses presenting back injury, in the search for information that would reveal any known etiology. The data acquisition and analysis was carried out in a company with 0.5% of carcasses downgraded per month due to this disease. The age at which the lesion starts, the presence of possible nutritional and/or toxic myopathies, and the analysis of the condemnation database for some zootechnical parameters were carried out. It was found in an anatomical study that damaged muscle vascularization with MDC was not evident. Macroscopic lesions in the Anterior Latissimus Dorsi muscle (ALD) were 89% bilateral (in 110 carcasses evaluated). Skin on the lesion was yellowish, with a subcutaneous volume increase, and after cutting the skin was odorless with the presence of an edematous and gel-like yellow-citrine fluid. ALD muscle was hemorrhagic on the lower and/or upper surface, showing increased consistency and pallor and adherence to the adjacent muscles, and after cutting increased thickness was verified when compared to muscles without lesions. Microscopically the lesion was characterized as polyphasic with some viable muscle fibers, hyaline degenerated fibers, floccular necrosis, regenerating muscle fibers and extensive fibrosis and fibro-adipose tissue. Highly vascular granulation tissue at the border of the necrotic muscle was found with large amounts of inflammatory mononuclear cells. Some ALD macroscopically damaged muscle had granulocytes cells. ALD and other muscles, without macroscopic injury, showed from mild to intense microscopic lesions, fiber degeneration (hyaline) and floccular necrosis being the major lesions in the former muscles. Microscopic lesions were found as early as the 23rd day of life. There were no significant changes observed in the hearts, but there was a diffuse pyknosis of myocytes in the gizzards. The kidneys and the bursa of Fabricius had injuries such as severe tubular necrosis and severe lymphoid depletion (>70%), respectively. Errors in the mineral and vitamin dosage in the premix (vitamin E, selenium and ionophores) fed to the chickens with MDC were found. However, seeds of Senna occidentalis were not found in the feed. Males of heavy strains, having higher average weight and older age at slaughter had the highest percentage of downgrading due to MDC (P<0.01). Therefore, MDC is polyphasic and occurs at different times of insult, affecting most frequently heavy and fast-growing chickens. Deficiency of vitamin E/selenium or toxic levels of ionophores may be contributing to the induction of this recently observed type of myopathy.