No description available.

The a of TNFa in title is the Greek alpha. / Thesis (MSc)--University of Stellenbosch, 2002. / ENGLISH ABSTRACT: Background: Cardiac hypertrophy is an adaptive process occurring in response to mechanical overload or tissue injury. The stimuli for cardiac hypertrophy are diverse and vary from increased afterload on the heart to cardiac remodeling in response to cytokines. Amongst others, obesity is characterized by excessive body weight resulting in metabolic disorders. This excess body weight necessitates an increased blood and oxygen delivery to the peripheral tissues, which is achieved by an elevated cardiac output. Total blood volume is also increased in the obese due to the increased tissue volume and vascularity. With time, the obesity induced increase in cardiac preload results in left ventricular hypertrophy and dilatation. Obesity is also associated with complications such as hypertension, insulin resistance and impaired glucose metabolism. In addition, adipose tissue has been implicated to contribute to elevated circulating TNFa levels in obesity and may contribute to the pathophysiology of the heart in obese individuals. The heart is a major cytokine-producing organ that generates amongst others tumor necrosis factor a (TNFa). TNFa is a proinflammatory cytokine, which acts to increase its own production, has cytotoxic and cytostatic effects on certain tumor cells and influences growth and differentiation in virtually all cell types including cardiomyocytes. Elevated levels of TNFa are detected peripherally in almost all forms of cardiac injury and in hypertrophic cardiomyopathy. These elevations are proposed to be deleterious to the heart, although an adaptive role for low levels of TNFa has been proposed. Aim: The aim of the study was to determine whether there is a correlation between obesity and serum, myocardial, and adipose tissue TNFa levels and cardiac hypertrophy. We also wished to determine whether the hearts from the obese animals functioned normally under normoxic conditions and whether they responded differently to ischaemia/reperfusion when compared with their concurrent controls. Materials and Methods: Male Sprague-Dawley rats (n=100) were fed a high caloric diet (HCD) containing 33% rat chow, 33% condensed milk, 7% sucrose and 27% water, or standard laboratory rat chow for 6-12 weeks. Food consumption, body weight gain, heart weight and tibia length were measured. Serum glucose, insulin and lipid levels were also determined. Hearts were excised and perfused on the isolated Working Heart perfusion apparatus and cardiac function was monitored and documented. Hearts were then subjected to 15 minutes of total global ischaemia at 370C, and reperfused for 30 minutes. Cardiac function was again documented. A separate series of hearts were freeze-clamped at different time points during the experimental protocol and stored in liquid nitrogen for the determination of myocardial TNFa and cGMP levels. Serum TNFa levels were determined after 12 weeks on the high caloric or normal/control diet. After 12 weeks on the diet myocardial TNFa levels of the HCD fed animals and their concurrent controls were determined before and during ischaemia. Adipose tissue and myocardial tissue TNFa levels were also determined after 6, 9 and 12 weeks on the respective diets. Myocardial cGMP levels were measured in the HCD fed rats and the control rats after 6, 9, and 12 weeks. These data were used as an indirect index to determine whether the myocardial NOcGMP pathway was activated in the normoxic hearts on the respective diets. Results: The body weight of the HCO fed animals was significantly higher compared with their respective controls after 12 weeks on the diet (459.9 ± 173.8 g and 271.5 ± 102.6 g respectively (p<0.05». The HCO fed animals also had heart weight to body weight ratios that were significantly greater compared with the controls (4.2 ± 0.1 mglg and 3.7 ± 0.1 mglg respectively (p<0.05». The plasma glucose levels of the HCO fed animals were higher than their respective controls (9.2 ± 0.3 mmoiII and 7.8 ± 0.3 mmoiII respectively (p<0.05)), but their insulin levels were similar (12.87 ± 1.02 IlIUlml and 12.42 ± 5.06 IlIU/ml). Plasma lipid profiles (plasma cholesterol, high density lipoprotein (HOL) cholesterol and plasma triacylglyceride (TAG)) were abnormal in the HCO fed animals compared with the control rats. Plasma TAG levels in the HCO fed animals were significantly higher compared with the control rats (0.664 ± 0.062 mmoiII and 0.503 ± 0.043 (p<0.05», while plasma cholesterol levels (1.794 ± 0.058 mmoIII and 2.082 ± 0.062 mmoiII (p<0.05» and HOL cholesterol levels were significantly lower (1.207 ± 0.031 mmoiII and 1.451 ± 0.050 mmoiII (p<0.05». Cardiac mechanical function was similar for both groups before ischaemia, but the percentage aortic output recovery was lower for the hearts from the HCO fed animals when compared with their controls (47.86 ± 7.87% and 66.67 ± 3.76 % respectively (p<0.05». Serum TNFa levels of the HCO fed animals were higher compared with the control animals (51.04 ± 5.14 AU and 31.46 ± 3.72 AU respectively (p<0.05», but myocardial TNFa levels remained lower in these animals (312.0 ± 44.7 pglgram ww and 571.4 ± 132.9 pg/gram ww respectively (p<0.05)). During ischaemia these myocardial TNFa levels increased above those of the controls (442.9 ± 12.4 pg/gram ww and 410.0 ± 12.5 pg/gram ww respectively (p<0.05)). The adipose tissue TNFa levels were significantly increased after 12 weeks on the high caloric diet compared with the control animals (4.4 ± 0.4 pg/gram ww and 2.5 ± 0.3 pg/gram ww respectively (p<0.05)). There was no significant difference in the myocardial cGMP levels of the HCD rats compared with the conrol rats after 6, 9 and 12 weeks. Conclusion: 1) The high caloric diet induced obesity, which lead to cardiac hypertrophy in this study. 2) There was a strong correlation between elevated adipose tissue and serum TNFa levels, and cardiac hypertrophy. 3) Elevated serum TNFa levels did not lead to activation of the myocardial NO-cGMP pathway in the normoxic hearts in this model. 4) The hypertrophied hearts from the HCD fed animals had poorer post-ischaemie myocardial functions than their concurrent controls. / AFRIKAANSE OPSOMMING: Agtergrond: Miokardiale hipertrofie is In aanpassing wat gebeur as In gevolg van meganiese oorbelading of weefsel beskadiging. Verskillende stimuli kan tot miokardiale hipertrofie aanleiding gee soos byvoorbeeld In verhoging in nalading, of miokardiale hermodellering in respons op sitokiene. Verhoging van voorbelading in vetsug mag ook tot hipertrofie aanleiding gee. Vetsug word gekenmerk deur In oormatige liggaamsmassa wat tot metaboliese versteurings lei. Die oormatige liggaamsmassa vereis In verhoging in bloed- en suurstofverskaffing aan die perifere weefsel wat deur In verhoging in die kardiale uitset vermag kan word. Die bloed volume van In vetsugtige individu word ook verhoog as gevolg van In verhoging in weefselvolume en vaskulariteit en met verloop van tyd induseer die verhoogde kardiale voorbelading linker ventrikulêre hipertrofie en dilatasie. Vetsug word ook met verskeie ander siekte toestande soos hipertensie, insulien weerstandigheid en versteurde glukose metabolisme, geassosieer. Vetweefsel dra ook by tot verhoging van tumor nekrose faktor alfa (TNFa) vlakke in die bloed, wat op sy beurt tot miokardiale hipertrofie mag bydra. TNFa is In proinflammatoriese sitokien wat sy eie produksie kan stimuleer. Dit het ook sitotoksiese en sitostatiese effekte op sekere tumor selle en kan groei en differensiasie in bykans alle seltipes, insluitende kardiomiosiete, stimuleer. Die hart kan ook TNFa produseer en verhoogde TNFa vlakke word feitlik in alle vorms van miokardiale besering en hipertrofiese kardiomiopatie waargeneem. Daar word voorgestel dat verhoogde TNFa vlakke vir die hart nadelig is, ten spyte van die vermoeding dat die sitokien In potensiële aanpassings rol by laer vlakke het. Doelstelling: Die doel van hierdie studie was om vas te stelof daar 'n verband tussen vetsug en serum, miokardiale en vetweefsel TNFa vlakke en miokardiale hipertrofie, bestaan. Ons het ook gepoog om te bepaal of harte van vetsugtige diere normaal funksioneer en of die response van sulke harte op isgemie-herperfusie van die van ooreenstemmende kontroles verskil. Materiaal en tegnieke: Manlike Sprague-Dawley rotte (n=100) is vir 6-12 weke op 'n hoë kalorie dieët (HKD) geplaas. Die HKD het uit 33% rotkos, 33% gekondenseerde melk, 7% sukrose en 27% water bestaan. Kontrole diere het standaard laboratorium rotkos ontvang. Voedselinname, liggaamsmassa toename, serum insulien, glukose en lipied vlakke is ook bepaal. Harte is geïsoleer en geperfuseer volgens die Werk Hart perfusie metode en hart funksie is gemonitor en gedokumenteer. Harte is vervolgens aan 15 minute globale isgemie by 3rC blootgestel en daarna weer vir 30 minute geherperfuseer waartydens hartfunksie weer gedokumenteer is. 'n Aparte groep harte is op spesifieke tydsintervalle gedurende die eksperimentele protokol gevriesklamp en in vloeibare stikstof gestoor vir die bepaling van miokardiale TNFa en sGMP vlakke. Serum TNFa vlakke is bepaal na 12 weke op die dieët. Na die diere 12 weke op die HKD was, is hierdie diere en hulooreenstemmende kontroles se miokardiale TNFa vlakke voor en na isgemie bepaal. Vetweefsel en miokardiale TNFa vlakke is ook onderskeidelik na 6, 9 en 12 weke bepaal. Miokardiale sGMP vlakke is in die HKD diere en in die kontrole diere na 6, 9 en 12 weke bepaal. sGMP vlakke is gebruik as 'n indirekte indeks van aktivering van die miokardiale NO-sGMP boodskapper pad. Resultate: Na 12 weke op die dieët was die liggaamsmassa van die HKD diere beduidend hoër in vergeleke met hulooreenstemmende kontroles (459.9 ± 173.8 g en 271.5 ± 102.6 g (p<0.05)). Die HKD diere se hart massa tot liggaam massa verhouding was ook beduidend hoër in vergelyking met die van kontroles (4.2 ± 0.1 mglg en 3.7 ± 0.1 mglg (p<0.05)). Alhoewel insulien vlakke dieselfde was (12.42 ± 5.06 j.lIU/ml en 12.87 ± 1.02 j.lIU/ml), was serum glukose vlakke van die HKD diere hoër as die van die ooreenstemmende kontroles (9.2 ± 0.3 mmoiii en 7.8 ± 0.3 mmoiii (p<0.05)). Plasma lipied profiele (HOL cholesterol, plasma cholesterol en trigliseriede) was abnormaal in die HKD diere. Plasma TAG vlakke in die HKD diere was beduidend hoër as die van die kontroles (0.664 ± 0.062 mmoiii en 0.503 ± 0.043 (p<0.05)), terwyl plasma cholesterol vlakke (1.794 ± 0.058 mmoiii en 2.082 ± 0.062 mmoiii (p<0.05)) en HOL cholesterol vlakke beduidend laer was (1.207 ± 0.031 mmoiii en 1.451 ± 0.050 mmoiii (p<0.05)). Miokardiale meganiese funksie was dieselfde vir beide groepe voor isgemie, maar die persentasie aorta omset herstel tydens herperfusie was laer in die HKD diere in vergelyking met die van kontrole diere (47.86 ±. 7.87% en 66.67 ± 3.76% (p<0.05)). Serum TNFa vlakke van die HKD diere was beduidend hoër as die van kontrole diere (51.04 ± 5.14 AU en 31.46 ± 3.72 AU (p<0.05)), maar miokardiale TNFa vlakke was laer (312.0 ± 44.7 pglgram nat gewig en 571.4 ± 132.9 pglgram nat gewig (p<0.05)). Die vetweefsel TNFa vlakke was ook beduidend verhoog na 12 weke op "n hoë kalorie dieët wanneer dit vergelyk word met die van kontrole diere (4.4 ± 0.4 pglgram nat gewig en 2.5 ± 0.3 pglgram nat gewig respektiewelik (p<0.05)). Daar was geenbeduidende verskille in die miocardiale vlakke van sGMP in die HKD diere in vergelyking met die kontroles na 6, 9 en 12 weke. Gevolgtrekkings: 1) "n Hoë kalorie dieët het in dié studie vetsug geïnduseer en tot miokardiale hipertrofie gelei. 2) Daar was "n positiewe korrelasie tussen verhoogde vetweefsel en serum TNFa vlakke, en miokardiale hipertrofie. 3) Verhoogde serum TNFa vlakke het nie tot die aktivering van die miokardiale NO-sGMP pad in hierdie model gelei nie. 4) Die hipertrofiese harte het tydens herperfusie ná isgemie swakker as hulooreenstemmende kontroles gefunksioneer.

published_or_final_version / abstract / Pathology / Master / Master of Philosophy

published_or_final_version / abstract / Surgery / Master / Master of Philosophy

No description available.

Kawasaki disease (KD) is a multisystem vasculitis that results in localized coronary artery elastin breakdown and aneurysm formation. It is the leading cause of acquired heart disease of children in North America. Despite conventional treatment, a significant proportion of patients continue to develop coronary sequelae. The mechanisms of arterial aneurysm formation in KD are not known. Using a murine model of KD, Lactobacillus casei cell wall extract-induced coronary arteritis, the processes leading to coronary aneurysm formation were examined. Vessel damage occurred as a result of the increased enzymatic activity of the elastase, matrix metalloproteinase (MMP)-9. MMP-9 protein and activity levels were elevated in the heart post-disease induction. Expression and activity were specific for and localized to inflamed coronary arteries. The pro-inflammatory cytokine, tumour necrosis factor (TNF)-α, was required for increasing local MMP-9 expression. Importantly, MMP-9-deficient animals had a significantly reduced incidence of elastin breakdown. Furthermore, in a cohort of KD patients, serum MMP-9 did not correlate with coronary outcome, highlighting the importance of local expression of this elastase. Intravenous immunoglobulin (IVIG) and aspirin/salicylate are therapeutic agents in current use for the treatment of KD, though their exact mechanisms of action in KD are not known. The biologic effects of IVIG and salicylate on critical stages of disease development were examined. IVIG and salicylate had differential effects on TNF-α expression, with therapeutic concentrations of IVIG inhibiting, and salicylate inducing, TNF-α expression leading to an indirect modulation of MMP-9 expression. Interestingly, TNF-α expression and MMP-9 activity were both directly inhibited by the metal-chelating drug doxycycline. Treatment of affected mice with doxycycline significantly improved coronary outcome. Inhibiting both the inflammatory response as well as the downstream effects of inflammation were of therapeutic value in this model of KD. These results taken together demonstrate the importance of MMP-9 in the pathogenesis of coronary artery aneurysms in KD. Targeting MMP activity holds the promise of transforming KD from the leading cause of acquired heart disease to a self-limited febrile illness.

Tesis para optar al Grado de Magister en Ciencias Animales y Veterinarias / Necrosis pancreática infecciosa (IPN) es una de las enfermedades más prevalentes y económicamente devastadoras en la cría de trucha arcoíris (Oncorhynchys mykiss) en todo el mundo. La vacuna como medida de control convencional ha mostrado resultados inconsistentes en las condiciones de producción. Por lo tanto, la mejora genética para resistencia a IPN representa una alternativa para la prevención de los brotes. El objetivo del presente trabajo fue estimar la heredabilidad y correlación genética para los caracteres de resistencia al virus IPN y peso corporal a cosecha (PC) en truchas arcoíris. Para determinar la resistencia genética al virus IPN se utilizaron datos de un total de 2.278 individuos de 58 familias de hermanos completos (descendencia de 30 padres y 58 madres), con una representación de 17 a 58 peces por familia en etapa de pre-smolt. Los peces fueron desafiados con virus lPN para inducir la enfermedad. También se registró PC en 13.241 individuos genéticamente relacionados de los peces desafiados de la misma población de cría. El pedigrí incluyó 20.529 individuos. El análisis se realizó definiendo la sobrevivencia a la enfermedad como día de muerte. Para el análisis genético se aplicó un modelo lineal mixto bivariado incluyendo resistencia al virus IPN y PC como variables dependientes; tanque:año:sexo como factor y edad a cosecha como covariable para PC y como covariable de peso final para resistencia a IPN, respectivamente. El efecto del animal, asociado al pedigrí de los individuos, fue incluido como efecto aleatorio para ambos caracteres. Para el peso de PC se incluyó además un efecto aleatorio asociado al ambiente común. El modelo fue ajustado mediante el procedimiento de máxima verosimilitud restringida. La heredabilidad estimada para resistencia a IPN fue de 0,39 ± 0.08 y para PC fue de 0,35 ± 0,06. La correlación genética entre resistencia a IPN y PC fue de 0,05 ± 0,25. Los resultados indican que la heredabilidad para ambos caracteres en esta población es moderada, y que no existe correlación genética significativa entre los 14 caracteres estudiados. La presencia de variación genética significativa tanto para resistencia a IPN como para PC y la no existencia de correlación genética entre ambos rasgos de interés productivo indica la posibilidad de mejorar ambos caracteres mediante selección artificial de forma simultáneo. / Infectious pancreatic necrosis (IPN) is one of the most prevalent and economically devastating in breeding rainbow trout (Oncorhynchus mykiss) worldwide diseases. The vaccine as conventional control measure has shown inconsistent results in production conditions. Therefore, breeding for resistance IPN represents an alternative for preventing outbreaks. The aim of this study was to estimate the heritability and genetic correlation for resistance characteristics virus IPN and harvest body weight (HW) in rainbow trout. To determine genetic resistance to the virus IPN data from a total of 2,278 individuals from 58 families of full siblings (offspring of 30 fathers and 58 mothers), with a representation of 17-58 fish per family in pre-smolt were used. Fish were challenged with virus lPN to induce disease. HW was also recorded in 13,241 genetically related individuals challenged fish of the same population breeding. The pedigree includes 20,529 individuals. The analysis is done by defining disease survival as a day of death. For genetic analysis bivariate linear mixed model including resistance to IPN virus and HW as dependent variables was applied; Tank: year: sex as a factor and age as covariate harvest for HW and as a covariate end weight for resistance to IPN, respectively. The effect of the animal, associated with the pedigree of individuals, was included as a random effect for both characters. For weight of HW also it includes a random effect associated with the common environment. The model was fitted by restricted maximum likelihood procedure. The estimated heritability for resistance to IPN was 0.39 ± 0.08 and HW was 0.35 ± 0.06. The genetic correlation between resistance to IPN and HW was 0.05 ± 0.25. The results indicate that the heritability for both traits in this population is moderate, and there is no significant genetic correlation between the traits studied. The presence of significant genetic variation for both resistance to IPN and HW and the absence of genetic correlation between the traits of productive interest indicates the possibility of improving both characters simultaneously by artificial selection form.

Memoria para optar al Título Profesional de Médico Veterinario / La actividad salmonicultora, en la última década, se ha consolidado como una de las industrias de mayor crecimiento dentro del que hacer económico de Chile. Los especialistas estiman que para el bicentenario de Chile, la Salmonicultora generará retornos cercanos a los 2.825 millones de dólares, con un volumen de producción de 565 mil toneladas netas exportables. Para alcanzar esos valores, se requerirá incubar unos 1.000 millones de ovas de origen nacional y unos 360 millones de ovas importadas, de no variar los actuales modelos de abastecimiento. Muchas enfermedades infectocontagiosas en salmónidos pueden ingresar a través de ovas embrionadas. Este estudio pretende cuantificar el riesgo de introducción, transmisión y diseminación de Anemia Infecciosa del Salmón (ISA) y Necrosis Pancreática Infecciosa (IPN) a través de la importación de ovas, usando el método Delphi. La utilización de la metodología Delphi permitió conocer en detalle el proceso de importación de ovas y contribuir en sus resultados con medidas de mitigación que fueron consenso dentro del panel de expertos consultados sobre aspectos de vigilancia epidemiológica, screening de reproductores, distancias entre centros, entre otros. Dentro de los resultados cabe destacar que la fase selección de los reproductores en el país de origen, la efectividad de la desinfección de las ovas en el transporte, la aplicación de técnicas diagnósticas para la detección de portadores sanos fueron algunos de los puntos identificados como críticos por los expertos consultados. Finalmente, se debe recordar que Chile de tiempo en tiempo sufrirá las consecuencias de la introducción y establecimiento de enfermedades en especies salmonídeas, esto amerita que los sistemas de alerta temprana y respuesta oportuna deben estar activados permanentemente junto a las medidas más adecuadas para reducir el riesgo (probabilidad y consecuencias) de enfermedades en especies acuáticas

O conceito de PDT é a fotoindução da citotoxicidade das células proliferativas envolvendo um agente fotossensibilizador, uma fonte de luz e oxigênio. Apesar de ser uma terapia eficiente no tratamento de várias neoplasias, a PDT apresenta algumas limitações dentre as quais a não seletividade em células do tecido hepático.O presente trabalho avaliou a correlação entre penetração luminosa e necrose, assim como a extensão da mesma em função da concentração do fotossensibilizador utilizado (Photogem&#61666;) e de três diferentes doses de energia. A transição do epitélio necrosado e do epitélio sadio, foi realizada após a irradiação de fígados normais de ratos previamente fotossensibilizados. O acúmulo do Photogem, administrado via endovenosa, no fígado, foi investigado através da espectroscopia de fluorescência. As fontes de luz utilizadas para irradiação foram um laser de diodo de 630nm e um dispositivo a base de LEDs (diodos emissores de luz). Observamos que o tecido hepático normal, fotossensibilizado, apresenta suas características ópticas alteradas, evidenciadas nos estudos de penetração da luz e alteração térmica durante a irradiação, refletindo na profundidade da necrose. Verificamos que a presença do FS no tecido alvo diminui a penetração da luz, levando a um aumento da temperatura, devido à grande quantidade de energia absorvida pelo FS, a qual é dissipada na forma de calor. Notamos uma abrupta delineação da necrose correspondendo à queda de intensidade luminosa no tecido iluminado. A profundidade de necrose obtida com o uso do LED apresentou uma pequena variação, devido à linha espectral do mesmo ser mais larga, quando comparado ao laser. Histologicamente o tecido hepático e irradiado apresentou necrose coagulativa, infiltrado inflamatório neutrofílico e necrose da veia centrolobular em todos os grupos experimentais; também observamos uma nítida delimitação entre o tecido epitelial normal e o tecido epitelial fotossensibilizado. Estes resultados serão importantes para o desenvolvimento de estratégias para um possível protocolo para aplicação da PDT em tumores malignos hepáticos. / The PDT concept is the photo induction of the citotoxicity of proliferating cells involving a photosensitizer agent, a light source and oxygen. Despite being an efficient therapy on the treatment of several neoplasias, PDT presents some restrictions including the non-selectivity in hepatic tissue cells. This work evaluated the correlation between light penetration and necrosis, as well as the extension of such as function of the concentration of the photosensitizer used (Photogem) and three different doses of energy. The necrosed epithelium and healthy epithelium transition was performed after the irradiation of normal livers of previously photosensitized rats. The Photogem accumulation, intravenously administrated, on the liver was investigated through fluorescence spectroscopy. The light sources used for irradiation were: diode laser operating at 630 nm and a LEDs (Light Emitting Diode) device. We observe that the photosensitized normal hepatic tissue presents its optical characteristics altered, which was previously evidenced on the studies of light penetration and thermal alteration during the irradiation, altering the necrosis depth. We checked that the photosensitizer presence on the target tissue decreases the light penetration leading to a temperature increase, due to a large amount of energy absorbed by the photosensitizer, which is dissipated by means of heat. We noticed an abrupt necrosis delineation corresponding to the drop of the light intensity on the irradiated tissue. When the LED was used, the necrosis depth presented little variation, due to its spectral line being larger when compared to the laser’s spectral line. Histological, the irradiated hepatic tissue presented coagulative necrosis, inflammatory infiltration neutrophilic and centrilobular vein necrosis in all experimental groups, we also observed a clear delimitation between normal epithelial tissue and photosensitized tissue. These results will be important to the development of strategies for a possible protocol for the PDT application on hepatic malign tumors.

Introdução: A classificação da gravidade da queimadura é determinada a partir da relação entre a superfície corporal queimada (SCQ) e a profundidade da lesão. Os fatores que influenciam a evolução da necrose na zona de estase que circunda a zona de necrose (coagulação) podem estar relacionados com a perfusão, inflamação e estresse oxidativo. No presente estudo avaliamos o efeito da glutamina, pois tem sido demonstrado ter papel importante na prevenção de lesão por isquemia e reperfusão, da inflamação e do estresse oxidativo. Objetivo: avaliar o efeito da glutamina na forma de aminoácido livre e dipeptídeo na evolução da necrose nos interespaços (zona de estase) da queimadura. Materiais e Métodos: Foram utilizados 30 ratos machos da linhagem Wistar. Em todos os animais foi feito a lesão por queimadura de terceiro grau com um pente de metal contendo quatro dentes e três interespaços pré aquecido em água à 98ºC. O Grupo 1- Controle (n=10) recebeu 7,4ml/kg de peso, de solução fisiológica a 0,9%, o Grupo 2- Dipeptídeo, recebeu 7,4 ml do dipeptídeo L-alanil-L-glutamina (1g/kg de L-glutamina e 0,6g/kg de L-Alanina) e o Grupo 3- AA-livre recebeu 1g/kg de L-glutamina e 0,6g/kg de L-alanina na forma de aminoácido livre, por gavagem, por 7 dias após a lesão por queimadura. As análises avaliadas foram por meio de fotografia (no momento 48 horas e 7 dias) e histopatologia (no 7º dia após a lesão), para avaliar a extensão da necrose, alterações isquêmicas nos interespaços (zona de estase), além da alteração da Glutationa. Resultado: Na avaliação fotográfica, houve redução significante da necrose especificamente no Grupo 3- AA-livre entre o momento 48 horas e sete dias (P=0,04). Na avaliação por histologia, globalmente houve redução da inflamação nos Grupos 2- Dipeptídeo e 3- AA-livre quando comparados com o Grupo 1- Controle (p< 0,01). Ainda nos grupos tratados houve tendência a redução de necrose na derme dos interespaços ( Grupo 1- Controle =0,95; Grupo 2- Dipeptídeo =0,73 e Grupo 3- AA-livre =0,8), mas essas diferenças não foram significantes. Os grupos tratados também apresentaram aumento do número de fibroblastos quando comparados ao Grupo 1- Controle (p<0,05). Na dosagem de Glutationa foi encontrado maior quantidade no Grupo 2- Dipeptídeo (p<0,05) quando comparado com o Grupo 1- Controle. Conclusão: A redução das lesões histológicas, redução da inflamação, manutenção de maior extensão dos interespaços, a maior quantidade de fibroblastos e o aumento da glutationa, com a administração de glutamina, observados no presente estudo, podem ter beneficiado a manutenção ou redução da evolução da necrose de queimadura em ratos.a inflamação, acelerou a cicatrização e regrediu a evolução da necrose das zonas de estase das queimaduras em ratos. / Introduction: The classification of burn severity is based on the relationship between the burned body surface (SCQ) and the depth of the lesion. Factors influencing the progression of necrosis in the stasis zone surrounding the area of necrosis (coagulation) may be related to perfusion, inflammation and oxidative stress. In the present study, we evaluated the effect of glutamine, as it has been shown to play an important role in the prevention of ischemia and reperfusion injury, inflammation and oxidative stress. Objective: to evaluate the effect of glutamine as a free amino acid and dipeptide on the progression of necrosis in the interspace (stasis zone) of the burn. Materials and Methods: Thirty male Wistar rats were used. In all animals a third degree burn injury was done with a metal comb containing four teeth and three interspaces preheated in water at 98ºC. Group 1- Control (n = 10) received 7,4 ml of 0.9% saline solution, Group 2- Dipeptide received 7.4 ml of dipeptide solution L-alanyl-L-glutamine (1g/k Lglutamine and 0.6g/k L-Alanine) and Group 3- Free AA received 1g/k L-glutamine and 0,6g/kg L-alanine as free amino acid, by gavage, for 7 days after burn injury. The analyzes evaluated were by means of photograph (in the time 48 hours and 7 days) and histopathology (on the 7th day after the injury), to evaluate the extent of necrosis, ischemic changes in the interspaces (stasis zone), besides the alteration of Glutathione . Results: In the photographic evaluation, there was a significant reduction of necrosis specifically in the 3-AA-free group between 48 hours and 7 days (P = 0.04). Histologically, there was a reduction in inflammation in Groups 2- Dipeptide and 3-AA-free when compared to Group 1-Control (p <0.01). Even in the treated groups there was a tendency to reduce necrosis in the interspaces dermis (Group 1-Control = 0.95, Group 2-Dipeptide = 0.73 and Group 3- AA-free = 0.8), but these differences were not significant. The treated groups also showed an increase in the number of fibroblasts when compared to Group 1- Control (p <0.05). In the dosage of Glutathione, a greater amount was found in Group 2 - Dipeptide (p <0.05) when compared to Group 1 - Control. Conclusion: The reduction of histological lesions, reduction of inflammation, maintenance of greater extension of the interspaces, the greater amount of fibroblasts and the increase of glutathione, with the administration of glutamine observed in the present study, may have benefited the maintenance or reduction of the evolution of necrosis of burn in rats.