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<p dir="ltr">Papilledema is the swelling of the optic disc resulting from increased cranial pressure. The diagnosis of papilledema is important not only to treat pathologies of the eye, but it also can be an important indicator for underlying brain pathology since the subarachnoid space surrounding the optic nerve is contiguous with the brain. Therefore increased pressure from the brain from pathologies such as hydrocephalus can be transmitted to the posterior eye. To study papilledema, a reproducible post hemorrhagic hydrocephalic rat model was used to study the changes of the retina, optic disc and optic nerve when exposed to high intracranial pressure. Multiple changes were noted in the post hemorrhagic hydrocephalic model including decreased thickness of the ganglion cell complex, decreased retinal thickness in the periphery in females, increased retinal thickness close to the optic nerve in males, increased optic disc width and diameter along with a decrease number of retinal ganglion cells. These findings were similar to findings in human patients with papilledema. Therefore, future studies are indicated using the post hemorrhagic hydrocephalic rat model to further understand the mechanism of papilledema progression and the use of possible therapeutics.</p>

The objective of this study was to evaluate the relationship between tissue oxygen saturation (StO2) and oxygen delivery index (DO2I). Oxygen delivery index is product of two factors arterial oxygen content (CaO2) and cardiac index (CI). In this study the relationship between DO2I and StO2 was evaluated by manipulating both of these factors independently. In phase one of the study, CaO2 was altered by manipulating the fractional inspired oxygen (FiO2) concentration. Anesthetized dogs were evaluated at both high (0.40 and 0.95) and low (0.15 and 0.10) FiO2 sequences. In phase two of the study, CI was altered by manipulating the volemic state. Anesthetized dogs were evaluated at hypovolemic, normovolemic and hypervolemic states. In each phase dogs were instrumented for thermodilution cardiac index (CI) and sartorius muscle StO2. Data collected included hemoglobin concentration, heart rate (HR), MAP, CI, StO2. Arterial oxygen content and DO2I were calculated at each time point. Data analysis included Pearson's correlation and mixed model ANOVA (p < 0.05). In both phases one (r = 0.97; p = 0.0013) and two (r = 0.97; p = 0.005) there was a strong correlation between StO2 and DO2I. Under the conditions of this study, there was a strong correlation between StO2 and DO2I, suggesting that StO2 may be used to estimate the adequacy of oxygen delivery in dogs. / Master of Science

African monkey species are natural hosts of simian hemorrhagic fever virus (SHFV) and develop persistent, asymptomatic infections. SHFV was previously shown to also cause a rapid onset fatal hemorrhagic fever disease in macaques. Infection of macaques with a new isolate of SHFV from persistently infected baboon sera, that showed high nucleotide identity with the lab strain LVR, resulted in viremia, pro-inflammatory cytokine and tissue factor production, and symptoms of coagulation defects. Primary macrophages and myeloid dendritic cell cultures from disease-susceptible macaques efficiently replicated SHFV and produced pro-inflammatory cytokines, including IL-6 and TNF-α, as well as tissue factor. Cells from disease resistant baboons produced low virus yields and the immunomodulatory cytokine IL-10. IL-10 treatment of macaque cells decreased IL-6 levels but had no effect on TNF-α levels, tissue factor or virus production suggesting that IL-10 plays a role in modulating immunopathology in disease-resistant baboons but not in regulating the efficiency of virus replication. SHFV is a member of the family Arteriviridae. The SHFV genome encodes 8 minor structural proteins. Other arteriviruses encode 4 minor structural proteins. Amino acid sequence comparisons suggest that the four additional SHFV minor structural proteins resulted from gene duplication. A full-length infectious clone of SHFV was constructed and produced virus with replication kinetics comparable to the parental virus. Mutant infectious clones, each with the start codon of one of the minor structural proteins substituted, were analyzed. All eight SHFV proteins were required for infectious virus production. The SHFV nonstructural polyprotein is processed into the mature replicase proteins by several viral proteases including papain-like cysteine proteases (PLPs). Only one or two PLP domains are present in other arteriviruses but SHFV has three PLP domains. Analysis of in vitro proteolytic processing of C- and N-terminally tagged polyproteins indicated that the PLP in each of the three SHFV nsp1 proteins is active. However, the nsp1α protease is more similar to a cysteine protease than a PLP. Analysis of the subcellular localization of the three SHFV nsp1 proteins indicated they have divergent functions.

A hemorragia gerada por metaloproteinases de venenos de serpentes é um fenômeno complexo que resulta na ruptura de capilares e extravasamento de sangue. O HF3 (fator hemorrágico 3) é uma metaloproteinase da classe P-IIIa, extremamente hemorrágica, isolada do veneno da serpente Bothrops jararaca. Análises de sua atividade proteolítica sobre proteínas isoladas mostraram que componentes do plasma e da matriz extracelular são hidrolisados pelo HF3. Estudos que utilizaram abordagens proteômicas para analisar os efeitos do HF3 na derme e plasma de camundongos evidenciaram novos alvos desta metaloproteinase, incluindo proteínas intracelulares, extracelulares e plasmáticas. Entretanto, os mecanismos envolvidos na alta atividade hemorrágica apresentada pelo HF3, principalmente no que se diz respeito ao papel da clivagem de proteínas plasmáticas no contexto da hemorragia, ainda não são conhecidos. Assim, o objetivo principal deste estudo foi analisar o degradoma do HF3 no plasma humano. Paralelamente, também realizamos a análise da atividade do HF3 sobre as proteínas do plasma da B. jararaca. Para tanto, abordagens para a depleção das proteínas mais abundantes e enriquecimento de proteínas pouco abundantes do plasma humano foram utilizadas visando minimizar o intervalo de concentração dinâmica de proteínas, e assim permitir a avaliação da atividade proteolítica do HF3 sobre um amplo espectro de proteínas, e possibilitar a detecção dos produtos de degradação por espectrometria de massas. Dessa forma, quatro amostras de plasma humano foram utilizadas neste estudo: plasma total, plasma depletado de albumina, plasma depletado das 20 proteínas mais abundantes e plasma enriquecido de proteínas pouco abundantes. A incubação das amostras de plasma humano com o HF3 foi realizada na proporção enzima:substrato 1:100 (p/p), por 2 h a 37°C. Decorrido o tempo de incubação, as frações peptídica e proteica foram analisadas. A identificação dos peptídeos presentes na fração peptídica do plasma, por espectrometria de massas, revelou os produtos oriundos da hidrólise de proteínas pelo HF3, e permitiu a análise dos pontos de clivagem. O efeito do HF3 sobre o plasma enriquecido de proteínas pouco abundantes também foi analisado por eletroforese em gel de SDS-poliacrilamida, seguida de digestão de proteínas in gel com tripsina, e identificação das proteínas presentes em bandas diferenciais, por espectrometria de massas. Considerando todas as abordagens utilizadas neste estudo, 62 proteínas plasmáticas foram identificadas como tendo sido clivadas pelo HF3. Algumas destas proteínas corroboram estudos anteriores e outras são consideradas como candidatas a substrato desta metaloproteinase. Dentre os novos alvos, destacam-se proteínas da cascata da coagulação sanguínea e do sistema complemento, além de inibidores de proteinases, sugerindo que esta metaloproteinase pode agir de maneira desregulada, não sendo inibida pelos inibidores plasmáticos, e causando o desequilíbrio da hemostasia. A atividade do HF3 sobre as proteínas do plasma da B. jararaca foi verificada pela sua incubação com o plasma total, resultando na geração de poucos peptídeos que, no entanto, não resultaram em identificação de substratos da metaloproteinase por espectrometria de massas. Em conjunto, nossos dados reforçam achados prévios sobre o repertório de substratos do HF3 no plasma humano, apontam novos substratos e fornecem pistas para a compreensão da atividade hemorrágica do HF3 / Hemorrhage induced by snake venom metalloproteinases is a complex phenomenon resulting in capillary disruption and blood extravasation. HF3 (hemorrhagic factor 3) is an extremely hemorrhagic, P-IIIa class metalloproteinase, isolated from the venom of Bothrops jararaca. The analysis of its proteolytic activity on isolated proteins showed that plasma and extracellular matrix proteins are hydrolyzed by HF3. Studies using proteomic approaches to analyze the effects of HF3 in the mouse skin and plasma showed new targets of this metalloproteinase, including intracellular, extracellular and plasma proteins. However, the mechanisms involved in the hemorrhagic process generated by HF3, particularly the role of the cleavage of plasma proteins in the context of the hemorrhage, remain not fully understood. Thus, the main objective of this study was to analyze the degradome of HF3 in human plasma. In parallel, we also carried out the analysis of the activity of HF3 on B. jararaca plasma. For this purpose, approaches for the depletion of the most abundant proteins and for the enrichment of low abundant proteins of the human plasma were used to minimize the dynamic range of protein concentration, in order to assess the proteolytic activity HF3 on a wide spectrum of proteins, and to detect the degradation products by mass spectrometry. Thus, four samples of human plasma were used in this study: whole plasma, albumin-depleted plasma, plasma depleted of the 20 most abundant proteins, and plasma enriched of low abundance proteins. Incubation of these samples with HF3 was carried out at a 1:100 (w/w) enzyme-to-substrate ratio, for 2 h, at 37°C. After the incubation time, the protein and peptide fractions were analyzed. The identification of peptides present in the plasma peptide fraction by mass spectrometry revealed the products from the hydrolysis of proteins by HF3 and allowed the analysis of the cleavage sites. The effect of HF3 on the sample of plasma enriched of low-abundance proteins was also analyzed by SDS-polyacrylamide gel electrophoresis followed by in gel protein digestion with trypsin of differential bands and identification by mass spectrometry. Considering all the approaches used in this study, 62 plasma proteins were identified as cleaved by HF3. Some of these proteins corroborate previous studies and others are considered as substrate candidates of HF3. Among the new targets, there are proteins of the coagulation cascade and of the complement system, as well as plasma proteinase inhibitors, suggesting that this metalloproteinase escapes inhibition and may act in an unregulated fashion causing the imbalance of hemostasis. The activity of HF3 on B. jararaca plasma proteins was analyzed by its incubation with whole plasma, as described above, and resulted in the generation of a low number of peptides, which, however, did not result in the identification of any substrate by mass spectrometry. Taken together, our data confirm previous findings on the repertoire of substrates of HF3 in the human plasma and suggest new substrate candidates that may contribute to the understanding of the hemorrhagic effect of HF3.

A presente análise das três séries históricas, compondo um total de 42 casos de hepatopatias fulminantes da região Amazônica, teve por objetivos o estudo de aspectos morfológicos e imuno-histoquímicos no diagnóstico diferencial entre febre amarela (FA), hepatite de Lábrea (HL) e de outras entidades. Visou, ainda, aprimorar o conhecimento de aspectos da morfogênese da morte hepatocelular, de eventual fibrose, relacionando-as aos padrões de regeneração e de lesões vasculares, conforme recentemente descrito na gênese de hepatopatias crônicas. Dentre o extenso painel de critérios histológicos aqui estudados, os padrões de morte hepatocelular e sua distribuição, incluindo corpos apoptóticos medio-zonais, assim como a balonização foram os achados mais característicos da FA, enquanto as células em mórula foram o principal achado na HL. Dezenove casos bem caracterizados (10 FA e 9 HL) foram então submetidos a estudos imuno-histoquímicos para a detecção dos antígenos da FA, AgHBs e antígeno do vírus da hepatite D (VHD), sendo então demonstrado que, em ambas as doenças, mas principalmente na HL, flebite, principalmente de ramos da veia porta, foi evidente e deve ter tido participação na patogênese do dano hepático, com extensa extinção parenquimatosa hepática e aproximação de espaços porta. O padrão de regeneração também foi marcante: nos casos de FA, um elevado índice de proliferação celular foi observado enquanto que, na HL, multinucleações e transformação pseudoacinar, associadas a depósitos portais de colágeno do tipo I e de fibras elásticas, foram encontrados. Concluindo, a pesquisa imuno-histoquímica de antígenos virais permitiu a caracterização etiológica dos casos destas importantes séries históricas de hepatopatias fulminantes da Amazônia, mesmo em amostras arquivadas em parafina por até sete décadas. Permitiu, ainda, o relato original de cinco casos de possível superposição de infecção pelos vírus da FA, VHB e/ou VHD. Dentre os aspectos histopatológicos, o quadro dominante na FA fulminante incluiu apoptose medio-zonal associada com flebite portal e um alto índice de proliferação celular, em pacientes sem evidência de dano hepático prévio. Por outro lado, a HL fulminante mostrou extensa necrose lítica de hepatócitos, associada à flebite portal e de veia hepática e à presença de células em mórula, em pacientes com evidências morfológicas de doença hepática crônica. / This study aimed at assessing morphological and immunohistochemical aspects useful for the differential diagnosis of yellow fever (YF), Labrea hepatitis (LH) and other entities by revisiting 42 fulminant hepatic failure cases, from three historical series from Amazon Basin. Additional studies were performed aiming at further understanding the morphogenesis of hepatocelular death, in relation to regeneration and fibrosis patterns and to vascular lesions, as recently described in chronic hepatic diseases. Among the extensive panel of histological criteria studied, liver cell death pattern and distribution, including midzonal apoptotic bodies, as well as hepatocelular ballooning degeneration were YF most characteristic findings, while morula cells were the major hint for LH. Five cases were herein suggested as coinfected with YF, HBV and/or HDV, a finding not previously reported. Nineteen well characterized cases (10 YF and 9 LH) were further submitted to immunohistochemical studies for YF antigen, HBsAg and Delta virus Ag. In both diseases, but mainly in LH, phlebitis, mainly of portal vein branches, was evident and closely related to the degree of hepatocellular damage, with severe hepatic parenchymal extinction and portal tract approximation. Regeneration pattern was also remarkable: in YF cases, a high hepatocellular proliferative index was detected whereas in LH, multinucleation and pseudo-acinar transformation, associated with portal type I collagen and elastic fiber deposition were found. In conclusion, immunohistochemical viral antigen detection yielded further etiological characterization of these important historical cases of fulminant hepatic failure from Amazon Basin, even in paraffin samples stored for up to seven decades. YF morphology depicted midzonal apoptosis, portal phlebitis and a high hepatocellular proliferative index, in patients without evidence of previous hepatic injury. On the other hand, fulminant LH showed extensive lytic hepatocellular necrosis, portal and hepatic vein phlebitis and the presence morula cells, in patients with morphological evidences of chronic liver disease.

Aproximadamente 5,8 milhões de pessoas morrem anualmente vítimas de trauma no mundo. A reposição volêmica inicial dos pacientes graves politraumatizados com choque hemorrágico tem características distintas hoje quando comparada à proposta não mais do que uma década atrás. A infusão reduzida de fluidos associada à transfusão precoce de hemoderivados é o padrão adotado em portadores de hemorragia maciça, no que se chama na literatura de damage control resuscitation (DCR). Entretanto, a administração precoce de componentes do sangue, implica em limitações de armazenamento, transporte, disponibilidade, compatibilidade, reações transfusionais e custo. Assim, estratégias medicamentosas que possam beneficiar o paciente politraumatizado no tratamento do sangramento devem ser desenvolvidas. As pesquisas atuais buscam medidas que possam agir na resposta inflamatória e na coagulopatia envolvidas nas lesões traumáticas e no choque hemorrágico. Desta forma, decidiu- se avaliar o potencial da administração precoce de Pentoxifilina (PTX) em associação com Ringer lactato (RL) e seus efeitos na coagulopatia associada ao trauma. Foi utilizado modelo experimental suíno de choque hemorrágico e politrauma. Foram utilizados 23 suínos, machos, da raça Landrace, com peso médio de 28,5 kg randomizados em 3 grupos: Controle (n=5), RL (n=5) e PTX (n=7). Os animais foram submetidos à anestesia geral, exceto o grupo controle, a uma fratura de fêmur, seguido de choque hemorrágico controlado e, por fim, uma lesão hepática como hemorragia não controlada. Foram analisados parâmetros hemodinâmicos, laboratoriais e gasometria, testes de coagulação padrão e tromboelastometria. Os animais submetidos ao experimento apresentaram taquicardia, hipotensão arterial, hipotermia, acidose, redução de hemoglobina e alteração nos testes de coagulação e viscoelásticos. O lactado no tempo Final mostrou-se mais elevado no grupo PTX, quando comparado ao grupo RL (p=0,01). Os dados da tromboleastometria não mostraram diferença entre os grupos submetidos ao experimento. No tempo Final, observou-se uma redução do fibrinogênio menor no grupo tratado com PTX, quando comparado ao grupo RL (p < 0,01). A análise dos efeitos da pentoxifilina associada à reanimação volêmica sugere melhora dos níveis de fibrinogênio após sua administração seguindo a hemorragia e trauma / Approximately 5.8 million people die each year victim of trauma worldwide. The initial volume replacement of severely injured patients with hemorrhagic shock has different characteristics today than a decade before. Low-volume fluid resuscitation associated with early transfusion of blood products is the standard adopted in patients with massive hemorrhage, so called damage control resuscitation (DCR). However, early administration of blood components implies limitations in storage, transport, availability, compatibility, transfusion reactions, and cost. Thus, drug strategies that may benefit the severely injured patient in the treatment of bleeding should be developed. Current research seeks measures that can modulate the inflammatory response and coagulopathy involved in traumatic injuries and hemorrhagic shock. Therefore, we decided to evaluate the role of early administration of Pentoxifylline (PTX) in association with RL and its effects on coagulopathy and traumatic inflammatory response. A porcine model of multiple trauma and hemorrhagic shock was used. Twenty-three Landrace male pigs were used, with a mean weight of 28.5 kg randomized into three groups: Control (n=5), RL (n=5), and PTX (n=7). The animals were submitted to general anesthesia (except the control group), femur fracture, followed by controlled hemorrhagic shock, and, finally, a hepatic injury (as uncontrolled hemorrhage simulation). Hemodynamic parameters, laboratory tests, standard coagulation tests and thromboelastometry were analyzed. The animals submitted to the experiment presented tachycardia, hypotension, hypothermia, acidosis, hemoglobin decrease and impaired coagulation and viscoelastic tests. Lactate levels at the end of the experiment were higher in the PTX group when compared to RL (p=0,01). Data extracted from thromboelastometric tests have shown no difference between the groups submitted to the protocol. Fibrinogen reduction (consumption) were significantly lower in the PTX group when compared to RL (p < 0,01). The analysis of pentoxifylline effects suggests less fibrinogen consumption after PTX administration

Introdução: Cistite Hemorrágica (CH) é uma grave complicação do Transplante de Células-Tronco Hematopoiéticas (TCTH) Alogênico. Sua incidência varia de 12 a 25,5%. A forma precoce desenvolve-se devido aos efeitos tóxicos de certos quimioterápicos usados no regime de condicionamento, especialmente Ciclofosfamida. Já a CH tardia ocorre a partir do terceiro dia após o TCTH e sua etiologia é multifatorial. Vários fatores de risco para o desenvolvimento de CH tardia foram descritos, incluindo Doença do Enxerto Contra o Hospedeiro (DECH) aguda, doador não relacionado, infecções por vírus urotrópicos, sexo masculino e condicionamento mieloablativo. Materiais e Métodos: O presente estudo tem como objetivos descrever a incidência de CH em pacientes adultos e pediátricos submetidos a TCTH alogênico e identificar fatores de risco associados ao desenvolvimento de CH nesta população. Foram analisados dados de prontuário de 347 pacientes submetidos a TCTH Alogênico no Hospital de Clínicas de Porto Alegre no período de Janeiro de 2001 a Dezembro de 2014. Resultados: CH ocorreu em 42 pacientes (12,1%, IC: 8,9 - 16%), em uma média de 53.4 dias após o procedimento (desvio padrão: 28.1 dias). Apenas 1 paciente (2,4%) desenvolveu CH precoce, com início dos sintomas no D+1. Entre os 41 pacientes que desenvolveram CH tardia, BK vírus foi o principal agente viral identificado. CH ocorreu em 12.8% dos pacientes que receberam condicionamento mieloablativo e em 10.5% dos restantes (P = 0,704). Dos 197 pacientes que apresentaram DECH aguda, 35 (17,8%) desenvolveram CH e somente 7 (4,9%) apresentaram CH na ausência de DECH aguda (P < 0,001). CH foi mais frequente também em pacientes do sexo masculino (P = 0,027). Conclusão: A incidência de CH em nossa amostra foi semelhante à encontrada em outros trabalhos. DECH aguda e sexo masculino estiveram associados a um maior risco de desenvolvimento de CH. / Introduction: Hemorrhagic cystitis (HC) is a serious complication of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) afecting 12 to 25.5% of the patients. The early-onset form of HC develops during or until 72 hours after the conditioning regimen containing high doses of certain chemotherapy drugs such as Busulfan and especially Cyclophosphamide. Late-onset HC occurs from the third day on after HSCT and its etiology is multifactorial. Several risk factors for the late-onset form have been reported including graft-versus-host disease (GVHD), unrelated donor, urotropic infections, male gender and myeloblative conditioning regimen. Methods: This study aims to evaluate the incidence of HC in adult and pediatric patients undergoing Allogeneic HSCT and to identify risk factors associated with the development of HC in this population. Medical records of 347 patients who underwent Allogeneic HSCT at Hospital de Clínicas, Porto Alegre, Brazil, from January 2001 to December 2014 were analyzed. Results: HC occurred in 42 patients (12.1% CI: 8.9 - 16%) at an average of 53.4 days after the procedure (standard deviation: 28.1 days). Only one of them developed early-onset HC, with onset of symptoms on D+1. Among the 41 patients who developed late-onset HC, BKV was the main identified viral agent. HC developed in 12.8% of the patients treated with myeloablative conditioning and in 10.5% of the remaining patients (P = 0.704). Of the 197 patients with acute GVHD, 35 (17.8%) developed HC and only 7 (4.9%) showed HC in the absence of GVHD (P<0.001). HC was also more frequent in males than females (P = 0.027). Conclusion: The incidence of HC in our sample was similar to that found in other studies. In our cohort of patients being male and having acute GVHD increased the risk of developing HC.

A presente análise das três séries históricas, compondo um total de 42 casos de hepatopatias fulminantes da região Amazônica, teve por objetivos o estudo de aspectos morfológicos e imuno-histoquímicos no diagnóstico diferencial entre febre amarela (FA), hepatite de Lábrea (HL) e de outras entidades. Visou, ainda, aprimorar o conhecimento de aspectos da morfogênese da morte hepatocelular, de eventual fibrose, relacionando-as aos padrões de regeneração e de lesões vasculares, conforme recentemente descrito na gênese de hepatopatias crônicas. Dentre o extenso painel de critérios histológicos aqui estudados, os padrões de morte hepatocelular e sua distribuição, incluindo corpos apoptóticos medio-zonais, assim como a balonização foram os achados mais característicos da FA, enquanto as células em mórula foram o principal achado na HL. Dezenove casos bem caracterizados (10 FA e 9 HL) foram então submetidos a estudos imuno-histoquímicos para a detecção dos antígenos da FA, AgHBs e antígeno do vírus da hepatite D (VHD), sendo então demonstrado que, em ambas as doenças, mas principalmente na HL, flebite, principalmente de ramos da veia porta, foi evidente e deve ter tido participação na patogênese do dano hepático, com extensa extinção parenquimatosa hepática e aproximação de espaços porta. O padrão de regeneração também foi marcante: nos casos de FA, um elevado índice de proliferação celular foi observado enquanto que, na HL, multinucleações e transformação pseudoacinar, associadas a depósitos portais de colágeno do tipo I e de fibras elásticas, foram encontrados. Concluindo, a pesquisa imuno-histoquímica de antígenos virais permitiu a caracterização etiológica dos casos destas importantes séries históricas de hepatopatias fulminantes da Amazônia, mesmo em amostras arquivadas em parafina por até sete décadas. Permitiu, ainda, o relato original de cinco casos de possível superposição de infecção pelos vírus da FA, VHB e/ou VHD. Dentre os aspectos histopatológicos, o quadro dominante na FA fulminante incluiu apoptose medio-zonal associada com flebite portal e um alto índice de proliferação celular, em pacientes sem evidência de dano hepático prévio. Por outro lado, a HL fulminante mostrou extensa necrose lítica de hepatócitos, associada à flebite portal e de veia hepática e à presença de células em mórula, em pacientes com evidências morfológicas de doença hepática crônica. / This study aimed at assessing morphological and immunohistochemical aspects useful for the differential diagnosis of yellow fever (YF), Labrea hepatitis (LH) and other entities by revisiting 42 fulminant hepatic failure cases, from three historical series from Amazon Basin. Additional studies were performed aiming at further understanding the morphogenesis of hepatocelular death, in relation to regeneration and fibrosis patterns and to vascular lesions, as recently described in chronic hepatic diseases. Among the extensive panel of histological criteria studied, liver cell death pattern and distribution, including midzonal apoptotic bodies, as well as hepatocelular ballooning degeneration were YF most characteristic findings, while morula cells were the major hint for LH. Five cases were herein suggested as coinfected with YF, HBV and/or HDV, a finding not previously reported. Nineteen well characterized cases (10 YF and 9 LH) were further submitted to immunohistochemical studies for YF antigen, HBsAg and Delta virus Ag. In both diseases, but mainly in LH, phlebitis, mainly of portal vein branches, was evident and closely related to the degree of hepatocellular damage, with severe hepatic parenchymal extinction and portal tract approximation. Regeneration pattern was also remarkable: in YF cases, a high hepatocellular proliferative index was detected whereas in LH, multinucleation and pseudo-acinar transformation, associated with portal type I collagen and elastic fiber deposition were found. In conclusion, immunohistochemical viral antigen detection yielded further etiological characterization of these important historical cases of fulminant hepatic failure from Amazon Basin, even in paraffin samples stored for up to seven decades. YF morphology depicted midzonal apoptosis, portal phlebitis and a high hepatocellular proliferative index, in patients without evidence of previous hepatic injury. On the other hand, fulminant LH showed extensive lytic hepatocellular necrosis, portal and hepatic vein phlebitis and the presence morula cells, in patients with morphological evidences of chronic liver disease.