Parkinson's disease : experimental in vitro model validation and the potential role of cofilin-1 in the pathophysiological mechanisms

The dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc) is responsible for the marked motor impairment observed in Parkinson's disease (PD). However, the molecular mechanisms underlying this are not completely understood. Since by the time of diagnosis, 50-70% of the dopaminergic neurons of the nigrostriatal pathway have already been degenerated, it is difficult to investigate the early-stage events of disease pathogenesis. Due to inaccessibility of the human brain to study initial pathogenic mechanisms of the disease, experimental models have been developed in an attempt to elucidate PD etiology and its progression. Nevertheless, PD models are a controversial issue in neuroscience research since it is challenging to mimic human neuronal complexity. Therefore, the lack of optimal models that recreate disease pathology is one of the causes of failure of clinical trials that have attempted to find new/better PD therapies. Taking this in consideration, the development of more suitable models is necessary to improve our knowledge regarding PD etiological mechanisms. Additionally, the understanding of the advantages and disadvantages of models already established would also be beneficial for PD research, which our group addressed by reviewing this subject. Considering this, we chose SH-SY5Y cells as a PD model for our studies. To investigate the initial stages of PD-induced neurodegeneration, our work focused in the role of cofilin-1, a protein involved in mitochondrial dysfunction caused by oxidant-induced-apoptosis, which are two pathogenic processes strongly related to PD. Hence, in the thesis, we aimed to validate the use of retinoic-acid-(RA)-differentiated SH-SY5Y cells as an in vitro model and use it to investigate the potential role of cofilin-1 in the initial molecular and cellular mechanisms of PD. Although SH-SY5Y cells are widely used in PD research, their major drawback is their lack of important neuronal features, such as low levels of proliferation and stellate morphology. On the other hand, SH-SY5Y cells can acquire a neuronal phenotype when treated with differentiation agents such as RA. Since several protocols have been described, the consequence of which may be the discrepancies observed among studies regarding neuronal and dopaminergic features. In Chapter I, we aimed to validate a RA-differentiation protocol for SH-SY5Y cells previously established by our research group, focusing upon characterization of neuronal features and its subsequent response to 6-hydroxydopamine (6-OHDA), a toxin widely used to induce dopaminergic degeneration. RA-differentiated SH-SY5Y cells have low proliferative rates, a pronounced neuronal morphology and high expression of genes related to synapse vesicle cycle, dopamine synthesis/degradation, and dopamine transporter (DAT). After exploring phenotypic differences between these two models, we verified that RA-differentiated cells were more sensitive to 6-OHDA toxicity than undifferentiated cells, which could be related to an increase of DAT immunocontent. Many lines of evidence have showed that DAT is responsible for 6-OHDA uptake in vivo. Once inside the neuron, 6-OHDA underwent auto-oxidation causing a significant increase in oxidative stress. However, toxin uptake is not an essential step in undifferentiated SH-SY5Y cells, as auto-oxidation occurs extracellularly. We showed here, for the first time, that RA-differentiated SH-SY5Y cells can mimic, at least in part, an important mechanism of the 6-OHDA-induced cell death found in previous in vivo studies. Hence, the cellular model established by our research group presents essential neuronal features, being a suitable model for PD research. In Chapter II, RA-differentiated SH-SY5Y cells were used as cellular model to investigate disease molecular mechanisms, focusing upon cofilin-1. Our previous data have shown that oxidation of non-phosphorylate (activated) cofilin-1 leads to mitochondrial dysfunction and cell death induced by apoptosis in tumour cells. Here we found that cofilin-1 played a role in early stages of neuronal apoptosis induced by 6-OHDA in our cellular model since cofilin-1 mitochondrial translocation precedes organelle dysfunction. Overexpression of wild type CFL1 resulted in increased sensitivity of SH-SY5Y cells to 6-OHDA-induced neuronal cell death. Furthermore, overexpression of non-oxidizable CFL1 containing Cys-to-Ala mutations (positions 39, 80 and 139) increased neuronal resistance to this toxin, suggesting that oxidation is an important step in 6-OHDA toxicity. Follow-up experiments were performed in order to evaluate clinically whether cofilin-1 pathway proteins content is altered in PD post mortem human brain. Our findings showed a significant decrease in p-cofilin-1/cofilin-1 ratio in PD patients, which indicates an increase in the amount of activated cofilin-1 available for oxidation. Moreover, through principal component analysis, the immunodetection of cofilin-1 pathway proteins were able to discriminate controls and PD individuals during the early-stage of neuropathological changings. Hence, we demonstrated, for the first time, a possible role for cofilin-1 in PD pathogenesis and its potential use as biomarker. Taken together, our data showed that RA-differentiated SH-SY5Y cells present terminally-differentiated dopaminergic neuron features, that are essential to mimic dopaminergic neurons. By using this cellular model and post mortem brain tissue, we also demonstrated a possible role for cofilin-1 in early steps of the neurodegeneration process found in PD, which it could impact drug and biomarker discovery researches

Representações do feminino na contística de Maria Aurora Carvalho Homem

Na contística de Maria Aurora Carvalho Homem, A Santa do Calhau (1992), Para Ouvir Albinoni (1995; 2003) e Leila (2005), impõe-se com naturalidade uma constante temática centrada nas experiências quotidianas do feminino. Considerando a relevância do contributo da literatura para a compreensão da condição da mulher e do seu papel na sociedade, procuramos explorar as representações do feminino na produção ficcional da autora. No conjunto dos contos, deparamo-nos com figurações de mulheres subjugadas à hegemonia masculina, de transgressoras e de mulheres emancipadas. As personagens, embora entidades ficcionais, testemunham o rumo trilhado pela mulher no encalce da autoconstrução de uma renovada identidade feminina, constituindo-se a escrita como meio de reflexão sobre o mundo

Dental amalgam electrode as voltammetric sensor to triazine-based pesticides determination: application in natural water samples

FAPEMIG - Fundação de Amparo a Pesquisa do Estado de Minas GeraisTrabalho de Conclusão de Curso (Graduação)This paper describes the use of a dental amalgam electrode (DAE) allied to square wave voltammetry (SWV) in the analytical determination of the triazine-based pesticides ametryn (AM), atrazine (AT) and simazine (SI) in natural waters. Experimental and voltammetric parameters were optimized as Brinton-Robinson buffer at pH 2.5, with pulse frequency of 100 s-1, pulse amplitude of 50 mV and scan increment of -2 mV, where the triazines presented well-defined irreversible voltammetric peaks, at -1.05 V, -0.97 V and -0.99 V for AM, AT and SI respectively. For AM and SI was observed a redox reaction controlled by diffusion rate and for AT a reaction controlled by adsorption kinetic. Besides, in AM occurred the reduction of bond carbon-SCH3 and in AT and SI the reduction of bond carbon-chloride. Analytical curves were constructed, and the voltammetric signals were directly proportional to concentration, and to all triazines, the detection limits were lower than the maximum of residues permitted in natural water by Brazilian Environmental Agency, 100 g L-1 (100 ppb) and around the obtained using traditional techniques and other electrodic surfaces. The recovery percentages, in pure electrolyte and natural waters, were around 100%, demonstrating that the methodology proposed is suitable for determining any contamination by AM, AT and SI natural waters samples

Chronicle myeloid leukemia and hiperviscosity syndrome: case report

BACKGROUND AND OBJECTIVES: Hyperleukocytosis (> 100 x 10(9)/L) is an uncommon presentation of chronic leukemias and it can present clinical symptoms of hyperviscosity syndrome. Hearing loss and blindness rarely occurs in patients with leukemia; however, it can be strong association with hyper-viscosity syndrome. The purpose of this paper is to report a case of acute hearing loss as the initial manifestation of acute leukemia and hyper-viscosity syndrome and also mainly aspects of the intensive care treatment. CASE REPORT: A 41 year-old, male patient, who has been complaining about dizziness for six months with no response to symptomatic medications, was admitted to the emergency department with acute hearing loss. The physical examination was normal except for a bilateral hearing loss without an apparent cause. Laboratory exams showed total leukocyte: 645.000 with 66.4% blasts, hemoglobin: 7.0, hematocrit: 20.5, urea: 94, creatinine: 1.59, K: 5.6, Na: 138, INR: 1.38, TTPa: 0.89, troponin lower than 0.2, CK: 218, CKMB: 50, uric acid: 11.1. After a first hypothesis of leukemia with a high risk of hyper-viscosity complications, the patient was admitted to the Intensive Care Unit for monitoring and treatment. A bone marrow biopsy was performed and than started hidratation, hydroxyurea, allopurinol, dexamethasone. According to hematologists the patient had a chronic myeloid leukemia. Leukopheresis was performed one week after admission when total blood leukocytes were around 488.000. Ten days after the procedure the patient had no improvement of the hearing loss but total leukocytes were 10.100. He was discharge to the ward and 2 weeks later went home to continue ambulatory treatment. CONCLUSIONS: The frequency of sensitive manifestations in patients with leukemia include not only visual and hearing loss but also many others manifestations such as conductive vertigo, facial palsy and infections. Hyperviscosity syndrome due to hyperleukocytosis is also a possible cause of sensorial loss, but the syndrome is often dependent on leukocyte counts greater than (>100 x 10(9)/L).This case is a representative of rare cases in which acute sensorineural hearing loss occurred as the initial manifestation of hyper-viscosity syndrome due to leukemia.JUSTIFICATIVA E OBJETIVOS: A hiperleucocitose (> 100 x 10(9)/L) em leucemia mielóide crônica não é uma apresentação comum e pode determinar manifestações clínicas de hiper-viscosidade. As perdas auditiva e visual observadas em pacientes com leucemia são consideradas sintomas incomuns, mas fortemente associados à síndrome da hiper-viscosidade. O objetivo deste estudo foi relatar o caso de um paciente que apresentou perda da audição como manifestação inicial de leucemia mielóide crônica e síndrome de hiper-viscosidade e rever aspectos relacionados a seu tratamento em Medicina Intensiva. RELATO DO CASO: Paciente do sexo masculino, 41 anos, com queixa de tontura havia seis meses sem resposta ao tratamento sintomático, foi admitido no serviço de emergência com perda auditiva aguda. Ao exame físico encontrava-se normal, exceto por perda auditiva bilateralmente. Os exames laboratoriais demonstraram leucocitose importante (645.000), com 66,4% de blastos com características mielóides, 13,6% bastões, 15,3% segmentados, 1,4% linfócitos, 3,3% eosinófilos e plaquetas de 225.000. Devido à suspeição de leucemia com risco elevado para síndrome de hiper-viscosidade, o paciente foi admitido para tratamento na unidade de terapia intensiva. Realizado mielograma e biópsia de medula óssea que confirmaram o diagnóstico de leucemia mielóide crônica. Iniciadas hidratação, hidroxiuréia, alopurinol e dexametasona. A leucoaferese foi realizada uma semana após a admissão, quando a contagem leucocitária estava em torno de 488.000. Dez dias após o procedimento, o paciente não apresentou melhora da audição, apesar da leucometria de 10.000. Recebeu alta hospitalar em duas semanas para continuidade do tratamento ambulatorial. CONCLUSÕES: As freqüências das manifestações sensitivas em pacientes com leucemia incluem além das perdas auditiva e visual, vertigem, paralisia facial e infecções. A síndrome de hiper-viscosidade decorrente da hiper-leucocitose é uma causa possível para as perdas sensitivas, ocorrendo geralmente com contagem leucocitária superior a (> 100 x 10(9)/L). Este caso é representativo de raro caso de perda auditiva decorrente da hiper-viscosidade por leucemia.UNIFESP-EPMInstituto Dante Pazzanese de CardiologiaAMIB AMBUNIFESP, EPMSciEL

Desempenho do comércio exterior em Minas Gerais: estrutura, vantagem comparativa e comércio intraindústria

The globalization, an international process evidenced in the 80's decade, has requested the government and economic agents an orientation to reach international levels of competitiveness by the various sectors of the economy. Besides this fact, Minas Gerais state is the second state exporter in Brazil. It emphasizes the importance of the analysis of the structure and behavior of the export sector, as well as their effects on different economic sectors in the period 1996 to 2008. The objective of this paper is to identify and analyze groups of products that Minas Gerais state has revealed comparative advantages, degree of concentration of products and destinations of exports, and intra-industry or inter-industry trade. The theoretical model is based on the Theory of International Trade and Competitiveness. The analysis procedure utilizes indexes of revealed comparative advantages, contribution to trade balance ratio, Gini-Hischaman and trade intra-industry indexes. The data were generated by the Brazilian Department of Commerce. The results showed high concentration in a few products, such as (09) Coffee, tea, and spices, etc. (26) mining industry, (71) natural or cultured pearls, and (72) iron and steel, and destination markets, such as EU, NAFTA and Asia. Finally, the paper indicates that international trade in Minas Gerais state is basically inter-industrial, therefore a trade type Herckscher - Olhin.Revealed comparative advantage, Trade intra-industry, Exports, International Relations/Trade,

In vitro histological evaluation of the surgical margins made by different laser wavelengths in tongue tissues

Background: Lasers have become standard tools for the surgical treatment of oral lesions. The purpose of this study is to determine the surgical margins and histologically evaluate the tissue thermal effects induced by different types of surgical instruments. Material and Methods: Cuts were made in pork tonguesâ mucosa with different lasers (Er:YAG at 2W with and without air / water spray and at 4W with and without air / water spray; CO2 at 3.5W and 7W in pulsed mode and at 7W in continuous mode; the diode laser at 3.5W and boost 3.5W in pulsed mode; Nd:YAG at 6W, 40Hz and electroscalpel at 5W and conventional scalpel as control. Macroscopic and microscopic morphological changes were evaluated. Results: The results of this study showed that the surgical instruments that caused greater tissue damage extension were: the Nd:YAG laser (670.68μm), the diode 3.5W and boost PW (626.82μm), the CO2 7W CW (571.18μm), the CO2 at 7W PW (485.45μm), the diode 3.5W PW (456.15μm), the electroscalpel (409.57μm) and lastly the CO2 laser 3.5W PW (306.19μm) and Er:YAG (74.66μm) laser, regardless of power, mode or air / water spray used. An association between the Tissue Damage Extension and the Degree of Carbonization (r = 0.789; P = 0.01), and an association between the Tissue Damage Extension and Regularity of the Incision were found (r = -, 299; P = 0.01). Conclusions: The results of this study suggest that lasers can be used in soft tissues biopsies of the oral cavity, enabling a correct histopathological analysis, as long as the biological effects of each laser type are considered. The Er:YAG laser revealed its potential for biopsies of the oral mucosa ensuring a successful histological evaluation and the CO2 laser at 3,5W in pulsed mode presented itself as the best choice for surgeries with hemostasis

Transição para a vida pós escolar de alunos com nee: Respostas educativas e recursos implementados pelas escolas.

Esta investigação tem o seu enfoque na problemática da Transição para a Vida Pós- Escolar de Alunos com NEE, nomeadamente as respostas educativas e os recursos implementados pelas escolas. Com base na revisão da literatura, procurou-se perceber a forma como os agrupamentos de escolas se organizam, quais as respostas educativas e que recursos são implementados, de modo a dar cumprimento ao definido pelo Decreto- Lei 3/2008 de 7 de Janeiro, nomeadamente no que respeita aos Planos Individuais de Transição e à Transição para a Vida Ativa. No estudo empírico contou-se com uma amostra participante de trinta profissionais, envolvidos no processo educativo de alunos a usufruir de Currículo Específico Individual e de Plano Individual de Transição. Foi utilizada a metodologia quantitativa, designadamente inquérito por questionário. O estudo permitiu evidenciar a complexidade intrínseca à Escola, sendo que esta organização não poderá ser a única responsável por todo o processo. A articulação entre escola, família e a comunidade é, portanto, imprescindívelinfo:eu-repo/semantics/publishedVersio

Cardiovascular complications related to cocaine use: case report

BACKGROUND AND OBJECTIVES: Cocaine is the most commonly used illicit drug and its acute and chronic effects are related to a variety of physiological changes, mainly in the cardiovascular system. This study is a case report of a patient with cardiomyopathy related to cocaine use. CASE REPORT: A 19 year old men, who has been using cocaine and crack since 15 years old, was admitted to the emergency department (ED) in February 2006 with progressive dyspnea during minimal efforts and bloody expectoration. During the physical exam it was observed legs edema, jugular stasis and dyspnea at rest. The echocardiogram demonstrated left ventricular hypocinesia, a 17 mm ventricular thrombus and a 12% ejection fraction. A bleeding from the left upper lobe was identified during a pulmonary bronchoscopy which was treated with arterial embolization. After 48h of the procedure, the patient was asymptomatic and an antithrombotic treatment with warfarin and enoxaparin was started. No obstruction was found at the cineangiography and the patient was discharged after clinical improvement. The patient was admitted again to the intensive care unit in July with intense chest pain and dyspnea at rest. A new cineangiography was performed and it was observed occlusion in the anterior descendent coronary artery. CONCLUSIONS: The cocaine acute effects are commonly seen at the ED but the chronic effects, as the cardiovascular manifestations, can take longer to be correlated as a side effect of cocaine use. Its prolonged use is related to left ventricular systolic dysfunction due to hypertrophy or myocardial dilation, atherosclerosis, arrhythmias, myocyte apoptosis and sympathetic damage.JUSTIFICATIVA E OBJETIVOS: A cocaína é uma droga ilícita amplamente utilizada e o seu uso tem sido associado a efeitos decorrentes da toxicidade aguda e crônica em praticamente todos os órgãos, particularmente no sistema cardiovascular. Este artigo visou descrever um caso de cardiomiopatia em paciente jovem usuário crônico de cocaína. RELATO DO CASO: Paciente do sexo masculino, 19 anos, usuário de cocaína por inalação e crack desde os 15 anos de idade. Foi internado em fevereiro de 2006 devido a dispnéia progressiva aos mínimos esforços e expectoração sanguinolenta. Ao exame físico apresentava edema nos membros inferiores, estase jugular e dispnéia em repouso. Foram observados no ecocardiograma: dilatação das quatro câmaras cardíacas, com hipocinesia difusa de ventrículo esquerdo (VE), trombo mural em VE de 17 mm e fração de ejeção de 12%. Realizada broncoscopia pulmonar que identificou sangramento em língula ativo, tratado com embolização. Após 48h do procedimento, o paciente manteve-se assintomático e sem expectoração sanguinolenta. Iniciado tratamento antitrombótico com warfarina e enoxaparina. A cineangiocoronariografia não evidenciou lesões obstrutivas e o paciente recebeu alta após melhora clínica. Re-internado em julho de 2006 com dor precordial de forte intensidade e dispnéia de repouso. Nova cineangiocoronariografia evidenciou oclusão de terço médio da artéria descendente anterior. CONCLUSÕES: Os efeitos agudos da cocaína freqüentemente motivam atendimento de emergência. Já as suas manifestações crônicas, como as doenças cardiovasculares, podem produzir alterações de difícil correlação futura ao seu consumo prévio. O uso prolongado da cocaína está relacionado à alteração da função sistólica ventricular esquerda por hipertrofia ou dilatação miocárdica, aterosclerose, disritmias cardíacas, apoptose de cardiomiócitos e lesão simpática.UNIFESPUniversidade São FranciscoUNIFESPSciEL

Liver ischemic necrosis and diabetes mellitus: case report

BACKGROUND AND OBJECTIVES: Hepatic infarction is characterized by parenchyma ischemic necrosis involving at least two acinis. It is extremely uncommon due to the arterial and portal venous blood supply. We report a case of a patient not know to have diabetes who developed massive areas of ischemic infarcts of the liver after episode of acutely diabetes decompensated. CASE REPORT: A 67 year-old hypertensive female who has been presenting, for the last 10 days, polydipsia, high urinary volume, visual and gait impairment, nausea and vomiting was admitted to the emergency room (ER). During the physical examination it was observed dehydration, skin discoloration, peripheral cyanosis, hypothermia, tachycardia, hypotension and mild diffuse abdominal pain. Admissional laboratory exams demonstrated total leukocytes: 16.800, Cr: 3.7, Ur: 167, Na: 133, K: 6.9, glucose: 561; arterial gasometry (O2 catheter: 2 L/min): pH: 6.93, pCO2: 12.1, pO2: 107, B.E.: -28.8, HCO3: 2.4, Sat 91.3%, lactato: 79; urinalysis: pH: 6; leukocytes: 13; density: 1015; erythrocytes: 19; protein: ++; glucose: +++; bilirubin: negative; ketonic bodies: + denote ketonemia. EKG: sharp T wave, right branch block. Patient was treated with intravenous insulin, hydration, sodium bicarbonate and ceftriaxone. After initial treatment, the laboratory exams showed Cr: 2.2, Ur: 122, Na: 162, K: 4.3, Ca: 6.4, glucose: 504, pH: 7.01, HCO3: 7.1, B.E.: -22. One day after admission the patient presented with important abdominal pain and peritoneal irritation, followed by difficulty for talking and somnolence; routine laboratory exams showed arterial gasometry: pH: 7.4, pCO2: 31, pO2: 68, BE: -4.4, HCO3: 19, SatO2: 93.5%; Ur: 95,Cr: 1.4, albumin: 2.4, Ca: 0.95, Na: 166, K:4, bilirubin: 0.5, bilirubin D/I: 0.2/0.3, Amylase: 1157, Gamma-GT: 56, AST 7.210, ALT: 2.470, SR (sedimentation rate): 15, Lipase: 84. Abdominal ultrasound was unremarkable. Patient respiratory function and conscience level worsened, requiring intubation. Despite all resuscitation efforts, she died. Necropsy showed multiple ischemic infarcts of the liver with vascular thrombosis, splenic infarcts, generalized visceral congestion and atherosclerosis of aorta and its branches. Pancreas was normal. CONCLUSIONS: The mechanisms of hepatic and splenic infarctions in this case were unclear. The following factors may have contributed to necrosis: vomiting and fever should be considered to induce dehydration and hypotension, which further decreased portal and hepatic arterial inflows; elevated level of catecholamine in hyperglycemic states might induce vasoconstriction effects; widespread atherosclerosis is commonly seen in diabetic and hypertensive patients. This case underlies the importance of searching for hepatic necrosis or infarction in any diabetic patient with elevated liver enzymes. Anticoagulation therapy should be instituted promptly upon recognition of vascular thromboses.JUSTIFICATIVA E OBJETIVOS: O infarto hepático é definido como necrose isquêmica do parênquima hepático envolvendo pelo menos dois ácinos. Trata-se de evento considerado raro devido ao duplo suprimento sangüíneo, arterial e venoso. O objetivo deste estudo foi relatar um caso de paciente não sabidamente diabética que desenvolveu extensas áreas isquêmicas de infarto hepático, após quadro de descompensação aguda da diabete. RELATO DO CASO: Paciente do sexo feminino, 67 anos, hipertensa, procurou o Pronto Socorro com queixas de polidipsia, poliúria, turvação visual, náuseas e vômitos, dificuldade para deambular, havia aproximadamente 10 dias. Ao exame físico foi observado desidratação, palidez cutânea, cianose periférica, hipotermia, taquicardia, hipotensão, dor abdominal leve e difusa. Exames laboratoriais mostraram: leucócitos: 16800, creatinina (Cr): 3,7, uréia (Ur): 167, Na: 133, K: 6.9, glicose: 561; gasometria arterial (cateter de oxigênio: 2 L/min): pH: 6.93, pCO2: 12.1, pO2: 107, BE: -28,8, HCO3: 2,4, Sat 91,3%, lact: 79; urina I: pH: 6,0; leucócitos: 13; densidade: 1015; eritrócitos: 19; proteína: ++; glicose: +++; bilirrubina: negativa; corpos cetônicos: + denotando cetonemia. Eletrocardiograma com onda T apiculada, bloqueio de ramo direito. A paciente foi tratada com insulina, hidratação, bicarbonato de sódio e introduzido antibioticoterapia. Após o tratamento inicial, os exames laboratoriais mostraram: Cr: 2,2, Ur: 122, Na: 162, K: 4,3, Ca: 6,4, glicose: 504, pH: 7,01, HCO3: 7.1, BE: - 22. Um dia após, a paciente apresentou importante dor abdominal acompanhada de irritação peritoneal, além de sonolência e dificuldade para falar; exames laboratoriais mostraram: pH: 7,4, pCO2 : 31, pO2: 68, BE: -4,4, HCO3: 19, Sat.O2: 93,5%; Ur: 95; Cr: 1,4, albumina: 2,4, Ca: 0,95, Na: 166, K:4, bilirrubina: 0,5, bilirrubina D/I: 0,2/0,3, amilase: 1157, Gama-GT: 56, AST 7.210, ALT: 2.470, VHS: 15, lipase: 84. Ultrasonografia abdominal não apresentou alterações significativas. Evoluiu com importante piora clínica, parada cardiorrespiratória e óbito. A necrópsia evidenciou múltiplas áreas de infarto hepático, trombose vascular, infarto esplênico, congestão visceral e aterosclerose de aorta e seus ramos e pâncreas normal. CONCLUSÕES: Os mecanismos de infarto hepático e esplênico neste caso não foram bem elucidados. Alguns fatores devem ter contribuído, tais como: desidratação e hipotensão devido a episódios de vômitos e febre que contribuem para diminuição do fluxo sanguíneo da veia porta e artéria hepática; o nível elevado de catecolaminas que ocorre em estado de hiperglicemia e cetoacidose metabólica pode induzir à vasoconstrição; aterosclerose difusa que é comumente vista em pacientes diabéticos e hipertensos. Este caso enfatiza a necessidade de investigar infarto hepático em pacientes diabéticos com cetonemia e com aumento de enzimas hepáticas. Anticoagulantes devem ser prontamente instituídos se houver trombose vascular.UNIFESP-EPMInstituto Dante Pazzanese de Cardiologia Divisão de PesquisaAMIB AMBUNIFESP, EPMSciEL