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Ciprofloxacin Exposure Leading to Fatal Hepatotoxicity: An Unusual CorrelationUnger, Carly, Al-Jashaami, Layth S. 22 September 2016 (has links)
No description available.
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Fatores associados à densidade mineral óssea de mulheres submetidas a transplante de fígado / Factors associated with bone mineral density of women submitted to liver transplantationBaccaro, Luiz Francisco Cintra, 1980- 16 August 2018 (has links)
Orientadores: Aarão Mendes Pinto Neto, Ilka de Fátima Santana Ferreira Boin / Dissertação (mestrado) - Universidade Estadual de Campinas. Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-16T10:07:53Z (GMT). No. of bitstreams: 1
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Previous issue date: 2010 / Resumo: Objetivos: avaliar a massa óssea e os fatores associados em mulheres submetidas a transplante de fígado em acompanhamento no Ambulatório da Unidade de Transplante Hepático do Hospital das Clínicas da Faculdade de Ciências Médicas da Universidade Estadual de Campinas Sujeitos e Métodos: estudo de corte transversal com mulheres transplantadas hepáticas em acompanhamento no Ambulatório da Unidade de Transplante Hepático do Hospital das Clínicas da Faculdade de Ciências Médicas da Universidade Estadual de Campinas. Foram incluídas todas as mulheres que realizaram transplante hepático há pelo menos um ano e com idade igual ou superior a 35 anos. Foram identificadas 33 mulheres que preenchiam os critérios de inclusão. Dessas, 6 não responderam ao contato telefônico e 4 não quiseram participar, sendo o número final de mulheres participantes igual a 23. Foi realizada entrevista, sempre pelo mesmo pesquisador, onde foram obtidos dados clínicos, sócio-demográficos e realizados exame físico geral e ginecológico. Após a avaliação clínica as mulheres foram encaminhadas para realização de exames laboratoriais (aspartato aminotransferase, alanina aminotransferase, fosfatase alcalina, gama glutamiltransferase, bilirrubina total e frações) e densitometria óssea de coluna lombar e fêmur. A análise estatística foi realizada através do teste exato de Fisher, OR simples e coeficiente de correlação de Spearman. Todas assinaram o termo de consentimento livre e esclarecido previamente à entrevista, e o estudo foi aprovado no Comitê de Ética em Pesquisa da UNICAMP. Resultados: A média de idade das mulheres foi de 52,5 ± 10,9 anos e a média de tempo pós transplante foi de 5,8 ± 3,1 anos. Do total de 23 mulheres incluídas no estudo, 56,5% apresentaram massa óssea alterada. Estar na pós menopausa foi fator de risco para diminuição da massa óssea: OR 69,0 (95% IC 2,89-1647,18; p < 0,0001). Ter idade superior a 44 anos na realização do procedimento aumentou o risco para diminuição da massa óssea: OR 49,50 (95% IC 3,84-638,43; p <0,0001). Ter idade superior a 49 anos aumentou o risco para diminuição na massa óssea: OR 13,33 (95% IC 1,78-100,15; p = 0,0123). Apresentar um período de tempo maior que 5,8 anos da realização do transplante foi fator protetor para diminuição na massa óssea: OR 0,11 (95% IC 0,02-0,78; p = 0,0361). Conclusão: mais da metade das mulheres transplantadas hepáticas apresentaram diminuição da massa óssea. O estado menopausal, a idade, a idade ao transplante e o tempo pós transplante foram os fatores associados à alteração da massa óssea em mulheres transplantadas hepáticas / Abstract: Objectives: to evaluate bone mass and risk factors associated with bone mass alterations in women undergoing liver transplantation followed at the Liver Transplant Outpatient Unit in the Clinics Hospital of the Campinas State University Medical School. Subjects and Methods: a cross-sectional study of women undergoing liver transplantation and followed at the Liver Transplant Outpatient Unit in the Clinics Hospital of the Campinas State University Medical School was carried out. All women aged 35 years or older who had received a liver transplant at least one year before enrollment were included in the study. Thirty-three women satisfied the criteria for study inclusion. Of the total, 6 did not respond to telephone contact and 4 declined to participate. As a result, the final number of women participating in the study was 23. An interview was conducted always by the same investigator for collection of clinical and sociodemographic data, as well as the performance of a general physical and gynecological examination. After clinical evaluation, the women underwent laboratory tests (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyltransferase, total and fractionated bilirubin) and bone mineral density measurement of the lumbar spine and femur. Statistical analysis was performed by Fisher's exact test, simple OR and Spearman's rank correlation coefficient. All women signed a written informed consent term prior to the interview. The study was approved by the Research Ethics Committee of UNICAMP. Results: The mean age of the women was 52.5 ± 10.9 years and mean time since transplantation was 5.8 ± 3.1 years. Of the total number (23) of women included in the study, 56.5% had alteration in bone mass. Being postmenopausal was a risk factor for decreased bone mass: OR 69.0 (95% CI 2.89-1647.18; p < 0.0001). Being over 44 years of age at the time of the surgical procedure increased the risk for decreased bone mass: OR 49.50 (95% CI 3.84-638.43; p < 0.0001). Being over 49 years of age increased the risk for decreased bone mass: OR 13.33 (95% CI 1.78-100.15; p = 0.0123). A period of time longer than 5.8 years since transplantation was a protective factor for decreased bone mass: OR 0.11 (95% CI 0.02-0.78; p = 0.0361). Conclusion: more than 50% of the women undergoing liver transplantation had decreased bone mass. Menopausal status, current age, age at the time of transplantation and time since transplantation were factors associated with bone mass alterations in women receiving a liver transplant / Mestrado / Tocoginecologia / Mestre em Tocoginecologia
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Polyketals: a new drug delivery platform for treating acute liver failureYang, Stephen Chen 22 October 2008 (has links)
Acute liver failure is a major cause of death in the world, and effective treatments are greatly needed. Liver macrophages (Kupffer cells) play a major role in the pathology of acute liver failure, and drug delivery vehicles that can target therapeutics to Kupffer cells have great therapeutic potential for treating acute liver failure. Microparticles, formulated from biodegradable polymers, are advantageous for treating acute liver failure because they can passively target therapeutics to Kupffer cells. However, existing biomaterials are not suitable for the treatment of acute liver failure because of their slow hydrolysis and acidic degradation products. In this dissertation, I present the development of a new class of biodegradable materials, termed aliphatic polyketals, which have considerable potential as drug delivery vehicles for the treatment of acute liver failure because of their neutral degradation products and tunable hydrolysis kinetics. The anti-inflammatory enzyme, superoxide dismutase (SOD), was delivered using polyketal microparticles to the liver for treating acute liver Failure. Our results demonstrated that polyketal microparticles significantly improved the efficacy of SOD in treating LPS-induced acute liver damage in vivo, as evidenced by decreased levels of serum alanine transaminase, which corresponds to the extent of damage in the liver, and serum level of tumor necrosis factor-alpha, which corresponds to the secretion of pro-inflammatory cytokines. The completion of this thesis research demonstrates the ability of polyketal-based drug delivery systems for treating acute inflammatory diseases and creates a potential therapy for enhancing the treatment of acute liver failure.
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Ūminio ir lėtinio paūmėjusio kepenų funkcijos nepakankamumo priežastys, išeitys ir prognozės kriterijai / Causes, outcomes and prognostic criteria of acute and acute-on-chronic liver failureČičinskaitė, Ilona 05 January 2006 (has links)
Acute liver failure (ALF) is a rather rare clinical syndrome developing due to an acute massive dysfunction of the liver cells in previously healthy persons (at least 8 weeks there was no diagnosis of any liver disease) resulting in rapidly progressing multiple organ dysfunction syndrome. Without liver transplantation 80-95 % of the patients die. Factors, influencing the outcome are etiology, the patient's age and the course of the disease. Spontaneous recovery, however, is possible in 5-60 % of ALF cases when regeneration of the liver starts, therefore the main goal of the treatment is to create the most favorable conditions for regeneration.
Causes of ALF may be different. The most common cause of ALF is viral hepatitis, but the prevailing causative agent of hepatitis is different in different countries. Drug-induced (acetaminophen, halotane) liver dysfunction ranks second. The order of other etiological factors according to their frequency is: mushroom (Amanita) poisoning, carbon tetrachloride toxicity, heat stroke, synthetic amphetamine ("Ecstasy") and disorders of liver blood vessels.
In cases of unfavorable prognosis for patients with ALF the only method of treatment with good prognosis is liver transplantation (LT). From 50 to 70 % of patients with lethal ALF prognosis survive after emergency LT. There is no unified ALF prognostic system or indications for LT in the world, therefore a precise individual prognosis for every patient and well-timed decision about LT are... [to full text]
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Imunomodulação da hepatite experimental aguda pela saliva de mosquito Aedes aegypti / Immunomodulation of acute experimental hepatitis by the Aedes aegypti mosquito salivaAssis, Josiane Betim de 11 September 2018 (has links)
Hepatite é uma condição inflamatória do fígado que pode ser autolimitada ou pode progredir para um quadro de fibrose, cirrose ou câncer. Uma das consequências mais graves associada ao dano hepático é a insuficiência hepática aguda (também conhecida como insuficiência hepática fulminante), cujas etiologias mais comuns são as infecções virais, a autoimunidade e o uso de medicamentos. Conhecendo as atividades biológicas das moléculas presentes na saliva dos insetos hematófagos, e com base em resultados anteriores do nosso grupo de pesquisa, acreditamos que os componentes salivares do mosquito Aedes aegypti possam ser empregados na prevenção e/ou tratamento de doenças inflamatórias. Assim, para avaliar o potencial terapêutico da saliva de A. aegypti em quadros de insuficiência hepática aguda, empregamos um modelo experimental amplamente utilizado para o estudo da hepatite autoimune, a hepatite experimental aguda induzida por concanavalina A (Con A) e um modelo de hepatotoxicidade induzida por acetaminofeno (APAP), comumente empregado para o estudo da lesão hepática induzida por fármaco. Nossos resultados demonstram que a exposição de animais às picadas de mosquitos A. aegypti reduz os níveis das enzimas alanino aminotransferase (ALT) em ambos os modelos e de aspartato aminotransferase (AST) no modelo de hepatite induzida por Con A. Além disso, o tratamento com a saliva foi capaz de reduzir os níveis de citocinas séricas IFN-&gamma, IL-6 e IL-2, bem como a expressão de IFN-&gamma no fígado no modelo de hepatite experimental aguda induzida por Con A e as citocinas séricas TNF-, IL-6, IL1 e IL-10 no modelo de hepatite tóxica induzida por APAP. Os animais injetados com Con A apresentaram um aumento das frequências de populações de células NK e macrófagos e a exposição às picadas reduziu essas alterações para níveis próximos aos do grupo controle. Da mesma maneira, a exposição aos mosquitos também reduziu as populações de células dendríticas, macrófagos e células NKT, que se apresentaram aumentadas no grupo de animais injetados com APAP. Tais dados demonstram que a saliva de A. aegypti é capaz de proteger os animais dos efeitos deletérios das hepatites avaliadas, devido à sua capacidade de modular a resposta inflamatória nos animais experimentais. Estudos futuros poderão caracterizar as moléculas responsáveis por essa atividade biológica, destacando seu potencial uso como opção para prevenção e/ou tratamento destas condições. / Hepatitis is an inflammatory condition of the liver that can be self-limiting or progress to fibrosis, cirrhosis or cancer. One of the most severe consequences associated with the hepatic damage is the acute liver failure (also known as fulminant hepatic failure). being viral infections, autoimmunity and use of medications the most common etiologies. Knowing the biological activities of the compounds present in the saliva of hematophagous insects, and based on previous results from our group, we believe that the salivary components of Aedes aegypti mosquitoes can be employed in the prevention and/or treatment of inflammatory diseases. Thus, to evaluate the therapeutic potential of A. aegypti mosquito saliva in acute liver failure, we employed a well-established model for the study of autoimmune hepatitis, acute experimental hepatitis induced by concanavalin A (Con A), and a model of hepatotoxicity induced by acetaminophen (APAP) commonly employed to study drug-induced liver injury. Our results demonstrate that the exposure of animals to A. aegypti mosquito bites reduces alanine aminotransferase (ALT) enzyme levels in both models and aspartate aminotransferase (AST) in the acute experimental hepatitis induced by Con A. In addition, the treatment with saliva was able to reduce the levels of the serum cytokines IFN-&gamma, IL-6 and IL-2, as well as the expression of hepatic IFN-&gamma in the in the model of acute experimental hepatitis induced by ConA as well as the serum cytokines TNF-, IL-6, IL-1, and IL-10 in the APAP-induced toxic hepatitis model. Animals injected with Con A presented an increase in the frequencies of NK cells and macrophages populations, and the exposure to the bites reduced this changes to levels close to that found in the control group. Likewise, mosquito exposure also reduced the populations of dendritic cells, macrophages and NKT cells that were increased in the group of animals injected with APAP. These data demonstrate that A. aegypti saliva is able to protect animals from the deleterious effects of the evaluated hepatitis, due to its ability to modulate the inflammatory response of the experimental animals. Future studies might characterize the molecules responsible for this biological activity, highlighting their potential use as an option for prevention and/or treatment of these conditions.
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Potencial terapêutico da s-nitrosoglutationa (GSNO) na insuficiência hepática aguda experimental induzida por paracetamolSantos, Felipe Miranda January 2012 (has links)
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Previous issue date: 2012 / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil / A intoxicação pelo paracetamol é a principal causa de insuficiência
hepática aguda (IHA) em vários países do ocidente. A hepatotoxicidade é mediada
por um metabólito intermediário reativo que depleta as reservas do antioxidante
endógeno glutationa (GSH). O tratamento precoce com n-acetilcisteína (NAC) é
recomendado para restabelecer a concentração fisiológica de GSH. A snitrosoglutationa
(GSNO) é uma molécula antioxidante derivada do GSH capaz de
reduzir o estresse oxidativo em diversos sistemas celulares e modelos
experimentais. OBJETIVO: Avaliar se GSNO é capaz de reduzir a taxa de
mortalidade, extensão da necrose hepática, manifestações bioquímicas e comparar
sua eficácia com NAC e GSH no tratamento da IHA experimental induzida por
paracetamol. METODOLOGIA: Camundongos isogênicos machos da linhagem
C57Bl/6 foram tratados por três semanas com água suplementada com etanol a
10%. Os animais foram divididos em cinco grupos. O grupo 1 (controle negativo)
recebeu solução salina 0,9%. Os demais grupos receberam 300 mg/Kg de
paracetamol para indução de IHA. Após 3 horas, o grupo 2 (controle positivo) foi
tratado com salina tamponada com fosfato (PBS) e os grupos 3, 4 e 5 foram
tratados, respectivamente, com 600 Umol/kg de NAC, GSH e GSNO. A eutanásia foi
feita 12 horas após a indução de IHA. A extensão da necrose hepática foi avaliada
por morfometria através do software IMAGEPRO-PLUS. Os níveis séricos de
transaminases e fosfatase alcalina foram avaliados como marcadores bioquímicos
de lesão hepática. A taxa de mortalidade foi avaliada em um experimento
independente, após uma dose de 350 mg/Kg de paracetamol. RESULTADOS: O
tratamento com GSNO 600 Umol/kg aumentou a taxa de sobrevida em relação aos
grupos tratados com NAC ou PBS. Entretanto, não houve diferença de mortalidade
entre os grupos GSNO e GSH. A avaliação morfométrica revelou menor extensão de
necrose hepática nos animais tratados com GSNO em comparação com NAC e
PBS. Houve redução de atividade sérica de ALT, mas não de AST no grupo GSNO
em comparação com PBS e NAC. Os níveis séricos de fosfatase alcalina, albumina,
ureia e creatinina não apresentaram diferenças entre os diversos grupos.
CONCLUSÃO: O tratamento com GSNO aumenta a taxa de sobrevida e reduz a
extensão de necrose hepática na IHA experimental por paracetamol. O GSNO
apresenta eficácia superior à NAC e idêntica ao GSH em dose equimolar. Estes
achados sugerem que o efeito protetor do GSNO parece independer da porção
nitroso da molécula. Possíveis mecanismos de proteção extra-hepáticos merecem
ser investigados / Paracetamol overdose is the main cause of acute liver failure (ALF)
in western countries. The hepatotoxicity is mediated by a reactive metabolite that
depletes the pool of glutathione (GSH), an endogenous antioxidant molecule. Early
treatment with n-acetylcysteine (NAC) is recommended to replenish the pool of GSH.
S-nitrosoglutathione (GSNO) is a potent antioxidant molecule that reduces oxidative
stress in several cellular systems and experimental models. OBJECTIVE: To
evaluate if GSNO reduces the mortality rate, the hepatocelular necrosis extension
and to compare its therapeutic efficacy with NAC and GSH in experimental ALF
induced by paracetamol. METHODS: Male mice were treated for three weeks with
alcohol 10% orally. The animals were divided in five groups. Group 1 (negative
control) received saline 0.9%. All the other groups received 300 mg/Kg paracetamol
for induction of ALF. After 3 hours, group 2 (positive control) received phosphate
buffered saline (PBS) and groups 3, 4 and 5 were treated respectively with 600
Umol/kg of NAC, GSH and GSNO. The animals were sacrificed after 12 hours of
induction of ALF. The area of liver necrosis was evaluated by morphometric analysis
with the software IMAGEPRO. Transaminases and alkaline phosfatase were
determined as markers of liver injury. Mortality rate was evaluated in an independent
experiment after a dose of 350 mg/Kg of paracetamol. RESULTS: GSNO treatment
(600 Umol/kg) significantly improved the survival rate compared to PBS and NAC
treatments. There was no statistical difference in survival rate between GSNO and
GSH groups. In addition, GSNO attenuated the area of liver necrosis in comparison
to NAC and PBS, but not to GSH. GSNO reduced the serum ALT, but not AST activity
in comparison to PBS and NAC. There was no statistical difference in alkaline
phosphatase, urea, creatinine and albumin among the groups that received
paracetamol. CONCLUSION: GSNO treatment augmented survival rate and reduced
the area of liver necrosis in comparison to NAC, but was equally as effective as GSH.
These findings suggest that the hepatoprotector effect of GSNO is independent of the
nitroso moiety of the molecule. Potential extra-hepatic mechanisms remain to be
evaluated.
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Real-time bioimpedance measurements of stem cellbased disease models-on-a-chipGamal, Wesam January 2016 (has links)
In vitro disease models are powerful platforms for the development of drugs and novel therapies. Stem-cell based approaches have emerged as cutting-edge tools in disease modelling, allowing for deeper insights into previously unknown disease mechanisms. Hence the significant role of these disease-in-a-dish methods in therapeutics and translational medicine. Impedance sensing is a non-invasive, quantitative technique that can monitor changes in cellular behaviour and morphology in real-time. Bioimpedance measurements can be used to characterize and evaluate the establishment of a valid disease model, without the need for invasive end-point biochemical assays. In this work, two stem cell-based disease models-on-a-chip are proposed for acute liver failure (ALF) and age-related macular degeneration (AMD). The ALF disease model-on-a-chip integrates impedance sensing with the highly-differentiated HepaRG cell line to monitor in real-time quantitative and dynamic response to various hepatotoxins. Bioimpedance analysis and modelling has revealed an unknown mechanism of paracetamol hepatotoxicity; a temporal, dose-dependent disruption of tight junctions (TJs) and cell-substrate adhesion. This disruption has been validated using ultrastructural imaging and immunostaining of the TJ-associated protein ZO-1. Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world with a need for disease models for its currently incurable forms. Human induced pluripotent stem cells (hiPSCs) technology offers a novel approach for disease modelling, with the potential to impact translational retinal research and therapy. Recent developments enable the generation of Retinal Pigment Epithelial cells from patients (hiPSC-RPE), thus allowing for human retinal disease in vitro studies with great clinical and physiological relevance. In the current study, the development of a tissue-on- a-chip AMD disease model has been established using RPE generated from a patient with an inherited macular degeneration (case cell line) and from a healthy sibling (control cell line). A reproducible Electric Cell-substrate Impedance Sensing (ECIS) electrical wounding assay was conducted to mimic RPE damage in AMD. First, a robust and reproducible real-time quantitative monitoring over a 25-day period demonstrated the establishment and maturation of RPE layers on microelectrodes. A spatially-controlled RPE layer damage that mimicked cell loss in AMD was then initiated. Post recovery, significant differences in migration rates were found between case and control cell lines. Data analysis and modelling suggested this was due to the lower cell-substrate adhesion of the control cell line. These findings were confirmed using cell adhesion biochemical assays. Moreover, different-sized, individually-addressed square microelectrode arrays with high spatial resolution were designed and fabricated in-house. ECIS wounding assays were performed on these chips to study immortalized RPE migration. Migration rates comparable to those obtained with ECIS circular microelectrodes were determined. The two proposed disease-models-on-a-chip were then used to explore the therapeutic potential of the antioxidant N-Acetyl-Cysteine (NAC) on hiPSC-RPE and HepaRG cell recovery. Addition of 10 mM NAC at the end of a 24h paracetamol challenge caused a slight increase in the measured impedance, suggesting partial cell recovery. On the other hand, no effect on case hiPSC-RPE migration has been observed. More experiments are needed to examine the effect of different NAC concentrations and incubation periods. The therapeutic potential of electrical stimulation has also been explored. A preliminary study to evaluate the effect of electrical stimulation on RPE migration has been conducted. An externally applied direct current electric field (DC EF) of 300 mV/mm was found to direct the migration of the immortalized RPE cell line (hTERT-RPE1) perpendicular to the EF. The cells were also observed to elongate and to realign their long axes perpendicular to the applied EF. The proposed tissue-on-a-chip disease models are powerful platforms for translational studies. The potential of such platforms has been demonstrated through revealing unknown effects of acetaminophen on the liver as well as providing deeper insights into the underlying mechanisms of macular degeneration. Combining stem cell technology with impedance sensing provides a high throughput platform for studying patient-specific diseases and evaluating potential therapies.
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Využitelnost chirurgických modelů akutního selhání jater v experimentu / Suitability of the surgical models of acute liver failure in experimental studyRyska, Ondřej January 2013 (has links)
Introduction The development of an appropriate animal model of ALF is paramount for the understanding of the disease pathogenesis and evaluation of potential therapeutic approaches. Acute liver failure (ALF) is a severe, usually rapidly progressive disease characterized by high mortality (60 - 90 %). Besides acute liver transplantation which faces a shortage of donors, the only possible therapeutic alternative is applying biological or non-biological liver support systems. To confirm the effectiveness of these methods, clinically relevant model of ALF on a large laboratory animal is essential. Surgically induced ALF models seem to be more reliable than models based on chemical intoxication. Ideal model of ALF has not yet been published. Surgical models are usually performed with devascularisation, large liver resection or hepatectomy. The aim of this work was to introduce three surgical models of ALF and evaluate their usefulness for testing biological and non-biological liver support systems. Materials and Methods Female laboratory pig weighing 35 - 45 kg was used for the experimental study. After induction of general anesthesia the thermodilution catheter was introduced via jugular vein. Femoral artery and vein were cannulated for invasive blood pressure monitoring and for infusions and...
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Avaliação morfofuncional do implante esplênico autógeno e sua relação com a histologia hepática em um modelo murino de injúria por paracetamolGrünewald, Sabrine Teixeira Ferraz 27 November 2015 (has links)
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Previous issue date: 2015-11-27 / O baço apresenta várias funções, como fagocitose de microrganismos, produção de imunoglobulinas e filtração do sangue. O baço também possui relação anatômica e funcional com o fígado, embora existam poucas pesquisas sobre esse aspecto. O modelo da esplenectomia seguida de implante esplênico autógeno é baseado na capacidade regenerativa do baço, sendo utilizado para estudo de suas funções. Já o modelo da injúria hepática química consiste na indução de lesão hepatocelular para avaliação da função hepática. O objetivo desse trabalho foi avaliar a função de filtração do baço no modelo de implante autógeno, e estudar sua relação funcional com o fígado no modelo de injúria hepática química. Cinquenta e dois camundongos BALB/C fêmeas foram randomizados nos grupos: operação simulada, esplenectomia total, esplenectomia e implante autógeno do baço em omento maior, e grupo controle. Após 7, 14 e 28 dias da cirurgia, a filtração esplênica foi avaliada com da contagem de corpúsculos de Howell-Jolly e eritrócitos com indentações. No 28º dia, os animais receberam paracetamol 400mg/kg por gavagem, sendo eutanasiados após 12 ou 24 horas. Realizou-se dosagem de transaminases hepáticas, e avaliação histológica do fígado e baço. Quanto a função de filtração, o grupo esplenectomizado demonstrou filtração insuficiente em todas as análises, enquanto o grupo do implante autógeno evoluiu com recuperação progressiva da função após o 14º dia. A avaliação histológica dos implantes mostrou, no 28º dia após a cirurgia, aspecto morfológico similar ao baço normal. A dosagem de transaminases após a injúria medicamentosa não permitiu uma definição quanto a influência do baço sobre as mesmas. A histopatologia hepática mostrou agravamento temporal da lesão, com necrose centrolobular mais intensa no grupo esplenectomizado que nos demais, sugerindo um papel protetor do baço nesse modelo de injúria. Assim, os implantes esplênicos apresentaram recuperação estrutural e funcional, demonstrando a capacidade do implante autógeno de resgatar a função de filtração do baço íntegro. De forma inédita, foi demonstrado que a integridade da função esplênica pode estar associada à função hepática, uma vez que a presença do baço ou do implante esplênico amenizou os efeitos da lesão hepática induzida quimicamente. / The spleen presents various functions such as phagocytosis of microorganisms, production of immunoglobulins, and blood filtration. The spleen has also an anatomical and functional relationship with the liver, although there are few studies on this topic. The model of splenectomy and autogenous implant of splenic tissue is based on the regenerative capacity of the spleen, being useful to study their functions. The chemical liver injury model consists of the induction of hepatocellular injury for assessment of liver function. The aim of this study was to assess the spleen filtering function of the splenic model, and to evaluate their functional relationship with the liver on the chemical liver injury model. Fifty-two BALB/C mice were randomized into groups: sham operated, total splenectomy, splenectomy and autologous implant of the spleen in the greater omentum, and control. After 7, 14 and 28 days after surgery, splenic filtration was assessed by counting Howell-Jolly corpuscles and erythrocytes with indentations. On day 28, animals received paracetamol at 400mg/kg by gavage and were euthanized after 12 or 24 hours for dosage of liver transaminases and histology of liver and spleen. Regarding the filtering function, the splenectomized group demonstrated insufficient filtration in all analyzes, while the autologous implant group developed progressive recovery of function after the 14th day. Histology of the implants showed, on the 28th day after surgery, morphological similarity to the normal spleen. The assessment of transaminases after drug injury did not allow a definition as to the influence of the spleen on liver function. Liver histology evaluation showed an exacerbation of the injury with time, with more intense centrilobular necrosis in the splenectomized group than in the other, suggesting a protective role of the spleen in liver injury model. Thus, splenic implants showed structural and functional recovery, demonstrating the ability of the autologous implant to revive the filtering function of the intact spleen. Furthermore, the integrity of splenic function may be associated with liver function, since the presence of the spleen or spleen implantation mitigated the effects of chemically induced liver injury.
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Modélisation de l'interaction entre l'hémodynamique hépatique et la régénération hépatique dans l'étude de l'insuffisance hépatique post hépatectomie / Modelisation of the interraction between liver hemodynamics and regeneration for the study of post hepatectomy liver failureBucur, Petru 23 January 2017 (has links)
La régénération hépatique après résection hépatique majeure ne se fait pas toujours de la même façon et une partie importante des facteurs déterminants de la régénération pourrait être liée aux constantes hémodynamiques hépatiques.Le but de nos travaux a été d'étudier cette relation en se basant notamment sur les modèles expérimentaux d'hépatectomie chez le gros animal. Nous avons étudié la régénération sur forme de volume mesuré en imagerie, examen anatomopathologique, prolifération des hépatocytes et des vaisseaux dans le parenchyme hépatique jusqu'à une reconstruction 3D du lobule hépatique.Nos résultats indiquent des liens forts entre l'hémodynamique et la qualité de la régénération et laissent entrevoir la possibilité d'agir sur les composantes hémodynamique. / Liver regeneration after liver resection does not occur in the same way in different conditions. A major determining factor of the regeneration could be the hemodynamic environment of the regenerating liver.The aim of our work was to study the relationship between liver regeneration and hemodynamic parameters, based mainly on experimental models of liver resection in large animals. We studied regeneration as CT scan volume, histopathology, hepatocyte proliferation and vessel neoformation inside the liver parenchyma, up to 3D reconstruction of the liver lobule.Our results show important relationships between liver hemodynamics and liver regeneration and let imagine the possibility to modulate hemodynamic parameters in order to modify liver regeneration.
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