Comparative study between fructose 1-6 bisphosphate and histidine-tryptophan-ketoglutarate in liver preservation in rats submitted to total cold ischemia

Purpose To compare Fructose-1,6-Bisphosphate (FBP) to Histidine-Tryptophan-Ketoglutarate (HTK) in liver preservation at cold ischemia. Methods Male rats (Sprague-Dawley: 280-340g) divided into three groups (n=7): Control; Fructose-1,6-bisphosphate (FBP); Histidine-Tryptophan-Ketoglutarate (HTK). Animals underwent laparotomy-thoracotomy for perfusion of livers with saline. Livers were removed and deposited into solutions. Mitochondria were isolated to determine State 3 (S3), State 4 (S4), Respiratory Control Ratio (RCR) and Swelling (S). Liver enzymes (AST, ALT, LDH) were determined in solution. At tissue, Malondialdehyde (MDA) and Nitrate (NOx) were determined. All parameters were analyzed at 0.6 and 24 hours of hypothermic preservation. Statistics analysis were made by Mann-Whitney test (p 0.05). Results Regarding ALT, there was a difference between FBP-6h/HTK-6h, lower in HTK. Regarding AST, there was a significant difference between FBP-24h/HTK-24h, lower in FBP. Regarding NOx, there was a difference between 0h and 6h, as well as 0h and 24h for both solutions. Regarding S3, there was a significant difference in 24h compared to Control-0h for both solutions, and a significant difference between FBP-6h/FBP-24h. Regarding S4, there was a difference between Control-0h/HTK-24h and FBP-24h/HTK-24h, higher in HTK. There was a difference between Control-0h/FBP-24h for Swelling, higher in FBP. Conclusion Fructose-1,6-Bisphosphate showed better performance at nitrate and aspartate aminotransferase compared to histidine-tryptophan-ketoglutarate.(AU)

Evaluation of Indigo carmine on hepatic ischemia and reperfusion injury

Purpose To evaluate the effects of treatment with Indigo Carmine (IC) on rat livers subjected to ischemia-reperfusion injury. Methods The animals were subdivided into 4 groups: 1.SHAM group(SH) - saline; 2.SHAM group with IC-2mg/Kg(SHIC); 3.IR group - rats submitted to ischemia and reperfusion with saline(IR); 4.IR group with IC-2mg/Kg(IRIC). The IR protocol consists of liver exposure and administration of drug or saline intravenously, followed by 60 minutes of ischemia and 15 of reperfusion. Liver samples were collected for biochemical analysis. Results State 3 of mitochondrial respiration showed a significant worsening of the IRIC group in relation to all others. State 4 showed a difference between IRIC and SHIC. The Respiratory Control Ratio showed statistical decrease in IR and IRIC versus Sham. The osmotic swelling showed significant difference between SHxIR; SHICxIRIC and SHxIRIC. There was a significant increase in ALT in the IRIC group in relation to all the others. Concerning the nitrate dosage, there was a decrease in the group treated with IC(IRxIRIC). There was no difference regarding the dosage of Malondialdehyde. Conclusion IC was not able to protect mitochondria from IR injury and proved to be a potentiating agent, acting in synergy with the IR injury promoting damage to the hepatocyte membranes.(AU)

Comparative study between fructose 1-6 bisphosphate and histidine-tryptophan-ketoglutarate in liver preservation in rats submitted to total cold ischemia

Purpose. To compare Fructose-1,6-Bisphosphate (FBP) to Histidine-Tryptophan-Ketoglutarate (HTK) in liver preservation at cold ischemia.. Methods. Male rats (Sprague-Dawley: 280-340g) divided into three groups (n=7): Control; Fructose-1,6-bisphosphate (FBP); Histidine-Tryptophan-Ketoglutarate (HTK). Animals underwent laparotomy-thoracotomy for perfusion of livers with saline. Livers were removed and deposited into solutions. Mitochondria were isolated to determine State 3 (S3), State 4 (S4), Respiratory Control Ratio (RCR) and Swelling (S). Liver enzymes (AST, ALT, LDH) were determined in solution. At tissue, Malondialdehyde (MDA) and Nitrate (NOx) were determined. All parameters were analyzed at 0.6 and 24 hours of hypothermic preservation. Statistics analysis were made by Mann-Whitney test (p<0.05).. Results. Regarding ALT, there was a difference between FBP-6h/HTK-6h, lower in HTK. Regarding AST, there was a significant difference between FBP-24h/HTK-24h, lower in FBP. Regarding NOx, there was a difference between 0h and 6h, as well as 0h and 24h for both solutions. Regarding S3, there was a significant difference in 24h compared to Control-0h for both solutions, and a significant difference between FBP-6h/FBP-24h. Regarding S4, there was a difference between Control-0h/HTK-24h and FBP-24h/HTK-24h, higher in HTK. There was a difference between Control-0h/FBP-24h for Swelling, higher in FBP.. Conclusion. Fructose-1,6-Bisphosphate showed better performance at nitrate and aspartate aminotransferase compared to histidine-tryptophan-ketoglutarate.(AU)

The cardiopulmonary bypass and cancer dissemination puzzle

Early cancer diagnosis, new therapies that increased survival of patients, besides the increasingly elderly population are some factors would be associated with possible cancer dissemination in patients under cardiopulmonary bypass (CPB) cardiac surgery. Also, the benefits, and risks, regarding long-term survival, have not yet been established. Therefore, cardiac surgery morbimortality may be superior in patients with cancer disease. Also, immunologic and inflammatory changes secondary to CPB can also increase tumor recurrence. After a brief introduction and CPB immunologic the two main topic subjects included: 1) Combined heart surgery and lung resection and; 2) Possible influence of neoplasia type. After observing the relative literature scarcity, we keep the opinion that “CPB has a modest association with cancer progression” and that “CPB and cancer dissemination should be a logical but unlikely association.”(AU)

Rivastigmine prevents injury induced by ischemia and reperfusion in rat liver

Purpose: To evaluate whether pre-treatment with rivastigmine is able to attenuate the I/R induced lesions in rat liver. Methods: SHAM animals or those submitted to I/R, non-treated or pre-treated with rivastigminine (2mg/kg) either 50 or 15 minutes before ischemia, were used. After I/R protocol, these animals were killed and their livers were harvested to measurement of the mitochondrial swelling as well as the malondialdehyde (MDA), nitrite and nitrate tissue concentration. Blood was also harvested for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) determinations. Results: I/R promoted a significant increase of mitochondrial swelling in the studied animals. This increase of mitochondrial swelling was partially prevented by rivastigmine, but only if administered 50 minutes before ischemia. No significant modification of MDA, nitrite or nitrate tissue concentrations was observed in consequence of I/R, followed or not by rivastigmine treatments. In addition, I/R elevated both AST and ALT. These elevations of serum enzymes were not reversed by the different rivastigmine treatments. Conclusions: Rivastigmine administered 50 minutes before ischemia attenuates I/R-induced mitochondrial swelling, that indicates liver injury. This protective effect may be related to a greater stimulation of alfa7nAChR present in the Kupffer cells by the non-methabolized ACh, leading to an attenuation of I/R-induced inflammation.(AU)

Liver ischemia and reperfusion injury. Pathophysiology and new horizons in preconditioning and therapy

It is well known that during hepatic operative procedures, it is often critical that the irrigation is interrupted to avoid possible bleeding, blood transfusions, variable intensities, and their short and long-term consequences. It was believed in the past that the flow interruption should not exceed 20 minutes, which limited the use of this maneuver. However, it has been postulated that ischemia could be maintained for more than 60 minutes in healthy livers. The present paper review includes: 1) A brief introduction to justify the rationale of the review design; 2) Aspects of the pathophysiology of the three stages of the liver ischemia-reperfusion injury; 3) The innate and acquired immunity; 4) Oxidative stress; 5) Apoptosis and autophagy, Some essential biomarkers (Tumor Necrosis Factor-α, nitric oxide, metalloproteinases); and, finally; 6) Preventive ("cheating") strategies, non-pharmacological and pharmacological options to treat the liver IR injury.(AU)

Evaluation of the therapeutic effect of methylene blue on the liver of rats submitted to ischemia and reperfusion

Purpose:To analyze the effect of methylene blue (MB) therapy during the liver ischemia-reperfusion injury (I/R) process.Methods:Thirty-five male Wistar rats were used, (70%) submitted to partial ischemia (IR) or not (NIR) (30%) were obtained from the same animal. These animals were divided into six groups: 1) Sham (SH), 2) Sham with MB (SH-MB); 3) I/R, submitted to 60 minutes of partial ischemia and 15 minutes of reperfusion; 4) NI/R, without I/R obtained from the same animal of group I/R; 5) I/R-MB submitted to I/R and MB and 6) NI/R-MB, without I/R. Mitochondrial function was evaluated. Osmotic swelling of mitochondria as well as the determination of malondialdehyde (MDA) was evaluated. Serum (ALT/AST) dosages were also performed. MB was used at the concentration of 15mg/kg, 15 minutes before hepatic reperfusion. Statistical analysis was done by the Mann Whitney test at 5%.Results:State 3 shows inhibition in all ischemic groups. State 4 was increased in all groups, except the I/R-MB and NI/R-MB groups. RCR showed a decrease in all I/R and NI/R groups. Mitochondrial osmotic swelling showed an increase in all I/R NI/R groups in the presence or absence of MB. About MDA, there was a decrease in SH values in the presence of MB and this decrease was maintained in the I/R group. AST levels were increased in all ischemic with or without MB.Conclusions:The methylene blue was not able to restore the mitochondrial parameters studied. Also, it was able to decrease lipid peroxidation, preventing the formation of reactive oxygen species.(AU)

Effects of hyperbaric oxygen therapy as hepatic preconditioning in rats submitted to hepatic ischemia/reperfusion injury

To analyze the role of hyperbaric oxygen therapy as hepatic preconditioning in rats submitted to hepatic ischemia and reperfusion. Wistar rats were randomly divided into three groups: SHAM, rats submitted to surgical stress without hepatic ischemia and reperfusion, I/R, rats submitted to total hepatic pedicle ischemia for 30 min, followed by 5 min of reperfusion; HBOI/R, rats submitted to 60 minutes of hyperbaric oxygen therapy at 2 atm and immediately submitted to the experimental protocol of ischemia and reperfusion. Liver function was assessed by measuring serum alanine aminotransferase and aspartate aminotransferase, as well as mitochondrial function by determining states 3 and 4 of mitochondrial respiration, respiratory control rate and mitochondrial permeability transition (mitochondrial swelling). The results were analyzed by the Mann-Whitney test and all P-values <0.05 were considered significant. There were significant differences in serum aspartate aminotransferase values in groups SHAM vs. HBOI/R, I/R vs HBOI/R, alanine aminotranferase in groups SHAM and I/R; State 3 in SHAM groups vs. I/R, SHAM vs. HBOI/R, State 4 in I/R vs HBOI/R groups, respiratory control rate in SHAM vs I/R groups; mitochondrial swelling in SHAM vs. I/R groups, and SHAM vs HBOI/R. Hyperbaric preconditioning improved hepatic mitochondrial function and decreased serum markers of liver injury in the ischemia and reperfusion process.(AU)

Effects of hyperbaric oxygen therapy on the liver after injury caused by the hepatic ischemia-reperfusion process

PURPOSE: To evaluate the effects of hyperbaric oxygen on rats submitted to hepatic ischemia and reperfusion. METHODS: Twenty-three Wistar rats were divided at random into 3 groups: SHAM, rats submitted to surgical and anesthetic stress without induction of hepatic ischemia/reperfurion; I/R, rats submitted to total ischemia of the hepatic pedicle for 25 min followed by 5 min of reperfusion; HBOI/R, rats submitted to 60 min of hyperbaric oxygen therapy at a pressure of 2 absolute atmospheres immediately after the experimental protocol of ischemia/reperfusion. Hepatic function was evaluated by quantitation of serum alanine aminotranferase (ALT) and aspartate aminotransferase (AST), and by mitochondrial function through the determination of states 3 and 4 of mitochondrial respiration, respiratory control ratio (RCR) and mitochondrial swelling. Data were analyzed by the Mann-Whitney test, with the level of significance set at p <0.05. RESULTS: There was a significant difference in state 3 values for the SHAM group vs I/R and I/R vs IRHBO, in state 4 values for the SHAM group vs I/R; and in mitochondrial swelling for the SHAM groups vs I/RHBO, SHAM vs I/R, and IR vs I/RHBO. CONCLUSION: The use of hyperbaric oxygen after I/R improved in a relative manner both the production of energy and the effects on the mitochondrial wall.(AU)

Hyperoxic preconditioning in partial liver ischemia

PURPOSE: To evaluate the effect of the hyperbaric oxygen (HBO) treatment as a pre-conditioning for I/R effects in the liver ischemia. METHODS: Fifty-seven male Wistar rats (260-300g) were submitted to the following procedures: SHAM; I/R, rats submitted to I/R, consisting of partial ischemia of 70% of the liver for 90 minutes followed by 15 minutes of reperfusion; HBO I/R 1 ATA, 30 minutes of HBO treatment at the pressure of 1 absolute atmosphere (ATA) during the ischemia time. HBO I/R 2 ATA, 30 minutes of HBO (2 ATA) during the ischemia time. Pre HBO I/R 30', rats submitted to 30 minutes of HBO (2 ATA) immediately before the I/R time. Pre HBO I/R 90', rats submitted to 90 minutes of HBO (2 ATA) immediately before the I/R time. RESULTS: There was a significant worsening of all the parameters of mitochondrial energy production (state 3, 4, RCR and Swelling) in the I/R group, when compared to the Sham group (I/R

Can joint analysis of postoperative MELD, base excess and blood lactate levels be used as an index of postoperative outcome for patients submitted to liver transplantation? / A análise conjunta do MELD pós-operatório, do base excess e dos níveis séricos de lactato pode ser usada como um índice prognóstico para pacientes submetidos a transplante de fígado?

PURPOSE: The objective of the present study was to evaluate the postoperative levels of classical or pure MELD and changes in lactate or base excess (BE) levels as possible predictive factors of the type of outcome of patients submitted to orthotopic liver trasplantation (OLT). METHODS: The study was conducted on 60 patients submitted to OLT at the University Hospital, Faculty of Medicine of Ribeirão Preto, USP, between October 2008 and March 2012. The 30 latest survivor (S) and non-survivor (NS) cases were selected. All liver transplants were performed using the piggy-back technique. ALT, AST, BE and blood lactate values were determined for each group at five time points (immediate preoperative period, end of hypothermal ischemia, 5 and 60 minutes after arterial revascularization and in the immediate postoperative period, when the postoperative MELD was also calculated. RESULTS: The aminotransferases reached a maximum increase 24 hours after surgery in both the S and NS groups. There was a significantly higher increase in BE and blood lactate in the NS group, especially after 5 minutes of afterial reperfusion of the graft, p<0.05. There was no significant difference in preoperative MELD between groups (p>0.05), while the postoperative MELD was higher in the NS than in the S group (p<0.05) CONCLUSION: Joint analysis of postoperative MELD, BE and blood lactate can be used as an index of severity of the postoperative course of patients submitted to liver transplantation.(AU)

OBJETIVO: O objetivo do presente estudo é avaliar os níveis do MELD clássico ou puro pós-operatório, alterações dos níveis séricos do lactado e BE, analisando-os como possíveis fatores preditivos do tipo de sobrevida de pacientes submetidos ao transplante ortotópico de fígado (OLT). MÉTODOS: Foram analisados 60 pacientes submetidos ao OLT (técnica de piggy-back) no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto-USP, entre Outubro 2008 e Março de 2012. Foram selecionados os 30 últimos casos de sobreviventes (S) e 30 de não-sobreviventes (NS). Avaliou-se para cada grupo, os valores ALT, AST, de base excess (BE) e lactato sanguíneos em cinco momentos (pré-operatório imediato, no final da isquemia hipotérmica, 5 e 60 minutos após a revascularização arterial e no pós-operatório imediato, quando também foi calculado o MELD pós-operatório. RESULTADOS: Com relação às aminotransferases, houve um aumento máximo após 24 horas de pós-operatório em ambos os grupos S e NS. Houve aumento significativo dos níveis de BE e lactato sanguíneo significativamente maior no grupo NS, sobretudo nos tempos após 5 minutos de reperfusão arterial do enxerto, p<0,05. Não houve diferença significativa entre o MELD pré-operatório em ambos os grupos (p>0,05). O MELD pós-operatório foi maior no grupo NS do que no grupo S (p<0,05). CONCLUSÃO: A análise conjunta do MELD pós-operatório, do BE e do lactato sanguíneo pode ser usada como índice de gravidade da evolução pós-operatória de pacientes submetidos ao OLT.(AU)

Effect of hyperbaric oxygen therapy on liver function during intermittent ischemia / Efeito da oxigenoterapia hiperbárica sobre a função hepática na isquemia intermitente

PURPOSE: To analyze the effects of hyperbaric oxygen therapy on liver function in rats previously subjected to ischemia and reperfusion. METHODS: A randomly distribution of 23 Wistar rats was conducted into three groups: SHAM, animals subjected to surgical stress without restricting blood flow by clamping the hepatic pedicle, IR, rats underwent hepatic vascular occlusion intermittently for two complete cycles of 15 minutes of ischemia followed by 5 min of reperfusion, IR / HBO, rats underwent hepatic pedicle clamping and thereafter exposed to hyperbaric oxygen pressure of 2 absolute atmospheres for 60 minutes. We evaluated liver function through mitochondrial function, determined by the stages 3 and 4 of respiration, respiratory control ratio (RCR) and mitochondrial permeability transition (Swelling). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also quantified . We analyzed the results using the Mann-Whitney test and were considered significant all results with p <0.05. RESULTS: There were significant differences between the results of stage 3 in SHAM vs IR group ; of the stage 4 in the groups IR vs SHAM and SHAM vs IR /HBO; of the Respiratory Control Ratio (RCR) in the group IR vs IR / HBO ; of alanine aminotransferase in the groups IR vs SHAM , SHAM vs IR/HBO and IR vs IR / HBO; aspartate aminotransferase in the groups SHAM vs IR and SHAM vs IR / HBO. CONCLUSION: The whole analysis of the mitochondiral function indicators permits us to conclude that the hyperbaric oxygen therapy acted as a protective agent of the mitochondrial function, minimizing the ischemia-reperfusion injury of the hepatic parenchyma.(AU)

OBJETIVO: Analisar os efeitos da oxigenoterapia hiperbárica sobre a função hepática de ratos previamente submetidos à isquemia e reperfusão. MÉTODOS: Realizou-se a distribuição aleatória de 23 ratos Wistar em três grupos: SHAM, animais submetidos ao estresse cirúrgico sem restrição de fluxo sanguíneo por clampeamento do pedículo hepático; IR ratos submetidos a oclusão vascular hepática de maneira intermitente em dois ciclos completos de 15 minutos de isquemia, seguidos por 5 min de reperfusão; IR/HBO, ratos submetidos ao clampeamento do pedículo hepático e ,ulteriormente , expostos a oxigenoterapia hiperbárica a pressão de 2 atmosferas absolutas durante 60 minutos. Avaliou-se a função hepática através da função mitocondrial, determinada pelos estados 3 e 4 da respiração mitocondrial, razão de controle respiratório(RCR) e transição de permeabilidade mitocondrial (Swelling) .Quantificou-se também alanina aminotransferase e aspartato aminotransferase séricas. Analisou-se os resultados pelo teste de Mann-Whitney e foram considerados significativos os valores de p < 0,05. RESULTADOS:Houve diferença significativa nos valores do estado 3 no grupo SHAM vs IR; estado 4 nos grupos SHAM vs IR, SHAM vsIR/HBO; Razão de Controle Respiratório(RCR) no grupo IR vs IR/HBO; alanina aminotransferase nos grupos SHAM vs IR, SHAM vs IR/HBO, IR vs IR/HBO; aspartato aminotransferase nos grupos SHAM vs IR , SHAM vs IR/HBO. CONCLUSÃO: A análise dos parâmetros mitocondriais como um todo permitiu concluir que a oxigenoterapia hiperbárica atuou como agente protetor da função mitocondrial, minimizando os efeitos deletérios da lesão de isquemia e reperfusão do parênquima hepático.(AU)

Effects of hyperbaric oxygen (HBO), as pre-conditioning in liver of rats submitted to periodic liver ischemia/reperfusion / Efeitos da oxigenoterapia hiperbárica como pré-condicionamento em fígados de ratos submetidos à lesão hepática de isquemia/reperfusão intermitente

PURPOSE: to assess the effect of hyperbaric oxygen (HBO) as pre-conditioning on periodic liver ischemia/reperfusion injury. METHODS: Thirty-six male Wistar rats were divided into 4 groups (SHAM, I/R , HBO-I/R and CONTROL). The surgical technique consisted of total clamping of the hepatic pedicle for 15 min followed by twice repeated reperfusion for 5 min (unclamping). HBO was applied in a collective chamber (simultaneous exposure of 4 rats) directly pressurized with oxygen at 2 ATA for 60 min. Hepatic mitochondrial function was determined using samples of the median lobe obtained after exactly 5 min of reperfusion for the analysis of mitochondrial respiration based on the determination of states 3 and 4, the respiratory control ratio and the transition of mitochondrial permeability (mitochondrial swelling).Data were analyzed by the Mann-Whitney test and the level of significance was set at p < 0.05. RESULTS: There was a statistically significant difference (p< 0.05) in state 3 between the CONTROL and I/R and HBO-I/R groups, in state 4 between the CONTROL and I/R and HBO-I/R groups; in respiratory control ratio (RCR) between the CONTROL and I/R and HBO-I/R groups and between the CONTROL and Sham groups, and in mitochondrial swelling between the CONTROL and I/R and HBO-/R groups and between the Sham and I/R and HBO-I/R groups. CONCLUSION: In this process of periodic ischemia and reperfusion, hyperbaric pre-conditioning did not improve significantly hepatic mitochondrial function.(AU)

OBJETIVO: Avaliar os efeitos da oxigenoterapia hiperbárica (HBO), como pré-condicionamento, em lesão hepática de isquemia/reperfusão intermitente. MÉTODOS: Foram avaliados 36 ratos Wistar machos, distribuídos em 4 grupos (SHAM, I/R , HBO - I/R e CONTROLE). A técnica operatória consistiu em pinçamento total do pedículo hepático durante 15min, seguido de reperfusão por 5 min (desclampeamento), por duas vezes. A aplicação de HBO foi realizada em câmara coletiva (exposição simultânea de 4 ratos) diretamente pressurizada com oxigênio a 2ATA, durante 60min. Determinou-se a função mitocondrial hepática através de amostras do lobo mediano colhidas com exatos 5min de reperfusão para análise da respiração mitocondrial, através da determinação dos estados 3 e 4, razão de controle respiratório e transição de permeabilidade mitocondrial (intumescimento osmótico - swelling mitocondrial).Os resultados foram analisados pelo teste de Mann-Whitney e foi considerado significativo todo valor de p < 0,05. RESULTADOS: Houve diferença estatistica significativa (p< 0,05) no Estado 3 nos grupos CONTROLE vs I/R e HBO - I/R, no Estado 4 nos grupos CONTROLE vs I/R e HBO - I/R; na Razão de controle respiratório(RCR) nos grupos CONTROLE vs I/R e HBO-IRe CONTROLE vs Sham e no Swelling mitocondrial nos grupos CONTROLE vs I/R e HBO - I/R, I/R vs HBO-IRe Sham vs I/R e HBO-IR. CONCLUSÃO: O pré-condicionamento hiperbárico não melhorou a função mitocondrial hepática significativamente neste processo de isquemia e reperfusão intermitente.(AU)

Clinical and regulatory protocol for the treatment of jaundice in adults and elderly subjects: a support for the health care network and regulatory system / Protocolo clínico e de regulação para o tratamento de icterícia no adulto e idoso: subsídio para as redes assistenciais e o complexo regulador

PURPOSE: Clinical interventions and controlled access to the health care system can be improved by a Regulatory System (RS) and Clinical and Regulatory Protocols (CRPs). The objective of the present paper is to present the methodology used for elaborating the CRPs. METHODS: The process used to elaborate the CPRs involved a scientific co-operation between university and health care system. Workshops were held and attended by primary care practitioners, RS team, and matrix team (university specialists supporting primary care practitioners). RESULTS: The treatment of jaundice in adults and elderly subjects is amongst the themes selected for elaborating the CRPs since jaundice is a medical sign frequently seen in four clinical scenarios involving distinctive diagnostic and therapeutic interventions which can be performed in different health care settings. Evaluation guidelines as well as the clinical and regulatory procedures were established for different health care settings. The most relevant clinical and regulatory interventions were expressed as algorithms in order to facilitate the use of CRPs by health care practitioners. CONCLUSION: It is expected that the implementation of this protocol will minimise the imbalance between the icteric patients' needs and the treatment modalities being offered, thus contributing to a more co-operative health care network.(AU)

OBJETIVO: As ações clínicas e de ordenação do acesso à rede de saúde podem ser aperfeiçoadas pelo Complexo Regulador (CR) e pelos Protocolos Clínicos e de Regulação (PCR). Nesse trabalho apresenta-se a metodologia de elaboração dos PCR mediante cooperação entre universidade e sistema de saúde. MÉTODOS: O processo utilizado para a elaboração dos PCR envolve oficinas com a participação de profissionais da atenção básica, do CR e das equipes matriciais (especialistas da universidade que dão suporte às equipes de atenção básica). RESULTADOS: Dentre os temas selecionados para elaboração dos PCR, incluiu-se a icterícia no adulto e no idoso. Trata-se de um sinal clínico que comporta quatro cenários de apresentação com distintos percursos diagnósticos e terapêuticos passíveis de serem executados em diferentes pontos da rede assistencial. As diretrizes de avaliação, bem como as decisões e ações clínicas e reguladoras cabíveis para os diferentes cenários foram estabelecidas desde a atenção básica até o hospital terciário. As ações clínicas e reguladoras mais relevantes foram colocadas em algoritmo para facilitar o emprego do protocolo pelos profissionais de saúde. CONCLUSÃO: Há a expectativa que a implementação desse protocolo possa minimizar o descompasso entre as necessidades dos pacientes ictéricos e a modalidade de serviço oferecida e, assim, contribuir para a configuração de uma rede assistencial mais cooperativa.(AU)

Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction / Avaliação da respiração mitocondrial de miócitos cardíacos em ratos ictéricos sumetidos à obstrução do ducto biliar

PURPOSE: The objective of the present study was to evaluate the capacity of the myocardium for energy production by the analysis of mitochondrial respiration in rats with jaundice submitted to bile duct ligature. METHODS: Sixteen male Wistar rats were divided into 2 Groups: Group SO submitted to nontherapeutic laparotomy (sham operation) and Group IC (icteric group) submitted to bile duct ligature. After 7 days, laparotomy was again performed in all animals for cardiac muscle extraction and analysis. Mitochondrial oxygen consumption was determined by stage 3 velocity and stage 4 velocity. The respiratory control ratio (RCR) was obtained by the ratio of stage 3 to stage 4 velocity. Statistical analysis was performed by the Mann-Whitney test, with the level of significance set at 5 percent (p<0.05). RESULTS: Statistical analysis revealed a significant drop in oxygen consumption during stage 3 mitochondrial respiration in group IC compared with SO, whereas the values obtained during stage 4 were basically identical for the two groups. Likewise, RCR values exhibited a significant reduction. CONCLUSION: The cellular respiration of the "jaundiced heart" is depressed. This was demonstrated by the reduced capacity of cardiac mitochondria to consume oxygen and synthesize ATP, supporting the idea of a latent cardiac impairment responsible for the hemodynamic decompensation occurring during cholestasis.(AU)

OBJETIVO: A proposta deste trabalho é avaliar a capacidade de produção energética do miocárdio mediante análise da respiração mitocondrial em ratos ictéricos submetidos à ligadura do ducto biliar. MÉTODOS: Foram utilizados 16 ratos Wistar machos divididos em 2 Grupos: Grupo SO , os quais foram submetidos à Laparotomia branca e Grupo IC, os quais sofreram ligadura do ducto biliar para o desenvolvimento de icterícia obstrutiva. Todos os animais após 7 dias de cirurgia foram submetidos à nova laparotomia para extração e análise do músculo cardíaco. O consumo de oxigênio pelas mitocôndrias foi determinado pela velocidade do estado 3 e velocidade do estado 4. A razão do controle respiratório (RCR) foi obtida pela relação entre as velocidades dos estados 3 e 4. A análise estatística foi feita pelo teste de Mann-Whitney com nível de significância de 5 por cento (p<0.05). RESULTADOS: Observou-se queda estatisticamente significante nos valores do consumo de oxigênio do estado 3 da respiração mitocondrial no grupo IC em relação ao SO, no entanto os valores para estado 4 permaneceram basicamente inalterados entre os grupos. Os valores de RCR entre os grupos também apresentaram diminuição significativa. CONCLUSÃO: A respiração celular do 'coração ictérico' está deprimida em decorrência da redução da capacidade da mitocôndria cardíaca em consumir oxigênio e sintetizar ATP, o que pode contribuir para a disfunção cardiovascular na vigência da colestase.(AU)

Bilioduodenal anastomosis in rats with extra-hepatic biliary obstruction is followed by lesions ischemia and reperfusion-induced / Lesão de isquemia e reperfusão em ratos com obstrução biliar extra-hepática submetidos à anastomose bilio-duodenal

PURPOSE: The aim of this study was to investigate alterations compatible with hepatic ischemia-reperfusion after bilioduodenal shunt (BD) in rats with obstructive jaundice (OB) . METHODS: Thirty six animals were divided into 6 experimental groups: CO1 and CO2 - control groups, sham-operated (SO) and evaluated 6 and 24 hours after, respectively; OB1 and OB2, - obstructive jaundice groups, sham-operated 15 days after bile duct ligature and evaluated 6 and 24 hours after SO, respectively; DBD1and DBD2 - obstructive jaundice groups evaluated ,respectively, 6 and 24 hours after BD performed 15 days after bile duct ligature. The parameters evaluated were serum total bilirubin, aminotransferase activity (AST, ALT), TNFalpha, liver mitochondrial functions and parenchymatous injury. RESULTS: Bilirubin decreased while aminotransferase activity increased 6 hours after BD (p<0.01); TNFalpha determination at the 6th hour after BD was higher than the one at the 24th hour (p<0.05); oxygen consumption in states 3 and 4 remained elevated in the BD initial phase , and liver cell damage worsened 24 hours after BD. CONCLUSION: The results demonstrated that surgical biliary decompression in obstructive jaundice is followed by alterations related to hepatic ischemia- reperfusion.(AU)

OBJETIVO: O objetivo do estudo foi investigar alterações compatíveis com o fenômeno de isquemia-reperfusão hepática em ratos com icterícia obstrutiva (OB) após derivação bilioduodenal (BD). MÉTODOS: Trinta e seis animais foram divididos em seis grupos experimentais: CO1 e CO2 - grupos controle avaliados com 6 e 24 horas após operação simulada (SO), respectivamente; OB1 e OB2 - grupos com obstrução biliar, submetidos a SO 15 dias após ligadura do ducto biliar, e avaliados em 6 e 24 horas após a SO, respectivamente; DBD1 e DBD2 - grupos com 15 dias de obstrução biliar, avaliados em 6 e 24 horas, respectivamente, após BD. Os parâmetros avaliados foram bilirrubinas, aminotranferases (ALT e AST), funções mitocondriais hepáticas, dosagem de TNFalfa e lesão do parênquima hepático. RESULTADOS: As bilirrubinas caíram após BD, enquanto as aminotransferases aumentaram 6 horas após BD (p<0,01). O TNFalfa mensurado na 6ª hora após a BD foi maior que o da 24ª hora (p<0,05). O consumo de oxigênio no estado 3 e 4 mantiveram-se elevados na fase inicial do BD e as lesões celulares hepáticas agravaram-se na 24ª hora pós BD. CONCLUSÃO: Os resultados demonstraram que a descompressão cirúrgica biliar na icterícia obstrutiva foi seguida de alterações que correspondem ao fenômeno de isquemia-reperfusão hepática.(AU)

The influence of treatment access regulation and technological resources on the mortality profile of acute biliary pancreatitis / A influência da regulação do acesso aos serviços de saúde e da incorporação tecnológica no perfil de mortalidade da pancreatite aguda biliar

PURPOSE: The influence of treatment access regulation and technological resources on the mortality profile of acute biliary pancreatitis (ABP) was evaluated. METHODS: The cases seen in a tertiary hospital were studied during two periods of time: 1995-1999 and 2000-2004, i.e., before and after the implementation of medical regulation. RESULTS: Among the 727 patients with acute pancreatitis, 267 had ABP and were classified according to APACHE II scores. The cases being referred to the tertiary hospital decreased from 441 to 286 (p < 0.001). The patients' profile regarding age, gender, severity, cholestasis incidence and mortality were similar during the first and second periods of study (n = 154 and n = 113, respectively). The number of patients with hematocrit > 44 percent was smaller during the second study period (p<0.002). The use of magnetic resonance cholangiography, videolaparoscopic cholecystectomy, and access to the ICU were found to be more frequent during the second study period. Regarding the deaths occurring within 14 days of hospitalisation, 73.4 percent and 81.3 percent were observed during the first and second study periods, respectively. CONCLUSION: Since the improvement in clinical and technological approach was not enough to modify the mortality profile of ABP, further studies on the treatment of inflammatory responses should be carried out.(AU)

OBJETIVO: Avaliou-se a influência do acesso aos recursos assistenciais e tecnológicos sobre a mortalidade na pancreatite aguda biliar (PAB). MÉTODOS: Os casos de PAB tratados num hospital universitário foram estudados em dois períodos: 1995 a 1999 e 2000 a 2004, antes e depois da implantação da Regulação Médica. RESULTADOS: Do total de 727 casos com pancreatite aguda atendidos, 267 apresentavam PAB e tiveram a gravidade avaliada pelo escore de APACHE II. Houve redução dos encaminhamentos de casos entre os períodos, de 441 para 286 (p < 0,001). O perfil dos pacientes com PAB no primeiro período (n = 154) e no segundo (n =113) foi semelhante quanto à idade, sexo, gravidade, incidência de colestase e mortalidade. A incidência de pacientes com hematócrito > 44 foi menor no segundo período (p < 0,002). O emprego de colangiografia por ressonância magnética, da colecistectomia por videolaparoscopia e do acesso à terapia intensiva foi significantemente maior no segundo período. A maioria dos óbitos ocorreu até os 14 dias de admissão, 73,4 por cento no primeiro período e 81,3 por cento no segundo. CONCLUSÃO:A melhora do suporte tecnológico e clínico não foi suficiente para modificar o perfil de mortalidade na PAB, o que indica a necessidade de avaliar terapêuticas para a sua resposta inflamatória.(AU)

Nonalcoholic fatty liver disease and obesity / Doença gordurosa não alcóolica do fígado e obesidade

PURPOSE: The aim of this review is to update concepts of the nonalcoholic fatty liver disease (NAFLD) and to establish a relationship between this condition and obesity. METHODS: By means of a comprehensive literature review where special attention was devoted to articles published in the last 5 years, NAFLD is discussed in view of new concepts, diagnosis, staging, and treatment. RESULTS: NAFLD is emerging as one of the main causes of chronic liver disease and it is believed to be the hepatic component of the metabolic syndrome, whose central features include obesity, hyperinsulinemia, peripheral insulin resistance, diabetes, dyslipidemia, and hypertension. The surgical treatment of morbid obesity is one of the options available for the treatment of NAFLD. CONCLUSION: Nonalcoholic fatty liver disease is strongly related with obesity.(AU)

OBJETIVO: O objetivo deste artigo foi atualizar conceitos com relação à doença gordurosa não alcoólica do fígado (DGNAF) e a sua intrínseca relação com a obesidade. MÉTODOS: Por meio de revisão bibliográfica, com atenção especial às publicações dos últimos 5 anos, o assunto foi abordado com relação à conceituação, ao diagnóstico, estadiamento e tratamento. RESULTADO: A DGNAF está emergindo como uma das maiores causas de doença crônica do fígado e representa o componente hepático da síndrome metabólica, caracterizada por obesidade, hiperinsulinemia, resistência periférica à insulina, diabete, hipertrigliceridemia e hipertensão. O tratamento cirúrgico da obesidade mórbida faz parte do arsenal terapêutico da DGNAF. CONCLUSÃO: O tema foi amplamente discutido, baseado em estudos recentes.(AU)

Psychological distress in patients listed for liver transplantation / Distress psicológico em pacientes na lista de espera para transplante de fígado

PURPOSE: To assess the level of depression in patients listed for liver transplantation. METHODS: Sixty-four adult patients, listed for liver transplantation, were submitted to psychological evaluation, including assessment of depression by means of the Beck Depression Inventory. RESULTS: Twenty-two percent of the patients had mild/major depression. The group consisted mainly of male patients aged 47 on average, with a history of alcohol abuse and a Meld (Model for End-Liver Disease) value of 14.5. Patients that had been awaiting liver transplant longer presented less severe liver disease according to the Child-Pugh criteria. CONCLUSION: It is extremely important to assess psychological distress in patients listed for liver transplantation. An interdisciplinary approach is essential to improve the patients' quality of life both in the pre- and post-transplant periods.(AU)

OBJETIVO: Avaliar o nível de depressão de doentes que aguardam em fila para transplante de fígado. MÉTODOS: Sessenta e quatro pacientes adultos, com indicação para transplante de fígado, foram submetidos à avaliação psicológica, incluindo depressão, através do Beck Depression Inventory, após a inclusão em lista de espera. RESULTADOS: Vinte e dois por cento dos pacientes apresentaram depressão moderada/grave. O perfil deste grupo foi caracterizado como sexo masculino, com idade média de 47 anos, presença de alcoolismo e Meld (Model for End-Liver Disease) de 14,5. Constatou-se que pacientes há mais tempo em lista apresentaram menor gravidade da doença hepática segundo a classificação de Child-Pugh. CONCLUSÃO: Ressalta-se a importância de avaliar o estado emocional de pacientes em fila de espera para transplante de fígado e da atuação interdisciplinar para melhoria da qualidade de vida dos pacientes, inclusive no pós-transplante.(AU)