Angiotensin II or epinephrine hemodynamic and metabolic responses in the liver of L-NAME induced hypertension and spontaneous hypertensive rats.

AIM: To study hepatic vasoconstriction and glucose release induced by angiotensin (Ang)II or Epi in rats with pharmacological hypertension and spontaneously hypertensive rat (SHR). METHODS: Isolated liver perfusion was performed following portal vein and vena cava cannulation; AngII or epinephrine (Epi) was injected in bolus and portal pressure monitored; glucose release was measured in perfusate aliquots. RESULTS: The portal hypertensive response (PHR) and the glucose release induced by AngII of L-NAME were similar to normal rats (WIS). On the other hand, the PHR induced by Epi in L-NAME was higher whereas the glucose release was lower compared to WIS. Despite the similar glycogen content, glucose release induced by AngII was lower in SHR compared to Wistar-Kyoto rats although both PHR and glucose release induced by Epi in were similar. CONCLUSION: AngII and Epi responses are altered in different ways in these hypertension models. Our results suggest that inhibition of NO production seems to be involved in the hepatic effects induced by Epi but not by AngII; the diminished glucose release induced by AngII in SHR is not related to glycogen content.

Correlação interobservador das alterações morfológicas das vias biliares em pacientes com esquistossomose mansoni pela colangiorressonância magnética / Evaluation of morphological changes of the biliary tree by magnetic resonance cholangiography in patients with schistosomiasis mansoni: interobserver agreement

OBJETIVO: Descrever as alterações das vias biliares pela colangiografia por ressonância magnética (CPRM) na esquistossomose hepatoesplênica e avaliar a concordância interobservador da CPRM na detecção de colangiopatia esquistossomótica. MATERIAIS E MÉTODOS: Estudo prospectivo e transversal em 24 pacientes com a forma hepatoesplênica da esquistossomose mansoni e em 6 pacientes sadios, como grupo controle, com avaliação da via biliar pela CPRM. As alterações da via biliar consideradas foram: distorção, afilamento, estenose, dilatação e irregularidade. Foi calculada a concordância interobsevador para alteração da via biliar com o teste de McNemar e o índice kappa (κ). RESULTADOS: A concordância interobservador na caracterização de distorção e afilamento da via biliar foi quase perfeita (κ = 0,867; intervalo de confiança [IC] 95 por cento [0,512-1,0] e κ = 0,865; IC 95 por cento [0,51-1,0], respectivamente). A concordância foi substancial para a estenose (κ = 0,78; IC 95 por cento [0,424-1,0]), moderada para dilatação (κ = 0,595; IC 95 por cento [0,247-0,942]) e regular para afilamento (κ = 0,229; IC 95 por cento [0,095-0,552]). CONCLUSÃO: As alterações observadas nas vias biliares foram, em ordem decrescente de ocorrência: distorção, afilamento, estenose, dilatação e irregularidade. A concordância interobservador para sinais de colangiopatia esquistossomótica foi quase perfeita para distorção e afilamento e substancial para estenose.

OBJECTIVE: To describe changes of the biliary tree demonstrated by magnetic resonance cholangiography (MRC) in patients with the hepatosplenic presentation of schistosomiasis mansoni, and evaluating the interobserver agreement in the detection of schistosomal cholangiopathy. MATERIALS AND METHODS: Prospective, cross-sectional study involving 24 patients with hepatosplenic schistosomiasis and 6 healthy patients (control group) submitted to biliary tree evaluation by MRC. The following changes of the biliary tree were considered: distortion, thinning, stenosis, dilation and irregularity. The interobserver agreement in the detection of biliary tree changes was calculated with the McNemar's test and the kappa index of agreement (κ). RESULTS: The interobserver agreement in the detection of distortion and thinning of the biliary tree was almost perfect (κ = 0.867; confidence interval [CI] 95 percent [0.512-1.0] and κ = 0.865; CI 95 percent [0.51-1.0], respectively). There was a substantial agreement for stenosis (κ = 0.78; CI 95 percent [0.424-1.0]), moderate agreement for dilation (κ = 0.595; CI 95 percent [0.247-0.942]) and mild agreement for thinning (κ = 0.229; CI 95 percent [0.095-0.552]). CONCLUSION: In a decreasing order of frequency, the changes of the biliary tree were observed: distortion, thinning, stenosis, dilation and irregularity. The interobserver agreement for signs of schistosomal cholangiopathy was almost perfect for distortion and thinning, and substantial for stenosis.

Endothelial markers in schistosomiasis patients with or without portal hypertension.

PURPOSE: To evaluate the serum levels of von Willebrand factor (vWF), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and endothelin-3 (ET-3) in patients with the isolated, inactive form of Schistosomiasis mansoni. Patients were classified into two groups: 10 patients without (SM group) and 18 with (PH group) portal hypertension. RESULTS: Serum albumin, VEGF, and vWF levels did not differ between the two groups (P > 0.05). The prothrombin time (INR), number of platelets, spleen size, splenic vein diameter, and endothelin levels differentiated the PH group, which showed decreased ET-1 (SM = 22.4 +/- 2.4 pg/ml and PH = 16.4 +/- 1.5 pg/ml; P = 0.034) and increased ET-3 (SM = 2.1 +/- 0.1 ng/ml and PH = 3.2 +/- 0.1 ng/ml; P = 0.000) levels. CONCLUSIONS: In patients with schistosomiasis and portal hypertension (presinusoidal type), the levels of VEGF and ET-1 differ from those reported in patients with cirrhosis.

Monitorização da aderência a tratamento experimental em população assintomática / Monitoring compliance to an experimental treatment in an asymptomatic population

Objetivo: Desenvolver estratégias para monitorar a aderência de pacientes ao tratamento experimental da colestase secundária à forma crônica isolada da esquistossomose com hipertensão portal. Métodos: Estudo experimental feito com 11 pacientes. Foram administradas 15 mg/kg/dia de ácido ursodesoxicólico duas vezes ao dia, durante 45 dias. A avaliação da aderência foi realizada com utilização da estratégia de contagem de comprimidos e entrevistas. Rresultados: A variação na contagem de comprimidos não influenciou a resposta laboratorial do paciente. A atividade sérica da γGT foi normalizada durante o tratamento, retornando a níveis elevados após a suspensão do medicamento. Cconclusões: As estratégias desenvolvidas foram eficientes, e mostram uma resposta laboratorial significativa em relação à diminuição da atividade sérica da γGT.

Avaliação da concordância entre ressonância magnética de ultra-sonografia na classificação de fibrose periportal em esquitossomóticos, segundo a classificação de Niamey / Agreement between magnetic resonance imaging and ultrasonography in the classification of schistosomal periportal fibrosis, according to Niamey's criteria

OBJETIVO: Avaliar a reprodutibilidade da ressonância magnética e a concordância entre a ultra-sonografia e a ressonância magnética na classificação da fibrose periportal em pacientes esquistossomóticos, segundo os critérios qualitativos de Niamey. MATERIAIS E MÉTODOS: Foi realizado estudo prospectivo e duplo-cego, entre fevereiro de 2005 e junho de 2006, em 20 pacientes (10 homens e 10 mulheres, idades entre 24 e 60 anos, média de 42,75 anos) com diagnóstico de esquistossomose mansônica. As imagens de ultra-sonografia e de ressonância magnética foram avaliadas por dois examinadores experientes de forma independente. Foi medida a concordância interobservador para a ressonância magnética e entre a ressonância magnética e a ultra-sonografia. RESULTADOS: A ressonância magnética apresentou resultados concordantes entre os observadores em 14 pacientes (70 por cento). Quando comparamos a ressonância magnética com a ultra-sonografia, obtivemos concordância em apenas seis pacientes pelo observador 1 (30 por cento) e em oito pacientes pelo observador 2 (40 por cento). CONCLUSÃO: A ressonância magnética tem boa reprodutibilidade na avaliação de fibrose periportal em pacientes com esquistossomose avançada, porém sua concordância com a ultra-sonografia é fraca.

OBJECTIVE: To evaluate the reproducibility of magnetic resonance imaging and the agreement between ultrasound and magnetic resonance imaging in the classification of periportal fibrosis in patients with schistosomiasis based on Niamey's qualitative criteria. MATERIALS AND METHODS: A prospective, double-blinded study was conducted between February 2005 and June 2006 with 20 patients (10 men and 10 women, with ages ranging between 24 and 60 years, mean age 42.7 years) diagnosed with schistosomiasis mansoni. Both ultrasound and magnetic resonance images were independently evaluated by two experienced observers. Interobserver agreement was evaluated for findings of periportal fibrosis on magnetic resonance images and in a comparison between magnetic resonance and ultrasound images. RESULTS: The analysis of magnetic resonance images showed total interobserver agreement in 14 patients (70 percent). The comparison between ultrasound and magnetic resonance imaging showed agreement between images in only six cases (30 percent) by observer 1, and in eight cases (40 percent) by observer 2. CONCLUSION: Magnetic resonance imaging presents a good reproducibility in the evaluation of periportal fibrosis in later stages of schistosomiasis, however, the correlation between magnetic resonance imaging and ultrasound is poor.

Hepatic conversion of angiotensin I and the portal hypertensive response to angiotensin II in normal and regenerating liver.

BACKGROUND AND AIM: Angiotensin I (AI) and angiotensin II (AII) induce a portal hypertensive response (PHR) and the liver is able to convert AI into AII to trough the action of the angiotensin-converting enzyme (ACE). Our purpose was to characterize angiotensin I liver conversion. METHODS: AI, AII or angiotensin (1-7) were used in monovascular or bivascular perfusions. RESULTS: The maximum gain in portal pressure induced by AII took place significantly earlier (P = 0.031) than that occurring after an equimolar AI infusion. The AI-induced PHR was abolished both by captopril or losartan, whereas the AII-induced PHR was not affected by captopril, but was abolished by losartan. Angiotensin (1-7) has no hemodynamic effect in the perfused liver. After partial hepatectomy, the AII-PHR pattern changes from a rapid return to baseline values to a pattern where there was no return to baseline values (3-7 days ex-surgery). In the bivascular perfusion system when AII was infused in the arterial branch in the retrograde mode of perfusion (peptide available only to the periportal zone), the PHR was at least 50% of that obtained when the prograde mode was used (peptide available to the periportal and perivenous zones). CONCLUSION: AI does not induce PHR; this effect is a result of its mandatory conversion into AII by the ACE and the sequential action of AII on the AII receptor type 1 located in the hepatic periportal zone. AII induced PHR pattern changes during liver regeneration.

Kallikrein-kinin system in hepatic experimental models.

The purpose of this brief review is to describe some characteristics of the kallikrein-kinin system (KKS) in the liver. The liver synthesizes kininogens and prekallikrein and the synthesis of both proteins is increased in rats during the acute phase reaction. It is also the main organ to clear tissue as well as plasma kallikrein from the circulation in normal and pathological conditions. Bradykinin (BK), yielded by the kallikrein-kinin system, is a potent arterial hypotensive peptide, but in the liver it induces a portal hypertensive response. The portal hypertensive action of bradykinin is mediated by B2 receptors located on sinusoidal cells of the periportal region and is followed by its hydrolysis by angiotensin-converting enzyme, which is primarily present in the perivenous (centrolobular) region.

Fate of bradykinin on the rat liver when administered by the venous or arterial route.

BACKGROUND AND AIM: Bradykinin (BK) infused into the portal vein elicits a hypertensive response via the B2 receptor (B2R) and is efficiently hydrolyzed by the liver. Our purpose was to characterize the mechanism of interaction between BK and the liver. METHOD: BK, HOE-140 (a B2R antagonist), des-R(9)-BK (a B1R agonist) and enzyme inhibitors were used in monovascular or bivascular perfusions and in isolated liver cell assays. RESULTS: Des-R(9)-BK did not elicit a portal hypertensive response (PHR); BK infused into the hepatic artery elicited a calcium-dependent PHR and a calcium-independent arterial hypertensive response (HAHR), with the latter being almost abolished by naproxen. BK has a predominant distribution in the extracellular space and an average hepatic extraction of 8% in the steady state. Hydrolysis products of infused BK (R(1)-F(5) and R(1)-P(7)) did not elicit PHR. Angiotensin converting enzyme (ACE) is concentrated in the perivenous region and B2R in the periportal region. Microphysiometry showed that BK (and not a B1 agonist) interacts with stellate cells and the endothelial sinusoidal/Kupffer cell fraction. This effect was inhibited by the B2R antagonist. CONCLUSIONS: Events can be summarized as: the hypertensive action of BK on sinusoidal cells of the periportal region is followed by its hydrolysis by ACE which is primarily present in the perivenous region; there is no functional B1R in the normal liver; BK induces HAHR via eicosanoid release and PHR by a distinct pathway on the B2R. Our data suggest that BK may participate in the modulation of sinusoidal microvasculature tonus both in the portal and the arterial routes.

Hemodynamic and metabolic effects of angiotensin II on the liver.

To ascertain the mechanism of interaction between angiotensins (AI and AII) and the liver, an angiotensin-converting enzyme inhibitor (captopril) and a receptor antagonist (losartan) were used. Monovascular or bivascular liver perfusion was used to assess both hemodynamic (portal and arterial hypertensive responses) and metabolic (glucose production and oxygen consumption) effects. Microphysiometry was used for isolated liver cell assays to assess AII or losartan membrane receptor-mediated interaction. Captopril abolishes portal hypertensive response (PHR) to AI but not the AII effect. AII infused via the portal pathway promotes calcium-dependent PHR but not a hypertensive response in the arterial pathway (AHR); when infused into the arterial pathway AII promotes calcium-dependent PHR and AHR. Losartan infused into the portal vein abolishes PHR to AII but not the metabolic response; when infused via both pathways it abolishes the hypertensive responses and inhibits the metabolic effects. Isolated liver cells specifically respond to AII. Sinusoidal cells, but not hepatocytes, respond to 10 nM losartan. We conclude that AI has to be converted to AII to produce PHR. Quiescent stellate cells interacts in vitro with AII and losartan. Hemodynamic responses to AII are losartan-dependent but metabolic responses are partially losartan-independent. AII hemodynamic actions are mainly presinusoidal.

[Educational program in schistosomiasis: a model for a methodological approach]. / Programa educativo em esquistossomose: modelo de abordagem metodológica.

OBJECTIVE: Lack of knowledge is one of the factors responsible for the persistence of infectious diseases in Brazil. This study had the objective of developing, implementing and evaluating a low-cost educational program using schistosomiasis patients as a model. METHODS: This was a descriptive study developed using a population of healthy people (group 1) and schistosomiasis patients (groups 2 and 3), with 20 individuals in each group. Teaching material (illustrated manual and album of leaflets) and a questionnaire consisting of 17 questions to evaluate the groups' knowledge were devised. The questionnaire was applied to groups 1 and 2 before and to group 3 after the educational program. The variables studied were the educational program, level of schooling, age, clinical form of schistosomiasis, symptoms, and the subject's performance when answering the questionnaire. For the statistical analysis, Fisher's exact test and variance analysis with one fixed factor were utilized. RESULTS: The educational program was evaluated in the form of four topics: cycle, clinical presentation, treatment and prevention of the disease. The median number of correct responses to the questionnaire was higher for group 3 than for groups 1 and 2, for all the topics dealt with. This median was also higher for group 2 than for group 1, for all topics except for the item "prevention". CONCLUSIONS: The educational process applied was efficient and improved the knowledge of the disease. It may provide an effective low-cost methodological model that can also be applied to combating other endemic diseases.

Programa educativo em esquistossomose: modelo de abordagem metodológica / Educational program in schistosomiasis: a model for a methodological approach

OBJETIVO: A falta de conhecimento é um dos fatores relacionados à persistência de doenças infecciosas no Brasil. O presente estudo tem como objetivo desenvolver, implementar e avaliar um programa educativo de baixo custo, usando como modelo portadores de esquistossomose. MÉTODOS: Estudo descritivo desenvolvido com população constituída por pessoas saudáveis (grupo 1) e esquistossomóticos (grupos 2 e 3), com 20 indivíduos em cada grupo. Foi elaborado material didático (manual ilustrado e álbum seriado) e um questionário de 17 questões para avaliar o conhecimento nos grupos. Nos grupos 1 e 2, o questionário foi aplicado antes e no grupo 3, depois do programa educativo. As variáveis estudadas foram: programa educativo, nível de escolaridade, idade, forma clínica da esquistossomose e sintomatologia e o desempenho dos indivíduos na resposta ao questionário. Para a análise estatística foram utilizados o teste exato de Fisher e análise de variância com um fator fixo. RESULTADOS: O programa educativo foi avaliado em quatro tópicos: ciclo, clínica, tratamento e prevenção da doença. Verificou-se que o grupo 3 apresentou mediana de respostas certas superior aos grupos 1 e 2 em todos os tópicos abordados. O grupo 2 apresentou mediana de respostas certas superior ao grupo 1 em todos os tópicos, exceto em relação ao tópico prevenção. CONCLUSÕES: O processo educativo aplicado foi eficiente, melhorou o conhecimento sobre a doença, podendo constituir-se num modelo de atuação efetiva e de baixo custo que também pode ser aplicado no combate a outras endemias.

Construcão e implementacão de acões de enfermagem em ambulatório de gastroenterologia / Construction and implementation of nursing actions in the gastroenterology outclinic

Em 1998, iniciou-se reestruturacão do Setor de Esquistossomose da Disciplina de Gastroenterologia da UNIFESP, com a implantacão do Servico de Enfermagem. Objetivo: desenvolver acões administrativas de enfermagem, sistematizacão da assistência e programa de orientacão ao esquistossomótico. Método: estudo descritivo, realizado no Ambulatório de Gastroenterologia que atende portadores de esquistossomose, nas suas diferentes formas clínicas. Resultados e discussão: a reestruturacão das atividades do Setor resultaram em: criacão de estrutura organizacional e implantacão da consulta de enfermagem; criacão e distribuicão dos folhetos explicativos e desenvolvimento do Programa de Educacão em Esquistossomose; início de projeto piloto de banco de dados de todos os clientes do ambulatório e do cadastro eletrônico da coleta de materiais biológicos. Conclusão: a iniciativa abriu nova oportunidade de atuacão para o enfermeiro e contribuiu para melhorar a qualidade do atendimento ambulatorial.

[Construction and implementation of nursing actions in the gastroenterology outclinic]. / Construção e implementação de ações de enfermagem em ambulatório de gastroenterologia.

UNLABELLED: The reorganization of the Schistosomiasis Sector of Gastroenterology at UNIFESP started in 1998, when the Nursing Service was implanted. OBJECTIVE: to develop administrative nursing actions, systematization of care and orientation program for the schistosomic patient. METHOD: a descriptive study carried out at the Gastroenterology Outclinic, which attends schistosomic patients of different clinical types. RESULTS AND DISCUSSION: the reorganization of activities in this Sector resulted in the creation of an organizational structure and the implantation of the nursing visit; creation and distribution of explanatory leaflets and development of the Schistosomiasis Education Program; beginning of the database pilot project with all outpatients and an electronic register of the collection of biologic material. CONCLUSION: this initiative opens up a new opportunity for nursing actions and contributes to quality improvement in ambulatory care.

Enzyme release from injured, preserved, and ex vivo reperfused liver does not indicate malfunction.

OBJECTIVE: We compared the enzyme release from preserved and ex vivo reperfused livers after acute injury or inflammatory stimulus with organ function. METHODS: Acute injury was induced by carbon tetrachloride and inflammation was induced by turpentine oil treatments. Livers were exsanguinated and preserved for 8 or 24 hr. Enzymes were measured in preservation and reperfusion solutions, and reperfused liver function was evaluated by O(2) consumption and bromsulphalein clearance. RESULTS: The release of lysosomal enzymes was negligible in the preservation solution, and that of alanine aminotransferase and lactate dehydrogenase was similar in all groups. Release of aspartate aminotransferase and of EC 3.4.24.15 was more than that of the controls. During reperfusion liver function was normal in the injured group. CONCLUSION: Release of enzymes, mainly aspartate aminotransferase and EC 3.4.24.15, into the preservation solution is a sensitive and early indicator of either inflammatory or acute injury alterations of the preserved liver, but does not reflect organ malfunction.

[Serum gamma-glutamyltransferase alteration in hepatic schistosomiasis doesn't correlate with parasitic load and precedes ultrasound alterations]. / Elevação da gamma-glutamiltransferase sérica na hepatopatia esquistossomótica não se correlaciona com a carga parasitária e precede alterações ultra-sonográficas.

BACKGROUND: Liver disorders are the major manifestations of schistosomiasis mansoni. Factors that account for increased concentrations of cholestasis-indicating enzymes in the hepatosplenic form of the disease are unknown. OBJECTIVE: To assess the correlation between increased gamma-glutamyltransferase serum levels and both the parasitic load and ultrasound alterations in patients with schistosomiasis. PATIENTS AND METHODS: Twenty-five patients with the chronic form of schistosomiasis were assessed for the presence or absence of increased enzymatic levels, for the parasitic load (low x medium/high) and for ultrasound parameters. Furthermore, analysis of prothrombin time and a platelet count were performed. RESULTS: Of the 25 patients, 13 showed increased gamma-glutamyltransferase plasma levels. No significant correlation was found between increased gamma-glutamyltransferase levels and the parasitic load, or between increased enzyme levels and ultrasound alterations. Nor did the prothrombin index or the platelet count differ between the two groups (normal gamma-glutamyltransferase levels and increased gamma-glutamyltransferase levels). CONCLUSION: The parasitic load explains no rise in gamma-glutamyltransferase plasma levels in patients with the chronic form of schistosomiasis, and conventional ultrasound is not a sensitive method to detect the alteration suggested by the increased enzyme level in those patients.

Elevação da gamma-glytamiltransferase sérica na hepatopatia esquistossomótica com a carga parasitária e precede alterações ultra-sonográficas / Serum gamma-glutamyltransferase alteration in hepatic schistosomiasis doesn't correlate with parasitic load and precedes ultrasound alterations

Liver disorders are the major manifestations of schistosomiasis mansoni. Factors that account for increased concentrations of cholestasis-indicating enzymes in the hepatosplenic form of the disease are unknown. OBJECTIVE: To assess the correlation between increased gamma-glutamyltransferase serum levels and both the parasitic load and ultrasound alterations in patients with schistosomiasis. PATIENTS AND METHODS: Twenty-five patients with the chronic form of schistosomiasis were assessed for the presence or absence of increased enzymatic levels, for the parasitic load (low x medium/high) and for ultrasound parameters. Furthermore, analysis of prothrombin time and a platelet count were performed. RESULTS: Of the 25 patients, 13 showed increased gamma-glutamyltransferase plasma levels. No significant correlation was found between increased gamma-glutamyltransferase levels and the parasitic load, or between increased enzyme levels and ultrasound alterations. Nor did the prothrombin index or the platelet count differ between the two groups (normal gamma-glutamyltransferase levels and increased gamma-glutamyltransferase levels). CONCLUSION: The parasitic load explains no rise in gamma-glutamyltransferase plasma levels in patients with the chronic form of schistosomiasis, and conventional ultrasound is not a sensitive method to detect the alteration suggested by the increased enzyme level in those patients