Adrenergic regulation during acute hepatic infection with Entamoeba histolytica in the hamster: involvement of oxidative stress, Nrf2 and NF-KappaB.

Oxidative stress and transcriptional pathways of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) are critically involved in the etiopathology of amebic liver abscess (ALA). In this work, we studied the relationship between the adrenergic nervous system and ALA in the hamster. ALA was visible at 12 h of infection. While 6-hydroxidopamine (6-OHDA) decreased infection, propranolol (ß-adrenergic blocker) treatment was associated with less extensive liver damage, and phentolamine treatment (α-adrenergic blocker) significantly reduced ALA compared to 6-OHDA and propranolol. Serum enzymatic activities of alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (γ-GTP) were increased at 12 h post-infection. Chemical denervation and α and ß-adrenergic blockers decreased ALT to normal levels, while 6-OHDA and propranolol showed a trend to decrease γ-GTP but phentolamine significantly reduced γ-GTP. Amebic infection increased oxidized glutathione (GSSG) and decreased both reduced glutathione (GSH) and the GSH/GSSG ratio. Propranolol and 6-OHDA showed a tendency to decrease GSSG. However, GSH, GSSG and GSH/GSSG returned to normal levels with phentolamine. Furthermore, amebic infection increased pNF-κB and interleukin-1ß (IL-1ß), and showed a tendency to decrease hemoxigenase-1 (HO-1), but not Nrf2. Chemical denervation showed a trend to decrease pNF-κB and IL-1ß, and neither Nrf2 nor HO-1 increased significantly. In addition, NF-κB and IL-1ß were attenuated by propranolol and phentolamine treatments, although phentolamine showed significant overexpression of Nrf2 and HO-1. This suggests that the adrenergic system may be involved in oxidative stress and in modulation of the Nrf2 and NF-κB pathways during ALA development.

Recurrent amebic liver abscesses over a 16-year period: a case report.

BACKGROUND: Amebic liver abscess is a rare disease in high-income countries. Recurrence of amebic liver abscess is even rarer with only a few previous reports. Here we present a patient who developed three subsequent amebic liver abscesses over a sixteen-year period. CASE PRESENTATION: A Caucasian male developed recurrent amebic liver abscesses, when aged 23, 27 and 39 years. Only on the first occasion did this coincide with a recent visit to the tropics. The patient received adequate treatment during each episode. Possible explanations are persistent asymptomatic carrier state, cysts passage in his family, re-infection or chance. CONCLUSION: We describe the unusual case of a healthy male who developed recurrent amebic liver abscesses over a long period despite adequate treatment. Possible pathophysiological explanations are explored.

Liver abscess presentation and management in Saudi Arabia and the United Kingdom.

BACKGROUND AND OBJECTIVES: Liver abscess (LA) is a well-described disease in the medical literature; however, information about its characteristics and outcome in the Middle East is lacking. We compared the mode of presentation, risk factors, management and outcome of LA patients in Saudi Arabia with cases from the United Kingdom (UK). DESIGN AND SETTING: Retrospective review of LA patients from three tertiary care centers (2 from Saudi Arabia and 1 from the UK) over a period of 10 years, from 1995 to 2005. PATIENTS AND METHODS: Data collected included demographic characteristics; clinical presentation; biochemical, microbiological and radiological findings; treatment modalities; and outcome. RESULTS: A total of 83 patients were diagnosed with LA, including 48 patients from Saudi Arabia and 35 patients from the UK. The mean (SD) age was 45.2 (20.3) years for those from Saudi Arabia and 55.4 (18.8) years for those from the UK (P=.022). The majority of the patients were males (70% from Saudi Arabia and 80% from the UK). Upper abdominal pain and fever were the commonest symptoms, each reported in 87% of the cases. Alkaline phosphatase elevation was the commonest liver function abnormality, seen in 66 (80%) patients. Organisms were isolated in 43 (52%) cases and the majority of these were coliforms (58%). Amebic liver abscesses occurred in 19 (23%) patients and all of those patients were either from or had traveled recently to the Indian subcontinent. Complete resolution of the abscesses was achieved in 66 (80%) patients with aspiration and/or antibiotics, and 9 (10.8%) patients died. On multivariate analysis, underlying malignancy, hypotension and chest signs at presentation were predictors of poor outcome (P=.008, .029 and .001, respectively). CONCLUSIONS: Successful resolution of LA is achievable in the majority of the cases, although underlying malignancy is associated with poor outcome. Amebic liver abscesses must be considered in patients with a history of travel to endemic areas.

Modulation of amoebic hepatic abscess by the parasympathetic system.

The neuro-immune network, in which the vagus nerve is involved, provides feedback between its afferent branches for signalling central nervous system from sites of injury through cytokines and its efferent branches, which release acetylcholine, an anti-inflammatory neurotransmitter. For gain insight into the parasympathetic mechanisms participating in the inflammatory response in the liver, we studied the effects of a vagotomy on the innate immune response in hamsters with amoebic liver abscess. At 7 days post-infection, compared to the control, liver parasympathectomy resulted in a larger abscess size, a greater production of collagen fibres, fewer trophozoites, increased serum levels of IL-10 and IFN-γ and increased numbers of IL-10 and IFN-γ-positive cells in situ, with no change in the number of macrophages and NK cells. Data indicate that the vagotomy disrupted the inflammatory response, causing an increase in the response against infection, then could favour the innervation of the liver by the sympathetic nervous system and would then take the control of the immune response by stimulating the conversion of macrophages to epithelioid cells; and through increased IL-10 production would induce the hepatic stellar cells to become myofibroblast collagen producer cells, thus forming a barrier of collagen and blocking trophozoite migration.

Participación del óxido nítrico durante el desarrollo del absceso hepático amebiano / Nitric oxide participation during amoebic liver abscess development

El óxido nítrico participa en funciones fisiológicas y fisiopatológicas, así como en el mecanismo de defensa del sistema inmunológico de mamíferos contra parásitos, virus y bacterias. La Entamoeba histolytica es un parásito protozoario causante de la amebiasis, la cual se caracteriza por el daño intestinal y la formación del absceso hepático amebiano (AHA). El desarrollo del absceso hepático amebiano en el hámster es similar al que desarrolla el humano, mientras que el ratón es resistente a la formación de este absceso, debido a un incremento en la producción de óxido nítrico. A diferencia del ratón, el desarrollo del absceso hepático amebiano en el hámster es debido a un exceso en la producción de óxido nítrico o posiblemente a una mayor susceptibilidad del hámster al daño producido por el óxido nítrico. Por lo tanto, sería importante realizar más estudios para determinar si en el humano, un exceso en la producción de óxido nítrico favorece la formación del absceso hepático amebiano.

Nitric oxide participates in both physiological and pathophysiological functions, and it plays an important role in the mammalian immune system in killing or inhibiting the growth of many pathogens, including parasites, viruses and bacteria. Entamoeba histolytica is a protozoan parasite that causes amoebiasis, which is characterized by intestinal damage and amoebic liver abscess development. The development of amoebic liver abscess in hamsters is similar to that in humans, whereas mice are resistant to amoebic liver abscess development due to an increase in nitric oxide production. Unlike in mice, amoebic liver abscess development in hamsters is due to an excess in nitric oxide production or possibly to a greater susceptibility of the hamster to damage caused by nitric oxide. Therefore, it could be important to elucidate if, in humans, an excess in nitric oxide production favors amoebic liver abscess development.

Pathogenesis of acute experimental liver amebiasis.

Classical descriptions of the pathology of amebiasis portray the parasite as the cause of tissue damage and destruction, and in recent years a number of amebic molecules have been identified as virulence factors. In this review we describe a series of experiments that suggest a more complex host-parasite relation, at least during the early stages of acute experimental amebic liver abscess in hamsters. The problems of extrapolating experiments in vitro to explain observations in vivo are discussed. The role of amebic cysteine proteases is examined and evidence presented to suggest that they are primarily related not to tissue damage but to amebic survival, which is required for the progression of the lesion. Inflammation is shown to be not only the major cause of tissue damage but also an absolute requirement for amebic survival in the liver, whereas complement and ischemia are not involved in the disappearance of the parasite in the absence of inflammation.

Roles of cell adhesion and cytoskeleton activity in Entamoeba histolytica pathogenesis: a delicate balance.

The protozoan parasite Entamoeba histolytica colonizes the human large bowel. Invasion of the intestinal epithelium causes amoebic colitis and opens the route for amoebic liver abscesses. The parasite relies on its dynamic actomyosin cytoskeleton and on surface adhesion molecules for dissemination in the human tissues. Here we show that the galactose/N-acetylgalactosamine (Gal/GalNAc) lectin clusters in focal structures localized in the region of E. histolytica that contacts monolayers of enterocytes. Disruption of myosin II activity impairs the formation of these structures and renders the trophozoites avirulent for liver abscess development. Production of the cytoplasmic domain of the E. histolytica Gal/GalNAc lectin in engineered trophozoites causes reduced adhesion to enterocytes. Intraportal delivery of these parasites to the liver leads to the formation of a large number of small abscesses with disorganized morphology that are localized in the vicinity of blood vessels. The data support a model for invasion in which parasite motility is essential for establishment of infectious foci, while the adhesion to host cells modulates the distribution of trophozoites in the liver and their capacity to migrate in the hepatic tissue.

Pyogenic and amebic liver abscesses.

Pyogenic and amebic liver abscesses are the two most common hepatic abscesses. Amebic abscesses are more common in areas where Entamoeba histolytica is endemic, whereas pyogenic abscesses are more common in developed countries. Pyogenic abscess severity is dependent on the bacterial source and the underlying condition of the patient. Amebic liver abscess is more prevalent in individuals with suppressed cell-mediated immunity, men, and younger people. The right lobe of the liver is the most likely site of infection in both types of hepatic abscess. Patients usually present with a combination of fever, right-upper-quadrant abdominal pain, and hepatomegaly. Jaundice is more common in the pyogenic abscess. The diagnosis is often delayed and is usually made through a combination of radiologic imaging and microbiologic, serologic, and percutaneous techniques. Treatment involves antibiotics along with percutaneous drainage or surgery.

Alcohol consumption, hepatic iron load and the risk of amoebic liver abscess: a case-control study.

OBJECTIVE: It is unknown why most amoebic liver abscess (ALA) cases occur in alcohol drinkers. In experimental studies, the presence of 'iron' potentiates the in-vitro growth of Entamoeba histolytica (E. histolytica), and is also known to increase its in-vivo invasiveness in animal infections. Chronic alcoholism increases the hepatic iron deposition. We hypothesized that ALA occurs more commonly in livers with a high iron load as in alcoholics. To test this hypothesis we compared the levels of iron between ALA and non-ALA cases belonging to alcoholic and non-alcoholic groups. METHODS: Out of a total of 48 ALA cases, 34 (70%) were alcoholics and 14 (30%) were non-alcoholics. After applying exclusion criteria, serum iron and liver iron stores were quantified in 20 ALA cases (10 alcoholic and 10 non-alcoholics) and compared with 20 non-ALA cases (10 alcoholics and 10 non-alcoholics). RESULTS: All patients of ALA had serum iron values within the normal range but higher than non-ALA cases. In the liver tissue, most patients with ALA had higher (grade II or III) iron deposition, than non-ALA cases (mostly grade I). Thus, patients with ALA, with or without alcohol indulgence, had higher iron levels when compared to the non-ALA cases. CONCLUSION: It appears that the higher incidence of ALA in alcoholic livers is possibly due to their higher iron content.

Infecções por "Entamoeba histolytica" / Entamoeba histolytica infections

Os autores discutem sobre as infecções relacionadas à Entamoeba histolytica, com o objetivo de proporcionar um melhor panorama do estado atual do problema

Efecto de la metilprednisolona en la amibiasis hepática experimental / Effect of methylprednisolone in experimental amebic liver abscess

Para examinar si la extensión de la necrosis tisular en la amibiasis hepática experimental en hamsters es proporcional a la magnitud de la respuesta inflamatoria inicial se comparó la evolución morfológica de las lesiones en presencia y en ausencia de dosis altas de metilprednisolona a las 10 hrs, 24 hrs, 72 hrs y 7 días. Se observó en los animales con metilprednisolona una respuesta inflamatoria inicial menor que en los controles y una extensión de las lesiones menor a los 7 días de evolución. La metilprednisolona no altera ni la actividad proteolítica ni la eritrofagocitosis de Entamoeba histolytica in vitro.

Amibiasis extraintestinal

Una vez Entamoeba histolytica penetra a la microcirculación de la pared del tubo digestivo, e independientemente de si el proceso invasor que la llevó hasta allí ha generado o no manifestaciones clínicas, los trofozoitos viables alcanzan la circulación portal y por vía hamatógena, pueden diseminarse a otros órganos, especialmente al hígado que es la primera estructura que se interpone en su camino. De la misma manera, pueden también alcanzar el cerebro. Por diseminación local a partir de un absceso hepático, pueden comprometer la pleura, el pulmón, los bronquios, el pericardio, el peritoneo o la piel de la pared abdominal. En conjunto, estas formas de amibiasis invasora se conocen como amibiasis extraintestinal para diferenciarlas de las formas intestinales de amibiasis invasora cuyo cuadro clínico y tratamiento publicamos en la pasada edición de Tribuna Médica. En la edición de julio se publicó la patogenia de la invasión amibiana y en la de junio el diagnóstico y tratamiento de la amibiasis asintomática.

Síndrome de Budd-Chiari transitorio debido a compresión venosa por abscesos hepáticos amibianos / Transitory Budd-Chiari syndrome secondary to compression of the veins by liver amebic abscess

Se describe el caso de un paciente con abscesos hepáticos amibianos que desarrolló síndrome de Budd-Chiari secundario a obstrucción de la vena cava inferior y venas suprahepáticas. Este es el segundo reporte en la literatura nacional de doble obstrucción venosa asociada con abscesos amibianos de hígado. Se revisa la literatura y se proponen recomendaciones diagnósticas

Absceso hepatico amebiano: revision de 29 casos / Amebiac hepatic abscess: review of 29 cases

Se realiza un análisis retrospectivo en el que se estudia 29 casos de absceso hepático de un total de 25.627 pacientes internados durante 6 años en los servicios de clínica pediatría y cirugía del Hospital "Vicente Corral Moscoso"; lo que representa el 0,11%. Se analizan en todos los casos las variables de: edad, sexo, procedencia, residencia, ocupación y antecedentes patológicos. Además se pormenoriza el estudio de los signos y síntomas del cuadro clínico: fiebre, ictericia, hepatomegalia, etc. Finalmente, se estudia la utilidad de los métodos diagnósticos, así como también los esquemas de tratamiento utilizados en cada caso. La relación entre los sexos fue de dos a uno en favor de los hombres. La dispersión estadística demuestra que los grupos más afectados están entre los 40 y 50 años. No se observó diferencia significativa en lo que se refiere al lugar de residencia. Las dos terceras partes de los pacientes no ingieren agua potable. El alcoholismo, poliparasitismo y paludismo, destacan entre los antecedentes patológicos previos con 42%, 10,34% y 13,79% respectivamente. Las manifestaciones clínicas predominantes fueron a) dolor en el hipocondrio derecho y/o epigastrio en todos los enfermos; b) hepatomegalia en el 64%; c) fiebre, astenia y anorexia en un 90%; d) ictericia en el 35% de casos. Los métodos hepática (37,9%), función diagnóstica (31%); laparotomía (27,5%) y laparoscopía (6,8%). En algunos pacientes se practicaron 2 o más de los metodos enunciados. El tratamiento fue clínico exclusivamente en el 72% de ls pacientes; en los restantes se procedio a la laparoscopía y/o laparotomía con drenaje