Background/AimsThe development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model.MethodsCirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor β (TGF-β) immunohistochemistry was analyzed.ResultsBiochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-β-secreting cells.ConclusionsTaken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-β via the blockage of α1- and β-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.

Although amebic brain abscess is a rare form of invasive amebiasis, when present, it is frequently lethal. This disorder always begins with the infection of the colon by Entamoeba histolytica trophozoites, which then travel to extra-intestinal tissues through the bloodstream. Amebic brain abscesses are produced when trophozoites invade the central nervous system. Computerized axial tomography scans can be used to diagnose the presence or absence of a brain abscess with a certainty of 100%. However, this diagnostic tool does not reveal the etiological agent of disease. By analyzing the clinical case of a patient that died due to untimely treatment of this malady, the present study aims to identify a diagnostic tool that can give a precise determination of the etiological agent and therefore permit adequate and opportune treatment. Currently, diagnosis of amebic brain abscess is often done by identification of the ameba in a biopsy or autopsy. By immunohistochemistry and immunofluorescence with specific antibodies, we identified the existence of E. histolytica, which presents proteins similar to Naegleria fowleri in its membrane.

In cases of fulminant amoebic colitis we have determined the interactions between Entamoeba histolytica trophozoites and immune cells in order to better understand the pathophysiology of amoebic colitis. Eleven specimens of amoebic colitis and five specimens of colon without amoebic lesions were studied. Trophozoites and immune cells were located by topographic stains, histochemistry and immunohistochemistry. Trophozoites were seen in both damaged and undamaged areas of the colonic mucosa. Specimens of fulminant amoebic colitis showed: (a) an increase in IgA+, IgG+ B cells and neutrophils; (b) a reduction in IgM+ B cells, CD8+ T cells, macrophages, eosinophils and mast cells; and (c) no change in the number of NK and CD4+ T cells. The cellular infiltrate in amoebic colitis may represent the combined effects of amoebic monocyte locomotion inhibitory factor and switching of IgM+ B cells to IgG+ and IgA+ plasma cells, induced by amoebic antigens. Tissue damage in the absence of trophozoites may result from ischaemia or host immune responses.

Summary Human fulminant amoebic colitis (FAC) is characterized by ulceration and inflammation of the colon. The specific mixture of pro‐inflammatory and anti‐inflammatory cytokines may participate in either the host defense or in the pathogenesis of amoebic colitis. Therefore, we studied the expression of IL‐8, IL‐10, IL‐4, TGF‐β and IFN‐γ in human FAC patients and controls through immunohistochemistry analysis. The number of cells expressing IL‐8, IL‐4 and IL‐10 was significantly enhanced in all FAC samples compared to the control samples. However, the expression of TGF‐ β in patients was low in the colonic mucosa and high in the lamina propria compared with the control. No expression of IFN‐γ was found in the controls or FAC samples. The production of IL‐8 by intestinal epithelial cells may play a role in the pathogenesis of amoebic infection, because this cytokine attracts neutrophils, which lead to an inflammatory reaction that results in tissue damage. The predominant expression of the macrophage down‐regulating cytokines, IL‐4, IL‐10 and TGF‐β, or the Th2‐type immune response could inhibit a cell‐mediated immune response, which in turn would facilitate parasite invasion in these tissues.

Amoebic liver abscesses (ALA) are the most frequent and severe extraintestinal clinical presentations of amoebiasis. During the early establishment of amoebae in the liver parenchyma, as well as during the extension of the tissue necrosis, parasites interact with the parenchymal liver cells and, as a consequence of these interactions, hepatocytes can be destroyed and host immune cells can become activated. However, little is known about the nature of these interactions in the liver or about the factors involved in the local immune response. In this investigation we studied the localization of Entamoeba histolytica trophozoites, TCD4+, TCD8+ cells, CD68+ macrophages and CD15+ neutrophils in human ALA using immunohistochemical techniques. Trophozoites were found close to undamaged hepatocytes in both lysed and non-lysed areas with either sparse or abundant inflammatory infiltrate. CD8+ cells were more abundant than CD4+ T cells. CD 68+ macrophages and CD15+ neutrophils were also detected, suggesting that neutrophils, macrophages and T cells might be related to the local host immune mechanisms in ALA. We also found that E. histolytica possesses proteins recognized by antibodies raised against inducible nitric oxide synthase.

An autopsy case with an incidentally discovered adenomatoid tumor (AT) arising in the right adrenal gland of a 34-yr-old man with AIDS is presented. The immediate cause of death was disseminated coccidioidomycosis. The affected right adrenal gland was partially substituted by a firm 3.O cm nodule enclosed by cortical adrenal tissue. Histologically, the tumor had the typical appearance of those adenomatoid neoplasms described in the genital tract. The mesothelial origin of the neoplasm was confirmed by immunopositive cells for low weight cytokeratin and vimentin. Uncommon neoplasms in the adrenal glands of AIDS patients include leiomyosarcomas, leiomyomas, and malignant nerve sheath tumors. This report may represent the first case of an adrenal gland AT in a patient with AIDS, and probably the third well-documented histologically and immunohistochemically adrenal gland AT.

In vitro studies have proved the presence of epitopes of CD59 in the surface of trophozoites of Entamoeba histolytica (E. histolytica). However, it has not been proved if CD59 molecules are expressed in the surface during the trophozoites' tissue invasion. The aim of the present study was to determine whether the complement-regulatory protein CD59 is present on trophozoites of E. histolytica in human colon. Eleven specimens of amoebic colitis were studied by immunohistochemistry and electron microscopy techniques with a monoclonal antibody against human CD59 molecule. Our results show that a CD59-like molecule is expressed in trophozoites of E. histolytica found in colonic amebic lesions. Also, a CD59-like molecule was detected by western blot analysis in whole lysate of E. histolytica as well as on the plasma membrane by immunocytochemistry. These results suggest that E. histolytica can use CD59-like protein against the lytic action of membrane attack complex.

Administration of ethanol (8%) or acetone (1%) to nursing dams in the drinking water, for 10 days, increased the nephrotoxicity of paracetamol (APAP) in the 14-day-old lactating offspring. The percentage of proximal tubular cells with evidence of necrotic damage in male rats was higher in those animals that received APAP (500 mg/kg, i.p.) and whose nursing rats were exposed to ethanol (25.0 ± 8.4%) or acetone (17.2 ± 1.2%), than in the group treated with APAP alone (10.6 ± 1.6%). The activity of urinary N-acetylglucuronidase was also significantly higher in the rats exposed translactationally to ethanol or acetone than in animals treated with the APAP alone. Nephrotoxicity showed a sexual dimorphic pattern with a higher toxicity in male than in female rats. The percentage of necrotic tubules in the male rats not exposed to inductor was 10.6 ± 1.6%, and in female rats 5.0 ± 1.4% (p < 0.05). Animals exposed to ethanol or acetone and treated with APAP showed less weight gain than the group treated only with APAP. Our results suggest that renal toxicity is enhanced in the nursing animals that were exposed, via maternal milk, to ethanol or acetone (inductors of cytochrome P₄₅₀2E1), than in the control animals. This circumstance may be relevant in alcoholic women while they are lactating.