Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms, either synchronously or metachronously. In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman with no evidence of tuberous sclerosis. A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature. Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small incidental hepatic PEComa and a high risky extramural gastric GIST, respectively. The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms. To our knowledge, this is the first report of PEComa in a patient with GIST. Hepatic lesions detected synchronously or metachronously in patients with GISTs may represent histogenetically distinct lesions and should be sampled to confirm or exclude metastatic GISTs. (C) 2008 WJG. All rights reserved.

Architecture of the caudal vena cava wall of the dog at the level of the liver caudate lobe

The vascular segment of the caudal vena cava of the dog at the level of the caudate lobe was shown to be intimately related to hepatic tissue through the hepatic capsule and parenchyma. The tunica adventitia of the caudal vena cava was formed mainly by smooth muscle cells with collagen and elastic fibers arranged in bundles. The thin tunica media of the vein was also formed by smooth muscle cells, collagen and elastic fibers arranged in bundles. The tunica intima presented an elastic sub-endothelial network. The hepatic segment of the caudal vena cava showed a myoconnective architecture and propulsive characteristics in terms of its hemodynamic pattern.

Morphological aspects of the liver of the Podocnemis expansa (Testudines, podocnemididae)

The liver of P. expansa was characterized morphohistologically. To this end, twenty livers from clinically healthy male and female Podocnemis expansa, weighing from 2.0 to 4,5 kg, supplied by the commercial breeder Fazenda Moenda da Serra, in Araguapaz, state of Goiás, Brazil, were analyzed macro-and microscopically. The coelomatic cavity was opened and the topography of the fresh organs was examined visually. After the histological preparation, the slides were stained with Hematoxylin and Eosin (HE), Periodic Acid-Schiff (PAS), Gomori Trichrome, Reticulin and Picrosirius. The liver of P. expansa is a voluminous organ with an approximately rectangular shape and brown coloration, varying from light to dark shades, and is divided into a right lobe, left lobe, and a central portion. The right lobe is the largest of the three portions. The gall bladder is located in a depression in the caudal portion of the right lobe, where the gall duct begins and empties into the duodenum. Histologically, the hepatocytes are arranged in the form of double cords surrounded by winding sinusoidal capillaries. In cross section, they resemble acini containing approximately two to five hepatocytes surrounding a probable central biliary canaliculus. The hepatocytes are polyhedral or pyramidal in shape, of uniform size, with a few central nuclei and others displaced peripherally, and the cytoplasm is little eosinophilic when analyzed by the HE staining technique. The parenchyma is supported by delicate reticular fibers surrounding hepatocytes and sinusoids. The parenchyma and perisinusoidal spaces contain large quantities of melanomacrophages, mainly close to the portal spaces.

Anti-inflammatory mechanisms of the annexin A1 protein and its mimetic peptide Ac2-26 in models of ocular inflammation in vivo and in vitro

Annexin A1 (AnxA1) is a protein that displays potent anti-inflammatory properties, but its expression in eye tissue and its role in ocular inflammatory diseases have not been well studied. We investigated the mechanism of action and potential uses of AnxA1 and its mimetic peptide (Ac2-26) in the endotoxin-induced uveitis (EIU) rodent model and in human ARPE-19 cells activated by LPS. In rats, analysis of untreated EIU after 24 and 48 h or EIU treated with topical applications or with a single s.c. injection of Ac2-26 revealed the anti-inflammatory actions of Ac2-26 on leukocyte infiltration and on the release of inflammatory mediators; the systemic administration of Boc2, a formylated peptide receptor (fpr) antagonist, abrogated the peptide's protective effects. Moreover, AnxA1-/- mice exhibited exacerbated EIU compared with wild-type animals. Immunohistochemical studies of ocular tissue showed a specific AnxA1 posttranslational modification in EIU and indicated that the fpr2 receptor mediated the anti-inflammatory actions of AnxA1. In vitro studies confirmed the roles of AnxA1 and fpr2 and the protective effects of Ac2-26 on the release of chemical mediators in ARPE-19 cells. Molecular analysis of NF-κB translocation and IL-6, IL-8, and cyclooxygenase-2 gene expression indicated that the protective effects of AnxA1 occur independently of the NF-κB signaling pathway and possibly in a posttranscriptional manner. Together, our data highlight the role of AnxA1 in ocular inflammation, especially uveitis, and suggest the use of AnxA1 or its mimetic peptide Ac2-26 as a therapeutic approach. Copyright © 2013 by The American Association of Immunologists, Inc.

Synergistic Anti-Inflammatory Activity of the Antimicrobial Peptides Human Beta-Defensin-3 (hBD-3) and Cathelicidin (LL-37) in a Three-Dimensional Co-Culture Model of Gingival Epithelial Cells and Fibroblasts

Given the spread of antibiotic resistance in bacterial pathogens, antimicrobial peptides that can also modulate the immune response may be a novel approach for effectively controlling periodontal infections. In the present study, we used a three-dimensional (3D) co-culture model of gingival epithelial cells and fibroblasts stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) to investigate the anti-inflammatory properties of human beta-defensin-3 (hBD-3) and cathelicidin (LL-37) and to determine whether these antimicrobial peptides can act in synergy. The 3D co-culture model composed of gingival fibroblasts embedded in a collagen matrix overlaid with gingival epithelial cells had a synergistic effect with respect to the secretion of IL-6 and IL-8 in response to LPS stimulation compared to fibroblasts and epithelial cells alone. The 3D co-culture model was stimulated with non-cytotoxic concentrations of hBD-3 (10 and 20 mu M) and LL-37 (0.1 and 0.2 mu M) individually and in combination in the presence of A. actinomycetemcomitans LPS. A multiplex ELISA assay was used to quantify the secretion of 41 different cytokines. hBD-3 and LL-37 acted in synergy to reduce the secretion of GRO-alpha, G-CSF, IP-10, IL-6, and MCP-1, but only had an additive effect on reducing the secretion of IL-8 in response to A. actinomycetemcomitans LPS stimulation. The present study showed that hBD-3 acted in synergy with LL-37 to reduce the secretion of cytokines by an LPS-stimulated 3D model of gingival mucosa. This combination of antimicrobial peptides thus shows promising potential as an adjunctive therapy for treating inflammatory periodontitis.

The Anti-Inflammatory Effects of the Methanolic Extract and Fractions from Davilla elliptica St. Hil. (Dilleniaceae) on Bothrops jararaca Envenomation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morphology and Histochemistry of the Liver of Carnivorous Fish Hemisorubim platyrhynchos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of chronic fluoride intake on the antioxidant systems of the liver and kidney in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pro-inflammatory effects of the aqueous extract of Echinometra lucunter sea urchin spines

The sea urchin, Echinometra lucunter, can be found along the Western Central Atlantic shores. In Brazil, it is responsible by circa 50% of the accidents caused by marine animals. The symptoms usually surpass trauma and may be pathologically varied and last differently, ranging from spontaneous healing in a few days, to painful consequences lasting for weeks. In this work, we have mimicked the sea urchin accident by administering an aqueous extract of the spine into mice and rats and evaluated the pathophysiological developments. Our data clearly indicate that the sea urchin accident is indeed a pro-inflammatory event, triggered by toxins present in the spine that can cause edema and alteration in the leukocyte-endothelial interaction. Moreover, the spine extract was shown to exhibit a hyperalgesic effect. The extract is rich in proteins, as observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but also contains other molecules that can be analyzed by reversed phase high-performance liquid chromatography. Altogether, these effects corroborate that an E. lucunter encounter is an accident and not an incident, as frequently reported by the victims.

Time sequence of the intensification of the liver glucose production induced by high-fat diet in mice

It is well established that the development of insulin resistance shows a temporal sequence in different organs and tissues. Moreover, considering that the main aspect of insulin resistance in liver is a process of glucose overproduction from gluconeogenesis, we investigated if this metabolic change also shows temporal sequence. For this purpose, a well-established experimental model of insulin resistance induced by high-fat diet (HFD) was used. The mice received HFD (HFD group) or standard diet (COG group) for 1, 7, 14 or 56?days. The HFD group showed increased (P?<?0.05 versus COG) epididymal, retroperitoneal and inguinal fat weight from days 1 to 56. In agreement with these results, the HFD group also showed higher body weight (P?<?0.05 versus COG) from days 7 to 56. Moreover, the changes induced by HFD on liver gluconeogenesis were progressive because the increment (P?<?0.05 versus COG) in glucose production from l-lactate, glycerol, l-alanine and l-glutamine occurred 7, 14, 56 and 56 days after the introduction of the HFD schedule, respectively. Furthermore, glycaemia and cholesterolemia increased (P?<?0.05 versus COG) 14?days after starting the HFD schedule. Taken together, the results suggest that the intensification of liver gluconeogenesis induced by an HFD is not a synchronous all-or-nothing process but is specific for each gluconeogenic substrate and is integrated in a temporal manner with the progressive augmentation of fasting glycaemia. Copyright (c) 2012 John Wiley & Sons, Ltd.

Morphological structure of the liver in tambaqui, Colossoma macropomum (Cuvier, 1818)

This research aimed to describe the macroscopic and microscopic liver of tambaqui, Colossoma macropomum, Teleost freshwater Family Characidae, of great economic interest for the Amazon basin. We used six juveniles aged between six month and one year, from the small holding Esteio, Alta Floresta/MT, that develops mainly fish farming. The body was photographed in situ, described macroscopically, and fragments were removed and processed by routine histological techniques through paraffin embedding and HE staining. The liver, located ventrally to the swim bladder and craniodorsally to the stomach, is brownish red and consisted of three lobes, the right lateral, the left lateral and the ventral lobe. Microscopically, the parenchyma consists of hepatocytes varying from irregular rounded hexagonal to round forms with a large and central nucleus, and arranged in linear strings limited by sinusoids and radiating to central veins, but with absence of liver lobules. The central veins are distributed throughout the parenchyma, while the portal space consists in most cases only of a hepatic vein and bile duct; elsewhere exist artery and duct. Formation of portal triads was not founde. Melano macrophages were frequently seen dispersed throughout the central parenchyma. The morphofunctional study of the digestive system of fishes of the Amazon basin is important to obtain knowledge about their weight gain, large scale production for human consumption and preservation of the species, and has also its importance for being used as bioindicators today.

The antioxidant response of the liver of male Swiss mice raised on a AIN 93 or commercial diet

Background: Reactive oxygen species (ROS) are formed under natural physiological conditions and are thought to play an important role in many human diseases. A wide range of antioxidants are involved in cellular defense mechanisms against ROS, which can be generated in excess during stressful conditions, these include enzymes and non-enzymatic antioxidants. The aim of this study was to evaluate the antioxidant responses of mice to two diets control, commercial and the purified AIN 93 diet, commonly used in experiments with rodents. Results: Malondialdehyde (MDA) and hydrogen peroxide (H2O2) concentrations and superoxide dismutase (SOD) and glutathione reductase (GR) activities determined in the liver were lower in the group of mice fed with the AIN 93 diet, while catalase (CAT) activity was higher in the same group, when compared to the group fed on the commercial diet. Liver glutathione peroxidase (GSH-Px) activity was similar in the groups fed on either AIN 93 or the commercial diets. Two SOD isoforms, Mn-SODII and a Cu/Zn-SODV, were specifically reduced in the liver of the AIN 93 diet fed animals. Conclusions: The clear differences in antioxidant responses observed in the livers of mice fed on the two diets suggest that the macro- and micro-nutrient components with antioxidant properties, including vitamin E, can promote changes in the activity of enzymes involved in the removal of the ROS generated by cell metabolism.

Boron determination in biological samples - Intercomparison of three analytical methods to assist development of a treatment protocol for neoplastic diseases of the liver with Boron Neutron Capture Therapy

Die Bor-Neuroneneinfang-Therapie (engl.: Boron Neutron Capture Therapy, BNCT) ist eine indirekte Strahlentherapie, welche durch die gezielte Freisetzung von dicht ionisierender Strahlung Tumorzellen zerstört. Die freigesetzten Ionen sind Spaltfragmente einer Kernreaktion, bei welcher das Isotop 10B ein niederenergetisches (thermisches) Neutron einfängt. Das 10B wird durch ein spezielles Borpräparat in den Tumorzellen angereichert, welches selbst nicht radioaktiv ist. rnAn der Johannes Gutenberg-Universität Mainz wurde die Forschung für die Anwendung eines klinischen Behandlungsprotokolls durch zwei Heilversuche bei Patienten mit kolorektalen Lebermetastasen an der Universität Pavia, Italien, angeregt, bei denen die Leber außerhalb des Körpers in einem Forschungsreaktor bestrahlt wurde. Als erster Schritt wurde in Kooperation verschiedener universitärer Institute eine klinische Studie zur Bestimmung klinisch relevanter Parameter wie der Borverteilung in verschiedenen Geweben und dem pharmakokinetischen Aufnahmeverhalten des Borpräparates initiiert.rnDie Borkonzentration in den Gewebeproben wurde hinsichtlich ihrer räumlichen Verteilung in verschiedenen Zellarealen bestimmt, um mehr über das Aufnahmeverhalten der Zellen für das BPA im Hinblick auf ihre biologischen Charakteristika zu erfahren. Die Borbestimung wurde per Quantitative Neutron Capture Radiography, Prompt Gamma Activation Analysis und Inductively Coupled Plasma Mass Spectroscopy parallel zur histologischen Analyse des Gewebes durchgeführt. Es war möglich zu zeigen, dass in Proben aus Tumorgewebe und aus tumorfreiem Gewebe mit unterschiedlichen morphologischen Eigenschaften eine sehr heterogene Borverteilung vorliegt. Die Ergebnisse der Blutproben werden für die Erstellung eines pharmakokinetischen Modells verwendet und sind in Übereinstimmung mit existierenden pharmakokinetische Modellen. Zusätzlich wurden die Methoden zur Borbestimmung über speziell hergestellte Referenzstandards untereinander verglichen. Dabei wurde eine gute Übereinstimmung der Ergebnisse festgestellt, ferner wurde für alle biologischen Proben Standardanalyseprotokolle erstellt.rnDie bisher erhaltenen Ergebnisse der klinischen Studie sind vielversprechend, lassen aber noch keine endgültigen Schlussfolgerungen hinsichtlich der Wirksamkeit von BNCT für maligne Lebererkrankungen zu. rn

Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06)

Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC).