Invariant Natural Killer T-cells and their subtypes may play a role in the pathogenesis of endometriosis.

OBJECTIVE: To evaluate the frequencies of iNKT cells and their subsets in patients with deep endometriosis. METHODS: A case-control study was conducted between 2013 and 2015, with 73 patients distributed into two groups: 47 women with a histological diagnosis of endometriosis and 26 controls. Peripheral blood, endometriosis lesions, and healthy peritoneal samples were collected on the day of surgery to determine the frequencies of iNKT cells and subtypes via flow cytometry analysis. RESULTS: The authors observed a lower number of iNKT (p = 0.01) and Double-Negative (DN) iNKT cells (p = 0.02) in the blood of patients with endometriosis than in the control group. The number of DN iNKT IL-17+ cells in the secretory phase was lower in the endometriosis group (p = 0.049). There was an increase in the secretion of IL-17 by CD4+ iNKT cells in the blood of patients with endometriosis and severe dysmenorrhea (p = 0.038), and severe acyclic pelvic pain (p = 0.048). Patients with severe dysmenorrhea also had a decreased number of CD4+ CCR7+ cells (p = 0.022). CONCLUSION: The decreased number of total iNKT and DN iNKT cells in patients with endometriosis suggests that iNKT cells play a role in the pathogenesis of endometriosis and can be used to develop new diagnostic and therapeutic agents.

Invariant Natural Killer T-cells and their subtypes may play a role in the pathogenesis of endometriosis

Abstract Objective To evaluate the frequencies of iNKT cells and their subsets in patients with deep endometriosis. Methods A case-control study was conducted between 2013 and 2015, with 73 patients distributed into two groups: 47 women with a histological diagnosis of endometriosis and 26 controls. Peripheral blood, endometriosis lesions, and healthy peritoneal samples were collected on the day of surgery to determine the frequencies of iNKT cells and subtypes via flow cytometry analysis. Results The authors observed a lower number of iNKT (p= 0.01) and Double-Negative (DN) iNKT cells (p= 0.02) in the blood of patients with endometriosis than in the control group. The number of DN iNKT IL-17+ cells in the secretory phase was lower in the endometriosis group (p= 0.049). There was an increase in the secretion of IL-17 by CD4+ iNKT cells in the blood of patients with endometriosis and severe dysmenorrhea (p= 0.038), and severe acyclic pelvic pain (p= 0.048). Patients with severe dysmenorrhea also had a decreased number of CD4+ CCR7+ cells (p= 0.022). Conclusion The decreased number of total iNKT and DN iNKT cells in patients with endometriosis suggests that iNKT cells play a role in the pathogenesis of endometriosis and can be used to develop new diagnostic and therapeutic agents.

Burdock (Arctium lappa L.) root attenuates preneoplastic lesion development in a diet and thioacetamide-induced model of steatohepatitis-associated hepatocarcinogenesis.

Nonalcoholic steatohepatitis (NASH) is considered growing risk factor for hepatocellular carcinoma development in high-income countries. Diet- and chemically induced rodent models have been applied for the translational study of NASH-associated hepatocarcinogenesis due to their morphological and molecular similarities to the corresponding human disease. Arctium lappa L. (burdock) root tea has been extensively consumed in Traditional Chinese Medicine due to its potential therapeutic properties. Indeed, the bioactive compounds of A. lappa root, as the polyphenols, have already showed antioxidant and anti-inflammatory properties in different in vivo and in vitro bioassays. In this study, we investigated whether burdock root ethanolic extract (BRE) administration attenuates NASH-associated hepatocarcinogenesis. Eight-week-old male Wistar rats received choline-deficient high-fat diet for 8 weeks and multiple thioacetamide doses for 4 weeks in order to induce NASH and preneoplastic glutathione-S-transferase pi (GST-P)+ preneoplastic foci. Subsequently, rats were treated with BRE (100 or 200 mg/kg body weight) or vehicle by oral gavage for 2 weeks. BRE displayed high levels of chlorogenic and caffeic acids and BRE administration reduced total fatty acid and lipid hydroperoxide levels, while increasing the activities of antioxidant superoxide dismutase and catalase enzymes in the liver. Furthermore, burdock intervention diminished the size of GST-P+ remodeling preneoplastic lesions (PNLs) and displayed a trend on reducing hepatocyte proliferation (Ki-67) inside them. These findings suggest that short-term exposure to BRE alleviated remodeling PNL development in NASH-associated hepatocarcinogenesis.

Recovery of the Cholangiocytes After Ischemia and Reperfusion Injury: Ultra-Structural, Hystological and Molecular Assessment in Rats.

INTRODUCTION: Ischemia-reperfusion (I/R) injury of the liver is a common area of interest to transplant and hepatic surgery. Nevertheless, most of the current knowledge of I/R of the liver derives from the hepatocyte and little is known of what happens to the cholangiocytes. Herein, we assess the sequence of early events involved in the I/R injury of the cholangiocytes. METHODS: Sixty Wistar rats were randomized in a SHAM group and I/R group. Serum biochemistry, histopathology, immunohistochemistry, transmission electron microscopy (TEM) and laser capture microdissection (LCM) were used for group comparison. RESULTS: There was peak of alkaline phosphatase 24 h after IR injury, and an increase of aspartate aminotransferase and alanine aminotransferase after 6 h of reperfusion, followed by a return to normal levels 24 h after injury. The I/R group presented the liver parenchyma with hepatocellular degeneration up to 6 h, followed by hepatocellular necrosis at 24 h. TEM showed cholangiocyte injury, including a progressive nuclear degeneration and cell membrane rupture, beginning at 6 h and peaking at 24 h after reperfusion. Cytokeratin-18 and caspase-3-positive areas were observed in the I/R group, peaking at 24-h reperfusion. Anti-apoptotic genes Bcl-2 and Bcl-xl activity were expressed from 6 through 24 h after reperfusion. BAX expression showed an increase for 24 h. CONCLUSIONS: I/R injury to the cholangiocyte occurs from 6 through 24 h after reperfusion and a combination of TEM, immunohistochemistry and LCM allows a better isolation of the cholangiocyte and a proper investigation of the events related to the I/R injury. Apoptosis is certainly involved in the I/R process, particularly mediated by BAX.

Hypervitaminosis A-induced hepatic fibrosis in a cat.

RATIONALE: The excessive intake of vitamin A in the form of vitamin concentrate, supplement or vitamin-rich liver can result in hypervitaminosis A in man and animals. Although osteopathologies resulting from chronic vitamin A intoxication in cats are well characterized, no information is available concerning feline hypervitaminosis A-induced liver disease. CLINICAL SUMMARY: We report the first case of hepatic stellate cell lipidosis and hepatic fibrosis in a domestic cat that had been fed a diet based on raw beef liver. Radiographic examination revealed exostoses and ankylosis between vertebrae C1 and T7, compatible with deforming cervical spondylosis. Necropsy showed a slightly enlarged and light yellow to bronze liver. Microscopic and ultrastructural analyses of liver tissues revealed diffuse and severe liver fibrosis associated with hepatic stellate cell hyperplasia and hypertrophy. These cells showed immunopositive staining for α-smooth muscle actin and desmin markers. The necropsy findings of chronic liver disease coupled with osteopathology supported the diagnosis of hypervitaminosis A. PRACTICAL RELEVANCE: As in human hepatology, if there is dietary evidence to support increased intake of vitamin A, then hypervitaminosis A should be considered in the differential diagnosis of chronic liver disease in cats.

Análise comparativa entre a vascularização arterial ventricular e do nó sinoatrial em corações de cães / Comparative analysis between both ventricular and sinoatrial node arterial vascularization in heart of dogs

Utilizamos nesta pesquisa 40 corações de cães adultos, machos e fêmeas, de idades variadas, que não portavam nenhuma afecção cardíaca. Os corações tiveram as artérias coronárias injetadas, separadamente, com Neoprene Látex 450, corado com pigmento vermelho, e posteriormente dissecados. Em todas estas preparações verificamos que na vascularização dos ventrículos predominava a artéria coronária esquerda que fornecia os ramos interventriculares paraconal e subsinuoso. Já, a região ocupada pelo nó sinoatrial ficava mais frequentemente (17 vezes, 42,5%) na dependência do ramo proximal atrial esquerdo ou de colateral deste vaso, oriundo do ramo circunflexo esquerdo, ou deste vaso associado ao ramo distal atrial direito (8 vezes, 20%), procedente do ramo circunflexo direito. Com menor frequência (14 vezes, 30%), a área tomada pelo nó sinoatrial, encontramos apenas colaterais do ramo circunflexo direito, mais exatamente somente o ramo distal atrial direito (10 vezes, 25%), apenas o ramo proximal atrial direito (3 vezes, 7,5%) ou ainda exclusivamente o ramo intermédio atrial direito (1 vez, 2,5%). Em um único caso (1 vez, 2,5%) no território do nó sinoatrial observamos apenas colateral do ramo circunflexo esquerdo, isto é o ramo distal atrial esquerdo. A análise destes resultados permite concluir, que nesta espécie não existe qualquer tipo de relação entre o tipo de vascularização dos ventrículos e a irrigação do nó sinoatrial. Sendo assim, considerar os ramos ventriculares isoladamente não é suficiente para um entendimento clínico-cirúrgico aplicado, uma vez que os ramos atriais apresentam uma importante contribuição para a vascularização do nó sinoatrial.

We analyzed 40 hearts of adult dogs, males and females of different ages, without cardiac disease. The hearts had the coronary arteries inject using Neoprene Latex 450, colored with red pigment, and which was then dissected. In the ventricular vascularization the left coronary artery was predominant and gave rise to the paraconal interventricular and subsinuous branches. The region occupied by the sinoatrial node was most frequently (17 times, 42.5%) in dependence of the left atrial proximal branch or in the collateral branch of that vessel, coming from the left circumflex branch, or this vessel was associated with the right atrial distal branch (8 times, 20%). With less frequency (14 times, 30%), in the area occupied by the sinoatrial node we found only the collaterals of the right circumflex branch, only the right atrial distal branch (10 times, 25%), only the right atrial proximal branch (3 times, 7.5%) or exclusively the right atrial intermediary branch (once, 2.5%). In just one case (once, 2.5%) in the area of the sinoatrial node we observed only the collateral of the left circumflex branch, i.e. the left atrial distal branch. According to our results we concluded that in this specie there is no relationship between the type of ventricular vascularization and irrigation of the sinoatrial node. In doing so, to consider just the ventricular branches is not sufficient for a clinical and surgical applied understanding, since the atrial branches make an important contribution to the sinoatrial node vascularization.