Ascidian (chordate-tunicate) and mammalian heparin enemas attenuate experimental diversion colitis

Alvarenga, Valter; Pacheco, Rodrigo; Esposito, Christiano Costa; Buongusto, Fernanda; Castelo-Branco, Morgana T.; Madi, Kalil; Belmiro, Celso R.; Pavão, Mauro S.G.; Souza, Heitor Siffert Pereira de; Schanaider, Alberto

doi:10.1016/j.surg.2013.06.057

Cited by 13 publications

(16 citation statements)

References 54 publications

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“…TNBS-induced colitis is one of the most common models of experimental colitis. The colonic mucosa is exposed to the contactsensitizing agent, trinitrobenzene sulfonic acid, a covalently reactive compound that attaches to autologous proteins and stimulates a delayed-type hypersensitivity response to the hapten-modified self-antigens 3,4 . Our group has begun to experiment with TNBS as an etiological agent of experimental colitis almost 10 years ago.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Seven days after the TNBS instillation, all animals were anesthetized as aforementioned and examined with a flexible fiberscope FB 120P with a diameter of 2.8 mm (Fujinon, Japan) assembled to a video camera for recording images. Two independent observers, using an adapted endoscopic index of colitis (3), scored the colonic injury analyzing the following parameters: hyperemia, number and size of vessels, bleeding, and mucous secretion, ranging from 0 to 4 4 .…”

Section: Model 1 (Tnbs)mentioning

confidence: 99%

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Rat models of high risk colorectal anastomoses

Alvarenga

Ferraz

Rolim³

et al. 2018

Acta Cir. Bras.

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To evaluate the most frequent surgical techniques of high-risk colorectal anastomoses in rats. Methods: Wistar rats were enrolled in three different models comprising inflammatory (TNBS enema), vascular (portal vein occlusion) or obstructive (a non-ischemic constricting ring) mechanisms associated with colonic anastomosis that had accomplished after these former lesions. Histological analyses (Hematoxylin and eosin and Picrosirius red) were performed. Results: All anastomoses techniques were associated with risk factors and had complications, mainly anastomotic leakage. In Study 1, the use of a pharmacological agent, trinitrobenzene sulfonic acid (TNBS) mimicked an inflammatory bowel disease such as Crohn's disease with 50% of anastomosis leakage, the higher percentage among all models tested. In Study 2, after portal ischemia followed by reperfusion it was observed a dense neutrophil infiltrate in the midst of necrotic tissue and fibrin at the anastomotic site and 5 days after the anastomosis, no collagen was produced. In Study 3, 5 days after the mechanical obstruction some denuded areas of epithelium with marked oedema of mucosa and submucosa were seen, at the anastomotic site and anastomosis group showed some reduction of collagen density when compared with Control/Sham group. Conclusion: All the experimental surgical techniques tested in rats were associated with high-risk colorectal anastomoses and were useful to study colonic anastomotic healing and intestinal leakage.

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Section: ■ Discussionmentioning

confidence: 99%

Section: Model 1 (Tnbs)mentioning

confidence: 99%

Rat models of high risk colorectal anastomoses

Alvarenga

Ferraz

Rolim³

et al. 2018

Acta Cir. Bras.

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“…2 ). Some of these molecules display less anti-coagulant activity but remain capable to interact with mammalian host cells, including modulating inflammatory response [ 89 , 129 ]. These molecules could be used as antagonists of HBP, decreasing macrophage invasion and disease progression (Fig.…”

Section: Glycosaminoglycans and Leishmania Infectimentioning

confidence: 99%

Leishmaniasis and glycosaminoglycans: a future therapeutic strategy?

et al. 2018

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Leishmania spp. depend on effective macrophage infection to establish and develop in mammalian hosts. Both metacyclic promastigotes and amastigotes are able to infect host cells, and thus they rely on several ligands that, when recognized by macrophage receptors, mediate parasite uptake. During macrophage primary infection with metacyclic forms from the insect vector and during amastigote dissemination via macrophage rupture, both infective stages have to cope with the host extracellular microenvironment, including extracellular matrix molecules. Glycosaminoglycans are abundant in the extracellular matrix and many of these molecules are able to interact with the parasite and the host cell, mediating positive and negative effects for the infection, depending on their structure and/or location. In addition, glycosaminoglycans are present at the surface of macrophages as proteoglycans, playing important roles for parasite recognition and uptake. In this review, we discuss glycosaminoglycans in the context of Leishmania infection as well as the possible applications of the current knowledge regarding these molecules for the development of new therapeutic strategies to control parasite dissemination.

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“…It has been proposed that the beneficial effects of LMWH on PE patients are correlated to an anti-inflammatory action. Heparin and its derivatives have been demonstrated to be effective against several inflammatory experimental conditions as mouse models of colitis [ 29 ], arthritis [ 30 ] and in patient with airways inflammatory disease [ 31 ]. Furthermore, it has been shown that, in an inflammation-model of mice treated with LPS, modified heparin with low/absent anticoagulatory capacity strongly inhibited expression of hepcidin, serum iron uptake regulator whose levels rise during inflammation [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

The HMGB1/RAGE Pro-Inflammatory Axis in the Human Placenta: Modulating Effect of Low Molecular Weight Heparin

et al. 2017

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We evaluated whether physiological and pre-eclamptic (PE) placentae, characterized by exacerbated inflammation, presented alterations in pro-inflammatory High Mobility Group Box 1 (HMGB1) and its Receptor of Advanced Glycation End products (RAGE) expression. Moreover, we investigated, in physiological placental tissue, the ability of Low Molecular Weight Heparin (LMWH) to modify HMGB1 structural conformation thus inhibiting RAGE binding and HMGB1/RAGE axis inflammatory activity. HMGB1, RAGE, IL-6 and TNFα (HMGB1/RAGE targets) mRNA expression were assessed by Real Time PCR. HMGB1, RAGE protein levels were assessed by western blot assay. Physiological term placental explants were treated by 0.5 U LMWH for 24 or 48 h. HMGB1 and RAGE expression and association were evaluated in LMWH explants by RAGE immunoprecipitation followed by HMGB1 immunoblot. HMGB1 spatial localization was evaluated by immuofluorescent staining (IF). HMGB1 expression was increased in PE relative to physiological placentae while RAGE was unvaried. 24 h LMWH treatment significantly up-regulated HMGB1 expression but inhibited HMGB1/RAGE complex formation in physiological explants. RAGE expression decreased in treated relative to untreated explants at 48 h. IF showed HMGB1 localization in both cytoplasm and nucleus of mesenchymal and endothelial cells but not in the trophoblast. IL-6 and TNFα gene expression were significantly increased at 24 h relative to controls, while they were significantly down-regulated in 48 h vs. 24 h LMWH explants. Our data depicted a new molecular mechanism through which LMWH exerts its anti-inflammatory effect on PE placentae, underlying the importance of HMGB1/RAGE axis in PE inflammatory response.

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Ascidian (chordate-tunicate) and mammalian heparin enemas attenuate experimental diversion colitis

Cited by 13 publications

References 54 publications

Rat models of high risk colorectal anastomoses

Rat models of high risk colorectal anastomoses

Leishmaniasis and glycosaminoglycans: a future therapeutic strategy?

The HMGB1/RAGE Pro-Inflammatory Axis in the Human Placenta: Modulating Effect of Low Molecular Weight Heparin

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