Proefschrift--Utrecht. / Bibliography: p. 101-104.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / 1,4-Cineol à um monoterpeno Ãter amplamente distribuido, o qual à um dos constituintes responsÃveis pelo odor do limÃo. O objetivo deste trabalho foi avaliar o efeito gastroprotetor de 1,4-Cineol (CIN 100 e 200 mg/Kg) nos modelos de lesÃo induzidas por etanol ou piroxicam em camundongos e, posteriormente, investigar os possÃveis mecanismos de aÃÃo farmacolÃgica envolvidos nesta aÃÃo. A administraÃÃo oral de 1,4-cineol 200 mg/Kg foi capaz de proteger a mucosa gÃstrica dos danos causados pelo etanol (0,2 ml/amimal, v.o). Esta gastroproteÃÃo foi tambÃm avaliada microscopicamente mostrando que CIN (200 mg/Kg, p.o.) diminuiu o edema na submucosa, o infiltrado inflamatÃrio e a hemorragia. 1,4-Cineol (100 e 200 mg/Kg, v.o.) tambÃm reduziu significantemente as lesÃes gÃstricas causadas pelo piroxicam (30 mg/Kg, s.c.). O mecanismo de gastroproteÃÃo de CIN foi examinado na dose de 200 mg/Kg no modelo de lesÃo gÃstrica induzida por etanol em camundongos. Nos animais prÃ-tratados com L-NAME (10 mg/Kg, i.p.), um inibidor da oxido nÃtrico sintetase, com glibenclamida (10 mg/Kg i.p.), uma substÃncia que bloqueia os canais de potÃssio ATP-dependente, ou com capsazepina (5 mg/Kg i.p.) um antagonista dos receptores vanilÃides TRPV-1, o efeito gastroprotetor de CIN nÃo foi significantemente inibido por estes mecanismos. Por outro lado, o efeito gastroprotetor de CIN foi revertido em animais prÃ-tratados com indometacina (10 mg/Kg v.o.), um inibidor nÃo seletivo da ciclooxigenase, demostrando que hà uma ativaÃÃo desta enzima no mecanismo de aÃÃo de CIN. Este trabalho avaliou tambÃm o mecanismo antioxidante de CIN como um agente gastroprotetor contra as lesÃes induzidas pelo etanol. Sob as nossas condiÃÃes experimentais, o modelo de induÃÃo pelo etanol causou mudanÃas nos sistema antioxidante da mucosa gÃstrica dos camundongos, como a diminuiÃÃo dos nÃveis de grupamentos sulfidrila (GSH) e da atividade da superÃxido dismutase (SOD), tambÃm mostrou um aumento da atividade da mieloperoxidade (MPO) e uma concentraÃÃo aumentada das espÃcies que reagem com o Ãcido tiobarbitÃrico (TBARS) como Ãndice de peroxidaÃÃo lipÃdica (LPO). 1.4-Cineol (200 mg/Kg, v.o.) no modelo de Ãlcera por etanol, nÃo interferiu na concentraÃÃo do GSH, mas permitiu a restauraÃÃo da atividade normal de SOD, nÃveis normais de LPO e de atividade da MPO. Estes dados sugerem que CIN 100 e 200 mg/Kg promovem gastroproteÃÃo contra lesÃes induzidas pelo etanol e/ou piroxicam em camundongos nos quais o mecanismo de aÃÃo incluem o envolvimento de prostaglandinas endÃgenas e uma potente atividade antioxidante. / 1,4-Cineole is a widely distributed monoterpene ether, which is one of the flavor constituents of lime juice. The aim of this work was to evaluate the gastroprotective effect of 1,4-Cineole (CIN 100 and 200 mg/Kg) on ethanol or piroxicam-induced lesions in mice and further investigate the possible pharmacological mechanisms involved in this action. The oral administration of 1,4-cineole 200 mg/kg was able to protect the gastric mucosa from ethanol injury (0.2 ml/animal, p.o.). This gastroprotection was also evaluated microscopically showing that CIN (200 mg/kg, p.o.) decreased the cell loss in the mucosa, submucosal edema, inflammatory infiltration and hemorrhage. 1,4-Cineole (100 and 200 mg/kg, p.o.) also reduced significantly the gastric lesions induced by piroxicam (30 mg/kg, s.c.). Gastroprotective mechanism of CIN was examined in the dose of 200 mg/kg, in the model of gastric lesions induced by ethanol in mice. In animals pretreated with L-NAME (10 mg/kg, i.p.), an inhibitor of nitric oxide synthase, or with glibenclamide (10 mg/kg, i.p.), a drug that blocks ATP-dependent potassium channels, or with capsazepine (5 mg/kg, i.p.), an antagonist of vanilloid receptor TRPV-1, the gastroprotective effect of CIN was not inhibited significantly, suggesting that the effect of CIN is not involved with this mechanisms. Otherwise, the gastroprotective effect of CIN (200 mg/kg, p.o.) was reverted in animals pretreated with indomethacin (10 mg/kg, p.o.), a nonselective inhibitor of cyclooxygenase, demonstrating that there is activation of these enzymes in the mechanism of action of CIN. This work also evaluated the antioxidant mechanism of CIN as gastroprotective agent against ethanol-induced lesions. Under our experimental conditions, the model of induction of ethanol injury caused changes in the antioxidant system of the gastric mucosa of mice as the decrease in the levels of sulfhydryl groups (GSH) and activity of superoxide dismutase (SOD), also showed increased activity of myeloperoxidase (MPO) and high concentration of species that react with thiobarbituric acid (TBARS) as index of lipid peroxidation (LPO). 1,4-Cineole (200 mg/kg, p.o.) in the model of ethanol did not interfere with the concentration of GSH, but allowed the restoration of normal SOD activity, normal levels of LPO and MPO activity. The data suggest that CIN 100 and 200 mg/kg promote gastroprotection against lesions induced by ethanol or piroxicam in mice whose mechanisms include the involvement of endogenous prostaglandins and potent antioxidant activity.

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy

No description available.

No description available.

Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 105-136).

Thesis (Ph. D.)--University of Hong Kong, 1987.

Thesis (Ph. D.)--University of Hong Kong, 1991.

The thesis investigates the role of psycotherapy in treating peptic ulcers, offering a new approach, "Re-evaluation Co-counseling," a peer cathartic therapy.

A live animal model of major haemorrhage using an implanted short gastric artery was devised to test the efficacy and safety of these endo-suture devices in vivo. Pulsatile arterial bleeding was successfully reproduced in eight pigs' stomachs through incision of the pre-buried vessels. Endoscopic suturing controlled the bleeding in all animals without obvious complications. The mean operating time with the Eagle Claw V was statistically shorter than that with the Eagle Claw II machine (3.6 verse 13.8 minutes, p<0.001). / A vessel-perfusion-manometry system was first established incorporating porcine stomach and splenic artery with the Erlangen model. / From these investigations, it is concluded that (1) Both the vessel-perfusion-manometry system and the animal arterial haemorrhage model are reliable, reproducible and realistic methods suitable for endoscopic experiment in the laboratory settings. (2) Either three-throw knot tied endoscopically or intracorporeal endo-loop ligation can secure vessels as large as 2mm in diameter enduring flow pressure greater than 200 mmHg. (3) It is possible to control massive arterial bleeding in stomach with endoscopic suturing using the novel apparatus with a curved needle. (4) The Eagle Claw V represents significant improvement over previous version, and is associated with ease of operation and higher security, which brings the technique closer to clinical applications. (Abstract shortened by UMI.) / Peptic ulcer remains the most common cause of upper gastrointestinal haemorrhage. Existing endoscopic haemostatic modalities cannot securely control massive ulcer bleeding from large eroded vessels. A well-designed endoscopic suturing device has the possibility to plicate large artery. In addition, it may provide enormous potential in other forms of endo-surgery. A novel suturing device using a curved needle, the Eagle Claw, was developed. The aims of this thesis were to evaluate the efficacy and safety of the Eagle Claw II and V in arresting artificial gastric bleeding from large vessel in a laboratory setting. These devices were tested both in vitro on the bench and in vivo in live animal models. / Hu Bing. / "August 2005." / Adviser: Ng Ekw. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3694. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 136-160). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.