RESUMO
INTRODUCTION: The aim of our work was to influence growth and histological changes in the wall of an experimentally induced aneurysm of the abdominal aorta in a large laboratory animal (domestic pig) by administering atorvastatin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor). MATERIAL AND METHODS: Within the scope of the above mentioned experimental work, we compared the growth rate of the aneurysm between the group influenced by statin administration (n=14) and the group without any pharmacological treatment (n=13). We also compared histological changes in the structure of the aortic wall in both groups with aneurysm and the wall of the aorta without aneurysm (n=6). RESULTS: During the 4-week follow-up, we did not prove a statistically significant difference in the growth rate of aneurysms between the above mentioned groups. The histological structure of the aneurysm walls, however, differed between the two groups. The structure of the wall in the group of animals influenced by statin administration resembled the structure of the aortic wall without aneurysm. CONCLUSION: The results presented demonstrate that statins do influence the composition of the aortic wall. In our opinion, the administration of statins could lead to changes resulting in a more stable aneurysmatic wall. We believe that patients with smaller aneurysms who are not indicated for surgery or endovascular treatment could be treated with statins. Stabilization of the aneurysmal wall could slow down the growth of the aneurysm and prevent its rupture.
Assuntos
Aneurisma da Aorta Abdominal/tratamento farmacológico , Antagonistas Colinérgicos/uso terapêutico , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirróis/uso terapêutico , Animais , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Atorvastatina , Imuno-Histoquímica , Sus scrofaRESUMO
INTRODUCTION: Inflammation within the abdominal aortic wall is generally considered a very significant ethiopathogenic factor in the development of abdominal aortic aneurysms. Proinflammatory cytokines are important mediators of inflammation within the abdominal aortic wall. AIM: The aim of the study was to research, whether plasmatic levels of certain proinflammatory cytokines, which can commonly be evaluated (TNFalpha, IL-1, -2, -6 a -8), play a significant role in the development of AAA. METHOD: The prospective non-randomized study included 345 patients with AAAs. The patients were assigned to 5 subgroups based on their symptoms and AAA diameters. The first subgroup included patients with symptomatic AAAs, including AAA ruptures (N = 69), the second subgroup included subjects with asymptomatic AAAs (N = 276) with AAA diameters up to 5 cm (N = 72), the third subgroup included 5 cm (N = 72), the fourth included 5-8 cm (N = 192) and the fifth subgroup included subjects with AAA diameters of more than 8 cm (N = 81). The mean age of patients was 74.1 +/- 7.8 years (56-84 y.o.a.). The male to female ratio was 5:1. The control group included 30 healthy volunteer subjects of similar age and male to female rates, who had no clinical signs of arterial disorders. Plasmatic levels of cytokines were evaluated from venous blood samples using ELISA (Bender, Austria) testing. Statistical assessment of the results was performed using ANOVA and Wilcoxon tests with Spearman's correlation. P values < 0.05 were considered significant. RESULTS: Plasmatic concentrations of proinflammatory cytokines were found to be statistically significantly higher in patients with AAAs compared to those in healthy volunteers. Plasmatic IL8 levels were significantly decreasing proportionally to decreasing AAA diameters (p < 0.05). TNFalpha levels were found to be significantly low in symptomatic patients with AAA ruptures (p < 0.05). CONCLUSION: The study confirmed the significance of proinflammatory cytokines levels monitoring in AAA patients. The authors showed that, for instance IL8 activity and to a certain extent TNFalpha activity, is the highest in small and developing AAAs. These findings would be significant for customized medication therapy aimed at blocking the effects of these factors on the inflammatory process within the AAA wall.
Assuntos
Aneurisma da Aorta Abdominal/sangue , Citocinas/sangue , Mediadores da Inflamação/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangueRESUMO
PURPOSE: This study investigated the prognostic importance of protein expression of ATP-binding cassette (ABC) transporters ABCC10 and ABCC11 in colorectal cancer. METHODS: Protein content of ABCC10 and ABCC11 was assessed in tumor tissue blocks of 140 colorectal cancer patients and associated with survival of patients with regard to 5-fluorouracil-based therapy. RESULTS: Low ABCC10 protein content in tumors increased hazard ratio of patient's death more than three times in comparison with high ABCC10-expressing tumors (P = 0.004). In contrast, the low ABCC11 content increased the hazard ratio of cancer recurrence in patients almost four times (P = 0.016). Analysis of patients treated with regimens based on 5-fluorouracil revealed that patients with low ABCC11 content in their tumors had shorter disease-free interval than those with higher content (P = 0.024). CONCLUSIONS: The present study shows for the first time that the protein expression of ABCC10 significantly associates with overall survival and the expression of ABCC11 with disease-free interval of colorectal cancer patients and provides strong impulse for further validation of their prognostic value in colorectal cancer.
Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Idoso , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
AIM: Observational studies in human patients and animal experiments suggested that statins have a potential in slowing the growth of small abdominal aortic aneurysms (AAA). Our aim was to quantify histological postoperative changes of AAA in porcine experimental model of AAA with and without administration of atorvastatin. METHODS: The AAA was induced by intraaortic infusion of porcine pancreatic elastase and subrenal application of plastic cuff. The AAA statin group (N.=14) received atorvastatin 1 mg/kg daily for 28 days, the other AAA group (N.=13) did not. The aortic diameter was measured by ultrasonography. Aortic samples were described using eleven quantitative histological parameters and compared with healthy aortae. RESULTS: There was no difference in aortic diameter between the AAA with statin when compared to AAA without statin. Administration of atorvastatin led to a better postoperative histological condition of the aortic elastin network, preservation of contractile phenotype of vascular smooth muscle, a higher density of vasa vasorum, it prevented thickening of intima and media. The increase in wall thickness in AAA without atorvastatin has not been accompanied by a proportional increase in number of vasa vasorum. CONCLUSION: The effects of atorvastatin seem to prevent the histopathological progression of AAA.