Effect of chronic restraint stress and alpha-lipoic acid on lipid peroxidation and antioxidant enzyme activities in rat peripheral organs.

OBJECTIVES: The aim of this study was to evaluate the effect of chronic restraint stress and alpha-lipoic acid (LA) administration on lipid peroxidation and antioxidant enzyme activities in rat peripheral organs. METHODS: Forty male wistar rats, aged 3 months were randomized to one of the following groups: control, restraint stress, LA treated and restraint stress+LA treated. Chronic restraint stress was applied for 21 days (1h/day) and LA (100 mg/kg/day) was administered intraperitoneally for the same period. RESULTS: Restraint stress had no statistically significant effect on lipid peroxidation, copper/zinc superoxide dismutase (Cu/Zn SOD), catalase (CAT) and glutathione peroxidase (GPx) activity in rat liver and heart, when compared to the control group. Lipid peroxidation, determined by measuring malondialdehyde (MDA) levels, was found to be increased in the kidney of restraint stress treated rats, compared to controls. Restraint stress-induced lipid peroxidation in the kidney was significantly decreased via LA treatment. Administration of LA also enhanced GPx and decreased Cu/Zn SOD activity in rat kidney, liver and heart, compared to the control group. CONCLUSIONS: The presented data shows that LA is a protective agent against restraint stress--the inducer of lipid peroxidation in the kidney. These findings also suggest that LA-induced changes in antioxidant enzyme activities in rat peripheral organs may contribute to their versatile effects observed in vivo.     

Inhibition of liver metastasis by all-trans retinoic acid incorporated into O/W emulsions in mice

All-trans retinoic acid (ATRA) was incorporated into lipid emulsions in an attempt to alter its distribution characteristics and improve its inhibition of liver cancer metastasis. Lipid emulsions composed of egg phosphatidylcholine, cholesterol, and soybean oil were the optimized carriers for ATRA delivery, as shown by the submicron particle size and high incorporation efficiency. The particle size and zeta potential of ATRA incorporated into emulsions were about 133 nm and -11 mV, respectively. In vitro drug release study demonstrated that the release of ATRA from emulsions was sustained in the absence and present of bovine serum albumin, suggesting that ATRA was stable when incorporated in emulsions. After intravenous administration in mice, [3H]cholesteryl hexadecyl ether incorporated into emulsion, which is the inherent distribution of emulsions, accumulated gradually mainly in the liver. The blood concentration and hepatic accumulation of [3H]ATRA incorporated into emulsion was significantly higher than that of serum dissolving [3H]ATRA, which represent the original distribution characteristic of free ATRA. In a murine liver metastasis model by colon adenocarcinoma, the liver metastasis number and liver weight were significantly reduced and the survival time of mice was prolonged following intravenous injection of ATRA incorporated into emulsions.     

Endothelin-1 actions on vascular smooth muscle cell functions as a target for the prevention of atherosclerosis

The formation and progression of atherosclerotic plaques followed by rupture, thrombus formation and vessel blockage leads to ischemic tissue damage and the clinical condition underlying most cardiovascular disease. Therapeutic agents for the prevention of atherosclerosis have all targeted epidemiologically-identified and relatively easily measured risk factors (e.g. lipids and blood pressure). This strategy has proven somewhat effective but is of less than optimal efficacy as rates of cardiovascular disease remain high. Treatment targeting the mechanisms of atherosclerosis in the vessel wall is a conceptually attractive proposition to complement the risk factor directed strategy. Vascular smooth muscle cells (VSMC) are the major cellular component of the vascular media and migration and proliferation leads to the formation of the neointima the development of which renders the vessels particularly sensitive to atherosclerosis. Numerous hormones and growth factors act on VSMC to cause migration, proliferation and the secretion of extracellular matrix and modulation or dysfunction of these processes is the most likely cause of atherosclerosis. Endothelin-1 (ET-1) is a 21 amino acid peptide that acts on 7 transmembrane G protein coupled receptors to elicit a plethora of responses that can modulate the behaviour of VSMCs and thus impact on the development of atherosclerosis. ET-1 is elevated in atherosclerotic plaques. People with diabetes have accelerated atherosclerosis and also show elevated plasma levels of ET-1. This review addresses the actions of ET-1 on VSMC and the signalling pathways through which it mediates its effects as the latter represent potential therapeutic targets for the prevention of atherosclerosis.     

Surgical treatment of postinfarction pseudoaneurysms of the left ventricle

BACKGROUND: Left ventricular pseudoaneurysm is a rare and frequently fatal complication of acute myocardial infarction. It occurs as a consequence of rupture of the ventricular free wall that gets confined by a portion of the pericardium. The purpose of this study was to present our surgical experience of postinfarction left ventricular pseudoaneurysms and to evaluate mid-term results. METHODS: The study population comprised five symptomatic patients diagnosed with left ventricular pseudoaneurysm and treated surgically in a short period of time. There were three males and two females. The mean age of the patients was 66.8 +/- 10.8 years. The diagnosis was made initially by echocardiography and subsequently confirmed by angiography. An additional cardiac magnetic resonance imaging study was performed in three patients. Surgical resection of the pseudoaneurysm was combined with an endoaneurysmorrhaphy procedure in all patients. Associated cardiac operations were performed in three patients. Definitive diagnosis of pseudoaneurysm was confirmed by histopathological evaluation of the excised wall in all patients. RESULTS: All patients survived the operation and were discharged to home care. The mean duration of hospital stay was 11.6 +/- 4.6 days. Patients were either in class I or II of New York Heart Association classification at discharge. All patients are still being followed after surgery with a mean follow-up period of 10.4 +/- 6.6 months with no further problems. CONCLUSION: Surgical repair is indicated in left ventricular pseudoaneurysm as it carries a high risk of rupture and sudden cardiac death. Surgical repair combined with an endoaneurysmorrhaphy procedure carries a low mortality risk and improves functional capacity.