The effects of tirofiban on peripheral markers of oxidative stress and endothelial dysfunction in patients with acute coronary syndromes.

BACKGROUND: Endothelial dysfunction and oxidative stress are believed to be central mechanisms in atherogenesis. We aimed to determine the effects of tirofiban on oxidative stress and neutrophil-endothelium interaction markers in patients with acute coronary syndromes (ACS). MATERIALS AND METHODS: We measured malondialdehyde (MDA), interleukin-6 (IL-6) and soluble endothelial intercellular and vascular adhesion molecules (sICAM-1 and sVCAM-1) on admission, at 48 and 72 h and on 5th day of hospitalization in 34 patients (age 66.5+/-1.8 years) with ACS. Patients with recurrent angina, changes on the electrocardiogram and/or elevated troponin I received intravenously tirofiban for 48 h and the others received normal saline. RESULTS: Baseline concentrations of all markers did not differ significantly and compared with placebo, tirofiban infusion markedly reduced MDA, IL-6, sICAM-1 and sVCAM-1 at 48 h (-31+/-6% vs. 84+/-49%, p=0.007, -12+/-14% vs. 23+/-10%, p=0.05, -20+/-6% vs. 36+/-25%, p=0.04 and -10+/-5% vs. 6+/-5%, p=0.02, respectively). Relative to baseline, significant reductions were observed for all 4 markers at 72 h and day 5 (p<0.05). CONCLUSION: Tirofiban potentiates the decline in oxidative stress and may reverse abnormal endothelial activation in patients with ACS. This benefit seems to remain over the following 5 days.

The Ca2+-sensitizer levosimendan improves oxidative damage, BNP and pro-inflammatory cytokine levels in patients with advanced decompensated heart failure in comparison to dobutamine.

AIM: To investigate the effect of a new inotropic drug, levosimendan compared with dobutamine on levels of brain natriuretic peptide (BNP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and malondialdehyde (MDA) in patients with severe decompensated heart failure. METHODS AND RESULTS: Twenty-nine consecutive patients (22 males and 7 females), mean age 70.5+/-9.9 years, with decompensated heart failure on standard medical therapy, were randomised to receive either a 24 h infusion of levosimendan (n=15) or dobutamine (n=14). Blood samples were drawn at baseline, 48 h and 5 days post infusion. Levosimendan produced a significant reduction in BNP compared to baseline, at both 48 h (744.1+/-100 vs 1136.3+/-93.7 pg/ml, p=0.04) and 5 days (446+/-119.3 vs 1136.3+/-93.7 pg/ml, p=0.03), while IL-6 values decreased after 5 days (4.8+/-1.3 vs 8.6+/-1.5 pg/ml, p=0.01). MDA levels were significantly lower 5 days after levosimendan compared to baseline (2.3+/-0.2 vs 3+/-0.3 microM, p=0.01). TNF-alpha levels did not differ between the groups. The comparison of percentage alteration compared to baseline showed that BNP (-44.5+/-7.6% vs 4.8+/-18.7%, p=0.025), MDA (-21.8+/-5.1% vs 14.9+/-8.5%, p=0.001) and IL-6 (-38.8+/-12.5% vs 70.2+/-24%, p=0.001) levels were significantly lower in the levosimendan group 5 days after treatment compared to the dobutamine group. CONCLUSIONS: Treatment with levosimendan in advanced decompensated heart failure exerts a beneficial hemodynamic, anti-inflammatory and antioxidant effect. These findings may give an insight into the favourable impact on mortality that levosimendan appears to have in published multicenter trials.

Assessment of the physicochemical stability of all-in-one parenteral emulsions for neonates according to USP specifications.

BACKGROUND: The purpose of this study was to describe the methodology to assess the stability of all-in-one (AIO) parenteral nutrition admixtures, containing glucose, proteins, and lipids, to the standards of U.S. Pharmacopoeia (USP <729>). The influence of calcium and commercially available lipid emulsions and amino acid solutions were also examined. METHODS: Four batches of 5 AIO admixtures containing calcium were compounded with commercially available lipid emulsions and amino acid solutions. Two of them contained calcium. Their stability was tested under conditions simulating clinical use. All the admixtures were assessed for criteria set by the USP <729>: (1) mean droplet diameter (MDD) and (2) percentage of volume weighted particles with diameter > 5 µm (PFAT5). RESULTS: All admixtures were within the specifications set by the USP with respect to the MDD at 0, 24, and 48 hours, but only those batches lacking calcium met the benchmarks set by the pharmacopoeia, with respect to PFAT5, on the day of preparation. CONCLUSIONS: The presence of calcium destabilized the admixtures, while the use of different commercial ingredients altered the admixtures' characteristics. Only 1 batch of the AIO admixtures studied was found to be compliant with USP <729> standards.

Therapeutic value of melatonin in an experimental model of liver injury and regeneration.

Melatonin has marked antioxidant properties. The aim of the present study was to evaluate the therapeutic effect of melatonin on acute liver injury induced in rats by carbon tetrachloride (CCl4), allyl alcohol (AA) and their combination. A total of 108 male Wistar rats were divided into 12 experimental groups according to their treatment regimen (n = 5-10 rats in each group). Melatonin (100 mg/kg body weight, BW) was administered 6 hr (a) after a single dose of CCl4 (intragastrically 0. 66 mL/kg BW diluted 1:1 v/v with corn oil); (b) a single dose of AA (intraperitonealy, 0.62 mmol/kg BW 1:50 v/v in 0.9% saline solution); and (c) a combination of the above substances. Rats were sacrificed at 24 and 48 hr post-toxin administration and the therapeutic effect of melatonin was investigated by assessment of histopathological changes and lipid peroxidation alterations determined by measuring tissue malondialdehyde plus 4-hydroxy-nonenal (MDA + 4-HNE), plasma MDA and plasma levels of liver enzymes. The levels of a key antioxidant, glutathione (GSH), were measured in liver tissue homogenates. Hepatic necrosis was significantly reduced in the melatonin-treated rats 48 hr after administration of CCl4, AA and CCl4 + AA. The levels of hepatic enzymes in plasma were found to be significantly reduced at 24 and 48 hr in the CCl4 + AA treated rats after melatonin administration. Additionally, MDA and MDA + 4-HNE concentrations were significantly reduced at 24 and 48 hr time-points in all groups that received melatonin. GSH levels were decreased in liver after the toxic substances administration, whereas melatonin reversed this effect. In conclusion, a single dose of melatonin decreased hepatic injury induced by CCl4, AA and CCl4 + AA. The inhibition of the oxidative stress and therefore lipid peroxidation by melatonin in CCl4 and AA administered animals, may constitute the protective mechanism of melatonin against acute liver injury.