Nadroparine-induced skin necrosis on a patient with essential thrombocythaemia: a case report

Skin necrosis is a rare but serious complication of subcutaneously administered low-molecular-weight heparin. We report a case of a 53-year-old female patient with skin necrosis induced by subcutaneous administration of nadroparine. The patient suffered from essential thrombocythaemia on a background of chronic myeloproliferative disease. She was admitted to our clinic with a subacute ileus due to endometriosis of the rectosigmoid junction. She underwent a high anterior resection and she received pre- and postoperative antithrombotic prophylaxis with subcutaneous nadroparine on a daily basis. On the 6th and 7th postoperative days, two skin necroses occurred at two injection sites

Lipoprotein [a] is cleared from the plasma primarily by the liver in a process mediated by apolipoprotein [a]

The cellular and molecular mechanisms responsible for lipoprotein [ a] (Lp[a]) catabolism are unknown. We examined the plasma clearance of Lp[ a] and LDL in mice using lipoproteins isolated from human plasma coupled to radiolabeled tyramine cellobiose. Lipoproteins were injected into wild-type, LDL receptor-deficient (Ldlr(-/-)), and apolipoprotein E-deficient (Apoe(-/-)) mice. The fractional catabolic rate of LDL was greatly slowed in Ldlr(-/-) mice and greatly accelerated in Apoe(-/-) mice compared with wild-type mice. In contrast, the plasma clearance of Lp[ a] in Ldlr(-/-) mice was similar to that in wild-type mice and was only slightly accelerated in Apoe(-/-) mice. Hepatic uptake of Lp[ a] in wild-type mice was 34.6% of the injected dose over a 24 h period. The kidney accounted for only a small fraction of tissue uptake (1.3%). To test whether apolipoprotein [ a] (apo[a]) mediates the clearance of Lp[a] from plasma, we coinjected excess apo[a] with labeled Lp[ a]. Apo[a] acted as a potent inhibitor of Lp[ a] plasma clearance. Asialofetuin, a ligand of the asialoglycoprotein receptor, did not inhibit Lp[ a] clearance. In summary, the liver is the major organ accounting for the clearance of Lp[ a] in mice, with the LDL receptor and apolipoprotein E having no major roles. Our studies indicate that apo[a] is the primary ligand that mediates Lp[a] uptake and plasma clearance

Macrophage-specific expression of group IIA sPLA(2) results in accelerated atherogenesis by increasing oxidative stress

Group IIA secretory phospholipase A(2) (sPLA(2)) isan acute-phase protein mediating decreased plasma HDL cholesterol and increased atherosclerosis. This study investigated the impact of macrophage-specific sPLA(2) overexpression on lipoprotein metabolism and atherogenesis. Macrophages from sPLA(2) transgenic mice have 2.5 times increased rates of LDL oxidation ( thiobarbituric acid-reactive substances formation) in vitro ( 59 +/- 5 vs. 24 +/- 4 nmol malon-dialdehyde/ mg protein; P LDLR-/-; n = 19) or wild-type C57BL/6 littermates (C57 BL/6 -> LDLR-/-; n = 19) and maintained for 8 weeks on chow and then for 9 weeks on a Western-type diet. Plasma sPLA 2 activity and plasma lipoprotein profiles were not significantly different between sPLA(2). LDLR-/- and C57BL/ 6 -> LDLR-/- mice. Aortic root atherosclerosis was increased by 57% in sPLA(2). LDLR-/- mice compared with C57BL/ 6 -> LDLR-/- controls ( P LDLR-/- compared with C57BL/6. LDLR-/- mice, indicating significantly increased in vivo oxidative stress in sPLA(2). LDLR-/-

Plasma bile acids are not associated with energy metabolism in humans

Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy controls (n = 12) were studied before and after 8 weeks of treatment with a BA sequestrant. In addition, patients with liver cirrhosis (n = 46) were investigated, since these display elevated plasma BA together with increased energy expenditure. This group was compared to gender-, age- and BMI-matched healthy controls (n = 20). Fasting plasma levels of total BA and individual BA species as well as resting energy expenditure were determined. In response to treatment with the BA sequestrant, plasma deoxycholic acid (DCA) levels decreased in controls (-60%, p < 0.05) and T2DM (-32%, p < 0.05), while chenodeoxycholic acid (CDCA) decreased in controls only (-33%, p < 0.05). Energy expenditure did not differ between T2DM and controls at baseline and, in contrast to plasma BA levels, was unaffected by treatment with the BA sequestrant. Total BA as well as individual BA species did not correlate with energy expenditure at any time throughout the study. Patients with cirrhosis displayed on average an increase in energy expenditure of 18% compared to values predicted by the Harris-Benedict equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to 20-fold) were increased over a wide range. However, neither total nor individual plasma BA levels correlated with energy expenditure. In addition, energy expenditure was identical in patients with a cholestatic versus a non-cholestatic origin of liver disease while plasma total BA levels differed four-fold between the groups. In conclusion, in the various (patho)physiological conditions studied, plasma BA levels were not associated with changes in energy expenditure. Therefore, our data do not support an important role of circulating BA in the control of human energy metabolism. © 2010 Brufau et al; licensee BioMed Central Ltd

Increased type IIA secretory phospholipase A(2) expression contributes to oxidative stress in end-stage renal disease

End-stage renal disease (ESRD) patients exhibit increased in vivo oxidative stress conceivably contributing to cardiovascular mortality. The type IIA secretory phospholipase A(2) (sPLA(2)) has proatherogenic activity. We explored the hypothesis that sPLA(2) contributes to oxidative stress generation and endothelial dysfunction in ESRD patients and transgenic (tg) mice. Patients with ESRD had increased in vivo oxidative stress as assessed by plasma isoprostane levels (p <0.001). Active sPLA(2) in plasma was substantially increased compared with healthy controls (1,156 +/- 65 versus 184 +/- 5 ng/dL, p <0.001) and correlated with plasma isoprostanes (r = 0.61, p <0.001). Correspondingly, human sPLA(2) tg mice display increased generation of reactive oxygen species within aortic vascular smooth muscle cells, leading to severe endothelial dysfunction (maximal vasodilation in response to 10 A mu mol/L acetylcholine, sPLA(2) 36 A +/- 8%, controls 80 A +/- 2% of phenylephrine-induced vasoconstriction). Increased vascular oxidative stress in sPLA(2) tg mice is dependent on the induction of vascular cyclooxygenase (COX)2 expression. Conversely, ESRD patients show increased formation of COX2-derived prostaglandins (p <0.05) correlated with plasma sPLA(2) (r = 0.71, p <0.05). Our data indicate that increased expression of sPLA(2) might represent a novel causative risk factor contributing to the increased cardiovascular disease morbidity and mortality in ESRD