Iron Status and Analysis of Efficacy and Safety of Ferric Carboxymaltose Treatment in Patients with Inflammatory Bowel Disease

Background and Aims:We analyzed iron deficiency and the therapeutic response following intravenous ferric carboxymaltose in a large single-center inflammatory bowel disease (IBD) cohort. Methods: 250 IBD patients were retrospectively analyzed for iron deficiency and iron deficiency anemia. A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose. Results: In the cohort (n = 250), 54.4% of the patients had serum iron levels 60 mu g/dl, 61.6% had ferritin >100 ng/ml, and 90.7% reached Hb >12/13 g/dl at follow-up (p < 0.0001 for all parameters vs. pretreatment values). The most frequent adverse event was a transient increase of liver enzymes with male gender as risk factor (p = 0.008, OR 8.62, 95% CI 1.74-41.66). Conclusions: Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients. Copyright (C) 2011 S. Karger AG, Base

Down-regulation of the global regulator SATB1 by statins in COLO205 colon cancer cells

Special AT-rich sequence binding protein 1 (SATB1) regulates the expression of more than 1,000 genes in tumor cells. SATB1 expression has been implicated in metastasis, and its silencing results in reduced cancer progression and the reversion of metastatic cells to normal appearance. Therefore, any compound causing down-regulation of SATB1 expression or activity may be exploited for its therapeutic potential in terms of cancer regression. Earlier studies showed that the 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase inhibitors (statin drugs), which are widely used to treat hypercholesterolemia, possess other pleotropic activities. These are now increasingly gaining attention for their cancer prevention abilities. However, the downstream interplay of the molecular mechanisms of such anti-cancer activities is unclear. Here, we show that SATB1 is down-regulated by statins in a time- and dose-dependent manner in COLO205 cells. This effect was statin-specific as the down-regulation of SATB1 was brought about by hydrophobic statins, such as simvastatin and fluvastatin, but not by hydrophilic pravastatin. Notably, treatment with mevalonate, an intermediate in the cholesterol and isoprenoid biosynthetic pathways, led to the inhibition of SATB1 down-regulation and cytotoxicity mediated by statins. Treatment with the proteasome inhibitors lactacystine and MG-132 inhibited the statin-mediated down-regulation of SATB1, suggesting that regulation occurs at the post-translational level. Thus, our results demonstrate a novel molecular mechanism for the anti-cancer activity of statin drugs in colon cancer cells, without invoking significant cytotoxicity

A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients

Background. Iron deficiency is a common cause of anaemia and hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) in non-dialysis-dependent chronic kidney disease (ND-CKD) patients. Current intravenous iron agents cannot be administered in a single high dose because of adverse effects. Ferric carboxymaltose, a non-dextran parenteral iron preparation, can be rapidly administered in high doses

HFE Gene Variants Modify the Association between Maternal Lead Burden and Infant Birthweight: A Prospective Birth Cohort Study in Mexico City, Mexico

<p>Abstract</p> <p>Background</p> <p>Neonatal growth is a complex process involving genetic and environmental factors. Polymorphisms in the hemochromatosis (<it>HFE</it>) iron regulatory genes have been shown to modify transport and toxicity of lead which is known to affect birth weight.</p> <p>Methods</p> <p>We investigated the role of <it>HFE C282Y</it>, <it>HFE H63 D</it>, and transferrin <it>(TF) P570 S </it>gene variants in modifying the association of lead and infant birthweight in a cohort of Mexican mother-infant pairs. Subjects were initially recruited between 1994-1995 from three maternity hospitals in Mexico City and 411 infants/565 mothers had archived blood available for genotyping. Multiple linear regression models, stratified by either maternal/infant <it>HFE </it>or <it>TF </it>genotype and then combined with interaction terms, were constructed examining the association of lead and birthweight after controlling for covariates.</p> <p>Results</p> <p>3.1%, 16.8% and 17.5% of infants (N = 390) and 1.9%, 14.5% and 18.9% of mothers (N = 533) carried the <it>HFE C282Y</it>, <it>HFE H63D</it>, and <it>TF P570 S </it>variants, respectively. The presence of infant <it>HFE H63 D </it>variants predicted 110.3 g (95% CI -216.1, -4.6) decreases in birthweight while maternal <it>HFE H63 D </it>variants predicted reductions of 52.0 g (95% CI -147.3 to 43.2). Interaction models suggest that both maternal and infant <it>HFE H63 D </it>genotype may modify tibia lead's effect on infant birthweight in opposing ways. In our interaction models, maternal <it>HFE H63 D </it>variant carriers had a negative association between tibia lead and birthweight.</p> <p>Conclusions</p> <p>These results suggest that the <it>HFE H63 D </it>genotype modifies lead's effects on infant birthweight in a complex fashion that may reflect maternal-fetal interactions with respect to the metabolism and transport of metals.</p

Supplementation with α-tocopherol or a combination of α-tocopheroland ascorbic acid protects the gastrointestinal tract of iron-deficientrats against iron-induced oxidative damage during iron repletion

Recently we have shown the susceptibility of Fe-deficient rat intestine to oxidative damage during Fe repletion. The role of dietary antioxidants like ascorbic acid, α-tocopherol and a combination of both in counteracting the oxidative stress was tested in this study. Five groups of thirteen weanling WKY female rats were fed with an Fe-deficient diet for a period of 5 weeks. Another set of thirteen rats received an Fe-sufficient diet and served as the control group (Con). Oral administration of either vehicle (D), 8 mg Fe alone (D+) or in the presence of 24 mg ascorbic acid (D++ C), 40 mg α-tocopherol (D++ E) or a combination of both (D++ C + E) per d for 15 d was carried out in Fe-depleted rats. The impact of this treatment protocol on Fe status, oxidative stress and antioxidant status at the site of Fe absorption was assessed. It was observed that though the indicators of Fe status were normalised on Fe supplementation, the oxidative stress as reflected by the levels of both thiobarbituric-acid reactive substances (TBARS) and protein carbonyls were significantly greater in D+and D++ C compared to D++ E, D++ C + E and Con groups. The mucosal cell DNA damage was seen in D+, D++ C and D++ E groups on electrophoresis. Functional integrity as assessed by the activities of alkaline phosphatase and lys-ala-dipeptidyl aminopeptidase were normalized in all the groups treated with the antioxidant(s). There were significant positive alterations in some of the endogenous antiperoxidative systems and in serum caeruloplasmin activity in D++ E and D++ C + E groups. Paradoxically, serum ascorbate levels were significantly lower in D++ C than in D++ E and D++ C + E groups. This could be due to the protection offered by α-tocopherol in the presence of Fe. It is concluded that supplementation of α-tocopherol alone or in combination with ascorbic acid protects the gastrointestinal tract of Fe-deficient rats against Fe-mediated oxidative damage during Fe repletion. However, ascorbic acid alone does not protect the gastrointestinal tract against Fe-induced oxidative stress.</jats:p

Supplementary Legends 1-3 from Statin-Induced Breast Cancer Cell Death: Role of Inducible Nitric Oxide and Arginase-Dependent Pathways

Supplementary Legends 1-3 from Statin-Induced Breast Cancer Cell Death: Role of Inducible Nitric Oxide and Arginase-Dependent Pathways</jats:p

Supplementary Figures 1-3 from Statin-Induced Breast Cancer Cell Death: Role of Inducible Nitric Oxide and Arginase-Dependent Pathways

Supplementary Figures 1-3 from Statin-Induced Breast Cancer Cell Death: Role of Inducible Nitric Oxide and Arginase-Dependent Pathways</jats:p