An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase.

In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by (1)H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent.

Iron deficiency and anaemia in bariatric surgical patients: causes, diagnosis and proper management

Obesity-induced chronic inflammation leads to activation of the immune system that causes alterations of iron homeostasis including hypoferraemia, iron-restricted erythropoiesis, and finally mild-to-moderate anaemia. Thus, preoperative anaemia and iron deficiency are common among obese patients scheduled for bariatric surgery (BS). Assessment of patients should include a complete haematological and biochemical laboratory work-up, including measurement of iron stores, vitamin B12 and folate. In addition, gastrointestinal evaluation is recommended for most patients with iron-deficiency anaemia. On the other hand, BS is a long-lasting inflammatory stimulus in itself and entails a reduction of the gastric capacity and/or exclusion from the gastrointestinal tract which impair nutrients absorption, including dietary iron. Chronic gastrointestinal blood loss and iron-losingenteropathy may also contribute to iron deficiency after BS. Perioperative anaemia has been linked to increased postoperative morbidity and mortality and decreased quality of life after major surgery, whereas treatment of perioperative anaemia, and even haematinic deficiency without anaemia, has been shown to improve patient outcomes and quality of life. However, long-term follow-up data in regard to prevalence, severity, and causes of anaemia after BS are mostly absent. Iron supplements should be administered to patients after BS, but compliance with oral iron is no good. In addition, once iron deficiency has developed, it may prove refractory to oral treatment. In these situations, IV iron (which can circumvent the iron blockade at enterocytes and macrophages) has emerged as a safe and effective alternative for perioperative anaemia management. Monitoring should continue indefinitely even after the initial iron repletion and anaemia resolution, and maintenance IV iron treatment should be provided as required. New IV preparations, such ferric carboxymaltose, are safe, easy to use and up to 1000 mg can be given in a single session, thus providing an excellent tool to avoid or treat iron deficiency in this patient population.

Intravenous iron in inflammatory bowel disease

The prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%). Both iron deficiency (ID) and anemia of chronic disease contribute most to the development of anemia in IBD. The prevalence of ID is even higher (45%). Anemia and ID negatively impact the patient's quality of life. Therefore, together with an adequate control of disease activity, iron replacement therapy should start as soon as anemia or ID is detected to attain a normal hemoglobin (Hb) and iron status. Many patients will respond to oral iron, but compliance may be poor, whereas intravenous (i.v.) compounds are safe, provide a faster Hb increase and iron store repletion, and presents a lower rate of treatment discontinuation. Absolute indications for i.v. iron treatment should include severe anemia, intolerance or inappropriate response to oral iron, severe intestinal disease activity, or use of an erythropoietic stimulating agent. Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses). After the initial resolution of anemia and the repletion of iron stores, the patient's hematological and iron parameters should be carefully and periodically monitored, and maintenance iron treatment should be provided as required. New i.v. preparations that allow for giving 1000-1500 mg in a single session, thus facilitating patient management, provide an excellent tool to prevent or treat anemia and ID in this patient population, which in turn avoids allogeneic blood transfusion and improves their quality of life.

Perioperative intravenous iron; an upfront therapy for treating anaemia and reducing transfusion requirements.

Perioperative anaemia, with iron deficiency being its leading cause, is a frequent condition among surgical patients, and has been linked to increased postoperative morbidity and mortality, and decreased quality of life. Postoperative anaemia is even more frequent and is mainly caused by perioperative blood loss, aggravated by inflammation-induced blunting of erythropoiesis. Allogenic transfusion is commonly used for treating acute perioperative anaemia, but it also increases the rate of morbidity and mortality in surgical and critically ill patients. Thus, overall concerns about adverse effects of both preoperative anaemia and allogeneic transfusion have prompted the review of transfusion practice and the search for safer and more biologically rational treatment options. In this paper, the role of intravenous iron therapy (mostly with iron sucrose and ferric carboxymaltose), as a safe and efficacious tool for treating anaemia and reducing transfusion requirements in surgical patients, as well as in other medical areas, has been reviewed. From the analysis of published data and despite the lack of high quality evidence in some areas, it seems fair to conclude that perioperative intravenous iron administration, with or without erythropoiesis stimulating agents, is safe, results in lower transfusion requirements and hastens recovery from postoperative anaemia. In addition, some studies have reported decreased rates of postoperative infection and mortality, and shorter length of hospital stay in surgical patients receiving intravenous iron.

Iron overload, an immunosuppression marker in HIV-infected patients.

Purpose: Iron overload (IO) has been associated with increased cardiovascular risk (CVR) and metabolic syndrome (MS) in the general population; both elevated CVR and MS are frequent in HIV- patients. Our aim was to analyze the prevalence of IO in a cohort of asymptomatic patients with HIV infection, and related factors. Methods: Cross-sectional study of a cohort of HIV outpatients in regular follow-up. Demographic, epidemiological, clinical, analytical and therapeutic data were collected. Patients completed a questionnaire about CVR factors and 10-year CV disease risk estimation (Framingham score), underwent a physical exam, and a fasting blood analysis. IO was defined as a plasma ferritin level higher than 200 m/L in women and 300 m/L in men. Results: 571 patients (446 men, 125 women), with a mean age of 43.2 years, sexual transmission of HIV in 68.5%, median CD4 count 474 cell/μL (IQR: 308-666), and 36.3% Aids cases 86.2% were on antiretroviral therapy (ART), and 74.8% of them had undetectable HIV viral load 14.6% met MS criteria, and mean CVR at 10 years was 6.67%. IO was detected in 11% of cases. Patients with IO were more immunosuppressed (CD4 count 369 vs 483/μL, p<0.0001), presented a higher prevalence of detectable HIV viral load (17.6% vs 8.9%; p<0.005), and of Aids cases (14.9% vs 8.7%; p<0.023), and lower plasma levels of cholesterol, HDLc and LDLc (154 vs 183, 34 vs 43, 93 vs 110 mg/dL, respectively; p<0.0001. In the multivariate analysis, the only related factor was CD4 count <350 cell/μL (OR 2.86, 95% CI 1.6-4.9; p<0.0001). IO was not associated with CVR nor with MS. Conclusions: IO is not uncommon in HIV patients, and it is only related with immunosuppression defined as CD4 count <350 cell/ mL, and in contrast to general population, it is not related with increased CVR nor with MS.

Iron metabolism, inflammation and anemia in critically ill patients. A cross-sectional study.

INTRODUCTION For critically patients, enteral immunonutrition results in notable reductions in infections and in length of stay in hospital, but not on mortality, raising the question as to whether this relate to the heterogeneous nature of critically ill patients or to the absence of the altered absorption of specific nutrients within the immunonutrient mix (e.g. iron). Immune-associated functional iron deficiency (FID) is not only one of the many causes or anaemia in the critically ill, but also a cause of inappropriate immune response, leading to a longer duration of episodes of systemic inflammatory response syndrome and poor outcome. OBJECTIVE This prospective cross-sectional study was undertaken to assess the prevalence of FID in critically ill patients during their stay in intensive care (ICU) in order to find the more appropriate population of patients that can benefit from iron therapy. METHOD Full blood cell counts, including reticulocytes (RETIC), serum iron (SI), transferring levels (TRF) and saturation (satTRF), serum TFR receptor (sTfR), ferritin (FRT) and C-reactive protein (CRP) were measured in venous blood samples from 131 random patients admitted to the ICU for at least 24 h (Length of ICU stay, LIS; min: 1 day; max: 38 days). RESULTS Anaemia (Hb < 12 g/dL) was present in 76% of the patients (Hb < 10 g/dL in 33%), hypoferremia (SI < 45 microg/dl) in 69%; satTRF < 20% in 53%; FRT < 100 ng/mL in 23%; sTfR > 2.3 mg/dL in 13%; and CRP > 0.5 mg/dL in 88%. Statistically significant correlations (r of Pearson; *p < 0.05, **p < 0.01) were obtained for serum CRP levels and WBC**, Hb*, TRF**, satTRF*, and FRT**. There was also a strong correlation between TRF and FRT (-0.650**), but not between FRT and satTRF or SI. LIS correlated with Hb*, CRP**, TRF*, satTRF* and FRT**. CONCLUSIONS A large proportion of critically ill patients admitted to the ICU presented the typical functional iron deficiency (FID) of acute inflammation-related anaemia (AIRA). This FID correlates with the inflammatory status and the length of stay at the ICU. However, 21% of the ICU patients with AIRA had an associated real iron deficiency (satTRF < 20; FRT < 100 and sTfR > 2.3). Since oral supplementation of iron seems to be ineffective, all these patients might benefit of iv iron therapy for correction of real or functional iron deficiency, which in turn might help to ameliorate their inflammatory status.