The detrimental effects of iron on the joint: a comparison between haemochromatosis and haemophilia.

Joint damage due to (recurrent) joint bleeding in haemophilia causes major morbidity. Although the exact pathogenesis has not been fully elucidated, a central role for iron is hypothesised. Likewise, in hereditary haemochromatosis joint destruction is caused by iron overload.

The relation between body iron stores and adipose tissue function in patients with manifest vascular disease.

Background: We investigated whether plasma ferritin levels through the pro-inflammatory effects of free iron are associated with adipose tissue dysfunction in a relevant population of patients with manifest vascular disease who would potentially benefit the most from further aetiological insights.

Materials And Methods: In a cohort of 355 patients with vascular diseases, the association between plasma ferritin and adiponectin levels was quantified using linear regression analysis. Interleukin-6 and adiponectin levels were measured in medium from pre-adipocytes and adipocytes after incubation with increasing concentrations of Fe(III)-citrate and after co-incubation with iron chelators or radical scavengers.

Identification and expression of iron regulators in human synovium: evidence for upregulation in haemophilic arthropathy compared to rheumatoid arthritis, osteoarthritis, and healthy controls.

Recurrent joint bleeding is the most common manifestation of severe haemophilia resulting in haemophilic arthropathy (HA). Iron plays a central role in the pathogenesis of the two main features of HA: synovitis and cartilage destruction. The aim of this study was to investigate the synovial presence of the iron regulator proteins ferroportin (FPN), hepcidin, haemoglobin scavenger receptor CD163 (CD163), feline leukaemia virus subgroup C (FLVCR), and heme carrier protein 1 (HCP-1).

Cyproterone acetate- and ethinyloestradiol-containing oral contraceptive as a risk factor for upper extremity deep venous thrombosis-a case report.

Deep venous thrombosis of the upper extremity (UEDVT) is a rare variety of deep venous thrombosis. Compared to lower-extremity deep venous thrombosis, less is known about the risk factors for primary UEDVT. We report on a 27-year-old woman with UEDVT extending from the jugular and subclavian veins to the elbow.

Intracellular labile iron promotes firm adhesion of human monocytes to endothelium under flow and transendothelial migration: Iron and monocyte-endothelial cell interactions.

Monocyte infiltration across the endothelium is part of the innate immune response, however it may contribute to severity of chronic conditions. We have investigated the effects of iron on the cytokine-mediated recruitment of monocytes to the endothelium, using a physiological flow model and a monocyte transendothelial migration model. Under flow, iron loading to endothelial cells promoted an increased number of tumor necrosis factor-alpha-mediated firm arrest of human monocytes.

Iron enhances endothelial cell activation in response to Cytomegalovirus or Chlamydia pneumoniae infection.

Background: Chronic inflammation has been implemented in the pathogenesis of inflammatory diseases like atherosclerosis. Several pathogens like Chlamydia pneumoniae (Cp) and cytomegalovirus (CMV) result in inflammation and thereby are potentially artherogenic. Those infections could trigger endothelial activation, the starting point of the atherogenic inflammatory cascade.

Endothelial activation and induction of monocyte adhesion by nontransferrin-bound iron present in human sera.

Nontransferrin-bound iron (NTBI) has been detected in iron overload diseases. This form of iron may exert pro-oxidant effects and modulate cellular function and inflammatory response. The present study has aimed to investigate the effects of serum NTBI on monocyte adherence to endothelium.

Bleomycin has antiviral properties against drug-resistant HIV strains and sensitises virus to currently used antiviral agents.

In this study we performed phenotypic assays to assess involvement of the cancer chemotherapeutic agent bleomycin (BLM) in replication inhibition of mutant HIV-1 viral strains. Three clinically relevant mutant HIV variants, including one containing the Q151M mutation conferring multinucleoside resistance, were equally as sensitive to BLM as the wild-type HXB2 strain. Long-term incubation of BLM with a wild-type HIV(Ba-L) strain did not alter the sensitivity of the strain to BLM (IC(50) of BLM 0.

Effects of rosuvastatin on postprandial leukocytes in mildly hyperlipidemic patients with premature coronary sclerosis.

We investigated whether pro-inflammatory aspects of the postprandial phase can be modulated by rosuvastatin in premature coronary artery disease (CAD) patients. Herefore standardized 8 h oral fat loading tests were performed off-treatment and after rosuvastatin 40 mg/d in 20 male CAD patients (50 +/- 4 years). The expression of leukocyte activation markers CD11a, CD11b, CD62L and CD66b was studied using flowcytometry.

Intracellular labile iron modulates adhesion of human monocytes to human endothelial cells.

Objective: Elevated iron stores and high plasma iron concentration have been linked to an increased risk of atherosclerosis. Iron may thereby affect the interaction of monocytes to endothelium, an initial event in the formation of atherosclerotic plaques.

Methods And Results: Addition of 10 mumol/L non-transferrin-bound iron to the incubation medium caused a 2-fold increase in monocyte adhesion to human umbilical vein endothelial cells (HUVECs).

Mechanism of inhibition of the human immunodeficiency virus type 1 by the oxygen radical generating agent bleomycin.

Alternative targets of attack of the human immunodeficiency virus (HIV) are necessary in light of infection persistence due to onset of resistance after conventional reverse transcriptase and protease inhibitor therapy. We have recently shown that the cancer chemotherapeutic agent bleomycin (BLM) dose-dependently inhibits HIV-1 replication. The mechanism of this viral inhibition in vitro was investigated.

Postprandial leukocyte increase in healthy subjects.

Atherosclerosis is an inflammatory disorder involving leukocytes and lipids. To study the relationship between leukocytes and lipids in vivo, leukocyte changes were determined in 14 healthy males (age, 23 +/- 3 years; body mass index [BMI], 21.9 +/- 1.

Human immunodeficiency virus type 1 replication inhibition by the bidentate iron chelators CP502 and CP511 is caused by proliferation inhibition and the onset of apoptosis.

Background: The iron chelators deferoxamine (DF) and deferiprone (CP20) have been shown to inhibit human immunodeficiency virus type 1 (HIV-1) replication in human peripheral blood lymphocytes (PBL). The orally active bidentate chelators CP502 and CP511, which also belong to the 3-hydroxypyridin-4-one family, but with higher affinities for iron than CP20, were monitored for their antiviral properties by checking for p24 antigen production and nuclear factor (NF)-kappaB activation, and their ability to induce apoptosis.

Materials And Methods: Human PBLs were isolated from HIV-1 seronegative donors and subsequently infected with HIV-1(Ba-L) for 2 h.

Iron chelation and hydroxyl radical scavenging reduce the inflammatory response of endothelial cells after infection with Chlamydia pneumoniae or influenza A.

Background: Chronic low-grade inflammation is associated with increased risk of vascular diseases. The source of inflammation is unknown but may well be chronic and/or repetitive infections with microorganisms. Direct infection of endothelial cells (ECs) may also be a starting point for atherogenesis by initiating endothelial procoagulant activity, increased monocyte adherence and increased cytokine production.

The chemotherapeutic agent bleomycin in a two-drug combination with zidovudine, ritonavir or indinavir synergistically inhibits HIV Type-1 replication in peripheral blood lymphocytes.

It has been suggested that the combination of cancer chemotherapy with antiviral therapy is helpful for the containment of lymphomas in HIV-infected patients. Since we have recently shown that the nucleic acid binding chemotherapeutic agent bleomycin in itself has antiviral properties, we looked to see if there was any possible synergy with current anti-HIV agents. Combinations of zidovudine, indinavir or ritonavir with bleomycin, synergistically inhibited HIV-1(AT) replication in stimulated peripheral blood lymphocytes (combination index at 50% virus inhibition was 0.

Chemiluminescence in inflammatory bowel disease patients: a parameter of inflammatory activity.

Background: Reactive oxygen species (ROS) are produced in excess in the inflamed mucosa and peripheral blood of patients with inflammatory bowel disease. These species have emerged as a common pathway of tissue injury in a wide variety of inflammatory and other disease processes. The present study was conducted to assess ROS production and to correlate this with parameters of inflammatory activity.

Glutathione and alpha-lipoate in diabetic rats: nerve function, blood flow and oxidative state.

Background: Increased oxidative stress is considered to be a causal factor in the development of diabetic complications, among which peripheral neuropathy. The pathophysiology of nerve dysfunction in diabetes has been explained both by reduced endoneurial microcirculation and alterations in endoneurial metabolism. It is unclear whether antioxidants primarily improve nerve blood flow or normalise systemic or endoneurial oxidative metabolism.

Effect of corticosteroids on nuclear factor-kappaB activation and hemodynamics in late septic shock.

Objective: To describe the underlying pathophysiologic mechanisms of the effect of corticosteroids in a patient with late septic shock.

Design: Case report.

Setting: The medical intensive care unit at University Medical Center Utrecht.

Iron and inflammatory bowel disease.

Both anaemia of iron deficiency and anaemia of chronic disease are frequently encountered in inflammatory bowel disease. Anaemia of iron deficiency is mostly due to inadequate intake or loss of iron. Anaemia of chronic disease probably results from decreased erythropoiesis, secondary to increased levels of proinflammatory cytokines, reactive oxygen metabolites and nitric oxide.

Anti-HIV effect of iron chelators: different mechanisms involved.

Background: Drugs for the treatment of AIDS have been directed to specific events in the human immunodeficiency virus (HIV-1) life cycle, aimed to stop viral replication by inhibition of reverse transcriptase or protease activity. Studies showing that oxidative stress and iron may be important in the activation of HIV-1 have focused attention on the potential therapeutic use of iron chelators.

Objectives: The goal of this review is to describe several possibilities as to how iron is involved in the replication of HIV and how iron chelation may interfere in this process.