Effect Of Iron Depletion Research Articles

Iron stores, response to alpha-interferon therapy, and effects of iron depletion in chronic hepatitis C.

We studied 81 patients with chronic hepatitis C to investigate the relationship between iron and alpha-interferon response. Sixty-one patients (group A) were given alpha-interferon irrespective of iron status, whereas 20 (group B) with iron overload, were iron depleted before alpha-interferon therapy. In group A, 21 patients responded to alpha-interferon and 40 were non-responders. Increased iron indices were significantly more frequent in non-responders than responders. Multivariate analysis showed that among the independent variables evaluated, only gamma-GT and liver iron concentration predicted therapy outcome. After phlebotomy treatment, serum alanine aminotransferase fell significantly both in patients of group B (196 +/- 122 IU/l vs 82 +/- 37 IU/l, p < 10(-6)) and in 12 non-responders of group A (198 +/- 89 IU/l vs 107 +/- 81 IU/l, p < 10(-6)). In 16 iron depleted patients, eight from each group, subsequent treatment with alpha-interferon produced a response in only one patient. These results suggest that increased liver iron is a negative prognostic factor for alpha-interferon response in chronic hepatitis C. Iron depletion had a beneficial effect on serum alanine aminotransferase in all the patients treated, but did not improve the response to alpha-interferon.

Effects of Iron-Depletion on Cell Cycle Progression in Normal Human T Lymphocytes: Selective Inhibition of the Appearance of the Cyclin A-Associated Component of the p33cdk2 Kinase

Iron removal by the chelating-agent deferoxamine (DFO) arrests cell cycle progression of activated human T cells in late G1 phase, before the G1/S border. The effects of the drug on molecules that regulate progression through the cell cycle were defined. DFO (10 mumol/L) inhibited induction of transcription of the cdc2 gene, but had no effect on accumulation of cdk2, cdk4, or interleukin (IL)-2-transcripts. No detectable p34cdc2 protein accumulated, but synthesis of the p33cdk2 protein was begun. It accumulated to normal levels during the first 20 to 30 hours of incubation in the presence of DFO. Furthermore, p33cdk2 was activated as an H1 histone kinase. As active p33cdk2 primarily represents complexes of the p33 protein with cyclin E or cyclin A, the effects of DFO on these cyclins were examined. Although the induction of synthesis and early accumulation of cyclin E and cyclin E-associated kinase activity appeared normal, the appearance of cyclin A and cyclin A-associated kinase activity were inhibited by DFO. However, the production of cyclin A mRNA appeared to be normal in the presence of DFO. A major effect of DFO in blocking cell cycle progression may be mediated through inhibition of the appearance of cyclin A protein and, therefore, a major component of p33cdk2 activity. The results also indicate that the p33cdk2/cyclin E activity produced in the presence of DFO was not sufficient for completion of the G1 phase of the cell cycle.

Effect of Iron Depletion on Protein Profiles of Bilophila wadsworthia

Pathogenicity of microorganisms is a multifactorial phenomenon. Host environment plays a role in the development of the infectious process. The presence of key nutrients, such as iron, may be important for the expression of virulence factors. Iron is an essential component of a wide variety of biochemical processes in microorganisms, and its availability is of major importance in bacterial pathogenesis. In response to a low level of available iron in vivo, the creation of high-affinity iron-uptake systems and of a number of iron-regulated membrane proteins is induced. Although relationships between iron and virulence factors of aerobes have been better studied, a few such studies have been carried out with regard to anaerobes (mainly Bacteroides fragilis) [ 1, 2]. As discussed by Duerden [3], there is as yet no clear understanding of many of the virulence factors of anaerobes. Little is known about the mechanisms of iron uptake used by anaerobic bacteria, and nothing about those of Bilophila wadsworthia. The purpose of this work was to study the properties of this recently recognized anaerobe in relation to iron metabolism. B. wadsworthia is an anaerobic, gram-negative, asaccharolytic, bileresistant, and strongly catalase-positive bacillus [4]. This bacterium was first isolated from patients with gangrenous and perforative appendicitis. This study sought to determine whether B. wadsworthia expressed iron-regulated outer-membrane proteins (OMPs) in an iron-depleted environment and whether these proteins were immunogenic. Iron-free reagents and materials were used to prepare the ironfree medium. In this work, all glassware was deferrated. Chemicals used to prepare the medium were of highest purity. The medium was one previously described, to which oxgall (2%) and pyruvate (10 mM) were added [5]. The medium components were deferrated with Chelex-100 resin (Bio-Rad Laboratories, Hercules, CA), except for MgSO4, amino acids, and vitamins. Medium without iron contained <0.04 tM Fe+++. Iron was added to a concentration of 100 iM in preparation of the ironcontaining medium. The final pH was adjusted to 7.0-7.1. Four strains of B. wadsworthia originally isolated from appendicitis case specimens were studied, including the reference strain ATCC 49260. They were all incubated for 14 days in 200-mL flask cultures (in media with and without iron) at 37?C in an anaerobic atmosphere. Detection of siderophores in culture supernatants was attempted by means of the method described by Schwyn and Neilands [6]. Preparation of the outer membrane was accomplished according to the method described by Sprott et al. [7]. Cells harvested by centrifugation were disrupted ultrasonically. Unbroken cells were discarded by centrifugation. The supernatant was treated with 2% Triton

Iron and chronic hepatitis C: Influence of iron stores on α-interferon response and effect of iron depletion

Iron and chronic hepatitis C: Influence of iron stores on α-interferon response and effect of iron depletion

Effects of iron depletion and sab-inhibitory concentrations of antibiotics on siderophore production by Staphylococcus aureus

The effect of various sub-MICs of oxacillin and amikacin, alone or in combination, on siderophore production by Staphylococcus aureus growing under iron-depleted conditions was evaluated. Siderophore production varied greatly from strain to strain, ranging from 3.0 to 383.4 microM of Desferal equivalents. Siderophore production by some S. aureus strains was reduced significantly (P less than 0.001) under some sets of conditions. However, siderophore excretion in cultures with amikacin was sometimes equal to or greater than control cultures. Thus, at some sub-MICs, the bacteria tested were able to increase siderophore production under metabolic stress. This phenomenon may be a secondary effect of the antibiotics upon intermediary metabolism as a consequence of inhibition of peptidoglycan or protein synthesis. Alternatively the antibiotics may decrease the cellular association of siderophore molecules.

Effect of iron depletion on cell-wall antigens of Candida albicans.

Cell walls were isolated from stationary-phase cultures of Candida albicans grown at 25 degrees C or 37 degrees C, in iron-depleted and iron-sufficient conditions. Proteins solubilised from cell-wall fractions were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Approximately 40 protein bands were detected by Coomassie blue staining in all wall extracts, regardless of temperature or other growth condition. Sera from patients with oral or systemic candidosis, from whom the isolates were obtained, and pooled normal human serum were examined for the presence of IgG and IgM antibodies to cell-wall proteins by Western blotting. Patient sera recognised more antigens than pooled normal human serum. In particular, an antigen of 44 kda was detected by IgG antibodies in the sera of patients and two antigens of 41 and 14 kda were detected by their IgM antibodies when the sera were used as probes against walls from iron-depleted cells, but not from iron-sufficient cells, grown at 25 degrees C. Two antigens of 45 and 40 kda were detected by IgM antibodies in the sera of patients tested against walls from iron-depleted but not from iron-sufficient cells grown at 37 degrees C. IgG antibodies did not distinguish between these wall preparations from cells grown at 37 degrees C. These results suggest that the specific cell-wall proteins induced during growth in iron-depleted conditions, as well as other proteins, were immunogenic and were recognised by the patients' antibodies.