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Effect of repeated injections of iron dextran on the haematological, serological and pathological changes in experimental avian tuberculosis.

Eight intramuscular injections of 200 mg/kg of iron (DFe), given as iron dextran twice weekly in the week before and the three weeks after intravenous infection with about 10(7.5) colony-forming units of Mycobacterium avium, significantly prolonged (by about 11 days) the mean 'time-to-death' of immature male fowl (Gallus domesticus) compared with corresponding regimes using dextran (Dx) only or saline, When a proportion of the birds were examined 21 days after infection many of the abnormalities associated with the disease, including a marked hypochromic anaemia, were less severe in DFe-treated than in the Dx- or saline-treated chicks and there were about 10- to 85-fold fewer viable tubercle bacilli in the liver and spleen of the DFe-treated birds.

Animals↗

Enhancement of survival in acute experimental fowl typhoid in chicks by the administration of iron dextran.

Chicks aged 15 days were infected orally with 10(6-4) living Salmonella gallinarum. Iron from iron dextran or ferric ammonium citrate (DFe and CFe respectively), in doses of 2-0 or 0-4 mg/kg given intramuscularly at the time of infection, had no effect on subsequent mortality compared with infected controls. Increasing the amount of CFe to the maximum (20 mg/kg) that was non-toxic intramuscularly was also ineffective but when the dose of DFe was increased to 20 or 50 mg/kg the survival rate rose sharply. If given at other times in relation to the time of infection, or more frequently, 50 mg/kg or more of DFe was less active. The increased survival rate among infected chicks given 50 mg/kg of DFe at the time of infection was accompanied by decreases in the severity of the morbid changes in the disease, and by reductions of between c 10- to 100-fold in the numbers of viable S gallinarum in the liver, spleen or blood at the height of the acute infection. DFe (50 mg/kg) given at the time of infection also eliminated the difference in the survival rate noted previously between infected chicks fed respectively with diets containing fish or meat meal as the sole source of supplementary protein.

Anemia↗

Cellular distribution of orally and intramuscularly administered iron dextran in newborn piglets.

Histochemical studies were performed on tissues from piglets of different ages treated orally with iron dextran soon after birth. The mucosal cells in the distal region of the small intestine were heavily laden with stainable iron granules during the first three days after the iron administration. The absorptive epithelial cells are desquamated within seven to ten days after birth. Consequently, the number of iron granules gradually diminishes during the first seven days after treatment and no iron granules are demonstrated 12 days after the administration of iron. The iron dextran complex is pinocytosed in newborn piglets and then transported via the lymphatic system. Thus the sinusoidal lining cells of the body and mesenteric lymph nodes are already heavily laden with iron granules 24 hours after oral treatment. This iron store is released only slowing during the first weeks of life. Great amounts of iron granules are demonstrated in the liver and spleen macrophages during the first week after the administration of iron. Due to the rapid utilization of iron in growing piglets these iron stores diminish sharply during the weeks following birth. The distribution of stainable iron in the lymph nodes, liver and spleen seven days after intramuscular injection of iron dextran in newborn piglets was comparable to that for oral administration at that stage of the experiment.

Administration, Oral↗

Endotoxin determination in viscous opaque solutions of iron dextran by Limulus amebocyte lysate.

LAL would not form a clot when mixed with a viscous, opaque parenteral preparation of iron dextran spiked with endotoxin. However, recoverable precipitate could be obtained by diluting the LAL iron dextran mixture with PBS and centrifuging. Although the pellet so formed was red colored the protein present could be quantitated by dissolving it in a Coomassie Blue stain solution. The very rapid change in color from reddish black to deep blue was measured quantitatively in a spectrophotometer and was sigmoidally related to the amount of endotoxin used to spike the iron dextran. This method is suggested to be generally useful to measure quantitatively endotoxin concentrations too low to form a clot with LAL but high enough to precipitate recoverable protein from LAL.

Animals↗

Intravenous iron-dextran therapy in the treatment of anemia occurring in surgical, gynecologic and obstetric patients.

An infusion of iron-dextran diluted in 1,000 milliliters of physiologic saline solution was given to 51 patients. The average hemoglobin response was 1.9 grams per deciliter per week. Mean corpuscular volume, mean corpuscular hemoglobin concentration and mean corpuscular hemoglobin deficits also were corrected. There were no allergic reactions. This is an extremely reliable and safe method of replenishing depleted iron in patients.

Adolescent↗

Thalamic afferents from the brain stem. An experimental study using retrograde single and double labelling with HRP and iron-dextran in the rat. II. Nucleus laterodorsalis and subnucleus compactus nuclei pedunculo-pontini.

The reticulo-thalamic projection arising from the ncl. latero-dorsalis and from the subncl. compactus nuclei pedunculo-pontini was studied in single and double experiments using 51 injections of HRP and/or iron-dextran. The ncl. latero-dorsalis projects to the midline nuclei, to the ncl. mediodorsalis and to the ncl. ventralis lateralis, and, together with the subncl. compactus, also to the anterior, intralaminar nuclei, to the ncl. ventralis basalis and ncll. posteriores. Part of the substantia grisea centralis pontis adjoining the oral pole of the ncl. latero-dorsalis sends out fibres throughout the region of the above listed nuclei while projecting only scantily to the anterior nuclei and to the ventrobasal complex. The projection from the ncl. laterodorsalis has a major contralateral component (about one third of the labelled cells) whereas the contralateral component arising from the subncl. compactus is very scanty. We found no topographic arrangement in the projection (though there were signs of a crude mediolateral organization). The projection, mainly from the ncl. latero-dorsalis, shows relatively dense collateralization (double-labelled cells): ipsi- as well as contralaterally to the intralaminar nuclei, or collaterals to the ipsilateral intralaminary nuclei and, at the same time, to the contralateral ncl. mediodorsalis. A similar, albeit smaller collateralization, was also seen in the ncl. pedunculo-pontinus, its subncl. compactus: ipsilateral collateralization between the anterior and intralaminar nuclei or between the anterior and posterior intralaminar nuclei of the ipsilateral side.

Animals↗

The effect of ligands on the uptake of iron by cells in culture.

Uptake of iron by a mammalian epithelial cell line (CNCM I-221) was shown to be dependent on the nature of the iron complex. Iron uptake was demonstrated by cytochemical staining and determination of redox-reactive iron in cell lysates. Three classes of ligands were investigated: (i) low molecular weight hydrophilic compounds, represented by ethylenediamine-tetraacetic acid (EDTA) and other charged ligands such as adenosine phosphates (ATP, ADP, AMP) and diethylenetriaminepentaacetic acid (DTPA), (2) low-molecular weight lipophilic ligands such as 8-hydroxyquinoline (8-HQ) and (3) a high molecular mass ligand, dextran. Iron complexed to 8-HQ accumulated intracellularly, the uptake rate of iron being 4.16 fmoles cell-1 h-1 of exposure at 37 degrees C or 3.86 fmoles cell-1 h-1 at 4 degrees C. Iron-dextran was endocytosed and retained in phagosomes. The uptake rate of iron following exposure to iron dextrans was found to be 5.6 fmoles cell-1 h-1 of exposure at 37 degrees C. In contrast to iron/8-HQ, uptake of iron dextran by cells was inhibited at 4 degrees C. Iron complexed to low molecular weight hydrophilic ligands was not taken up by cells. Cytotoxicity was measured by reduction of plating efficiency or tritiated thymidine incorporation. These tests showed that toxic effects of added iron were demonstrable only in cells exposed to the complex with 8-HQ.

Adenosine Diphosphate↗