Iron deficiency anemia in pregnancy: Comparison of total dose infusion using iron dextran complex to oral iron therapy.
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A combined preparation, biofer, was studied, defining its clinical and pharmacological capacity. Featuring in its composition are: normal bovine gammaglobulin, 8.0 g; ferridextran (dextrofer-100), 32 cm2 (= 3.2 g Fe); cuprum sulfuricum, 0.32 g (= 0.08 Cu); Co chloride, 0.18 g (= 0.08 Co); cyancobalamin, 0.0032 g; and protein hydrolysate up to 100 cm3, at pH = 7.0-7.2. The local and total tolerance of animals for biofer was studied along with the acute toxicity, absorption, and retention in the body of test animals and calves as well as the antianemic action in albino mice and calves. It was found that at 4 degrees C to 8 degrees C the shelf life of biofer was 2 years. Its LD50 at subcutaneous injection to albino rats was 11.7 cm3/kg body mass. At the rate of 0.6 cm3/kg (i/m) rabbits did not manifest local and total intolerance; at 1.8 cm3/kg there was no local inflammation, however, a transient drop of appetite was seen; at 3 cm3/kg rabbits manifested intoxication with exitus. At i/m introduction to rabbits and calves biofer was more slowly absorbed than dextrofer-100. The liver and spleen of animals injected with biofer showed higher values for copper. In i/m application to anemic albino rats biofer showed a better antianemic effect than dextrofer-100. In calves it activated to a better extent both erythropoiesis and leukopoiesis.
Rats and guinea pigs developed pronounced erythrocytosis at one to four months after unilateral intrarenal (ir) injection of nickel subsulfide (Ni3S2). For example, at two months after ir administration of Ni3S2 (5 mg) to rats, blood hematocrit values averaged 70 +/- 3 percent (p less than 0.001 vs. 48 4/- 2 in controls); at two months after ir administration of Ni3S2 (20 mg) to guniea pigs, blood hematocrit values averaged 67 +/- 6 percent (p less than 0.001 vs. 49 +/- 1 percent in controls). Hamsters and gerbils did not develop erythrocytosis after ir injection of Ni3S2 (5 mg/animal). Administration of Ni3S2 to rats by intrasplenic injection did not increase blood hematocrit; splenectomy did not prevent erythrocytosis in rats that received ir injection of Ni3S2. Erythrocytosis in rats was completely blocked by excision of the Ni3S2-injected kidney but was unaffected by excision of the non-injected kidney. Partial inhibition of Ni3S2-induced erythrocytosis in rats occurred after simultaneous ir injection of Mn, Cu, or Al dusts, benzo(a)pyrene, or subcutaneous (sc) infusion of sodium diethyldithiocarbamate. Erythrocytosis induced by ir injection of Ni3S2 was augmented by ir injection of Cr dust or intramuscular (im) administration of iron-dextran. Erythrocytosis occurred in rats after ir implantation of Ni3S2 within semi-permeable cellulose tubules, indicating that phagocytosis of Ni3S2 particles is unnecessary for erythropoietic stimulation. Erythropoietin (Ep) activity in rat serum increased sixfold at two weeks after ir injection of Ni3S2 (p less than 0.001 vs. controls), but Ep activity in pooled extracts of Ni3S2-treated rat kidneys did not increase significantly. This study identifies several factors that influence erythropoietic stimulation by Ni3S2, and furnishes salient information concerning the pathogenesis of Ni3S2-induced erythrocytosis.
Information on compatibility of nutrients and drugs with parenteral nutrient (PN) solutions is reviewed and evaluated. Precipitation of calcium phosphate when calcium and phosphate salts are added can be affected by pH, amino acid concentration, amino acid product, temperature, sequence of additives, specific salt used, and time since admixture; precipitate formation can occur gradually over 24 hours. Insulin is chemically stable in PN solutions, but adsorption to the infusion system can cause decreased availability. Poor delivery of vitamin A via PN solutions has been reported. The sodium bisulfite content of amino acid injections may cause degradation of thiamine, but studies simulating clinical use are needed. Folic acid stability in PN solutions has been demonstrated, and phytonadione appears to be stable. Drug administration via PN solutions may be advantageous when fluid intake is restricted or peripheral vein access is limited and in home PN therapy. Summarized are results of studies involving heparin, cimetidine hydrochloride, aminophylline, amphotericin B, iron dextran, hydrochloric acid, corticosteroids, narcotics, metoclopramide, digoxin, and fluorouracil. Many antibiotics are probably stable, especially when administered by co-infusion rather than by direct mixture in the PN solution container. When lipids are mixed in the same container with amino acid-dextrose solutions, compatibility and stability of electrolytes, vitamins, and trace elements must be reassessed. Practical research is needed, and availability of additives should be studied in specific patient populations and for specific PN formulations. Valid conclusions are dependent on careful study design.
To determine whether supplemental iron (Fe) administration to newborn pigs reared in concrete pens not only prevents anemia, but renders the pigs more susceptible to Escherichia coli-induced diarrheal disease, pigs were given a large or a small dose of Fe IM or orally before or after challenge exposure with E coli. The controls were challenge-exposed pigs not given Fe and pigs not challenge exposed (Fe-treated and nontreated groups). Although the mortality of the pigs challenge exposed with E coli and administered a large oral dose of Fe shortly after birth was greater than that of the challenge-exposed pigs given no Fe, differences in mortality were not noted between any of the groups tested when the Fe was injected IM. The Fe-treated survivors had severe diarrhea (oral Fe administration) or mild diarrhea (IM Fe administration) for longer periods than did the nontreated survivors. All challenge-exposed pigs treated with a large dose of Fe gained less weight than the nontreated pigs during the diarrheal period and for several days thereafter. Beyond this time period, the weight gain of the Fe-treated pigs was substantially greater than that of their nontreated littermates; the weight gain of the pigs given a small dose of Fe was intermediate. Hemoglobin and hematocrit values of the pigs shortly after birth and weekly thereafter revealed that within 2 weeks, both sets of values from the pigs treated with a large dose of Fe were within acceptable laboratory limits and substantially greater than the values obtained for the nontreated pigs, which were severely anemic.
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The virulence-enhancing interaction of baker's yeast and different iron preparations (ferric ammonium citrate and iron dextran) was tested in mice challenged with Salmonella typhi and Vibrio cholerae (Inaba and Ogawa) strains. The virulence-enhancing effect of the yeast + iron combination increased significantly as compared to that of either yeast or iron alone. Toxicity assays of the single and combined baker's yeast and iron preparations by the mouse weight gain test have shown that the combinations are considerably more toxic than either single agent, probably owing to the presence of yeast. Examination of the single and combined preparations for influence on body temperature of mice has revealed a general hypothermic action, which was strongest in the combinations, owing again to the yeast. Theoretical considerations on the underlying mechanism of the virulence-enhancing effect have supported the hypothesis that the effect might be associated with the strong hypothermic action produced by baker's yeast and baker's yeast + iron combinations, in as much as hypothermia increases the production of siderophores which ensure the acquisition of iron indispensable for bacterial growth.
Studies were carried out with the iron dextran preparation-100 and vitamin B12 at 100 gamma, applied to 80 pigs of 10 sows of the Camborough hybrid on two swine breeding complexes of different raising technologies. The pigs were divided into 4 groups of animals each. The Ist group was treated with dextrofer, the IInd--with dextrofer + vit. B12, the IIIrd--with vit. B12, and the IVth was left as control. The hemoglobin rate, erythrocyte, count, iron, and live-weight were followed up. It was found that the hemoglobin values at birth with the Ist group on the two complexes were within the range of 8.89 +/- 1.3 to 10.24 +/- 1.36 g/100 cm-3, while with the IInd group they were higher at weaning--11.8 +/- 0.48 g/100 cm3. The IIIrd and IVth group showed very low values at weaning--7.47 +/- 0.46 g/100 cm3 and 6.35 +/- 1.05 cm3. The twofold injection at a 7-day interval did not alter essentially the hemoglobin values. The pigs of the IInd group, injected twice, had much higher values of the erythrocyte count--7.58 +/- 0.09 T/L. The liveweight of the pigs of all four groups from the 7th day on ranged from 2.15 to 2.4 +/- 0.2 kg. Following a twofold injection with the pigs of the IInd group it rose to 6.1 +/- 0.14 kg. Similar proved the data concerning the iron in the blood plasma. Its values were highest with the pigs of the IInd group which were injected twice--38.86 +/- 1.7 mol/l.
Comparative investigations were carried out on the absorption, antianemic action, and growth effect with newborn pigs with FB-82 and dextrofer-100 (an iron dextran complex with 100 mg Fe3+ per cm3) injected i/m. The FB-82 is a combined preparation of 3500000 IU Tylosine tartrate, 0.008 g cyanocobalamin, 0.5 g pyridoxine hydrochloride, 0.1 g tartaric acid, and iron dextran up to 100 cm3 (= 100 mg Fe3+/cm3). Dextrofer-100 enriched with 50 mg Zn, 0.5 mg Co, 200 micrograms cyanocobalamin, and 100 mg pyridoxine hydrochloride for 100 cm3 under the compound name of fericin was also used to compare the anti-anemic effect of FB-82 and dextrofer-100. It was found that FB-82 applied to newborn pigs in a single dose of 2 cm3, i/m, was well absorbed; it developed high concentrations of tylosine in the plasma, and its sideremia and antianemic action were similar to those induced by an equivalent (with regard to iron) amount of dextrofer-100, whereas the result concerning the hematocrit value was better. Compared to dextrofer-100 the FB-82 preparation have better protection to pigs (lowered the mortality rate) and induced better development of the animals. Fericin did not differ essentially from FB-82 in terms of its effect on the red blood picture, however, the percent of protected pigs was lower.
Comparative studies were carried out with dextrofer-100 with B12 and dextrofer-100 in terms of acute toxicity (albino mice), absorption (rabbits, pigs, and lambs), deposition of iron in the liver and spleen (rabbits, pigs, and lambs) and antianemic action (pigs and lambs). It was found that LD50 of dextrofer-100 with B12 at i/v introduction into 18-20-gram albino mice was 1750 mg Fe3+/kg body mass; with regard to toxicity it was shown to correspond to the British Veterinary Code. The toxicity of dextrofer-100, studied by the same test, was practically undeterminable. By the level of sideremia dextrofer-100 with B12 did not differ essentially from dextrofer-100 and was said to belong to preparations with rapid absorption. It was most rapidly absorbed in pigs, rabbits and lambs following next. It supplied enough iron to the reticuloendothelial organs--in pigs it was (on a percent basis) highest in the liver, and in lambs--in the spleen. In pigs on the 10th day following treatment with dextrofer-100 with B12 the liver was shown to have vitamin B12 5 times as much. By its antianemic effect at i/m application to newborn pigs and lambs dextrofer-100 with B12 did not differ essentially from dextrofer-100 (its action was negligibly broader), however, it was beneficial to the growth of pigs.
Iron injection in beef calves during the 1st week after birth increased their PCV, hemoglobin (Hb) concentrations, mean corpuscular volumes (MCV), and mean corpuscular Hb (MCH). These increases persisted between weeks 2 and 12. The RBC count during the 1st week after birth had a positive correlation with the PCV and Hb concentrations and a negative correlation with the MCV and MCH. There was a positive correlation between the serum iron concentration of the dams and their MCV and mean corpuscular Hb concentration. There was also a positive correlation between the MCV and MCH of the dam and their calf's MCH. Seemingly, iron injection did not affect weight gain during the first 18 weeks of life.