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[Application to the study of connections in the CNS of the retrograde axonal transport of an iron-dextran complex].

The retrograde axonal transport of an iron-dextran complex was observed in neurons of the substantia nigra and of the intralaminar nuclei of the thalamus, after previous injection into the striatum. The histochemical demonstration of iron is simple and rapid, and can be combined with that of horseradish peroxidase, under precise conditions in the sequence of reactions. The iron-dextran complex revealed to be a valuable material for neuronal connectivity studies in the central nervous system.

Animals

Double labelling of blanched neurons in the central nervous system of the rat by retrograde axonal transport of horseradish peroxidase and iron dextran complex.

The retrograde axonal transport of an iron-dextran complex leads to a labelling of neural cell bodies in the central nervous system (CNS) of the rat. This tracer and horseradish peroxidase (HRP) can both be demonstrated histochemically in same cell bodies of intralaminar thalamic neurons in the central lateral nucleus, after injection of iron-dextran in the striatum and injection of HRP in the motor cortex. This is made possible by processing the sections first for HRP and then for ferric ions by Perl's reaction. This method allows an accurate demonstration of divergent axonal projections and is compatible with cytoarchitectonic studies on the same sections.

Animals

Evolution of cytoplasmic fibrillar bodies induced by lead in rat and mouse kidneys.

Characteristic cytoplasmic and intranuclear fibrillar bodies were produced, within 24 hours, in epithelial cells of the proximal convoluted renal tubules of rats and mice by injecting a single dose of lead acetate either intraperitoneally (100 mug Pb/g) or into the heart (10 mug Pb/g). The frequency of cytoplasmic fibrillar bodies (CFB) rose during the first 4 days following injection of lead and diminished thereafter. Ten days after intracardiac injection of lead no CFB were found; 10 days after intraperitoneal injection, they were still present, though probably in diminished number. Disappearance of CFB may be related to autophagocytosis. Intranuclear fibrillar bodies did not disappear, perhaps because nuclei lack a lysosomal apparatus. Within the first 3 days after injection of lead, clusters or paracrystalline arrays of ferritin molecules were frequently situated in the immediate vicinity of CRB or abutted against CFB; after the third day, little or no ferritin was found near CFB. Intramuscular injection of iron-dextran complex (50 mg Fe/ml) 24 hours prior to intraperitoneal administration of lead did not increase incidence or size of ferritin clusters in the vicinity of CFB in rats. The presence of ferritin near CFB may have been an indirect consequence of inhibition, by lead, of synthesis of heme prosthetic groups.

Animals

[Experimental study of a combination preparation of a ferrodextran complex, gamma-globulin, trace elements and vitamins].

A combined preparation was produced, containing the Bulgarian ferrodextran complex, edema-disease gamma-globulin, microelements (Co, Mn, Cu), and vitamins (B1, B6, PP), pro uso veterinario. It was found that the product (B-50), kept under ordinary conditions in the course of one year, does not change its physicochemical properties and is not distinguished substantially by toxicity (Fe3+/kg liveweight) from the initial ferrodextran complex, but is resorbed more slowly following its muscular application to rabbits. B50 combines the properties of the fast-resorbing ferrodextran preparations giving slight local coloration with those of preparations having antianemic, growth-stimulating, and resistance enhancing effects.

Anemia, Hypochromic

Iron deficiency anaemia in a rural area in Nigeria. Evaluation of diagnosis and treatment with imferon.

In 32 pregnant women with packed cell volume (PCV) of 30% or less (Hb 10 g/100 ml or below), iron depletion was present in 87.5% and megaloblastic changes in 84.5% as judged by bone marrow findings. Parenteral iron gave statistically significant rise in the PCV (p less than 0.001) in those who received iron therapy compared with control group with no iron therapy. Routine iron administration during pregnancy is therefore indicated in this population.

Anemia, Hypochromic

Systemic reactions with total dose infusion of iron dextran complex in obstetric patients.

Iron dextran complex (Imferon) total dose infusion (TDI) was used to treat iron deficiency anemia in 310 obstetric patients. Systemic reactions were reported for 13.5% of the group. Most (90.5%) of the severe reactions occurred during the test dose, while 66.6% recorded during or after TDI were mild. Antihistamine premedication included administration of promethazine hydrochloride to 104 patients and intramuscular and intravenous drip chlorpheniramine hydrogen maleate to 206 patients. Total systemic reactions were statistically greater with intramuscular promethazine hydrochloride than with intramuscular and intravenous chlorpheniramine maleate (p less than 0.001). On the other hand, the rates of severe reactions and reactions during the test dose were similar for both antihistamine schedules (p greater than 0.05). The incidence of all systemic reactions was the same for pregnant and postnatal women (p greater than 0.05), but severe reactions were more frequent among pregnant than postnatal patients (p less than 0.001). There were no fatalities.

Anemia, Hypochromic

Uptake and retrograde axonal transport of various exogenous macromolecules in normal and crushed hypoglossal nerves.

Macromolecular tracers were injected into the tongue or around a crush in mouse hypoglossal nerves. At various times thereafter, the tracers were histochemically localized on the basis of peroxidase activity. The distribution of reaction product was then examined using light microscopy in order to study the influence of molecular charge and size on uptake and retrograde axonal transport from the periphery or from the crushed axon. Of various proteins with peroxidase activity, horseradish peroxidase and cytochrome-c showed the greatest penetration into axons proximal to the crush. Following injection into the tongue, intra-axonal cytochrome-c was detectable in some of the peripheral branches but not any of the other proteins. Retrograde transport to the nerve cell bodies was demonstrated for horseradish peroxidase and cytochrome-c, both from the tongue and from the axonal crush but not for microperoxidase, myoglobin, hemoglobin, lactoperoxidase and catalase. The number of neuronal cell bodies having detectable reaction product was higher for peroxidase-injected than for cytochrome-c-injected animals. Ferritin and iron-dextran (Imferon) also accumulated in hypoglossal neurons, but this could be detected only after repeated injections into the tongue. Uptake and retrograde transport from the tongue or from the crush occurred both for anionic and for cationic horseradish peroxidase. This is interpreted as evidence against absolute specificity in the uptake and transport of macromolecules on the basis of electrical charge.

Animals

Interaction between Ferastral and plasma factors.

Ferastral, iron-poly (sorbitol-gluconic acid) complex, in aqueous solution is completely adsorbed by magnesium carbonate; Ferastral in serum solution is only partially adsorbed by magnesium carbonate. Adsorption by magnesium carbonate removes the fraction of Ferastral in serum solution which donates iron more readily to transferrin. It is suggested that this fraction comprises the smaller molecular species of the Ferastral complex and that these species have a faster rate of absorption from an intramuscular injection site than the larger molecular species of the iron complex preparation. These findings shed some light on the patterns of serum transferrin bound iron compared with serum Ferastral concentrations which occur with time after intramuscular Ferastral injection.

Adsorption

The assay of iron-poly (sorbitol-gluconic acid) complex (Ferastral) and its separation from transferrin in serum.

A new iron-poly (sorbitol-gluconic acid) complex (Ferastral) has been studied. A method of assay is described. The iron complex may be separated from serum transferrin using a Sephadex DEAE A50 column. This binds the iron complex and elutes iron-transferrin which can then be assayed. It is shown that the assay of serum transferrin unsaturated binding capacity using excess 59FeCl2 and MgCO3 adsorption, is valid in the presence of Ferastral. Serum unsaturated iron binding capacity may therefore be used to follow the binding of Ferastral iron by transferrin. These methods may be used to follow the distribution of iron in plasma after an intramuscular injection of Ferastral.

Chromatography, Ion Exchange

Transfer of iron from Ferastral and other organic complexes to transferrin as measured by reticulocyte uptake.

The transfer of iron from the iron carbohydrate complexes, Ferastral, Imferon, and Jectofer, and from ferric chloride has been studied by the effect of such transfer in reducing reticulocyte uptake of 59Fe from labelled transferrin. There are plasma factors which augment the transfer of iron from complex to transferrin. The pattern of transfer from Ferastral and from Imferon are similar: at concentration of 5000 microgram/100 ml and 1250 microgram/100 ml in plasma these complexes transfer about 0.8% and 1.7%, respectively. Jectofer transfers about four times these amounts under similar conditions. In the case of Ferastral there is evidence of an equilibrium between transferrin-bound and Ferastral-bound iron. The characteristics of Ferastral assessed in this way suggest that it may prove suitable for therapeutic use as a total dose infusion.

Cells, Cultured

Serum ferritin assay and iron status in chronic renal failure and haemodialysis.

Forty-four patients with chronic renal failure on haemodialysis for four months to eight years were studied. All recieved intravenous iron dextran 100 mg on alternate weeks. Serum ferritin concentrations correlated well with body iron stores estimated by grading the bone marrow stainable iron. Altogether 34 patients showed increased bone marrow iron stores and serum ferritin concentrations greater than controls; four patients showed absence of iron in the marrow, and three of these had subnormal serum ferritin concentrations. Serum ferritin assay represents the best method of repeatedly monitoring the exact amount of iron therapy needed by patients with chronic renal failure, particularly those on regular haemodialysis.

Adult

Peripheral nerve injection injury: an experimental study.

In an attempt to answer questions regarding nerve injection injuries, we injected 11 agents in current use and commonly administered by intramuscular injection into the sciatic nerves of adult Wistar rats. Equal volumes of normal saline were used as control. We harvested the sciatic nerves at various times after injection and examined them by both light and electron microscopy. We performed myelinated nerve fiber counts and constructed histograms. Any impairment of motor function was also noted. We gave injections to 79 animals a total of 158 times; 116 injections were directly into the nerve fascicle (intrafascicular) and 42 were into the epineural tissue (extrafascicular). The results revealed considerable variation in the degree of nerve fiber injury according to the agent injected. Minimal damage resulted from the injection of iron-dextran, meperidine, and cephalothin, and maximal nerve injury followed the injection of penicillin, diazepam, and chlorpromazine. The site of injection was crucial. Intrafascicular injection was invariably associated with severe nerve injury, but, with few exceptions, extrafascicular injection resulted in minimal damage. The quantity of drug injected was also important in determining the degree of injury. Large, heavily myelinated fibers were more susceptible to injection injury than smaller, thinly myelinated nerve fibers. The effect of the injected drug seemed to be related to injury of the nerve fiber unit--both the axon and the Schwann cell with its myelin sheath. Regeneration in damaged nerves was a constant finding; even the most severely injured nerves, with total axonal degeneration, underwent subsequent regeneration.

Animals

Hereditary hemorrhagic telangiectasia. A case with hepatocellular carcinoma and acquired hepatocerebral degeneration.

A patient with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease), treated with ethinyl estradiol, multiple blood transfusions, and iron-dextran, developed hepatocellular carcinoma and acquired hepatocerebral degeneration. In addition to the carcinoma, the liver contained extensive arteriovenous maliformations, telangiectasis, and changes of Osler atypical cirrhosis. The carcinoma possibly had its genesis in the presence of an ocongenic serum hepatitis virus, or the cirrhosis, or both.

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