Effects of iron deficiency and iron overload on manganese uptake and deposition in the brain and other organs of the rat

Manganese (Mn) is an essential trace element at low concentrations, but at higher concentrations is neurotoxic. It has several chemical and biochemical properties similar to iron (Fe), and there is evidence of metabolic interaction between the two metals, particularly at the level of absorption from the intestine. The aim of this investigation was to determine whether Mn and Fe interact during the processes involved in uptake from the plasma by the brain and other organs of the rat. Dams were fed control (70 mg Fe/kg), Fe-deficient (5-10 mg Fe/kg), or Fe-loaded (20 g carbonyl Fe/kg) diets, with or without Mn-loaded drinking water (2 g Mn/L), from day 18-19 of pregnancy, and, after weaning the young rats, were continued on the same dietary regimens. Measurements of brain, liver, and kidney Mn and nonheme Fe levels, and the uptake of 54Mn and 59Fe from the plasma by these organs and the femurs, were made when the rats were aged 15 and 63 d. Organ nonheme Fe levels were much higher than Mn levels, and in the liver and kidney increased much more with Fe loading than did Mn levels with Mn loading. However, in the brain the increases were greater for Mn. Both Fe depletion and loading led to increased brain Mn concentrations in the 15-d/rats, while Fe loading also had this effect at 63 d. Mn loading did not have significant effects on the nonheme Fe concentrations. 54Mn, injected as MnCl2 mixed with serum, was cleared more rapidly from the circulation than was 59Fe, injected in the form of diferric transferrin. In the 15-d-rats, the uptake of 54Mn by brain, liver, kidneys, and femurs was increased by Fe loading, but this was not seen in the 63-d rats. Mn supplementation led to increased 59Fe uptake by the brain, liver, and kidneys of the rats fed the control and Fe-deficient diets, but not in the Fe-loaded rats. It is concluded that Mn and Fe interact during transfer from the plasma to the brain and other organs and that this interaction is synergistic rather than competitive in nature. Hence, excessive intake of Fe plus Mn may accentuate the risk of tissue damage caused by one metal alone, particularly in the brain.     

Placental copper transport in the rat. II: Effect of maternal copper deficiency

Copper (Cu) placental transport presents a steep downhill gradient from mother to fetus. This process could be altered by low-molecular-weight (LMW) ligands and maternal Cu deficiency. We compared the ratio of Cu transfer from dam-to-fetus in Cu-deficient (CuDf) and Cu-sufficient (CuSf) rats in the last day of gestation. Anaesthetized dams were iv injected 79 mumol/kg (5 mg/kg) of either Cu acetate [Cu (AcO)2]; Cu+L-histidine, 1:10. [Cu(His)10]; Cu-(glycyl-glycyl-L-histidine) [Cu(GGH)], or saline. Dam and fetal blood, as well as placentae were obtained at 0, 10, 20, 40 and 60 min. At time 0, CuDf dams had lower plasma Cu than CuSf dams (8.3 +/- 1.2 versus 26.7 +/- 1.1 mumol/l), but CuDf fetuses plasma Cu was unchanged. This resulted in a more favourable mean fetal: maternal plasma Cu ratio in the CuDf fetuses (0.61) than in the CuSf fetuses (0.21). Dam plasma Cu was unaffected by the chemical form of Cu injected. In CuDf fetuses lower plasma Cu was observed with Cu(GGH) and Cu (His)10 at 20 min than in the CuSf. In the presence of these LMW ligands CuDf placentae retained more Cu than those of the CuSf group. CuDf was associated ultrastructurally with extensive lipid deposition in dam hepatocytes and, to a lesser extent, in CuDf fetal liver. These results indicate that in CuDf, LMW ligands increase placental uptake of Cu, without improving placenta-fetus transport. Although the rat fetus is well adapted to intrauterine CuDf, it may also be susceptible to hepatic lipid infiltration when the dam is CuDf.     

Effects of thiamin deficiency on acetylcholine levels and utilization in vivo in rat brain

Cerebral regional acetylcholine (ACh) levels and utilization were studied in vivo in thiamin deficient (TD), pair-fed asymptomatic (PFC) and ad libitum fed control (ALC) rats. ACh levels in the cortex, corpus striatum, midbrain, diencephalon and brainstem of TD rats were comparable to those observed in the control groups. However, ACh utilization was slightly to moderately (10-41%) decreased in cortex, midbrain, diencephalon and brainstem. The decrease was significantly different in the midbrain of TD rats as compared to PFC and ALC rats.     

Effect of rat placental culture supernatants on cellular and humoral immune responses

PROBLEM: To evaluate the effect of rat placental culture supernatants (PS) on spontaneous, mitogen- and alloantigen-induced lymphoproliferation, antibody synthesis regulation, and symmetric/asymmetric antibody ratio. METHOD OF STUDY: The effect of PS was determined: (a) on cell proliferation of murine hybridoma cells and on spontaneous or ConA-induced proliferation of murine and rat splenocytes by thymidine incorporation; (b) on rat or mouse cell-mediated cytotoxicity (CMC) by 51Cr release; and (c) on antibody synthesis by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: With 20% PS, hybridoma cell inhibition was 37% and that of splenocytes up to 60%, whereas it was 75 and 43%, respectively, in the presence of ConA. Despite marked cell death, hybridoma proliferation index increased significantly. There was a drop in total antidinitrophenylated (DNP) immunoglobulin G1 (IgG1) antibody production and an increase in asymmetric antibody percentage, correlating with placental supernatant concentration. CONCLUSIONS: Rat placental culture supernatants inhibit cell proliferation in all cases, diminish total antibody production, and increase the percentage of asymmetric antibodies by the hybridoma, and they increase antibody production by rat splenocytes.     

Effects of copper deficiency and copper deficiency coupled with high dietary iron or molybdenum on phagocytic cell function and response of calves to a respiratory disease challenge

A study was conducted to determine the effects of supplementing a diet marginally deficient in copper (Cu) with iron (Fe), molybdenum (Mo), or Cu on phagocytic cell function and disease resistance of calves. Thirty-one calves were born to heifers fed a corn silage-based diet containing 4.5 mg of Cu/kg. Treatments consisted of 1) control (CON; no supplemental Cu, Fe, or Mo), 2) 600 mg of Fe added/kg (FE), 3) 5 mg of Mo added/kg (MO), or 4) 10 mg of Cu added/kg of DM (CU). Activity of superoxide dismutase was lower (P < .06) in neutrophils from MO vs CON or CU calves at 170 d of age. bactericidal activity of neutrophils from MO calves tended (P = .15) to be lower compared with those from CU calves at 70 d of age. Calves were inoculated intranasally with live infectious bovine rhinotracheitis virus (IBRV) 2 d after weaning, followed by intratracheal administration of Pasteurella hemolytica 5 d later. Iron- and Cu-supplemented calves exhibited higher (P < .01) body temperatures and lower (P < .06) feed intakes following IBRV inoculation compared with CON and MO calves. Copper-supplemented calves had higher levels of plasma tumor necrosis factor (TNF) than MO calves at weaning (P < .05) and tended to have higher plasma TNF (P = .11) than FE and MO calves 5 d after IBRV inoculation. These data indicate that dietary levels of Mo and Cu can affect body temperature and feed intake responses to disease by affecting TNF and perhaps other cytokines.     

Effects of zinc deficiency on protein synthesis and expression of specific mRNAs in rat liver

The effects of zinc deficiency on protein synthesis and expression of specific mRNAs were assessed in rat liver. Zinc deficiency had no apparent effect on liver weight, protein content, or RNA content when these properties were compared with values obtained using pair-fed rats. However, zinc deficiency resulted in a lower rate of hepatic protein synthesis. The decreased rate of protein synthesis was due to a decrease in the rate of synthesis of proteins retained in the liver, with no apparent change in the synthesis of secreted proteins. Analysis of expression of specific gene products, as assessed by in vitro translation of total RNA followed by two-dimensional gel analysis, showed that the expression of only a few mRNAs was altered by zinc deficiency. The patterns of change in gene expression resulting from zinc deficiency varied from almost complete repression to full expression. In additional studies, cDNA clones to serum retinol-binding protein and transthyretin were used to examine the effect of zinc deficiency on the relative abundance of mRNA for these two proteins. The relative abundance of mRNA for transthyretin was specifically elevated as a result of zinc deficiency. In contrast, the relative abundance of mRNA for hepatic serum retinol-binding protein was increased in both zinc-deficient and pair-fed rats. Therefore, the observed change in mRNA for serum retinol-binding protein was apparently at least in part due to the inanition that accompanies zinc deficiency. Overall, the results suggest that zinc can regulate the synthesis of specific proteins in rat liver through changes in the relative abundance of specific mRNAs.     

Effects of riboflavin deficiency on the ultrastructure of rat sciatic nerve fibers

Ultrastructural studies indicate that riboflavin deficiency induced by either dietary restrictions alone or with the addition of the antagonist galactoflavin severely affects the structural integrity of myelin lamellae. The degenerative process induced by riboflavin deficiency is time dependent. Nonmyelinated nerve fibers are not affected ultrastructurally by the deficiency. Cellular organelles of both myelinated and nonmyelinated nerve fibers remain intact and presumably functional.     

Effects of SiCp reinforcement by electroless copper plating on properties of Cu/SiCp composites

Abstract

Silicon carbide reinforced copper matrix composites containing 50–80 vol.-%SiC_p were fabricated by hot pressing copper coated SiC_p powder. The results show that the densification, thermal expansion coefficients, flexural strength, and thermal conductivity of Cu/SiC_p composites reinforced by electroless copper plating and their corrosion resistance in 5%NaCl solution are better than those without electroless plating. Physical properties and flexural strength of the composites decrease with an increase in SiC_p content, whereas the corrosion resistance increases with an increase in SiC_p volume fraction. By observing the fracture surface after a flexural test, it can be seen there are two types of fracture model: the cracking of Cu/SiC_p interface and the pulling out of SiC_p particles. The experiment also proved that the bonding strength of the Cu/SiC_p interface and the pressure of the hot pressing operation are the two main factors which influence the fracture of these composites.     

Effects of magnesium deficiency on strength, mass, and composition of rat femur

Era is an Escherichia coli GTPase that is essential for cell viability and is peripherally associated with the cytoplasmic membrane. Both immunoelectron microscopy and subcellular-fractionation experiments have shown that Era is present in cytoplasmic as well as membrane-associated pools. These data led to speculation that the mechanism of action of Era may require cycling between membrane and cytoplasmic sites. In order to investigate this possibility, an in vitro binding assay was developed to characterize the binding of Era to membrane fractions. Competition and saturation binding experiments suggest that a site that is specific for Era and capable of binding up to 5 ng of Era per microgram of membrane protein is present in membrane preparations. The binding curve is complex, indicating that multiple equilibria describe the interaction. The binding of Era to this putative receptor is dependent on guanine nucleotides; binding cannot be measured in the absence of nucleotide, and neither ATP nor UTP can substitute. Subfractionation of cell walls showed that the guanine nucleotide-dependent binding site was present in fractions enriched in cytoplasmic membrane. These data provide evidence that Era may be involved in a GTPase-receptor-coupled membrane-signaling pathway that is essential for growth in E. coli.     

Effects of some chelating agents on urinary copper excretion by the rat

In order to estimate the potential advantages of new chelating agents which can enhance copper excretion in the chronic copper intoxication arising in Wilson's disease, the relative ability of none chelating agents to induce the urinary excretion of copper was compared with that of D-penicillamine (DPA) and triethylenetetramine.2HCl (TRIEN), all given ip at 1 mmol/kg to male Sprague-Dawley rats. The compounds examined were as follows: tris(2-aminoethyl)-amine.3HCl (TREN), tetraethylenepentamine.5HCl (TETREN), pentaethylenehexamine.6HCl (PENTEN), 1,4,7,11-tetraazaundecane.4HCl (TAUD), 1,5,8,12-tetraazadodecane.4HCl (TADD), 1-N-benzyltriethylenetetramine.4HCl (BzTT), 4,7,10,13-tetraazatridecanoic acid.2H2SO4 (TTPA), 1,10-bis(2-pyridylmethyl)-1,4,7,10-tetraazadecane.4HCl (BPTETA), and N,N-bis(2-pyridylmethyl)-4-(aminomethyl)benzoic acid (4ABA). Of these, BzTT, TTPA, and 4ABA are new chelating agents not previously reported. The factors by which these chelating agents enhanced copper excretion over control (untreated) levels were as follows: DPA, 7.2; TREN, 1.6; TRIEN, 4.0; TETREN, 10.1; PENTEN, 7.8; TAUD, 7.8; TADD, 2.6; TTPA, 5.6; BzTT, 1.8; and 4ABA, 5.5. The results indicate that it may well be possible to develop additional chelating agents which are equal or superior to those now used in the treatment of Wilson's disease, as well as structural types whose immunological properties may be significantly different from DPA or TRIEN, the compounds currently used in the clinic for this disorder.     

Effects of vitamin E deficiency on vasomotor activity and ultrastructural organisation of rat thoracic aorta

1. The effects of vitamin E deficiency were evaluated in aortic rings isolated from rats maintained on a diet deficient in vitamin E. 2. Endothelium-dependent vasodilator responses to acetylcholine (ACh) and calcium ionophore, A23187, were reduced in preparations from treated animals, compared to the age-matched controls. The maximal vasodilation to ACh was 66.4 +/- 9 (n = 4) and 38.8 +/- 7 (n = 4) % in control and 10 month-treated preparations, respectively. 3. The endothelium-independent vasodilator responses to sodium nitroprusside as well as the concentration-dependent contractile responses to noradrenaline, did not differ between treated and control preparations. 4. Electron microscopic examination of vascular segments and revealed that, following vitamin E deficiency, normal tissue organisation was disrupted, the endothelial monolayer either not being in contact with the underlying tissue or being absent in most of the areas analysed. 5. It is concluded that during vitamin E deficiency both morphological disruption and functional impairment of endothelium occur without observable modification of muscle cell function and morphology.     

The effect of glypondin on glycogen and protein accumulation in rat organs

Rats were treated for 21 days with 20, 30 and 40 mg/kg Glypondin dissolved in the drinking water. The weight-increasing effect of Glypondin was studied in rat organs. In the liver a significant rise in the concentration of TCA-soluble glycogen was demonstrated. In the myocardium and m. gastrocnemius the concentration of both the labile and glycogen was unchanged. In the m. gastrocnemius of rats treated with Glypondin a significant rise in the concentration of noncollagenous protein was demonstrated.     

Chymotrypsin gene expression in rat peripheral organs

Cdc25, the dual-specificity phosphatase that dephosphorylates the Cdc2-cyclin B complex at mitosis, is highly regulated during the cell cycle. In Xenopus egg extracts, Cdc25 is associated with two isoforms of the 14-3-3 protein. Cdc25 is complexed primarily with 14-3-3epsilon and to a lesser extent with 14-3-3zeta. The association of these 14-3-3 proteins with Cdc25 varies dramatically during the cell cycle: binding is high during interphase but virtually absent at mitosis. Interaction with 14-3-3 is mediated by phosphorylation of Xenopus Cdc25 at Ser-287, which resides in a consensus 14-3-3 binding site. Recombinant Cdc25 with a point mutation at this residue (Cdc25-S287A) is incapable of binding to 14-3-3. Addition of the Cdc25-S287A mutant to Xenopus egg extracts accelerates mitosis and overrides checkpoint-mediated arrests of mitotic entry due to the presence of unreplicated and damaged DNA. These findings indicate that 14-3-3 proteins act as negative regulators of Cdc25 in controlling the G2-M transition.     

Self-diffusion of copper in Cu−Al solid solutions

Self-diffusion coefficients of copper in Cu?Al solid solutions in the concentration interval 0 to 19 at. pct Al and in the temperature range 800° to 1040°C have been determined by the residual activity method using the isotope Cu⁶⁴. The values of the self-diffusion coefficients in the concentration interval 0 to 14.5 at. pct Al satisfy the Arrhenius relation and their temperature dependence can be expressed by the following equations $$\eqalign{ & D_{Cu}^{Cu} = \left( {0.43_{ - 0.11}^{ + 0.15} } \right) exp \left( { - {{48,500 \pm 700} \over {RT}}} \right) cm^2 /\sec \cr & D_{Cu - 2.80 at. pct Al}^{Cu} = \left( {0.46_{ - 0.16}^{ + 0.23} } \right) exp \left( { - {{48,000 \pm 900} \over {RT}}} \right) cm^2 /\sec \cr & D_{Cu - 5.50 at. pct Al}^{Cu} = \left( {0.30_{ - 0.07}^{ + 0.09} } \right) exp \left( { - {{47,000 \pm 600} \over {RT}}} \right) cm^2 /\sec \cr & D_{Cu - 8.83 at. pct Al}^{Cu} = \left( {0.46_{ - 0.09}^{ + 0.11} } \right) exp \left( { - {{47,100 \pm 500} \over {RT}}} \right) cm^2 /\sec \cr & D_{Cu - 11.7 at. pct Al}^{Cu} = \left( {0.61_{ - 0.13}^{ + 0.17} } \right) exp \left( { - {{47,200 \pm 600} \over {RT}}} \right) cm^2 /\sec \cr & D_{Cu - 14.5 at. pct Al}^{Cu} = \left( {4.2_{ - 1.5}^{ + 2.2} } \right) exp \left( { - {{51,110 \pm 1000} \over {RT}}} \right) cm^2 /\sec \cr} $$ An analysis of the results leads to the conclusion that, in the concentration interval 0 to 11.7 at. pct Al, the frequency factor and activation enthalpy concentration dependences can be described by the following equations whereD _0Cu ^Cu and ΔH _Cu ^Cu are diffusion characteristics for self-diffusion in pure copper,X _Al is the atomic percent of aluminum, andK andB are experimental constants.     

The radiographic manifestations of bone changes in copper deficiency

The bone changes in infants with copper deficiency are typified by osteopenia and the symmetrical appearance of sickle-shaped metaphyseal spurs. Four examples are demonstrated and the differential diagnosis is extensively discussed.     

Anemia and neutropenia due to copper deficiency in enteral nutrition

Although thrombomodulin (TM) in circulating blood is regarded as an indicator of vascular endothelial disorders, blood TM levels are also known to be affected by renal dysfunction. We measured plasma TM levels in primary glomerular disease (PGD) and lupus glomerulonephritis (GN) with the EIA method, and assessed the extent to which renal dysfunction and endothelial disorders contribute to plasma TM levels in these diseases. The plasma TM/serum creatinine (TM/Cr) ratio was significantly higher in lupus GN patients than in PGD patients or normal controls. A significant positive correlation was found between plasma TM and serum Cr levels in both PGD and lupus GN patients, but the slope (A) of the regression line (TM = A.Cr+B) in lupus GN patients was significantly steeper than in PGD patients. We conclude that plasma TM levels are greatly influenced by renal dysfunction, but that not only renal dysfunction but endothelial disorders may be an important determinant of increased plasma TM levels in diseases such as lupus GN.