Excessive iron storage in a patient with Wilson's disease

We report on an otherwise healthy female, mother of two children, with severe decompensated liver cirrhosis due to an iron overload and Wilson's disease. The patient was considered heterozygote for hemochromatosis on the basis of the autosomal recessive inheritance for hemochromatosis, the frequency of the hemochromatosis gene, and the laboratory parameters defining her iron overload. The case is interesting because of the coincidence of Wilson's disease and excessive iron storage. Correspondence to: D. Haussinger     

Sodium conductance in calcium channels of guinea-pig ventricular cells induced by removal of external calcium ions

An inward current characterized by a slow inactivation, was induced when the extracellular Ca^2– concentration was reduced by EGTA. It was suppressed by replacing external Na^– with Tris⁺ or by D-600, increased by epinephrine, and was not affected by TTX. These findings suggest that this current is carried by Na⁺ ions through the Ca channels. The Na current decreased in amplitude as the concentration of external divalent cations was elevated. Blocking the Na current by divalent cations could be approximated by a bimolecular interaction between divalent cation and channel, with a dissociation constant of 1.2 M for Ca²⁺ and 60 M for Mg²⁺. Single channel currents were recorded in the cell-attached configuration. With a pipette solution of pCa=7.5 or pCa>8, the single channel I-V relationship was linear and the slope conductance was 70–75 pS. For 40 mV depolarizations from the resting potential, unitary currents were smaller at pCa=6 than at pCa=7.5. However, single channel events, which were observed after the repolarizing step to the resting potential, were much the same amplitude. The open time histogram was fitted with a single exponential having a time constant of 1.9 ms at around –40 mV (pCa>8, with 5 M Bay K 8644 in the bath solution), which was decreased with increasing the Ca²⁺ concentration in the pipette solution. Noise power spectra of patch currents at pCa=6 revealed a high-frequency component at around 1500 Hz. These results suggest that Ca binding to the sites with a high affinity for Ca²⁺ blocks the Na conductance in Ca channels. Reduction of the unitary current at higher concentrations of Ca²⁺ might be attributed to a rapid block by Ca²⁺.     

Electrical behaviour in a line of anterior pituitary cells (GH cells) and the influence of the hypothalamic peptide, thyrotrophin releasing factor

Anterior pituitary cells of the GH line, which secrete prolactin spontaneously, showed spontaneous action potential activity. Thyrotrophin releasing factor, which increases secretion in these cells, caused a prompt increase of action potential frequency. Potassium, another secretagogue, depolarized the cells and sometimes initiated a burst of action potentials at the onset of this effect. The action potentials persisted in tetrodotoxin-containing and Na-free media, but were suppressed by the Ca-channel blocker, methoxyverapamil. Moreover, elevating the extracellular Ca²⁺ concentration increased the amplitude of the action potentials. These action potentials therefore have a prominent Ca component. This endows them with a particular interest since secretory activity of these cells is known to be dependent on extracellular Ca²⁺. Ba²⁺, which can substitute for Ca²⁺ in maintaining secretion, also substituted for Ca²⁺ in the maintenance of the action potentials. In addition, Ba²⁺ prolonged action potentials remarkably: tetraethylammonium was less effective in this regard.The several parallels between known secretory behaviour and electrical phenomena encourage the view that analysis of electrical activity in anterior pituitary cells may provide useful clues to events involved in stimulus-secretion coupling and in the secretory control exerted by the brain.     

Localization of calcium ions in mixed synapses of Mauthner neurons during exposure to substances altering the conductivity of gap junctions

The pyroantimonate method was used to study the distribution of calcium ions in the mixed synapses of Mauthner neurons after exposure to substances altering the electrotonic conductivity of these synapses mediated by gap junctions (GJ). Ecdysone, an agent which increases GJ conductivity, produced precipitates of calcium pyroantimonate coating the whole postsynaptic surface of the GJ area, making them strongly asymmetrical. Precipitate granules were also seen to appear in the clefts of desmosome-like contacts (DLC). Chlorpromazine, which decreases GJ conductivity, produced precipitates in GJ clefts and on the pre- and postsynaptic membranes. No precipitate formed in DLC clefts. These results demonstrate that ecdysone acts as an agent selectively increasing GJ conductivity without affecting DLC function. Chlorpromazine had a double action, blocking conduction through both GJ and DLC. Thus, studies of agents altering GJ permeability require consideration of the possibility that they may interact with actin-containing structures also involved in the transport of the electrotonic signal.Translated from Morfologiya, Vol. 125, No. 3, pp. 32–35, May–June, 2004.     

Effect of iron on the surface, degradation and ion release properties of phosphate-based glass fibres

Phosphate-based glass fibres (PGF) have the unique characteristic of being completely soluble in an aqueous environment, releasing bioactive and biocompatible ions. They have been proposed as tissue engineering scaffolds for craniofacial skeletal muscle regeneration, where myoblasts are seeded directly onto the fibres. Studies have shown that these cells have a preference in their initial attachment to fibres of certain composition and size, which in turn control the rate of degradation. This study investigated the relationship between the surface properties, degradation properties and ion release (cationic and anionic species) by altering the chemical composition of the PGF. Iron oxide (Fe2O3) was incorporated into glasses containing P2O5 (50 mol%), CaO (30 mol%) and Na2O (20 mol%). Six glass compositions with Fe2O3 ranging from 0 to 5 mol% by replacing the equivalent Na2O mol% were investigated. Contact angle measurements showed that polar interactions occurring on the glass surfaces diminished with increasing Fe2O3 content. This behaviour was reflected in the estimated surface energies of the glasses, where the overall surface energy decreased with increasing Fe2O3 content due to the decrease in polar or acid/base component. The incorporation of up to 5 mol% Fe2O3 into PGF resulted in a significant reduction in the degradation rate (by two orders of magnitude), which can be related to the formation of more hydration resistant P-O-Fe bonds. However, the degradation rate increased with decreasing fibre diameter (comparing average diameters of 31.6 +/- 6.5 microm versus 13.1 +/- 1.3 microm) for a given mass of fibre, and this is related to the surface area to volume ratio. Taken together the results suggest that fibres with the larger diameters and containing 3-5 mol% Fe2O3 could initially be a more durable scaffold than ones with 1 or 2 mol% Fe2O3 for initial cell attachment.     

Spectral electroencephalographic correlates of iron status: Tired blood revisited

For some time, clinical reports have described impairment of affective and cognitive functions in iron deficient persons. Recent studies suggest that both brain biochemistry and cognitive performance capacity may be disrupted by inadequate intake of dietary iron, but the relationship of the possible neurophysiological effects to psychological ones is unclear. To examine the relationship of iron status to simultaneous measures of cortical activation and cognitive performance, 8 channels of electroencephalographic (EEG) data were recorded during a resting period and during the performance of several cognitive tasks in two groups of men. The EEG data were spectrally analyzed, and measures of total power and frequency of peak power in each of several bands of the power spectrum for each channel were used as predictors in multiple regression analyses with serum iron and serum ferritin as alternative criteria. Measures of power in the delta frequency in the resting period appeared relevant to iron status in both groups, perhaps indicating alertness or arousal level. Consistently in these regressions, the asymmetry of the EEG appeared relevant to iron and ferritin. These findings suggest that the combination of EEG and performance measures may help characterize the neuropsychological effects of trace element nutrition.     

Effects of 4-aminopyridine on the turnover of monoamines in the central nervous system of the rat

Summary The effects of 4-aminopyridine (4-AP) on the turnovers of 5-hydroxytryptamine, dopamine and noradrenaline in the central nervous system of rats were studied by means of amine disappearance following inhibition of tryptophan or tyrosine hydroxylase. 4-AP (3 mg/kg i.p.) did not change the utilizations of 5-hydroxytryptamine or dopamine but it markedly accelerated that of noradrenaline in the brain and in the spinal cord. This stimulatory effect of 4-AP was completely dependent on nerve impulses since no effect was observed following an acute section of the noradrenaline nerves to the spinal cord. The effect of 4-AP was blocked by the-adrenoreceptor stimulating agent clonidine. Pentylenetetrazole, at a dose producing similar behavioural changes as 4-AP, caused only a slight stimulation of the noradrenaline turnover. 4-AP might enhance the flux of calcium ions into nerve terminals during depolarization, and thus increase the release of noradrenaline, whereas this process might be of less importance in the dopamine and the 5-hydroxytryptamine nerves.     

Endogenous and exogenous nitric oxide enhance the DNA strand scission induced by tert-butylhydroperoxide in PC12 cells via peroxynitrite-dependent and independent mechanisms, respectively

A short-term exposure to tert-butylhydroperoxide (tB-OOH) promoted a concentration-dependent formation of DNA single-strand breaks in PC12 cells. These events were paralleled by an increase in the cytosolic concentration of Ca2+ that was in part cleared by the mitochondria. Unlike the extent of Ca2+ mobilization and/or mitochondrial Ca2+ clearance, the DNA strand scission evoked by the hydroperoxide was markedly reduced by the nitric oxide (NO) scavenger 2-phenyl-4,4,5,5-tetramethylimidazolin-1-oxyl-3-oxide (PTIO) or by the NO synthase inhibitor N-nitro-L-arginine methylester (L-NAME). Inhibitors of electron transport (rotenone and myxothiazol), ruthenium red (RR, a polycation which inhibits the calcium uniporter of mitochondria), or peroxynitrite scavengers (Trolox and L-methionine) were as effective as PTIO or L-NAME in inhibiting the DNA-damaging response mediated by tB-OOH. Rotenone, RR or peroxynitrite scavengers did not further reduce the residual DNA cleavage observed following treatment with tB-OOH in L-NAME-supplemented cells. Exogenous NO also increased the DNA damage caused by tB-OOH in L-NAME-supplemented cells and this response was blunted by RR or by inhibitors of electron transport but was insensitive to peroxynitrite scavengers. We conclude that both endogenous and exogenous NO enhance the DNA cleavage generated by tB-OOH in PC12 cells. However, only endogenous NO set the bases for an involvement of peroxynitrite in this DNA-damaging response.     

脓毒症大鼠生物喋呤首要限速酶与铁代谢的实验研究

目的探讨腹腔感染致脓毒症时重要器官生物喋呤首要限速酶即:三磷酸鸟苷环水解酶I(GTP-CHI)、铁代谢的病理生理意义。方法腹腔感染致脓毒症模型采用盲肠结扎穿孔法(CLP),用逆转录-聚合酶链反应方法测定24只大鼠肝、肺、肾等组织三磷酸鸟苷环水解酶I(GTP-CHI)mRNA的表达;用分光光度法测定其铁含量。结果脓毒症大鼠2h时肝、肺、肾组织GTP-CHImRNA的表达显著增多,而铁含量变化不显著。结论GTP-CHImRNA参与了腹腔感染所致脓毒症的发生、发展过程,而与铁代谢的关系有待于进一步研究。