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The diagnostic and prognostic value of eardrum mobility in otitis media with effusion.

Diagnostic and prognostic values of eardrum mobility were determined by pneumatic otoscopy in 37 patients (56 ears) having otitis media with effusion (OME). Eardrum mobility was impaired or lost in less than half of the ears (46.4%), while a tympanogram detected 77.8% of OME. In 27 of the 37 patients (42 of the 56 ears), aeration of the middle ear space was examined by CT and demonstrated that the presence or absence of aeration was significantly correlated with the presence or absence of eardrum mobility. In another 38 children (62 ears with OME), effect of antibiotics was correlated with eardrum mobility before treatment, and the improvement rate was found to be significantly higher in ears with positive mobility of eardrum (34.3%) than in ears without eardrum mobility (10.0%). These results indicate that eardrum mobility is a good prognostic indicator of OME rather than its diagnostic indicator alone.

Acoustic Impedance Tests↗

Do MRI findings correlate with mobility tests? An explorative analysis of the test validity with regard to structure.

To find out whether segmental magnetic resonance imaging (MRI) findings such as intervertebral disc degeneration (DD) and facet joint osteoarthritis (FJO) are associated with motion deficiencies as seen in common mobility tests and observed range of motion (ROM). A total of 112 female subjects, nurses and office workers, with and without low back pain, were examined by clinical experts, and lumbar mobility was measured including modified Schober, fingertip-to-floor distance (FTFD) and ZEBRIS motion analysis. An MRI of the lumbar spine was made. Mobility findings were correlated with segmental morphologic changes as seen on MRI at the levels of L1-2 through L5-S1. Only a few statistically significant correlations between MRI findings and the results of the mobility tests could be found. Lateral bending was weakly and negatively correlated to DD and FJO but only on the level of L5-S1. The FTFD showed a weak positive correlation to endplate changes on the level of L4-5. When ROM is observed by clinical experts, there are several significant relationships between MRI findings and the observed motion. There is a highly significant segmental correlation between DD and disc form alteration as seen on MRI on the level of single motion segments. Pain history and current pain level did not moderate any association between MRI and mobility. There is no clear relationship between the structural changes represented by MRI and the measured mobility tests used in this study. Our findings suggest that close observation of spinal motion may provide at least equal information about the influence of spinal structures on motion than the commonly used measured mobility tests do.

Adult↗

A quantitative assessment of the significance of molecular mobility as a determinant for the stability of lyophilized insulin formulations.

PURPOSE: The purpose was to explore a method for quantitatively assessing the contribution of molecular mobility to the chemical reactivity of amorphous solids. Degradation of insulin in lyophilized formulations containing trehalose and poly(vinylpyrrolidone)(PVP) was chosen as a model system, and the temperature- and glass transition temperature (Tg)-dependence of the degradation rate was analyzed to obtain the relative contributions of molecular mobility and that of the chemical activational barrier reflected in the energy of activation. METHODS: Insulin degradation and dimerization in lyophilized trehalose and PVP formulations were monitored at various relative humidities (6-60% RH) and temperatures (10-60 degrees C) by reverse-phase high-performance liquid chromatography (HPLC) and high-performance size-exclusion chromatography (HP-SEC), respectively. The Tg and fragility parameter of the lyophilized insulin formulations were determined by differential scanning calorimetry (DSC). RESULTS: Insulin degradation in the initial stage was describable with first-order kinetics for both of the trehalose and PVP formulations. The temperature- and Tg-dependence of the degradation rate indicated that the reactivity of insulin in the trehalose formulation is affected by molecular mobility at low humidity (12% RH), such that the ratio of the observed rate constant (k') to the rate constant governed only by the activational barrier (k) was 0.051 at the Tg. At higher humidities, in contrast, the value of k'/k was much higher (0.914, 0.978, and 0.994 for 23% RH, 33% RH, and 43% RH, respectively), indicating that insulin degradation rate is determined predominantly by the activational barrier. For insulin degradation in the PVP formulation at temperatures below Tg, the contribution of molecular mobility to the degradation rate appeared to be negligible, as the extrapolated value of t90 at the Tg exhibited a large difference between the formulations with differing Tg values (because of differing water contents). CONCLUSIONS: The reactivity of insulin in the trehalose and PVP formulations can be described by an equation including factors reflecting the activational barrier (activation energy and frequency coefficient) and factors reflecting the molecular mobility (Tg, fragility parameter and a constant representing the relationship between the molecular mobility and the reaction rate). Thus, analysis of temperature dependence based on the proposed equation allows quantitative assessment of the significance of molecular mobility as a factor affecting chemical reactivity.

Calorimetry, Differential Scanning↗

Mobilization of iron from crocidolite asbestos by certain chelators results in enhanced crocidolite-dependent oxygen consumption.

The reactivity of iron on crocidolite asbestos with dioxygen was determined and compared with iron mobilized from crocidolite. Ferrozine, a strong Fe(II) chelator, was used to demonstrate that iron on crocidolite was redox active. More Fe(II) was mobilized from crocidolite (1 mg/ml) by ferrozine anaerobically (11.2 nmol/mg crocidolite/h) than aerobically (6.6 nmol/mg/h) in 50 mM NaCl, pH 7.5, suggesting that Fe(II) on crocidolite reacts with O2 upon aqueous suspension. However, suspension of crocidolite in 50 mM NaCl, pH 7.5, did not result in a measurable amount of O2 consumption. The addition of reducing agents (1 mM) increased the amount of Fe(II) on crocidolite, and addition of ascorbate resulted in 0.4 nmol O2 consumed/mg crocidolite/min. Therefore, iron on crocidolite had limited redox activity in the presence of ascorbate. However, mobilization of iron from crocidolite increased its redox activity. Citrate, nitrilotriacetate (NTA), or EDTA (1 mM) mobilized 79, 32, or 58 microM iron, respectively, in preincubations up to 76 h, and increased O2 consumption upon addition of ascorbate to 2.8, 7.6, or 22.0 nmol O2 consumed/mg/min, respectively. This activity depended only upon the presence of a component(s) mobilized from crocidolite by the chelators. Pretreatment of crocidolite with the iron chelator desferrioxamine B (10 mM) inhibited O2 consumption. The results of the present study suggest that iron on or in crocidolite is responsible for the redox activity of crocidolite, but that mobilization of iron by chelators such as citrate, NTA, or EDTA greatly enhances its redox activity. Thus, iron mobilization from crocidolite in vivo by low-molecular-weight chelators may lead to the increased production of reactive oxygen species which may damage biomolecules, such as DNA.

Anaerobiosis↗

Lateral mobility of phospholipids in the external and internal leaflets of normal and hereditary spherocytic human erythrocytes.

The lateral diffusion coefficients (D) and the mobile fractions of the fluorescent phospholipid N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phosphatidylethanolamine (NBD-PE) and of membrane proteins labelled with fluorescein isothiocyanate, were measured by fluorescence photobleaching recovery on erythrocytes from healthy persons and from a hereditary spherocytosis patient. Measurements of lipid probe mobility were performed on ghosts labelled by NBD-PE exclusively at the external monolayer, or at both sides of the membrane. Our results indicate the following: (1) The mean values and the temperature dependence of D are different at the external and internal membrane leaflets. (2) In both normal and HS ghosts the mobile fraction of NBD-PE in the external monolayer does not depend significantly on temperature. On the other hand, the mobile fraction in the internal monolayer is reduced as the temperature is decreased. (3) At low temperatures, the mobile fraction of NBD-PE in the internal monolayer of spherocytic ghosts is significantly lower than the mobile fraction in the internal monolayer of normal ghosts. (4) No differences were observed between the mobilities of membrane proteins in normal and in spherocytic ghosts. However, differences were observed between the two cell populations in the temperature-dependence of the intrinsic fluorescence of unlabelled membrane proteins. The implications of these results for membrane phospholipid asymmetry and for cytoskeletal interactions with the internal lipid monolayer are discussed.

Erythrocyte Membrane↗

Effects of ethanol on lateral and rotational mobility of plasma membrane vesicles isolated from cultured mouse myeloma cell line Sp2/0-Ag14.

Intramolecular excimerization of Py-3-Py and fluorescence polarization of DPH were used to evaluate effects of ethanol on the rate and range of the lateral mobility and the range of the rotational mobility of bulk bilayer structures of the Sp2/0-PMV. In a concentration-dependent manner, ethanol increased the rate and range of the lateral mobility and the range of the rotational mobility of bulk bilayer structures of Sp2/0-PMV. Selective quenching of DPH by trinitrophenyl groups was utilized to examine the range of transbilayer asymmetric rotational mobility of the Sp2/0-PVM. The anisotropy (r), limiting anisotropy (r(infinity)) and order parameter (S) of DPH in the inner monolayer were 0.022, 0.029 and 0.063, respectively, greater than calculated for the outer monolayer of the Sp2/0-PMV. Selective quenching of DPH by trinitrophenyl groups was also used to examine the transbilayer asymmetric effects of ethanol on the range of the rotational mobility of the Sp2/0-PMV. Ethanol had a greater increasing effect on the range of the rotational mobility of the outer monolayer as compared to the inner monolayer of the Sp2/0-PMV. It has been proven that ethanol exhibits a selective rather than nonselective fluidizing effect within the transbilayer domains of the Sp2/0-PMV.

Animals↗

Studies on the degradation of high mobility group non-histone chromosomal proteins.

During the isolation of high mobility group non-histone proteins from calf thymus chromatin by methods described previously (e.g. Goodwin, G.H., Nicolas, R.H. and Johns, E.W. (1975) Biochim. Biophys, Acta. 405, 280--291) protein degradation occurs resulting in a number of proteins appearing in the chromatin extracts which are not present in high mobility group protein preparations in which proteolysis has been completely inhibited. These extra proteins, formerly numbered high mobility group proteins 3, 5, 6 and 8, are thus probably degradation products of other nuclear proteins, produced during the isolation procedure. From the amino acid analyses, tryptic peptides and N-terminal sequences, it is concluded that high mobility group protein 3 is probably a degradation product of high mobility group protein 1. The amino acid analysis of high mobility group protein 8 is very similar to that of the N-terminal half of histone H1 suggesting that high mobility group protein 8 is a degradation product of this histone.

Amino Acids↗

Early mobilization in the treatment of Colles' fracture: a 3 year prospective study.

Ninety consecutive women with unilateral Colles' fractures were randomized into two different treatment groups. The control group was treated for 5 weeks in conventional short-arm, below the elbow plaster of Paris casts. The other group (N = 45) was treated similarly in plaster casts for 3 weeks and then had flexible casting applied for the remaining 2 weeks which allowed for early joint mobilization. Functional recovery was assessed by measuring grip strength and joint mobility at intervals over the 3 years. Radiographic and overall assessments were also made during 3 year course of study. Virtually all patients reported greater comfort after switching to the flexible casting. Mean grip scores and joint mobilities were higher at all time points with early mobilization, reaching levels of statistical significance at 6 months for grip score and at 3 months for joint mobility. By 3 years most differences between treatment groups had resolved. We found no evidence that early mobilization was detrimental to recovery. We conclude that early mobilization is a satisfactory treatment option for Colles' fracture, and may, in fact, hasten functional recovery.

Adult↗

Dependence of the electroosmotic mobility on the applied electric field and its reproducibility in capillary electrophoresis.

Experimental results on the electroosmotic mobility in fused-silica capillaries are presented for different applied voltages and solutions of different pH. The electroosmotic mobility is shown to be dependent on the applied voltage and this dependence cannot be attributed to the temperature effects. Results of the electroosmotic mobility measurements are found to be dependent also on the electrophoresis unit they have been performed in. The explanation given and the relevant theory presented are based on the hypothesis that these effects are produced by a radial electric field inevitably existing in any electrophoresis unit. The concept of the limiting electrophoretic mobility, i.e. extrapolated to the zero applied voltage, is introduced in order to characterize the properties of the solution-wall interface. The slope of the electroosmotic mobility dependence on the applied voltage depends on the solution pH and the surroundings of the capillary. Theoretical estimations agree well with both experimentally found limiting mobilities and slopes. Long-term variations of the electroosmotic mobility are supposed to be related with the cation penetration into the capillary wall.

Electrochemistry↗

Assessment of oral implant mobility.

Most of the implant literature suggests that successful dental implants are immobile and any detected mobility indicates implant failure. This study evaluated the ability of the Periotest instrument to measure implant mobility in a controlled in vitro model with a sample of 56 in vivo implants. In the in vitro portion of the study, implant model mobility was determined by an axial testing machine (0 to 5 N at 0.2 mm/minute) and the Periotest instrument. The comparison showed a high level of correlation (Pearson's r 0.984). The load that the Periotest placed on the implants during mobility measurements was approximately 5 N, depending on the compliance of the test object. The in vivo portion evaluated the range of mobility of 56 clinically successful endosseous implants. The range of mobility as determined by the Periotest instrument was -6 to +2. This range corresponds to an in vitro model displacement (5 N load) of 0.038 mm to 0.113 mm with a mean of 0.066 mm +/- 0.018 mm (SD). These data demonstrate that clinically successful implants are not immobile, but have a range of mobility.

Analysis of Variance↗

A comparison between muscarinic receptor occupancy, inositol 1,4,5-trisphosphate accumulation and Ca2+ mobilization in permeabilized SH-SY5Y neuroblastoma cells.

Electrically permeabilized SH-SY5Y neuroblastoma cells have been used to examine the relationship between receptor occupation by muscarinic agonists, inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) accumulation and Ca2+ mobilization from intracellular stores. The kinetics, concentration-dependence and guanine nucleotide-sensitivity of these responses have been characterized for the agonists, carbachol, arecoline and oxotremorine. Carbachol stimulated Ins(1,4,5)P3 accumulation and Ca2+ mobilization with an EC50 value approximately 50 microM, only slightly lower than the apparent affinity of this agonist for the "free" receptor (100 microM). Arecoline and oxotremorine were partial agonists, mobilizing 45 and 21% of the Ca2+ mobilized by carbachol, and yielded EC50 values for both Ins(1,4,5)P3 and Ca2+ responses, similar to their binding affinity. Guanosine 5'-O-3 thio-triphosphate (GTP gamma S) markedly enhanced the responses elicited by all three agonists. Carbachol became significantly more potent for both Ins(1,4,5)P3 accumulation (EC50 = 4.1 microM) and Ca2+ mobilization (EC50 = 0.25 microM), revealing a separation of the dose-response relationships. GTP gamma S caused a smaller separation of the responses elicited by arecoline (Ca2+ mobilization EC50 = 0.9 microM; Ins(1,4,5)P3 accumulation EC50 = 3.6 microM), and only enhanced maximal responses for oxotremorine. These data reveal that the functional coupling of muscarinic receptors to activation of phosphoinositidase C and subsequent Ca2+ mobilization from intracellular stores is maintained after electrical permeabilization. Furthermore, this model has been used to reveal differences in the relative activities of muscarinic agonists and how they are influenced by a hydrolysis-resistant guanine nucleotide.

Arecoline↗

Conjugal mobility of the multicopy plasmids NTP1 and NTP16.

Mobilization of the multicopy plasmid NTP16, like that of ColE1, is promoted by a range of conjugal plasmids. However, the mechanisms employed for NTP16 mobilization differ between groups. Mobilization by the IncI1 plasmid R64 requires trans-acting products from NTP16 plus a cis-acting region of the small plasmid. In contrast, this system is used inefficiently by the F plasmid and instead, a high-frequency conduction process occurs. Analysis of exconjugant cells reveals that F-mediated mobilization of NTP16 frequently involves rearrangements of NTP16 DNA, promoted by the Tn1000 transposon of F and/or by the kanamycin resistance transposon (Tn4352) of NTP16. Possible mechanisms for the high-frequency F-mediated mobilization of NTP16 are discussed. The plasmid NTP1, which is closely related to NTP16, is also mobilized efficiently by R64. It is not however efficiently mobilized by F, demonstrating the requirement for the Tn4352 element, which is not present in this plasmid, for effective F-mediated transfer.

Conjugation, Genetic↗

A histamine derivative increases intracellular calcium mobilization and oxidative metabolism in HL-60 cells.

Past work in our laboratory has shown that a derivative of histamine, histamine-trifluoromethyl-toluidide (HTMT), has surprising tissue specificity on lymphocytes and can produce remarkable immunosuppression. This study focuses on the effects of HTMT on Ca2+ mobilization and oxidative metabolism in undifferentiated and DMSO-differentiated HL-60 cells. HTMT caused two phases of increases in intracellular calcium concentrations ([Ca2+]i) in HL-60 cells. The responses were dose dependent, with similar EC50 values (1.7 x 10(-5) M for undifferentiated and 1.5 x 10(-5) M for differentiated cells). The increase in [Ca2+]i in differentiated cells was much greater than in undifferentiated cells. The maximum responses were observed after the undifferentiated cells were incubated with DMSO for 7 days. The increase in [Ca2+]i induced by HTMT in both types of cells was competitively antagonized by high concentrations of histamine but not by classic histamine receptor antagonists (H1, H2, or H3). The inhibitory effects of histamine on [Ca2+]i accumulation in differentiated cells were partially reversed by histamine H2 receptor antagonist ranitidine, whereas in undifferentiated cells, the effects of histamine on Ca2+ mobilization were not affected by ranitidine. Other cAMP elevating agents did not inhibit increases in [Ca2+]i in undifferentiated cells but did affect [Ca2+]i in differentiated cells. The enhanced response in [Ca2+]i mobilization after differentiation of HL-60 cells appeared to be the result of an increase in the expression/function of receptors for HTMT. One interesting feature of this regulation was the fact that cAMP per se did not regulate HTMT induced Ca2+ mobilization in undifferentiated cells but inhibited the mobilization in differentiated cells. HTMT caused the generation of reactive oxygen species in both undifferentiated and differentiated HL-60 cells as measured by chemoluminescence and the levels of generation correlated with the mobilization of [Ca2+]i. In addition, the EC50s for the HTMT induced calcium mobilization and the generation of reactive oxygen species were similar, as was the case for histamine induced inhibition (Ki) in both cell types. The data imply a second messenger role for Ca2+ in HTMT induced neutrophil activation.

Binding Sites↗

Mobility of the osteotomy site following Le Fort I osteotomy stabilized by titanium plate osteosynthesis.

PURPOSE: This study analyzed whether titanium plate osteosynthesis prevents mobility after Le Fort I osteotomy and, if not, how long the osteotomized segment is mobile. PATIENTS AND METHODS: In 10 patients aged 17 to 49 years, three metal bone markers were inserted below and three above the osteotomy during the Le Fort I procedure, each set forming a triangle. The patients were examined at intervals until 1 year postoperatively. At each examination two sets of x-ray stereograms were obtained; one in rest and one with pressure applied to the anterior part of the maxilla. The difference in position of the maxillary segment in relation to the reference segment between the two sets of stereograms, ie, the mobility, could thus be recorded. Findings of 0.4 degrees and 0.2 mm are considered significant. RESULTS: Immediately after surgery mobility in the osteotomy site was found in 7 of the 10 patients. One year postoperatively mobility in the osteotomy site was still found in four patients. CONCLUSION: Titanium plate osteosynthesis does not prevent mobility between the osteotomy segments after Le Fort I osteotomies. The osteotomized segment may remain mobile at least until 12 months after surgery. During this period the impact of the functional matrix may cause migration of the segment.

Adolescent↗

The significance of extension and impaired mobility in cancer of the vocal cord.

The criteria for T2 glottic cancer staging in the UICC classification are extension to the supra- or subglottic region combined or not with impaired mobility of the vocal cord. The prognostic significance of these factors is examined in this study. Patients with T2A lesions (normal mobility, 33 patients) have an uncorrected actuarial 5 year survival of 54%, and a local control rate with radiotherapy alone of 62%. Patients with T2B lesions (impaired mobility, 28 patients) have a survival of 40% and a local control rate of 65% with radiation only. After rescue surgery, local control is obtained in 81% of T2A patients and 68% of T2B patients. While local control rates with radiotherapy alone were the same in T2A and T2B patients, final survival was lower for T2B patients because of less successful salvage surgery. While no significant differences in local control were found for different mucosal spread patterns, local control was excellent (87%) with radiotherapy alone in eight patients with mobility impairment without extension beyond the true cord, indicating that impaired mobility by itself is not a bad prognostic factor, but only when it is combined with tumor extension. In 9 patients with T2B tumors, a laryngectomy was performed immediately after initial radiotherapy (40 or 50 Gy) when the tumor persisted or the vocal cord mobility did not return to normal. None of these patients had a local recurrence after surgery. The total local control in all 37 T2B patients together was 78% (compared with 81% in T2A patients). The adverse prognostic influence of impaired mobility seems to have been eliminated by the treatment policy of surgery for those patients with poor regressions after radiotherapy. A dose-response relation can not be demonstrated in T2 glottic cancer for the dose range between 50 and 70 Gy.

Female↗

Mobilization of PAH and PCB from contaminated soil using a digestive tract model.

Environmental contaminants are mainly incorporated by ingestion. In general only those contaminants mobilized by the digestive juices are available for absorption in the digestive tract, while pollutants still fixed to indigestible particles leave the body without any effect. To evaluate the different health risks arising from the ingestion of individual types of polluted soil or other materials, we developed an in vitro test system which simulates the transition of pollutants from contaminated materials into digestive juices by means of a standardized artificial gastro-intestinal model. The test system simulates the influence of the acidic environment of the stomach (gastric model) followed by the neutral or slightly alkaline environment of the small intestine (gastro-intestinal model). Investigations on small amounts of polluted soil, sewage sludge, asphalt, metal scrap and blast sand showed that the mobilization of polycyclic aromatic hydrocarbons (PAH) and polychlorinated biphenyls (PCB) by artificial gastric juice reaches 3% up to 22% of the pollutant concentration introduced into the test system. Elutions of the contaminated materials under gastric and subsequently under intestinal conditions with bile concentrations of 3 g/l resulted in PAH- and PCB-mobilizations in the range of 5% up to 40%. The degree of mobilization depends considerably on supplementary food material added to the test system. Lyophilized milk increased the fraction of mobilized PAH and PCB to 40%-85%. Application of the test system on 22 different contaminated soils showed that the mobilization of PAH under gastro-intestinal conditions with the addition of lyophilized milk ranged from 7% up to 95%, and the mobilization of PCB ranged from 32% up to 83%. This indicates that the test system can be a useful tool for evaluating the individual health risks arising from polluted soil or other materials.

Animals↗

Host cell-dependent lateral mobility of viral glycoproteins.

The lateral mobility of viral envelope proteins on the plasma membranes of infected cells is an important factor in both virus assembly and pathogenesis. The envelope glycoproteins of measles and human parainfluenza virus are mobile on the surfaces of infected HeLa cells and undergo lateral redistribution in the presence of specific antibody, forming unipolar caps. In contrast, no such redistribution was observed with influenza virus hemagglutinin (HA) or vesicular stomatitis virus (VSV) G glycoproteins on infected HeLa cell surfaces. However, the HA and G glycoproteins were both found to be mobile in the plasma membrane of CV-1 cells, or human or murine peritoneal macrophages. These results indicate that host cell-dependent as well as virus-specific factors are involved in determining viral glycoprotein mobility. No significant differences in the patterns of synthesis of influenza or VSV viral proteins were found in the various cell types examined. The HA and G proteins, when expressed from vaccinia virus recombinants, were each found to be immobile in HeLa cells and mobile in CV-1 cells, thus indicating that the host cell-dependent differences in mobility are an intrinsic property of each viral glycoprotein molecule and not the result of interaction with other viral components. It is suggested that the association of viral glycoproteins with either the cytoskeleton or membrane-associated cellular proteins may be related to the observed differences in lateral mobility.

Animals↗

Ethanol-induced iron mobilization: role of acetaldehyde-aldehyde oxidase generated superoxide.

Superoxide radicals, a species known to mobilize ferritin iron, and their interaction with catalytic iron have been implicated in the pathogenesis of alcohol-induced liver injury. The mechanism(s) by which ethanol metabolism generates free radicals and mobilizes catalytic iron, however, is not fully defined. In this investigation the role of hepatic aldehyde oxidase in the mobilization of catalytic iron from ferritin was studied in vitro. Iron mobilization due to the metabolism of ethanol to acetaldehyde by alcohol dehydrogenase was increased 100% by the addition of aldehyde oxidase. Iron release was favored by low pH and low oxygen concentration. Mobilization of iron due to acetaldehyde metabolism by aldehyde oxidase was completely inhibited by superoxide dismutase but not by catalase suggesting that superoxide radicals mediate mobilization. Acetaldehyde-aldehyde oxidase mediated reduction of ferritin iron was facilitated by incubation with menadione, an electron acceptor for aldehyde oxidase. Mobilization of ferritin iron due to the metabolism of acetaldehyde by aldehyde oxidase may be a fundamental mechanism of alcohol-induced liver injury.

Acetaldehyde↗