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Injury by electrical forces: pathophysiology, manifestations, and therapy.

The pathogenesis and pathophysiologic features of electrical injury are more complex than once thought. The relative contributions of thermal and pure electrical damage depend on the duration of electric current passage, the orientation of the cells in the current path, their location, and other factors. If the contact time is brief, nonthermal mechanisms of cell damage will be most important and the damage is relatively restricted to the cell membrane. When contact time is much longer, however, heat damage predominates and the whole cell is affected directly. These parameters also determine the anatomic tissue distribution of injury. Damage by Joule heating is not known to be dependent on cell size, whereas larger cells are more vulnerable to membrane breakdown by electroporation. Cells do survive transient plasma membrane rupture under appropriate circumstances or if therapy is instituted quickly. If membrane permeabilization is the primary cellular pathologic condition, then injured tissue may be salvageable and the challenge for the future is to identify a technique to reseal the damaged membranes promptly. Present standards of care for electrical injury require a fully staffed and well-equipped intensive care unit, available operating suites, and the availability of the full range of medical specialists. Major teaching hospitals with burn centers may be the ideal setting for the treatment of an electrical trauma victim. After the initial resuscitation, efforts are directed primarily towards preventing additional tissue loss mediated through the compartment syndrome, compressive neuropathies, or the presence of necrotic tissue. Renal and cardiac failure caused by the release of intracellular muscle contents into the circulation must be prevented. Attention can then be directed towards maximizing tissue salvage and preventing late skeletal and neuromuscular complications. Reconstructive procedures that transfer healthy tissue from a distance are necessary to optimize the functional value of the remaining tissue. Finally, unless the patient is rehabilitated psychologically, the real benefit from other sophisticated care will not be fully realized. These goals are important throughout the acute care of the patient. In the future, new guidelines for treating electrical trauma will be based on a clearer understanding of the relevant pathophysiologic features. These strategies will rely on improved diagnostic imaging and on reversing the fundamental problem of cell membrane damage. Moreover, complex biochemical and organ system pathophysiologic interactions will require careful management. If successful, research efforts presently underway should improve the prognosis of victims after electrical trauma.

Burns, Electric↗

Effect of decreased retinal illumination on frequency doubling technology.

PURPOSE: To investigate the effect of changes in retinal illumination on Frequency Doubling Technology (FDT). METHODS: Five eyes, of 5 adults who were free from identifiable ocular pathology, were examined using the Snellen chart and the Pelli-Robson chart, conventional automated perimetry, and the full threshold N-30 program of FDT. Each test was performed with and without a 0.9, 1.5, or 2.4 log unit neutral-density (ND) filter placed before the eye. Furthermore, the influence of pupil diameter on FDT test results was compared after treatment with pilocarpine or cyclopentolate with the influence of ND filters. RESULTS: All tests showed a decrease in sensitivity with decreasing retinal illumination. Frequency Doubling Technology showed an especially pronounced and significant decrease in sensitivity. The maximum mean threshold difference in FDT results with ND filter was 31.2 dB while that with the Humphrey Field Analyzer and the Pelli-Robson chart were 13.3 dB and 0.66 log contrast, respectively. The mydriatic state of the pupil increased the sensitivity of FDT and the miotic state decreased it to about the same extent as the the 0.9 ND filter. CONCLUSION: The change in retinal illumination has more impact on FDT than on spatial contrast tests and conventional automated perimetry. It is important to take this into account in evaluating FDT results.

Adaptation, Ocular↗

The blindness of Saint Paul.

The Book of Acts in the Bible relates the story of St Paul's sudden blindness and subsequent recovery of vision. St Paul was walking along when he saw a bright light; he fell down and awoke blind. He remained blind for three days, at which time his vision returned from a "laying on of hands." Numerous theories have been proposed to account for this event. A review of the available evidence suggests that there are six additional previously unreported possible causes, which are enumerated in detail.

Arterial Occlusive Diseases↗

High tension electrical injury from a telephone receiver.

A high tension (13000 V) electrical injury to a young man from telephone receiver is described. The current entered the telephone circuit due to contact with a high tension live wire running close to the telephone wire 2 km away from the site of incidence.

Adult↗

Mechanism-based inactivation of cytochrome P450 3A4 by L-754,394.

Mechanism-based inactivation of human liver P450 3A4 by L-754,394, a Merck compound synthesized as a potential HIV protease inhibitor, was investigated using recombinant P450 3A4. Enzyme inactivation was characterized by a small partition ratio (3.4 or 4.3 +/- 0.4), i.e., the total number of metabolic events undergone by the inhibitor divided by the number of enzyme inactivating events, lack of reversibility upon extensive dialysis, no decrease in the characteristic 450-nm species relative to control, and covalent modification of the apoprotein. The major and minor products formed during the inactivation of P450 3A4 were the monohydroxylated and the dihydrodiol metabolites of L-754,394, respectively. L-754,394 that had been adducted to P450 3A4 was hydrolyzed under the conditions used for SDS-PAGE, Ni(2+) affinity chromatography, and proteolytic digestion. In addition, the modification was not stable to the acidic conditions of HPLC separation and CNBr digestion. The labile nature of the peptide adduct and the nonstoichiometric binding of the inactivating species to P450 3A4 precluded the direct identification of a covalently modified amino acid residue or the peptide to which it was attached. However, Tricine SDS-PAGE in combination with MALDI-TOF-MS and homology modeling, allowed I257-M317 to be tentatively identified as an active site peptide, while prior knowledge of the stability of N-, O-, and S-linked conjugates of activated furans implicates Glu307 as the active site amino acid that is labeled by L-754, 394.

Binding Sites↗

Power measurements of spark discharge experiments.

An accurate and precise knowledge of the amount of energy introduced into prebiotic discharge experiments is important to understand the relative roles of different energy sources in the synthesis of organic compounds in the primitive Earth's atmosphere and other planetary atmospheres. Two methods widely used to determine the power of spark discharges were evaluated, namely calorimetric and oscilloscopic, using a chemically inert gas. The power dissipated by the spark in argon at 500 Torr was determined to be 2.4 (+12%/-17%) J s-1 by calorimetry and 5.3 (+/- 15%) J s-1 by the oscilloscope. The difference between the two methods was attributed to (1) an incomplete conversion of the electric energy into heat, and (2) heat loss from the spark channel to the connecting cables through the electrodes. The latter contribution leads to an unwanted effect in the spark channel by lowering the spark product yields as the spark channel cools by mixing with surrounding air and by losing heat to the electrodes. Once the concentrations of the spark products have frozen at the freeze-out temperature, any additional loss of heat from the spark channel to the electrodes has no consequence in product yields. Therefore, neither methods accurately determines the net energy transferred to the system. With a lack of a quantitative knowledge of the amount of heat loss from the spark channel during the interval from ignition of the spark to when the freeze-out temperature is reached, it is recommended to derive the energy yields of the spark products from the mean value of the two methods with the uncertainty being their standard deviation. For the case of argon at 500 Torr, this would be 3.8 (+/-50%) J s-1.

Argon↗

Morphological and functional state of the heart during magnetic storm.

Magnetic storm modulates morphological and functional state of the heart and the related systems. Changes in cardiomyocyte ultrastructure induced by changes in geomagnetic activity were studied in experiments on rabbits. We describe a possible mechanism underlying changes in cardiac activity in intact animals induced by geomagnetic perturbations. The most pronounced alterations of cardiomyocyte ultrastructure were observed during the major phase of magnetic storm.

Animals↗

Lightening.

Explore the source record for details and available documents.

History, 18th Century↗

Replacement of the distal glycine 139 transforms human heme oxygenase-1 into a peroxidase.

The human heme oxygenase-1 crystal structure suggests that Gly-139 and Gly-143 interact directly with iron-bound ligands. We have mutated Gly-139 to an alanine, leucine, phenylalanine, tryptophan, histidine, or aspartate, and Gly-143 to a leucine, lysine, histidine, or aspartate. All of these mutants bind heme, but absorption and resonance Raman spectroscopy indicate that the water coordinated to the iron atom is lost in several of the Gly-139 mutants, giving rise to mixtures of hexacoordinate and pentacoordinate ligation states. The active site perturbation is greatest when large amino acid side chains are introduced. Of the Gly-139 mutants investigated, only G139A catalyzes the NADPH-cytochrome P450 reductase-dependent oxidation of heme to biliverdin, but most of them exhibit a new H(2)O(2)-dependent guaiacol peroxidation activity. The Gly-143 mutants, all of which have lost the water ligand, have no heme oxygenase or peroxidase activity. The results establish the importance of Gly-139 and Gly-143 in maintaining the appropriate environment for the heme oxygenase reaction and show that Gly-139 mutations disrupt this environment, probably by displacing the distal helix, converting heme oxygenase into a peroxidase. The principal role of the heme oxygenase active site may be to suppress the ferryl species formation responsible for peroxidase activity.

Glycine↗

Disruption of an active site hydrogen bond converts human heme oxygenase-1 into a peroxidase.

The crystal structure of heme oxygenase-1 suggests that Asp-140 may participate in a hydrogen bonding network involving ligands coordinated to the heme iron atom. To examine this possibility, Asp-140 was mutated to an alanine, phenylalanine, histidine, leucine, or asparagine, and the properties of the purified proteins were investigated. UV-visible and resonance Raman spectroscopy indicate that the distal water ligand is lost from the iron in all the mutants except, to some extent, the D140N mutant. In the D140H mutant, the distal water ligand is replaced by the new His-140 as the sixth iron ligand, giving a bis-histidine complex. The D140A, D140H, and D140N mutants retain a trace (<3%) of biliverdin forming activity, but the D140F and D140L mutants are inactive in this respect. However, the two latter mutants retain a low ability to form verdoheme, an intermediate in the reaction sequence. All the Asp-140 mutants exhibit a new peroxidase activity. The results indicate that disruption of the distal hydrogen bonding environment by mutation of Asp-140 destabilizes the ferrous dioxygen complex and promotes conversion of the ferrous hydroperoxy intermediate obtained by reduction of the ferrous dioxygen complex to a ferryl species at the expense of its normal reaction with the porphyrin ring.

Heme Oxygenase (Decyclizing)↗