If It Smells Like a Duck, It Might Be an Asthma Subphenotype
Now beginning to be heard above the constant din of powerful marketing efforts to the converse, a growing wave of physicians have been shouting “asthma is not a diagnosis.” Indeed, asthma is but a symptom, categorically on par with diarrhea. Imagine determining the optimum treatment strategy for diarrhea based almost entirely on whether it was “mild,” “moderate,” or “severe,” and “intermittent” or “persistent.” Imagine striving to control excessive stooling while neglecting to consider the cause. Imagine trying to study the genetics of diarrhea. Imagine attempting to examine the efficacy of a new drug by enrolling everyone with diarrhea, regardless of mechanism, in one giant study and expecting the results to be applicable to an individual patient. Now, what applies to diarrhea applies equally well, or equally poorly, to that symptom complex we still refer to as “asthma.”
Variable airway narrowing leading to wheeze can be caused by bronchospasm, inflammatory cell accumulation, mucous plugging, surfactant dysfunction, airway edema, airway vascular congestion, or abnormal structure and function of the airways. Each of these mechanisms of wheeze and air trapping has multiple underlying potential causes. It is no wonder that a one-size-fits-all strategy for managing asthma leaves many insufficiently diagnosed and wrongly treated, for many of the underlying mechanisms are left undiscovered or unaddressed.
To optimize our therapeutic strategies, we are making increasing strides to seek the underlying causes for each individual patient’s asthma using various tests. These efforts to subphenotype the patient’s asthma are in effect efforts to make a true diagnosis. We determine whether or not inhalant allergies might be driving an inflammatory process. We try to guess if gastroesophageal reflux is a contributor to a patient’s symptoms. We are starting to measure exhaled nitric oxide and induced sputum characteristics, thereby quantifying at least a small proportion of the myriad components of the nebulous entity known as inflammation, at which we otherwise blindly direct our therapies. These efforts are noteworthy.
In this issue of AJRCCM(pp. 986-990), Carraro and colleagues (1) continue the efforts of an expanding contingent of researchers to develop means for acquiring biochemical information about the narrow and difficult-to-access passages that lead to our alveoli. They studied exhaled breath condensate-a body fluid easy to obtain (easy on patients), but difficult to assay (hard on scientists) (2). Using nuclear magnetic resonance (NMR) signals derived from concentrated exhaled breath condensate, Carraro and colleagues have identified NMR spectroscopy patterns that, at least post hoc, well differentiate patients with clinically identified asthma from control subjects. Although the human nose cannot sense these patterns, the magnetic nose can. Of course, how such high-tech testing as NMR spectroscopy of breath condensate compares to the gold-standard asthma diagnostic method can never be determined, for there is no gold-standard asthma diagnostic method-quite simply because asthma is not a diagnosis.
These NMR signal patterns in exhaled breath condensate may not only serve as phenotypic discriminators but may also open a window on airway biochemical disturbances underlying airway cellular dysfunction. In other words, they may help us find the disease in each patient that leads to his or her asthma symptoms. We are moving down a path from DNA genomics, through RNA expression , through proteomics, and now on to metabolomics. Each step down this path takes us closer to the direct cause of the physiologic disturbance .
In this preliminary, but novel, methodologic study, Carraro and colleagues speculate that the particular NMR chemical patterns they identify in patients with asthma symptoms may be attributable to abnormal acetylation and oxidation biochemistry of the asthmatic airway. Such chemical pathways are known to exist in humans
(3), although their pathologic relevance in the lungs is completely unknown. As with many breath assays, dilution effects and oral contribution have not yet been well controlled, and prospective analysis based on the post hoc NMR patterns has not yet been done. But this study will be the first of many, and it may be that abnormal acetylation chemistry joins redox disturbance, airway acidification, and abnormal nitrosothiol chemistry as targets for new pharmacologic therapies aimed at addressing the metabolic disturbances of the airway. Noninvasive assays, such as NMR spectroscopic patterning of breath condensate, when validated sufficiently, can be anticipated to assist in identifying which patients are most likely to benefit from any such new therapies. Instead of testing oral antioxidants, inhaled alkaline buffers, and nitrosothiol supplementation as therapies for asthma, we can instead more appropriately test these compounds as specific treatments for “airway redox disturbance,” “airway acidity,” and “nitrosothiol deficiency,” using the asthma symptoms as but one important outcome variable. In such a fashion, testing new therapeutic compounds can be performed in those patients having the relevant metabolic disturbance as identified with objective testing, as opposed to just seeing if the drug works in asthma.
A future short of breath? Possible effects of climate change on smog
Smog arrives in U.S. northeastern and midwestern states with the summer’s merciless heat and still air, a brown haze that hangs in the sky until cool air rolls in and provides a welcome respite. In Los Angeles and Missoula, it thickens in mountain basins like soup in a pot. Houston’s smog worsens in September, when sea breezes off the Gulf of Mexico die down. For the rest of the world, although the composition and severity of smog can vary greatly from region to region, a pattern has emerged: Warm temperatures, pollutants, and sunlight often work together to produce unhealthy conditions, the dangers of which are just now becoming known. The United States and other countries have attempted to address the issue of air pollution. On “bad air days,” when particularly smoggy conditions are predicted, newscasters or authorities urge people to take public transportation and warn asthmatics and others with heart or lung conditions to stay indoors.
As more has become known about what meteorological conditions favor smog formation, predictions for the next day’s air quality have become increasingly accurate. But what about the long-term picture? In coming decades, climate change will likely have a large impact on temperatures at the Earth’s surface and on day-to-day weather patterns. Will higher temperatures at the surface favor smog formation? Or will these higher surface temperatures contribute to lofting of the smoggy air toward higher layers of the atmosphere? How will changes in cloud cover impact surface air quality? If a warmer atmosphere can hold more water vapor, will cloud cover increase, thereby slowing down the production of smog? Finally, how will developing countries adopt new technologies without further degrading their air quality in a changing world?
Smog consists of a mixture of chemicals, some in gas-phase and some in the form of tiny particles. Smog starts with the emissions of gases like nitrogen oxides, volatile organic compounds (VOCs), and sulfur dioxide, and of particles like organic carbon and soot. Many of these constituents form during combustion processes. Every time someone starts a car or a coal-fired power plant kicks in, the high temperatures of combustion cause the release of more smog precursors into the air. But some smog precursors have natural sources. For example, for reasons that are not entirely clear, many trees and grasses emit VOCs like isoprene or a class of molecules called monoterpenes. Plant biologists are still trying to sort out why plants evolved to emit these chemicals and what protective effect the molecules could have on leaf structure. Even tiny organisms in soil emit high quantities of N[O.sub.x] as they convert other forms of nitrogen into usable energy.
But this short answer–that higher temperature means worsening air quality–neglects many competing and complicating factors. For example, the source gases that form secondary organic particles condense less readily at higher temperatures, which could mean fewer such particles in the atmosphere in the future.
One of the main factors influencing pollution levels is the frequency and duration of stagnation episodes. Stagnant air traps air pollution, allowing the chemicals to interact and the products of emissions to accumulate. Stagnation episodes typically occur during the summer, when the heat and humidity can become unbearable, but they can occur at other times of the year as well. In December 1952, a cold air mass moved off the English Channel and parked over London for five days. The cold air trapped the plumes of soot emanating from coal-fired stoves and factories, leading to a thick, dirty haze. This smog event, known as the Great Smog of 1952, may have led to as many as 12,000 premature deaths in the days and months that followed.
In the coming decades, as climate changes, will such stagnation episodes take place more frequently? Will they last longer when they occur? To understand how future climate change could affect stagnation episodes, it is helpful to think about how such episodes in the present-day atmosphere come and go. Over mid-latitudes, stagnation is one phase of an endlessly repeating weather pattern. First, a cold front comes through from the west, bringing rain and cool weather. After the passage of the cold front, winds weaken, the sky clears, and temperatures begin to climb. The air may stagnate. Soon another cold front arrives. A wedge of cool or cold air pushes in, lifting the warm (and possibly polluted) air eastward and poleward. What drives these cold fronts is the Earth’s heat imbalance. The sun deposits most of its energy in the tropics, and the ocean and atmosphere respond with several mechanisms that redistribute that energy. Cold fronts contribute to this redistribution by pushing warm air toward the colder, higher latitudes.
It should be emphasized, however, that all the studies described above made one very large assumption: that the emissions of smog precursors related to human activity would stay constant through future decades. In fact, it is quite possible that such emissions will decline, as new technology is put in place and existing regulations on pollution are tightened. The main value of these studies is that they make clear the climate change penalty that will be needed to overcome to meet air quality standards.
Particles have a more complicated role influencing climate. Most particles, such as sulfate or organic particles, reflect incoming sunlight like tiny mirrors and therefore lead to cooling. Soot particles, on the other hand, absorb incoming sunlight and outgoing infrared radiation, making the net effect of these particles difficult to calculate. Some studies have suggested that plumes of soot and sulfate particles emanating from South Asia may have led to local cooling of the Indian subcontinent, diminishing the strength of summer monsoon. This effect could counteract the warming influence of greenhouse gases, which most models predict will intensify the monsoon.
Dyes from Enzyme-Mediated Oxidation of Aromatic Amines
This paper characterizes reaction products from the oxidoreductase enzymatic conversion of aromatic amines to dyes that have an affinity for wool fibers. The dyes are identified with the aid of mass spectrometry, FTIR, ^sup 1^H-NMR, combustion analysis, and by comparison of experimental and calculated [lambda]^sub max^ data. The results of these analyses indicate that the dyes are binuclear and trinuclear aromatic compounds, depending on the number of available coupling sites in the precursor molecules and the number of reactants employed in the coupling step. Pathways associated with this enzyme-induced formation of dyes are proposed that involve a two-electron oxidation of 1,4-diamines to electrophilic diimines.
Oxidoreductase enzymes include laccase, which is a polyphenol oxidase enzyme that belongs to the family of blue copper oxidases. A typical laccase molecule is 60-80 kDa, of which 15-20% is carbohydrates such as mannose, galactose, hexoseamine, glucose, arabinose, and fucose. The protein constituent of these enzymes contains 520-550 amino acid residues [17, 18], and the three different copper centers that are primarily responsible for enzyme activity are known to undergo single-electron reductions in the presence of oxidizable substrates such as aryl diamines, polyphenols, polyamines, aminophenols, and lignin [2, 8, 10, 18]. The reduced form of laccase can be oxidized by molecular oxygen in order to replenish its catalytic activity.
Recent studies in our laboratories determined that water-soluble arylamines such as 1-3 may be oxidized alone or in certain combinations to produce colorants with an affinity for wool [1,7]. While this work included studies leading to precursor structure-color relationships, the exact chemical structures of these products were not established. Since such information was deemed critical to the optimization of this interesting new technology, we have undertaken the current study.
To this end, we have isolated and characterized the yellow dye produced from diamine 1 and the blue dye from a mixture of amines 2 and 3, since both dyes produced promising results in screening studies. We have characterized the isolated products with the aid of mass spectrometry, FTIR, ^sup 1^H-NMR, combustion analysis, and by comparison of experimental and calculated [lambda]^sub max^ data. We then use the results of these analyses to determine plausible pathways to product formation.
All chemicals in this study came from the Aldrich Chemical Company, Fisher Scientific Company, or TCI America. Thin layer chromatography involved Whatman silica gel (250 µm, 60[Angstrom]) glass-backed plates and column chromatography involved 60[Angstrom]4 silica gel. TLC solutions were prepared by dissolving the dye-containing freeze-dried solids (15 mg) in distilled water (0.5 ml), the plates were spotted 10 mm from the bottom edge, and eluents were allowed to travel 60 mm. The principal TLC eluent was ethyl acetate : ethanol : water (2:1:1), which was designated as eluent 1. Other useful eluents are reported elsewhere [141.
Visible absorption spectra were obtained with a Varian Gary 3 uv-visible spectrometer. Elemental analysis was performed by Atlantic Microlab Inc., Norcross, Georgia. FTIR spectra were recorded on a Nicolet 510 P FTIR spectrophotometer using a Continuum microscope. Mass spectra were recorded by a Jeol HX110 double-focusing mass spectrometer, and ^sup 1^H-NMR spectra were recorded on a Bruker 500 MHz spectrometer. A Data Color International Spectraflash 600 Plus reflectance spectrophotometer was used to obtain color strength data on dyed wool fabrics.
Geometric optimizations were performed with the PM3 method in CAChe MOPAC 6.0, part of the CAChe Worksystem [3], on an Apple Macintosh Quadra 950 equipped with 64 MB RAM, a 40 MHz CXP RISC coprocessor, and a 3D stereoscopic monitor. Absorption maxima were calculated using PiSystem98 [12] on a 400 MHz Pentium II personal computer.
Dye formation was achieved by dissolving or suspending the amines (0.5 mM) in water (50 ml) at pH 5 with O. IM Britton-Robinson buffer and adding the enzyme Myceliophthora thermophila laccase (150 LACU), where 1 LACU (one laccase enzyme activity unit) is the amount of enzyme that catalyzes the conversion of 1 µM syringaldazine per minute at the following analytical conditions: pH 5.5, 23.2 mM acetate buffer, 19 µM syringaldazine, and 30°C. The solution was stirred at 60°C for 1 hour. Freeze-dried solids containing reaction products and enzyme were prepared by Novo Nordisk BioChem North America.
Molecular Dynamics Simulation of Deoxy and Carboxy Murine Neuroglobin in Water
Globins are respiratory proteins that reversibly bind dioxygen and other small ligands at the iron of a heme prosthetic group. Hemoglobin and myoglobin are the most prominent members of this protein family. Unexpectedly a few years ago a new member was discovered and called neuroglobin (Ngb), being predominantly expressed in the brain. Ngb is a single polypeptide of 151 amino acids and despite the small sequence similarity with other globins. it displays the typical globin fold. Oxygen, nitric oxide, or carbon monoxide can displace the distal histidine which, in ferrous Ngb as well as in ferric Ngb, is bound to the iron, yielding a reversible adduct. Recent crystallographic data on carboxy Ngb show that binding of an exogenous ligand is associated to structural changes involving heme sliding and a topological reorganization of the internal cavities; in particular, the huge internal tunnel that connects the bulk with the active site, peculiar to Ngb. is heavily reorganized. We report the results of extended (90 ns) molecular dynamics simulations in water of ferrous deoxy and carboxy murine neuroglobin, which are both coordinated on the distal site, in the latter case by CO and in the former one by the distal His^sup 64^(E7). The long timescale of the simulations allowed us to characterize the equilibrated protein dynamics and to compare protein structure and dynamical behavior coupled to the binding of an exogenous ligand. We have characterized the heme sliding motion, the topological reorganization of the internal cavities, the dynamics of the distal histidine, and particularly the conformational change of the CD loop, whose flexibility depends ligand binding.
Globins are water-soluble respiratory proteins that reversibly bind dioxygen and other small ligands at the iron of a hone prosthetic group (hat is buried in a highly conserved ?-helical globin fold. Hemoglobin (Hb) and myoglobin (Mh) are lhe most prominent members of this protein family (1). In 2000, neuroglobin (Ngb), anew member of the vertebrate globin family, was discovered (2).
Ngb, a single polypeptideof 151 amino acids, is expressed in the nervous tissues. Despite the small sequence similarity Io the other glohins (
Binding of O2, CO. and NO to the ferrous heme iron displaces His^sup 64^(E7l. Io yield a reversible adducl. This reaction implies a competition between the exogenous ligand and the endogenous HisM(E7). lhe rupture of the sixth coordination bond being a prerequisite for binding. The kinetics of this process has been studied by stopped-flow and by laser photolysis of the adducts of reduced Ngb with (X CO. and NO (5-11). Rapid mixing kinetic data showed that binding of an exogenous ligand to reduced deoxy Ngb is slow (t^sub 1/2^ = ~1 s) and ligand concentration independent, as expected. The three-dimensional structure has been solved by x-ray crystallography for the unliganded ferric Ngb from man and mouse (3.4) and for the CO-bound ferrous form (12). The latter article showed that binding of CO is associated to structural changes involving a significant hcme sliding and a lopological reorganization of the inlernal cavities; in particular, the huge internal tunnel connecting the bulk to the active siie (a peculiarity of Ngh) is topologically reorganized.
The physiological role of Ngb is not well understood. Average Ngb concentration seems loo low (
Molecular dynamics (MD) simulations have provided important insight into the structure and function of globins such as Mb and Hh ( 15-20). Recently, extended MD simulations allowed us to follow the CO migration in the interior of myoglobin. as well as the effects of mutations and trapped CO on the Mh structure and cavities dynamics (21,22), in correlation wilh experimental studies (23-25).
This article reports the results of extended (W ns) MD simulations ofdeoxy and carhoxy murinc Ngh in water. The purpose is to compare the structural dynamics of deoxy and carhoxy Ngh in solution, in particular the heme group motion and the related internal cavities lluctualions that appear so peculiar compared to other glohins. To this end, the same oxidation stale has been chosen. Stalling from the crystallographic coordinates ( 12). our MD results show a large amplitude motion of the heme in NgbCO and a corresponding large fluctuation of the cavities. In addition, we have documented a flip/flop motion of the CD loop upon CO binding, which is correlated to the Hisw(E7) configuration and seems to he particularly significant to evaluate the possible role of Ngb as a molecular signal transducer involved in neuroprotection (26.27).
METHODS
The start my coordinates employed for the simulations were taken from the x-ray structure of CO-bound ferrous murinc Ngb al 1.7 [Angstrom] resolution (PDH entry 1w92) (12): in the case of deoxy Ngh, we useil the 1.5 A resolution structure of murine ferric bis-histidine Ngh (PDB entry 1q1f) (4). The cryslallographic structures were obtained with a Ngh mutant (C55S/CI20S). since the presence ol oxidizable cysteines in the wild-type protein hindered crystallization. Murine ferric Ngh shows the presence of two different protein conformers (relative occupancy ~70:30) due to heterogeneity of the heme group orientation, tor a 180° rotation around the ?-? meso axis (4,28); also the proximal His^sup 96^(FX) and the distal His^sup 64^(E7) histidines assume two conformations, with the same ratio of occupancy. In the deoxy Ngh simulation, we have used the en stal structure ol lhe conformer with the major occupancy and simply assigned the ferrous oxidation state to the metal.
To determine the partial charges of lhe hexacoordinaled heme in deoxy and carhoxy Ngh. we performed the quantum chemical calculations on the isolated bis(imidazole) iron^sup II^ porphyrin [Fe^sup II^P(lm)^sub 2^] complex and the carhoxy-imidazole iron^sup II^ porphyrin [Fe^sup II^P(CO)(lm)] complex, respectively. Density functional calculations. Beeke’s three parameters exchange (21Jl. and Lee. Yang. Parr correlation (B3LYP) (30) were performed. All our quantum chemical calculations were carried out using the GAMESS US package (31). In the GROMOS force field. the heme iron neighbor has hccn defined through a single charge group with the following partial atomic charges: 0.4 e for the iron and -0.1 e for the Jour pyrrolic nitrogen atoms. Therefore, we have chosen to change only the iron charge group. We used the Ahlrichs VTZ basis set (32) for the iron and the 6-311+G* basis set for the nitrogen atoms of the heme and the helcmatorm of the imida/ole and carbon monoxide molecules. We have used the 3-21G basis set for the rest of the system and for all hydrogen atoms. The partial charges have been obtained from the CHELPTi algorithm, and lhe lined charges have been constrained in exactly reproduce lhe total charge and ihe calculated dipole moment of the system. In conclusion we have chosen lhe follow ing set of partial charges: for deoxy Ngh. 0.3 e for lhe iron and -0.075 e tor the pyrrolic nitrogen atoms, while for carboxy Ngh. 0.6 e for lhe iron and -0.15 e for the heme nitrogen atoms: for the CO hound Io ihe hexacoordinated ferrous heme. we have used 0.17 e for Ihe carbon and -0.17 e for the oxygen atom.
Each protein was solvaled in a box with explicit single-point charge water molecules (33). large enough Io contain the protein and 0.8 nm of solvent on all sides. The total number of atoms for the systems was ~21,000).
MD simulations were performed with the GROMACS software package (34) using GROMOSWi force field (35). ‘Hie additional parameters for hexacoordinated heme and bound CO were taken from the GR(JMOS forcefield parameter sels 53Aft (3d). Simulations were earned oui al constant temperature of 300 K within a lixed-volume rectangular box using peritidic boundary conditions. The LINCS algorithm l37l Io constrain lionil lengths and Ihe rotoiraiislaiional constrain! algorithm (.1Si were useil. Oie initial velocities were taken randomly from a Maxwellian distribution al 300 K and the temperature was held constant by Ihe isothermal algorithm (39). By using dummy hydrogen atoms (40), a lime step of 4 Is could he ehosen: we have also redistributed Ihe water oxygen mass on the hydrogen alinm to improve me stability of Ihe simulations. ‘Pie partifle mesh F.wald method (41) was used for llie ealeuiaiion of ilie long-range interactions with a grid spacing of 0.12 nm eomhined with a founh-order B-spline interpolation 10 compulc the polential and forces in between grid pojnis. A nonhoiid pair list cutoff of 9.0 [Angstrom] was used and Ihe pair lisl was updated even four time steps. For all systems, the solvent wa.s relaxed by energj minimization followed by 100 ps of MD al 300 K. while resiraining prnicin alomie positions with a harmonie polential. The systems were then minimized wilhout resirainls and their temperature brought to 300 K in a siepwise manner: 50 ps Ml) runs were famed oui ai 50, 100, 150, 200, 250, and 300 K. before starting the produelion runs at 300 K.
We used ilie essential dummies technique (42) to characterize the dynamical behavior of the protein.
The package SURFNET (43) was used lor detecting the cavities and calculating lheir volumes. In this program, gap regions are delined hy tilling the empty regions in ihe inlerior of ihe molecule with gap spheres of variable raduis (R^sub min^ = 1.0 [Angstrom] and R^sub max^ = 3.0 [Angstrom]. in our case I. These spheres are ihen used to compute a three-dimensional density map that, when contoured, defines the surface of the gap region. Cavity volumes were evaluated without taking into account the presence of the water and of CO in the case of carhoxy Ngh simulation, A cavity is considered exposed if the SURFNET program shows a continuity between the cavity and the solvent.
RESULTS
The root mean-square deviation of C^sub ?^, atoms (data not shown), obtained from deoxy anil carhoxy Ngb (NgbCO) simulations with respect to lheir crystallographic structures, shows that within 15 ns the two trajectories reach values of ~1.8 [Angstrom] and ~2.4 [Angstrom], for the dcoxy Ngh and NgbCO respectively; a small drift is then observed up to 90 ns. The residue-based root mean-square llucluation for C?, (data not reported) shows thai ihe main root mean-square fluctuation difference between deoxy and NgbCO is located around the residue Glu^sup 80^. in the EF loop. The drastic reduction of the EF loop lluciiiation in NgbCO with respect lo deoxy is in agreement with the x-ray diffraction dala (12).
The motion of the henie in the NgbCO simulation was monitored with the essential dynamics analysis, which was performed on all the heme atoms (with the exception of the terminal propionic chains). The eigenvectors with large eigenvalues correspond to the principal directions of motion of the heme group. The motion associated to the first eigenvector (Fig. 1 A) is revealed to be. essentially, a rolotranslalional displacement in the direction from D to B pyrrole rings (Fig. 2): the two extreme heme configurations onto the Iirsl essential eigenvector correspond Io a tolal displacement of ~1.85 [Angstrom] for the heme iron. The rotation around an axis parallel to the macrocycle average plane, centered in ihe iron atom and in the direction connecting the A and C pyrrole rings, is ~9° for the two extreme configurations. This rototranslational motion corresponds to the heme sliding movement observed in comparing the crystal structures of NghCO and melNgh (12). Il has to he noted that the position, which corresponds to the positive value of the trajectory projection (Fig. 1 A), is not allowed in NghCO crystal structure, due to close contacts between the CO hound to the hcme and the distal HisM(E7); however, a displacement of the latter (
The free energy landscape of the heme displacement was calculated by the use of the potential of mean force method (45), as reported in Fig. 1 B. The abscissa refers to a direction connecting the two extreme positions of the heme in the simulation. The free energy plot shows a minimum at 1.7 [Angstrom], a position corresponding to that seen in the inetNgb crystal structure. The position of the heme in the NghCO crystal structure (~0.3 [Angstrom] in Fig. 1 Ii) corresponds to an almost flat region whose free energy value is ~5 kJ/mol higher than the minimum.
Check it out: air cleansing in healthcare facilities
When heating, ventilation, and air conditioning (HVAC) systems in healthcare facilities perform their purpose well, they “… a) maintain the indoor air temperature and humidity at comfortable levels for staff, patients, and visitors; b) control odors; c) remove contaminated air; d) facilitate air-handling requirements to protect susceptible staff and patients from airborne health-care-associated pathogens; and e) minimize the risk for transmission of airborne pathogens from infected patients,” stated the Centers for Disease Control and Prevention (CDC) in their “Guidelines for Environmental Infection Control in HealthCare Facilities.” (1) The report goes on to say, “Decreased performance of healthcare facility HVAC systems, filter inefficiencies, improper installation, and poor maintenance can contribute to the spread of health-care-associated airborne infections.” (1)
The standard for air-cleansing in healthcare facilities is filtration. (1) Basically it works by bringing outdoor air into the system, where it meets with a low-efficiency filter, which removes large particulate matter and many microorganisms. The air then enters the distribution system where it’s conditioned to appropriate temperature and humidity levels. Then it passes through an additional bank of filters for further cleaning before being delivered to each zone of the building. After distribution, the air is withdrawn through a return duct system and sent back to the HVAC unit. Some of the “returned” air is exhausted to the outside; the remainder is mixed with outdoor air for dilution and filtered for removal of contaminants. Air from “soiled” areas has particular exhaust needs. For example, toilet-room air usually is exhausted directly to the atmosphere through a separate duct exhaust system, and air from the rooms of tuberculosis patients is exhausted to the outside, if possible, or passed through a high-efficiency particulate air (HEPA) filter before recirculation. (1).
There are five methods of filtration, with varying levels of efficiency: 1) straining (low filter efficiency), which removes large particles; 2) impingement (low efficiency), in which particles collide with the fibers of the filter and stick, sometimes with aid of adhesives; 3) interception (medium efficiency), where particles become entrapped in the filter and attached to its fibers; 4) diffusion (high efficiency), where small particles moving erratically collide with and remain attached to filter fibers; and 5) electrostatic (high efficiency), in which negatively charged particles are attracted to positively charged filter fibers. (1)
Features and functions to look for
David M. Shagott, president, Abatement Technologies Inc, Suwanee, GA, offered good advice on features and functions purchasers should look for in a good air-cleansing system. “I’d include filtration efficiency; airflow; functionality in the healthcare environment; safety and security features; ease of use; mobility, if the device must be moved from area to area; manufacturer experience and expertise; and product approvals. Too many of the devices sold to healthcare facilities are simply general-purpose air cleaners re-positioned as medical devices. The potential risks require much more.”
Yes, indeed, when examining air-cleansing systems, it’s important to investigate whether the system is appropriate for use in a healthcare facility and whether vendors can back up the claims made for their products. Regulatory and advisory agencies such as the CDC, American Institute of Architects, the Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), and the Joint Commission are several of the agencies whose guidelines should be consulted by wise purchasers to educate themselves as to whether the product they’re considering acquiring meets standards.
Shagott highlighted the importance of meeting standards set by leading regulatory and advisory agencies. “Abatement Technologies stems are tested and certified by Intertek Testing Services to the Occupational Safety and Health Administration, United Laboratories, Canadian Standards Association, and National Electrical Code safety standards, and have FDA 510C clearance as class II medical devices. Many states selected them as their prime or sole means to meet Health Resources and Services Administration Critical Benchmark 2.2, and several major hospital buying groups have selected Abatement as their sole or prime vendor for HEPA devices.”
He described specifically how Abatement Technologies’ air-cleansing systems meet the needs of their customers: “Abatement Technologies makes two types of main healthcare filtration devices: HEPA-CARE systems, used for negative-pressure isolation of infectious patients, positive-pressure protective isolation, or continuous air cleansing in other areas with high infection risks; and HEPA-AIRE (stainless-steel cabinets) and Predator (rotational-molded polyethylene cabinets) portable air scrubbers, used to meet infection control risk-assessment requirements for isolating particulates released into the air during indoor construction and maintenance activities.”
Many companies offer HEPA filtration devices, so it pays to do a little investigative work. Biosense Inc., San Jose, CA, for example, offers the Recirculator II, which they bill as smallest, quietest, lowest cost portable solution for airborne threats in the country. IQAir, Santa Fe Springs, CA, offers low-maintenance, induct air cleaners with HyperHEPA technology, which they claim are up to 100 times more effective in removing allergens, bacteria, viruses, and dust than in-duct filter systems. It’s said to be quiet and invisible because it’s installed in existing HVAC ductwork. IQAir also touts ultra-low pressure drop technology, which allows air to pass through the filter more easily than with other in-duct air filters. To see a video of how it works, go to http:// www.iqair.us/commecial/hvacair cleaners.
Lending filtration a hand
More isn’t always better, but cleansing the air in healthcare facilities is one of those cases where it could be. There are certain measures that can be used to augment the work of filters in decontaminating the air. One of those methods is ultraviolet (UV) germicidal irradiation (GI); however, the CDC cautions that, whereas UVGI can be used as an adjunct air-cleaning measure, it cannot replace HEPA filtration. “As a supplemental air-cleaning measure, UVGI is effective in reducing the transmission of airborne bacterial and viral infections in hospitals, military housing, and classrooms, but it has only a minimal inactivating effect on fungal spores. UVGI is also used in air handling units to prevent or limit the growth of vegetative bacteria and fungi.” (1)
Steril-Aire Inc., Burbank, CA, “manufactures a line of multi-patented ‘UVC Emitters’ that use ultraviolet-C (UVC) energy, the most germicidal wavelength in the UV spectrum, to kill or deactivate microbial contaminants,” Robert Scheir, president, told Healthcare Purchasing News. “Installed in a hospital air-handling system, this UVC energy can destroy 90% to 99% of infectious microbes, depending on the number of air changes per hour, reducing them to a level far below what it lakes to infect most patients and staff. UVC has the ability to improve indoor air quality and reduce nosocomial infections. It works against all strains of influenza; other viruses including colds, SARS, measles, and German measles; and bacteria including tuberculosis, Legionella, pneumonia, and whooping cough. It also kills mold and organic growth in the air-conditioning coils, allowing air handlers to return to peak operating efficiency for energy savings.”
Scheir also highlighted the importance of seeking out air-cleansing products that meet standards and suggested checking out Steril-Aire’s claims: “The EPA, in conjunction with the U.S. Department of Homeland Security, has released test reports on several leading brands of UVC devices. In these tests, the Steril-Aire UVC Emitter achieved 99.96% destruction in a single pass on airborne bacteria, 99% on viruses, and 96% on spores. It also achieved the highest “dose-per-watt” of any product tested. The full reports are useful for comparing the different devices and may be accessed at http://www.epa.gov/ nhsrc/news/news 062606.html. In addition, Steril-Aire has both utility data and anecdotal reports from hospitals showing 15% to 29% reductions in HVAC energy costs since adopting UVC, as well as anecdotal reports indicating significant reductions in nosocomial rates where Steril-Aire UVC is installed.”
“Because of the many benefits of UVC, we are confident these devices will someday be found in every healthcare facility, as well as in every air-conditioned school, commercial and industrial building, and home,” said Scheir.
Zentox Corporation, Newport News, VA, also offers an air purifier employing UV light, the Photox system. Robert Kim, Photox business manager, recommended that purchasers look for a complete system, one that removes dirt, chemical vapors, and odors. “The Photox series is an advanced indoor air purification system based on photocatalytic oxidation technology. It traps particulates; breaks down vapors commonly found in healthcare facilities, such as odors from urine, feces, and wounds, as well as odors such as formaldehyde and alcohol, often found in laboratories within hospitals; and inactivates airborne contaminants including bacteria, viruses, and mold spores. The destruction of contaminants occurs inside the unit. It filters and oxidizes air at the same time, but does not produce ozone as some electronic air cleaners do.”
Photox can be used in patient rooms, emergency rooms, operating rooms, laboratories, auditoriums, and reception areas, noted Kim. “The Photox system is portable, runs 24/7, is lightweight, and has a small footprint. The largest unit, Photox 500, weighs 45 pounds, measures 18″ by 18″ by 38″, and purifies air over an area of 4,000 square feet. The Photox 100W is considerably smaller at 8 pounds and can be mounted on the wall in a patient room or can be placed on a table. It’s very quiet; it won’t interfere with the patient’s sleep.”
Kim also emphasized the importance of meeting standards, noting that Photox is certified to be safe, meeting UL electrical safety standards. “Photox has been performance tested by EMSL Analytical Inc, laboratories. You don’t want an untried, unproven product.”
Prophylaxis for the environment
STERIS Corporation (Mentor, OH)’s VaproSure Sterilizer is not an air-cleansing system per se, but it has an interesting relation to air cleansing. “The HEPA filter is an important part of an effective infection control program in that it can reduce the spread of airborne contaminants; it cannot, however, destroy antibiotic-resistant or other pathogens that may be present on the surfaces throughout a patient room. In this sense, the VaproSure Sterilizer can be complementary to HEPA filtration,” said Matthew Mitchell, director of industrial decontamination solutions.
The VaproSure Sterilizer uses Vaprox Sterilant, an EPA- registered (#58779-4) sterilant for the sterilization of all exposed surfaces in hospital rooms. “The technology is recognized as a broad-spectrum sterilant, meaning it can destroy spores, bacteria, fungi, and viruses, like an autoclave,” explained Mitchell.
The VaproSure Sterilizer is particularly applicable to outbreaks due to emerging and reemerging infectious diseases; “however,” said Mitchell, “the VaproSure system can also be used prophylactically. It has been adopted in Europe in intensive-care units, operating rooms, patient rooms, bum units, and ambulances. It also has been used for over a decade in pharmaceutical, laboratory, and research applications to provide sterile environments.”
Chronic Alcoholism Alters Systemic and Pulmonary Glutathione Redox Status
Rationale: Previous studies have linked the development and severity of acute respiratory distress syndrome with a history of alcohol abuse. In clinical studies, this association has been centered on depletion of pulmonary glutathione and subsequent chronic oxidant stress.
Objectives: The impact on redox potential of the plasma or pulmonary pools, however, has never been reported.
Methods: Plasma and bronchoalveolar lavage fluid were collected from otherwise healthy alcohol-dependent subjects and control subjects matched by age, sex, and smoking history.
Measurements and Main Results: Redox potential was calculated from measured reduced and oxidized glutathione in plasma and lavage. Among subjects who did and did not smoke, lavage fluid glutathione redox potential was more oxidized in alcohol abusers by approximately 40 mV, which was not altered by dilution. This oxidation of the airway lining fluid associated with chronic alcohol abuse was independent of smoking history. A shift by 20 mV in plasma glutathione redox potential, however, was noted only in subjects who both abused alcohol and smoked.
Conclusions: Chronic alcoholism was associated with alveolar oxidation and, with smoking, systemic oxidation. However, systemic oxidation did not accurately reflect the dramatic alcohol-induced oxidant stress in the alveolar space. Although there was compensation for the oxidant stress caused by smoking in control groups, the capacity to maintain a reduced environment in the alveolar space was overwhelmed in those who abused alcohol. The significant alcohol-induced chronic oxidant stress in the alveolar space and the subsequent ramifications may be an important modulator of the increased incidence and severity of acute respiratory distress syndrome in this vulnerable population.
Keywords: glutathione; alcoholism; oxidative stress; pulmonary
The lungs are constantly exposed to environmental and endogenous oxidants. The ability to neutralize these oxidants is essential to maintain pulmonary health. There are major differences between cellular and extracellular compartments in concentration of the thiol/disulfide systems and the relative redox states. Since Cantin and colleagues’ report, published in 1987, on the high glutathione (GSH) concentration in the airspace (more than 20- fold than that in the plasma and over 90% in the reduced form), GSH has been considered a primary antioxidant in the alveolar space (1). Although the alveolar space is exposed to the oxidants present in cigarette smoke, the alveolar GSH pool is increased by 80% with no significant oxidant stress, as evidenced by the minimal shift toward the oxidized moiety oxidized glutathione (GSSG) (1). In the airspace, this high GSH concentration defends the lung against endogenously produced oxidants as well as environmental oxidants. Limited availability of GSH in the alveolar space is associated with a number of pulmonary diseases, including cystic fibrosis, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, idiopathic interstitial pneumonia, and diffuse fibrosing alveolitis (2-4).
Previous studies reported a 2.7-fold elevation in the risk for ARDS in otherwise healthy alcohol abusers (5-7). Although the underlying cause remains unclear, recent research has elucidated a number of potential contributors, with one of the major causes being chronic oxidative stress. As outlined in a review by Guidot and Hart (8), the alcoholic lungs in ethanol-fed animal models are under increased oxidative stress, have altered nitric oxide metabolism, express abnormal amounts of transforming growth factor (TGF)-?, and are in a chronic proinflammatory state, with up-regulated expressions of IL-1? and tumor necrosis factor (TNF)-?. In this animal model, chronic ethanol ingestion depleted the GSH pool in the alveolar epithelial lining fluid (ELF) by as much as 80% (9). In clinical studies, chronic alcohol abuse resulted in a similar 80% decrease in the GSH pool of bronchoalveolar lavage fluid (BALF) (10). This decrease in GSH was accompanied by a fourfold increase in GSSG and was indicative of chronic oxidant stress. Altered homeostasis of the GSH/GSSG thiol pair was present even after 1 week of abstinence (11) and was independent of cirrhosis (10, 12). Therefore, these studies demonstrated that a history of alcohol abuse resulted in chronic oxidant stress in the alveolar space. Maccarrone and Ullrich suggested that the consideration of the redox state may be more reflective of the physiologically and pathological effects of oxidative stress than the mere absolute amounts of antioxidants and oxidants (13). Therefore, we examined the concentrations and redox potential of GSH and GSSG in the alveolar lining fluid and plasma pools of subjects stratified by both smoking and alcohol abuse. Some of these data were previously reported in abstract form (14).
METHODS
Subject Enrollment
Recruitment of subjects who have been chronically dependent on alcohol was made at the detoxification unit at the Veterans’ Affairs Hospital in Atlanta, Georgia. Nonsmoking and smoking control subjects were enrolled from those who replied to postings at the different Emory University hospitals as well as from the community. The details of the recruitment process and selection criteria were previously reported (10). Basically, the alcoholic status was confirmed by a score of greater than 3 on the Short Michigan Alcohol Screening Test (SMAST) survey. Those with a score of 0 were considered as control subjects. Exclusion criteria included subjects with a prior history of cardiac disease, liver dysfunction, kidney disease, diabetes mellitus, lung disease, human immunodeficiency virus infection, gastrointestinal bleeding, or concomitant illicit drug use.
Collection and Processing of BALF
The lavage procedure on subjects with and without a history of alcohol abuse was performed as previously described (10). A flexible fiberoptic bronchoscope (model BF-1T20D; Olympus America, Inc., Melville, NY) was passed transnasally into a subsegmental bronchus of the right middle lobe in all subjects. Once wedged, 150 ml of sterile saline (three 50-ml aliquots) were injected and immediately aspirated into 50-ml suction traps under continuous low-pressure suction. Ten milliliters of blood were obtained from a peripheral vein within 10 minutes of the bronchoscopy. The BALF was immediately filtered through coarse gauze and centrifuged (750 × g for 10 min) to remove cellular elements. The acellular portion was stored at -80
Protein and pH Measurements of BALF
The pH of BALF samples was measured on 200 ?l of aliquots using a Beckman microelectrode probe (Beckman Coulter Co., Fullerton, CA). The protein concentration in the samples was analyzed using the Pierce Better Bradford Coomassie assay (Pierce Chemical Co., Rockford, IL).
HPLC Measurement of Thiols
BALF and plasma samples were preserved immediately after collection in a 5% perchloric acid solution containing iodoacetic acid (6.7 ?M) and boric acid (0.1 M). The preservation fluid also contained 5 ?M of the internal standard ?-glutamyl-glutamate (?-Glu-Glu). This step was completed within 30 minutes of collection to prevent degradation or oxidation of GSH. After protein removal, samples were derivatized with dansyl chloride and separated on a 10-?m Ultrasil amino column by HPLC (Waters 2690; Waters Corp., Milford, MA). Fluorescence detection was recorded by two detectors (Waters 474 and Gilson model 121 [Gilson, Inc., Middleton, WI]). The concentrations of GSH and GSSG were calculated by quantitating the integrated areas relative to that of ?-Glu-Glu. Dilution due to the lavage procedure was corrected using the urea method (15). The concentration of urea in all the samples was obtained with an adopted Berthelot method from Pointe Scientific, Inc. (Canton, MI) and has a sensitivity range of 0.05 to 150 mg/dl. The urea dilution factor is equal to [urea]plasma/[urea]BALF.
Redox Potential Calculations
The redox potential (Eh) of the GSH/GSSG thiol pair in the plasma and the BALF were calculated with the Nernst equation, Eh = Eo RT/nF ln [disulfide]/([thiol1] [thiol2]). The Eo is the standard potential for the redox couple,Ris the gas constant, T is the absolute temperature, n is 2 for the number of electrons transferred, and F is Faraday’s constant. The standard potential Eo for the 2 GSH/GSSG couple was -264 mV at pH 7.4. Adjustment for pH as appropriate was made by a 5.9-mV change in Eo with every 0.1 decrease in pH.
Statistical Analysis
Correlation between values for each subject was determined by Spearman or Pearson analysis depending on results of test for normality. Group mean or median comparisons were made with the Student t test or the nonparametric Mann-Whitney test, as appropriate. Statistical significance was obtained with p .
Oxidation diminishes HDL’s ‘goodness.’ - high-density lipoproteins, the ‘good’ lipoproteins
Atherosclerosis begins when “foam cells” rich in lipids (mostly cholesterol) accumulate along artery walls. Researchers at the University of California, San Diego, showed that when a buildup of reactive molecules in the body causes low-density lipoproteins (LDLs) to undergo a chemical transformation known as oxidation, macrophages — cells that help LDLs unload their cholesterol — change into foam cells (SN: 4/30/88, p.279).
Ordinarily, HDLs — the so called “good” lipoproteins — can withdraw cholesterol from foam cells and target it for removal from the body. But researchers at Kyoto University in Japan have now demonstrated that oxidized HDLs lose much of their ability to do this. The new data “suggest that oxidative modification of HDL may stimulate development of atherosclerosis” by limiting its removal of cholesterol from faom cells, report Yutaka Nagano and his colleagues in the Aug. 1 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES.
Oxidation-Reduction Reactions
OXIDATION-REDUCTION REACTIONS
CONCEPT
Most people have heard the term "oxidation" at some point or another, and, from the sound of the word, may have developed the impression that it has something to do with oxygen. Indeed it does, because oxygen has a tendency to draw electrons to itself. This tendency, rather than the presence of oxygen itself, is actually what identifies oxidation, defined as a process in which a substance loses electrons. The oxidation of one substance is always accompanied by reduction, or the gaining of electrons, on the part of another substance—hence the term "oxidation-reduction reaction," sometimes called a redox reaction. The world is full of examples of this highly significant form of chemical reaction. One such example is combustion, or an even more rapid form of combustion, explosion. Likewise the metabolism of food, as well as other biological processes, involves oxidation and reduction reactions. So, too, do a number of processes that take place on the surfaces of metals: when iron rusts; when copper turns green; or when aluminum forms a coating of aluminum oxide that prevents it from rusting. Oxidation-reduction reactions also play a major role in electrochemistry, which has a highly useful application to daily life in the form of batteries.
A chemical reaction is a process whereby the chemical properties of a substance are changed by a rearrangement its atoms. The change produced by a chemical reaction is quite different from a purely physical change, which does not affect the fundamental properties of the substance itself. A piece of copper can be heated, melted, beaten into different shapes, and so forth, yet throughout all those changes, it remains pure copper, an element of the transition metals family.
But suppose a copper roof is exposed to the elements for many years. Copper is famous for its highly noncorrosive quality, and this, combined with its beauty, has made it a favored material for use in the roofs of imposing buildings. (Because it is relatively expensive, few middle-class people today can afford a roof entirely made of copper, but sometimes it is used as a decorative touch—for instance, over the entryway of a house.) Eventually, however, copper does begin to corrode when exposed to air for long periods of time.
Over the years, exposed copper develops a thin layer of black copper oxide, and as time passes, traces of carbon dioxide in the air contribute to the formation of greenish copper carbonate. This explains why the Statue of Liberty, covered in sheets of copper, is green, rather than having the reddish-golden hue of new, uncorroded copper.
EXTERNAL VS. INTERNAL CHANGE.
The preceding paragraphs describe two very different phenomena. The first was a physical change in which the chemical properties of a substance—copper—remained unaltered. The second, on the other hand, involved a chemical change on the surface of the copper, as copper atoms bonded with carbon and oxygen atoms in the air to form something different from copper. The difference between these two types of changes can be likened to varieties of changes in a person's life—an external change on the one hand, and a deeply rooted change on the other.
A person may move to another house, job, school, or town, yet the person remains the same. Many sayings in the English language express this fact: for instance, "Wherever you go, there you are," or "You can take the boy out of the country, but you can't take the country out of the boy." Moving is simply a physical change. On the other hand, if a person changes belief systems, overcomes old feelings (or succumbs to new ones), changes lifestyles in a profound manner, or in any other way changes his or her mind about something important—this is analogous to a chemical change. In these instances, the person, like the surface of the copper described above, has changed not merely in external properties, but in inner composition.
"LEO THE L ION S AYS 'GER'"
Chemical reactions are addressed in depth within the essay devoted to that subject, which discusses—among other subjects—many ways of classifying chemical reactions. These varieties of chemical reaction are not all mutually exclusive, as they relate to different aspects of the reaction. As noted in the review of various reaction types, one of the most significant is an oxidation-reduction reaction (sometimes called a redox reaction) involving the transfer of electrons.
As its name implies, an oxidation-reduction reaction is really two processes: oxidation, in which electrons are lost, and reduction, in which electrons are gained. Though these are defined separately here, they do not occur independently; hence the larger reaction of which each is a part is called an oxidation-reduction reaction. In order to keep the two straight, chemistry teachers long ago developed a useful, if nonsensical, mnemonic device: "LEO the lion says 'GER'." LEO stands for "Loss of Electrons, Oxidation," and "GER" means "Gain of Electrons, Reduction."
Many, though not all, oxidation-reduction reactions involve oxygen. Oxygen combines readily with other elements, and in so doing, it tends to grab electrons from those other elements' atoms. As a result, the oxygen atom becomes an ion (an atom with an electric charge)—specifically, an anion, or negatively charged ion.
In interacting with another element, oxygen becomes reduced, while the other element is oxidized to become a cation, or a positively charged ion. This, too, is easy to remember: oxygen itself, obviously, cannot be oxidized, so it must be the one being reduced. But since not all oxidation-reduction reactions involve oxygen, perhaps the following is a better way to remember it. Electrons are negatively charged, and the element that takes them on in an oxidation-reduction reaction is reduced—just as a person who thinks negative thoughts are "reduced" if those negative thoughts overcome positive ones.
O XIDATION N UMBERS
An oxidation number (sometimes called an oxidation state) is a whole-number integer assigned to each atom in an oxidation-reduction reaction. This makes it easier to keep track of the electrons involved, and to observe the ways in which they change positions. Here are some rules for determining oxidation number.
1. The oxidation number for an atom of an element not combined with other elements in a compound is always zero. 2. For an ion of any element, the oxidation number is the same as its charge. Thus a sodium ion, which has a charge of +1 and is designated symbolically as Na + , has an oxidation number of +1. 3. Certain elements or families form ions in predictable ways: a. Alkali metals, such as sodium, always form a +1 ion; oxidation number = +1. b. Alkaline earth metals, such as magnesium, always form a +2 ion; oxidation number = +2. c. Halogens, such as fluorine, form −1 ions; oxidation number = −1. d. Other elements have predictable ways to form ions; but some, such as nitrogen, can have numerous oxidation numbers. 4. The oxidation number for oxygen is −2 for most compounds involving covalent bonds. 5. When hydrogen is involved in covalent bonds with nonmetals, its oxidation number is +1. 6. In binary compounds (compounds with two elements), the element having greater electronegativity is assigned a negative oxidation number that is the same as its chargewhen it appears as an anion in ionic compounds. B ATTERIES USE OXIDATION-REDUCTION REACTIONS TO PRODUCE ELECTRICAL CURRENT . (Lester V. Bergman/Corbis . Reproduced by permission.) 7. When a compound is electrically neutral, the sum of its elements' oxidation states is zero. 8. In an ionic chemical species, the sum of the oxidation states for its constituent elements must equal the overall charge.
These rules will not be discussed here; rather, they are presented to show some of the complexities involved in analyzing an oxidation-reduction reaction from a structural stand-pont—that is, in terms of the atomic or molecular reactions. For the most part, we will be observing oxidation-reductions phenomenologically, or in terms of their outward effects. A good chemistry textbook should provide a more detailed review of these rules, along with a table showing oxidation numbers of elements and binary compounds.
Oxidation-reduction reactions are easier to understand if they are studied as though they were two half-reactions. Half the reaction involves what happens to the substances and electrons in the oxidizing portion, while the other half-reaction indicates the activities of substances and electrons in the reduction portion.
REAL-LIFE APPLICATIONS
C OMBUSTION AND E XPLOSIONS
As with any type of chemical reaction, combustion takes place when chemical bonds are broken and new bonds are formed. It so happens that combustion is a particularly dramatic type of oxidation-reduction reaction: whereas we cannot watch iron rust, combustion is a noticeable event. Even more dramatic is combustion that takes place at a rate so rapid that it results in an explosion.
Coal is almost pure carbon, and its combustion in air is a textbook example of oxidation-reduction. Although there is far more nitrogen than oxygen in air (which is a mixture rather than a compound), nitrogen is very unreactive at low temperatures. For this reason, it can be used to clean empty fuel tanks, a situation in which the presence of pure oxygen is extremely dangerous. In any case, when a substance burns, it is reacting with the oxygen in air.
As one might expect from what has already been said about oxidation-reduction, the oxygen is reduced while the carbon is oxidized. In terms of oxidation numbers, the oxidation number of O XIDATION-REDUCTION REACTIONS FUEL THE SPACE-SHUTTLE AT TAKE-OFF . (Corbis . Reproduced by permission.) carbon jumps from 0 to 4, while that of oxygen is reduced to −2. As they burn, these two form carbon dioxide or CO 2 , in which the two −2 charges of the oxygen atoms cancel out the +4 charge of the carbon atom to yield a compound that is electrically neutral.
An empirical correlation between secondary structure content and averaged chemical shifts in proteins
ABSTRACT It is shown that the averaged chemical shift (ACS) of a particular nucleus in the protein backbone empirically correlates well to its secondary structure content (SSC). Chemical shift values of more than 200 proteins obtained from the Biological Magnetic Resonance Bank are used to calculate ACS values, and the SSC is estimated from the corresponding three-dimensional coordinates obtained from the Protein Data Bank. ACS values of ^sup 1^Ha^sub alpha^ show the highest correlation to helical and sheet structure content (correlation coefficient of 0.80 and 0.75, respectively); ^sup 1^H^sub N^ exhibits less reliability (0.65 for both sheet and helix), whereas such correlations are poor for the heteronuclei. SSC estimated using this correlation shows a good agreement with the conventional chemical shift index-based approach for a set of proteins that only have chemical shift information but no NMR or x-ray determined three-dimensional structure. These results suggest that even chemical shifts averaged over the entire protein retain significant information about the secondary structure. Thus, the correlation between ACS and SSC can be used to estimate secondary structure content and to monitor large-scale secondary structural changes in protein, as in folding studies.
Aurichalcite: 79 Mine, Gila County, Arizona
Everyone likes blue minerals. Most of them contain significant copper, and it is often a good guess that blue crystals on gossany matrix are one of a relatively large possible number of secondary copper minerals. Some are quite rare, others are common, and most can be only tentatively identified on sight. One such mineral, aurichalcite, is traditionally available from a number of localities at a modest price; consequently, at least one specimen of this attractive mineral is likely present in most collections. It is a traditional favorite of micromounters. Specimens are particularly fragile, making periodic replacement an occasional necessity for heavily used collections. Because of aurichalcite’s attractiveness, often nagging similarity to other species, and surprisingly wide distribution, it has been recommended as a Connoisseur’s Choice topic.
Aurichalcite varies from pale green to sky-blue; some specimens exhibit sprays of color-zoned acicular crystals that vary from relatively dark blue near the central part or base of the group progressively to a paler blue at the extremities of the crystals. It is often transparent and has a silky to pearly luster. It has perfect (010) and (100) cleavages, is quite soft with a Mohs hardness of between 1 and 2, and has a measured density of 3.96.
Aurichalcite is monoclinic (2/m) and is pseudo-orthorhombic in appearance as a consequence of twinning. It is most often seen as acicular to lathlike crystals with prominent (010) faces and wedgelike terminations; crystals to 3 cm long have been reported. Many aurichalcite crystals occur in tufted divergent sprays or may be densely intergrown to form thick crusts. Less commonly it is seen as columnar, laminated, or granular masses.
Aurichalcite is a carbonate-hydroxide of zinc and copper with the formula [(Zn,Cu).sub.5][(C[O.sub.3]).sub.2][(OH).sub.6]. Some analyses show the presence of calcium, usually in amounts of less than 1 percent. It is easily confused visually with the chemically similar but structurally different mineral rosasite, (Cu, [(Zn,Cu).sub.5][(C[O.sub.3]).sub.2][(OH).sub.6].
Aurichalcite is a secondary mineral formed in oxide zones of deposits containing primary zinc and copper sulfides. Although generally considered to be a rare mineral, it is of widespread occurrence and is often associated with other minerals of collector interest, including malachite, azurite, cuprite, smithsonite, hemimorphite, hydrozincite, and rosasite. A good discussion of the general occurrence of aurichalcite and related minerals in oxidized zinc deposits can be found in Heyl and Bozion (1962). Aurichalcite is also one of the many minerals that form during the oxidation of slag produced by relatively primitive smelting processes and has been described in the European collector literature from such occurrences.
Although good aurichalcite specimens have been found in many mines of the and western United States, its occurrence in the more humid eastern states is apparently unusual. Nevertheless, it has been reported from several Maine localities, including the Harborside mine at Brooksville, Hancock County, and the Lubec lead mine and prospects at Pembroke, Washington County. It has also been found at the old lead mines at Middletown, Middlesex County, Connecticut; as good micromount material at the Mahan lead mines (Loudville mines), Easthampton, Hampshire County, Massachusetts; the old Gorham (Mascot mine), Coos County, New Hampshire; as pale blue rosettes of pearly plates in calcite veins cutting trap rock at Moore, the long-abandoned iron mine at Andover, and as an accessory mineral at Franklin and Sterling Hill, Sussex County, New Jersey; at the Conklin quarry near Lincoln, Providence County, Rhode Island; as radiating acicular crystals on dolomite at Bamford, Lancaster County, the famous Wheatley mines locality at Phoenixville, Chester County, the Cedar Hill quarry, Lan caster County, and the Jones mine, Berks County, Pennsylvania; and as blue tufts on goethite from the Pontiac mine, Halifax County, Virginia.
Aurichalcite is a rare secondary mineral in Mississippi Valley-type lead and zinc deposits. It has been reported from the weathered portions of zinc deposits formerly mined in Boone, Marion, Searcy, and Newton counties, Arkansas. Notable are the Beulah, Red Cloud, and Philadelphia mines of the Rush Creek district, Marion County. It has been described from similar occurrences in the Joplin area of Jasper County and from Washington County, Missouri; and the Eberle mine, Iowa County, and Belmont and Calamine mine areas, Lafayette County, Wisconsin. It was a rare accessory mineral in the oxidized portions of the Flambeau mine massive sulfide orebody at Ladysmith, Rusk County, Wisconsin.
Aurichalcite has been described from eight Colorado counties (Eckel 1997). The best-known occurrences are in the general Leadville district of Lake County. Here, it was found in modest abundance in several stopes in the Ibex mine (Emmons, Irving, and Loughlin 1927) and was a minor accessory mineral in the Belgin and Rattling Jack mines. It has been found in oxidized ores of the First National and Julia-Fisk mines and high on Sherman Mountain in the Continental Chief mine. The Sherman mine has produced small, well-formed, pale blue, acicular aurichalcite crystals associated with cerussite, hemimorphite, smithsonite, rosasite, and barite. Sherman Mountain-area replacement deposits, many of which contain small amounts of aurichalcite, extend into the Alma area of Park County; the best-known and most productive of such properties is the Hilltop mine. Other Colorado aurichalcite localities include the Mantle mine in Yampa River Canyon, Moffat County; dumps of the Green Mountain mine in Cunningham Gulch north of Silverton, San Juan County; the Sedalia copper mine, Chaffee County; the Tuckerville prospects, Hinsdale County; the Doctor mine on Spring Creek in the Tincup district, Gunnison County; and the Jones mine in the Central City district, Gilpin County.
Aurichalcite has been noted from a variety of localities in the United Kingdom. It is widely distributed in the Northern Pennines of Durham and old Yorkshire where it has been described from the Closehouse, Brandybottle, Wetgroves, and Turf Pits mines. It is similarly distributed in ores of the English Lake district, Cumbria, where it has been found in the Deer Hills, Driggith, Dry Gill, Old Sandbeds, Old Potts Gill, Roughton Gill, and Silver Gill mines. It is also reported from the Greystones quarry and Penberthy Croft, Cornwall; the Golconda, Wapping, Black Ox, and other mines, Derbyshire; and the Waterbank, Bag, Chadwick, and Clayton mines, Ecton, Staffordshire. Aurichalcite has been found in small amounts in the Dollar mine at Burn of Sorrow and many of the old mines in the Leadhills-Wanlockhead district, Scotland. Interestingly, it has been described from no less than twenty-five scattered localities in Wales, many of which are quarries, and others are mines including the Gwaithddu at Ponterwyd, Cwmrheidol; the Pensarn at TreTaliesin, Lllangynfelyn; and the Cwmystwyth at Upper Llanfihangel-y-Creuddyn, to name only a few.
There are a relatively large number of European aurichalcite localities reported in the literature, many of them having produced collectible micromount material. It has been found in a variety of Austrian localities such as those in Carinthia that include the Friesach-Huttenberg area, the Gailtaler Alpen and Karnische Alpen Mountains, the Hohe Tauern Mountains, and the Karawanken Mountains; the old mines at Annaberg, Lower Austria; the old lead mines in Sill Valley, Tyrol; and the Erzwies mines and Kaiserer and Lohning quarries in the Rauris Valley area, Salzburg. Aurichalcite and associated minerals have been found in the Salsigne mine, Aude Languedoc-Roussillon; the Couloumier mine and at Laguepie, Midi-Pyrenees; the famous copper occurrences at Chessy, at La Verriere, and at Le Penay, Rhone-Alpes, France. More than sixty German aurichalcite localities have been described. These include such well-known occurrences as mines in the Freiberg and Schwarzenberg districts, Saxony; the Rosenberg and other mines in the Bad Ems district and mines of the Eifel Mountains, Rhineland-Palatinate; mines and quarries in the Valbrt, Marsberg, and Siegerland areas of North Rhine-Westphalia; the St. Andreasberg, Clausthal, and other districts in Lower Saxony; and mines of the Badenweiler, Schauinsland, and Belchen districts and the Munstertal, St. Blasien, Todtnau, Waldshut, and Wolfach areas of the Black Forest, Baden-Wurttemberg. Good aurichalcite has been collected from a number of Italian localities including fine specimens from Sardinian mines such as the Santa Lucia, Murvonis, Montevecchio, Rosas, Sa Duchessa, and Baccu Locci; other Italian localities are Serrabottini, Boccheggiano, Campiglia Marittima, Vottena, and Stazzema, Tuscany; Mount Cengio, Veneto; Cava dell’Oro and the Bric Gettina mine, Liguria; and the Paglio Pignolino mine, Dossena, Lombardy. Several Swiss aurichalcite localities are mentioned in the literature including Noveggia, Malcantone, Ticino, and several sites near Mont Chemin, Wallis. Specimen-quality aurichalcite has been found in the Kamareza mines (especially the Jean Baptiste and Hilarion mines), the Elafos mines, the Sounion mines, and the Esperanza mine in the Laurion district, Greece.
On the Iberian Peninsula, collectible aurichalcite has been reported from the Andara mine in the Pico de Europa Mountains, Asturias; the Berta quarry and mines near Arres, Bossost, and Vielha e Mijaran in the Aran Valley, Catalonia; and the San Valentin mine, Murcia, Spain. It has also been collected at the Palhal mine, Aveiro district, and at Paradinha, Viseu district, Portugal.
Several Eastern European countries have been sources of good aurichalcite specimens. In Romania it has been found in pale blue acicular aggregates to 2 cm at Moldova Noua, as pale blue reniform aggregates on magnetite at Dognecca, and at Baita Bihor where it occurs as lamellar crystals in vugs with hemimorphite, smithsonite, and calcite. Pale blue aurichalcite crystals to 5 mm have been reported from Ochtina, Lubietova, and Spania Dolina, Slovakia. It is a relatively rare mineral in the well-known copper deposits of Rudabanya, and it occurs in the oxidized zone of sulfide deposits at Paradsasvar in the Matra Mountains, Hungary.
There are scattered aurichalcite localities in Australia. It occurs as sky-blue acicular crystals associated with hydrozincite and hemimorphite at the Billy Springs mine near Mount Fitton (Noble, Just, and Johnson 1983), and at the Mount Malvern mine, Clarendon, South Australia. It is also reported from Ashburton Downs, Western Australia; Limestone Creek, Benambra and Boulder Flat, Errinunra River, Victoria; Broken Hill, New South Wales; the True Blue mine in the Kangaroo Hills, Kennedy North district, Queensland; Moline and Pine Creek, Northern Territory; and the Colebrook mine at Rosebery, Tasmania.
A number of African localities have produced good aurichalcite. These include Tsumeb, Namibia, where crystals to 1 cm have been collected; the Kabwe mine (Broken Hill), Zambia; the Leeuwenkloof mine, South Africa; and the Kipushi mine, Shaba, Congo. In recent years, excellent aurichalcite similar to that from the Ojuela mine, Mapimi, Mexico, has reached the collector market from a locality given as M’Fouati, Congo.
Other interesting aurichalcite localities include the Shah-Kuh mine, Esfahan Province, Iran, where very attractive specimens have been recovered; the type locality at the Loktevskii mine in the west Altai Mountains, Siberia, Russia; the Nura-Taldy tungsten deposit, Kazakhstan; Vratsa Oblast, Bulgaria; the Los Azules mine, Chile; Pampa Grande, Bolivia; Daye, Hubei Province, China; the Kawazu, Ogoya, Hirao, and Kamegai mines on Honshu Island, Japan; the Cho Dien mine, Bac Kan Province, Vietnam; and the Konnerudkollen, Damasen and Lykkens Prove mines, Norway.