CNS Hypomyelination Disrupts Axonal Conduction and Behavior in Larval Zebrafish.

Myelination is essential for central nervous system (CNS) formation, health and function. As a model organism, larval zebrafish have been extensively employed to investigate the molecular and cellular basis of CNS myelination, because of their genetic tractability and suitability for non-invasive live cell imaging. However, it has not been assessed to what extent CNS myelination affects neural circuit function in zebrafish larvae, prohibiting the integration of molecular and cellular analyses of myelination with concomitant network maturation. To test whether larval zebrafish might serve as a suitable platform with which to study the effects of CNS myelination and its dysregulation on circuit function, we generated zebrafish myelin regulatory factor (myrf) mutants with CNS-specific hypomyelination and investigated how this affected their axonal conduction properties and behavior. We found that myrf mutant larvae exhibited increased latency to perform startle responses following defined acoustic stimuli. Furthermore, we found that hypomyelinated animals often selected an impaired response to acoustic stimuli, exhibiting a bias toward reorientation behavior instead of the stimulus-appropriate startle response. To begin to study how myelination affected the underlying circuitry, we established electrophysiological protocols to assess various conduction properties along single axons. We found that the hypomyelinated myrf mutants exhibited reduced action potential conduction velocity and an impaired ability to sustain high-frequency action potential firing. This study indicates that larval zebrafish can be used to bridge molecular and cellular investigation of CNS myelination with multiscale assessment of neural circuit function.SIGNIFICANCE STATEMENT Myelination of CNS axons is essential for their health and function, and it is now clear that myelination is a dynamic life-long process subject to modulation by neuronal activity. However, it remains unclear precisely how changes to myelination affects animal behavior and underlying action potential conduction along axons in intact neural circuits. In recent years, zebrafish have been employed to study cellular and molecular mechanisms of myelination, because of their relatively simple, optically transparent, experimentally tractable vertebrate nervous system. Here we find that changes to myelination alter the behavior of young zebrafish and action potential conduction along individual axons, providing a platform to integrate molecular, cellular, and circuit level analyses of myelination using this model.

Intersection as key locations for bearded capuchin monkeys (Sapajus libidinosus) traveling within a route network.

There is evidence that wild animals are able to recall key locations and associate them with navigational routes. Studies in primate navigation suggest most species navigate through the route network system, using intersections among routes as locations of decision-making. Recent approaches presume that points of directional change may be key locations where animals decide where to go next. Over four consecutive years, we observed how a wild group of bearded capuchin monkeys used a route network system and Change Point locations (CPs) in the Brazilian ecotone of Cerrado-Caatinga. We built 200 daily routes of one wild bearded capuchin group. We used ArcGIS, the Change Point Test, Spatial Analysis in Macroecology (SAM), and statistical models to test the hypothesis that wild bearded capuchins use CPs located along routes in a different fashion than they use the CPs located at intersections of routes. A logistic regression model was used to determine the landscape variables affecting capuchins' directional changes at intersections or along routes. CPs at intersections were important points of travel path changes, whereas CPs along routes represented a zig-zag movement along the routes following the landscape features. CPs at intersections were associated with steeper terrains and shorter distances from important resources, along with better visibility of the home range. Our results support the hypothesis that intersections among routes in the route network system are located at points where monkeys have the best visibility available to make decisions on where to visit next.

Psychiatry NCHD referrals to the local emergency department in the context of an in-house primary care service.

OBJECTIVES: Patients with psychiatric illness are at increased risk of developing non-psychiatric medical illnesses. There have been positive reports regarding the integration of primary care services into mental health facilities. Here, we evaluate the appropriateness of psychiatry non-consultant hospital doctors (NCHD) transfers to the local emergency department (ED) in the context of an in-house primary care service. METHODS: We reviewed the inpatient transfers from St Patrick's University Hospital (SPUH) to the local ED at St James' Hospital (SJH) from 1 January 2016 to 31 December 2017. We used inpatient admission to SJH as our primary marker of an appropriate transfer. RESULTS: 246 inpatients were transferred from SPUH to the SJH ED for medical review in the years 2016 and 2017. 27 (11%) of these were referred to the ED by the primary care service. 51% of those referred were admitted with similar rates of admission for both general practitioner (n = 27, 54% admitted) and NCHD initiated referrals (n = 219, 51% admitted). Acute neurological illness, concern regarding a cardiac illness, and deliberate self-harm were the most common reasons for referral. CONCLUSION: Our primary finding is that, of those transferred to ED by either primary care or a psychiatry NCHD, a similar proportion was judged to be in need of inpatient admission. This indicates that as a group, psychiatry NCHD assessment of acuity and need for transfer was similar to that of their colleagues in primary care.

The decision-making processes of pharmacists in inland Australia--a pilot study.

INTRODUCTION: Little research has been conducted analysing the organisational risks that compound and trigger dispensing and medication errors. This pilot study appraises the attitudes to and behaviours related to the dispensing errors of pharmacists practising in diverse venues and roles in inland Australia. METHODS: Twelve pharmacists working in the Riverina (Wiradjuri country) participated in a structured interview consisting of a brief survey and open-ended questions. The interviews were audio-recorded for transcription, then analysed by the interviewer for emerging themes. In this pilot study, the attitudes and actions of pharmacists in response to dispensing errors were explored to determine the nature of organisational strategies implemented to detect and recover 'slips, lapses and mistakes'. The rationale behind investigating attitudes and actions stems from the theory of planned behaviour. RESULTS: While many common themes emerged, the attitudes of each pharmacist were unique. The strategies implemented to prevent errors were venue-specific and purpose-designed to the training level of the staff and physical environment. A diverse mix of attitudes was represented by the sample, with no correlation between worksite, sex, age or role identified. Trends may emerge because, in regard to dispensing errors, subjective norms and perceived behavioural control play a greater role in forming the intention to act, rather than personal attitudes. The majority of examples given by participants was discussion of recorded errors and near misses, which included changes to procedures implemented to prevent the same error occurring. This culture of continuous quality improvement was the overarching common theme. Other common themes were the role of technology in the supply of medicines, privacy implications when drawing staff from a rural or regional centre, workload concerns with regard to management responsibility and the impact of the way error management was demonstrated during the formative early years of practice. Distraction from dispensing, through management roles in pharmacies with moderate prescription volumes, was a common contributor to errors. CONCLUSION: A culture of continuous quality improvement exists amongst pharmacists in Inland Australia, which would benefit from improved dialogue about the impact of organisational risks on the rate of dispensing errors. The safety culture, and behaviour modelling experienced during the internship program has a profound impact on the perceived behavioural control of young pharmacists. This year instils mores, which may be the result of independent survival in remote and regional settings, rather than compliance with professional practice standards. While many of the pressures and demands of minimising errors are common across the profession; unique, venue specific strategies are commonly implemented in the cycle of continuous quality improvement in regional and remote settings.

Human keratinocyte growth factor effects in a porcine model of epidermal wound healing.

Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family (hence the alternative designation FGF-7). It is produced by stromal cells, but acts as a mitogen for epithelial cells. We examined the effects of topically applied KGF on healing of wounds in a porcine model. In partial-thickness wounds, KGF stimulated the rate of reepithelialization (p < 0.0002), associated with a thickening of the epidermis (p < 0.0001). Epidermis from KGF-treated full-thickness wound sites was significantly thicker (0.31 +/- 0.22 mm) compared with mirror image control sites (0.18 +/- 0.12 mm) (p < 0.0001). Moreover, the majority (77%) of KGF-treated wounds exhibited epidermis with a deep rete ridge pattern as compared with control sites. These effects were observed as early as 14 d and persisted for at least 4 wk. KGF treatment also increased the number of serrated basal cells associated with increased deposition of collagen fibers in the superficial dermis adjacent to the acanthotic epidermis. Electron microscopy revealed better developed hemidesmosomes associated with thicker bundles of tonofilaments in the serrated cells. The pattern of epidermal thickening observed in KGF-treated wounds resembled psoriasis. Psoriasis is a disease associated with epidermal thickening, parakeratosis as well as hyperproliferation that extends beyond the basal layer. In striking contrast to psoriasis, KGF-treated wounds exhibited normal orthokeratotic maturation, and proliferation was localized to the basal cells. Our present findings have significant implications concerning the role of KGF as a paracrine modulator of epidermal proliferation and differentiation.

Jarosite as an indicator of water-limited chemical weathering on Mars.

The Mars Exploration Rover Opportunity identified the ferric sulphate mineral jarosite and possible relicts of gypsum at the Meridiani Planum landing site. On Earth, jarosite has been found to form in acid mine drainage environments, during the oxidation of sulphide minerals, and during alteration of volcanic rocks by acidic, sulphur-rich fluids near volcanic vents. Jarosite formation is thus thought to require a wet, oxidizing and acidic environment. But jarosite on Earth only persists over geologically relevant time periods in arid environments because it rapidly decomposes to produce ferric oxyhydroxides in more humid climates. Here we present equilibrium thermodynamic reaction-path simulations that constrain the range of possible conditions under which such aqueous alteration phases are likely to have formed on Mars. These calculations simulate the chemical weathering of basalt at relevant martian conditions. We conclude that the presence of jarosite combined with residual basalt at Meridiani Planum indicates that the alteration process did not proceed to completion, and that following jarosite formation, arid conditions must have prevailed.

The effects of ambient particulate matter on human alveolar macrophage oxidative and inflammatory responses.

Epidemiologic and occupational studies demonstrated that ambient particulate matter (PM) and diesel exhaust particles (DEP) exert deleterious effects on human cardiopulmonary health, including exacerbation of pre-existing lung disease and development of respiratory infections. The effects of ambient PM on lung cell responsiveness are poorly defined. Human alveolar macrophages (AM) were exposed to SRM 1649 (Washington, DC, urban dust; UD), SRM 2975 (forklift diesel exhaust particles; DEP), and fine or coarse ambient PM collected in Chapel Hill, NC, during the late fall (November) and early summer (June) of 2001-2002. AM were subsequently incubated with lipopolysaccharide (LPS), phorbol myristate acetate (PMA), or calcium ionophore A23817 for 6 or 24 h after PM exposure. UD and DEP markedly suppressed O2- release 24 h post-PM exposure. UD exposure significantly inhibited tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 release after exposure to 10 nanog/ml LPS. DEP significantly suppressed only TNF-alpha and IL-6 release. Suppressed cytokine release may also be produced by reduced cellular cytokine production. Data suggested that decreased cytokine release is not produced by the presence of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon. Comparison of TNF-alpha release after LPS, PMA, or A23817 revealed that suppressive effects of UD are LPS dependent, whereas inhibitory effects of DEP may work across multiple mechanistic pathways. November and June Chapel Hill PM exposure stimulated TNF-alpha and IL-8 release before LPS exposure. Fine and coarse November PM exposure markedly suppressed TNF-alpha release 6 h after LPS stimulation, but appeared to exert a stimulatory effect on IL-8 release 24 h after LPS exposure. June fine and coarse PM suppressed IL-8 release after LPS exposure. Data suggest that seasonal influences on PM composition affect AM inflammatory response before and after bacterial exposure. Overall, delayed or inhibited AM immune responses to LPS after PM exposure suggest human exposure to ambient PM may enhance pulmonary susceptibility to respiratory infections.

Cloning of herpes simplex type 1 DNA fragments in a bacteriophage lambda vector.

DNA isolated from defective and nondefective virions of herpes simplex type 1 (HSV-1) (strain Patton) was digested with restriction endonucleases, and the resulting DNA fragments were inserted in the EK2 coliphage vector lambdagtWES . lambdaB. The recombinant DNA was encapsidated in vitro under P4 maximum containment conditions. These lambda-HSV1 hybrids were purified and amplified, and the DNA was isolated in the P4 facility. DNA, free of viable phage and bacteria, was removed from P4 conditions and analyzed. Represented among the hybrids studied to date are DNA fragments from about 50 percent of the normal HSV-1 genome. The hybrids derived from defective HSV-1 DNA fragments demonstrate the existence of many similar but not identical classes of defective genomes.

A systematic review of cardiovascular responses associated with ambient black carbon and fine particulate matter.

BACKGROUND: Exposure to fine particulate matter (PM2.5), an ambient air pollutant with mass-based standards promulgated under the Clean Air Act, and black carbon (BC), a common component of PM2.5, are both associated with cardiovascular health effects. OBJECTIVES: To elucidate whether BC is associated with distinct, or stronger, cardiovascular responses compared to PM2.5, we conducted a systematic review. We evaluated the associations of short- and long-term BC, or the related component elemental carbon (EC), with cardiovascular endpoints including heart rate variability, heart rhythm, blood pressure and vascular function, ST segment depression, repolarization abnormalities, atherosclerosis and heart function, in the context of what is already known about PM2.5. DATA SOURCES: We conducted a stepwise systematic literature search of the PubMed, Web of Science and TOXLINE databases and applied Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines for reporting our results. STUDY ELIGIBILITY CRITERIA: Studies reporting effect estimates for the association of quantitative measurements of ambient BC (or EC) and PM2.5, with relevant cardiovascular endpoints (i.e. meeting inclusion criteria) were included in the review. Included studies were evaluated for risk of bias in study design and results. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias evaluations assessed aspects of internal validity of study findings based on study design, conduct, and reporting to identify potential issues related to confounding or other biases. Study results are presented to facilitate comparison of the consistency of associations with PM2.5 and BC within and across studies. RESULTS: Our results demonstrate similar associations for BC (or EC) and PM2.5 with the cardiovascular endpoints examined. Across studies, associations for BC and PM2.5 varied in their magnitude and precision, and confidence intervals were generally overlapping within studies. Where differences in the magnitude of the association between BC or EC and PM2.5 within a study could be discerned, no consistent pattern across the studies examined was apparent. LIMITATIONS: We were unable to assess the independence of the effect of BC, relative the effect of PM2.5, on the cardiovascular system, nor was information available to understand the impact of differential exposure misclassification. CONCLUSIONS: Overall, the evidence indicates that both BC (or EC) and PM2.5 are associated with cardiovascular effects but the available evidence is not sufficient to distinguish the effect of BC (or EC) from that of PM2.5 mass.

Human keratinocyte culture. Identification and staging of epidermal cell subpopulations.

Stratification of human epidermal cells into multilayered sheets composed of basal and suprabasal layers (resembling the stratum germinativum and stratum spinosum of the epidermis) was studied in a dermal component-free culture system. Although no stratum corneum developed in vitro, this culture system provided a method to study early events in human keratinocyte differentiation. Multiparameter flow cytometric analysis of acridine orange-stained epidermal cells from these cultures revealed three distinct subpopulations differing in cell size, RNA content, and cell cycle kinetics. The first subpopulation was composed of small basal keratinocytes with low RNA content and a long generation time. The second subpopulation consisted of larger keratinocytes, having higher RNA content and a significantly shorter generation time. Finally, the third subpopulation contained the largest cells, which did not divide, and represent the more terminally differentiated keratinocytes. This in vitro approach provides discriminating cytochemical parameters by which the maturity of the epidermal cell sheets can be assessed prior to grafting onto human burn patients.

Metabolic capacity regulates iron homeostasis in endothelial cells.

The sensitivity of endothelial cells to oxidative stress and the high concentrations of iron in mitochondria led us to test the hypotheses that (1) changes in respiratory capacity alter iron homeostasis, and (2) lack of aerobic metabolism decreases labile iron stores and attenuates oxidative stress. Two respiration-deficient (rho(o)) endothelial cell lines with selective deletion of mitochondrial DNA (mtDNA) were created by exposing a parent endothelial cell line (EA) to ethidium bromide. Surviving cells were cloned and mtDNA-deficient cell lines were demonstrated to have diminished oxygen consumption. Total cellular and mitochondrial iron levels were measured, and iron uptake and compartmentalization were measured by inductively coupled plasma atomic emission spectroscopy. Iron transport and storage protein expression were analyzed by real-time polymerase chain reaction and Western blot or ELISA, and total and mitochondrial reactive oxygen species (ROS) generation was measured. Mitochondrial iron content was the same in all three cell lines, but both rho(o) lines had lower iron uptake and total cellular iron. Protein and mRNA expressions of major cytosolic iron transport constituents were down-regulated in rho(o) cells, including transferrin receptor, divalent metal transporter-1 (-IRE isoform), and ferritin. The mitochondrial iron-handling protein, frataxin, was also decreased in respiration-deficient cells. The rho(o) cell lines generated less mitochondrial ROS but released more extracellular H(2)O(2), and demonstrated significantly lower levels of lipid aldehyde formation than control cells. In summary, rho(o) cells with a minimal aerobic capacity had decreased iron uptake and storage. This work demonstrates that mitochondria regulate iron homeostasis in endothelial cells.

Expression of anionic glutathione-S-transferase and P-glycoprotein genes in human tissues and tumors.

The development of multidrug resistance in MCF-7 human breast cancer cells and the acquisition of broad resistance to xenobiotics in rat hyperplastic nodules are both associated with increased P-glycoprotein (mdr) gene expression as well as changes in activities of intracellular detoxication enzymes; among these changes is a significant increase in the activity of the anionic isozyme of glutathione-S-transferase (GST). We have isolated a cDNA encoding the human anionic glutathione-S-transferase, GST pi-1, from a cDNA library constructed from multidrug-resistant MCF-7 cells. The deduced amino acid sequence of GST pi-1 shows that while the human anionic GST displays 85% nucleotide and amino acid sequence homology to the rat anionic isozyme, it is markedly less related to human basic GST isozymes. We have examined the expression of GST pi and P-glycoprotein in 170 specimens of human tissues and tumors. P-Glycoprotein RNA expression was positive in eight of 23 lymphomas and two of 12 colon tumors; however, many other normal and malignant tissues, including lung, bladder, and breast tumors, had low or undetectable levels of P-glycoprotein RNA expression. In contrast, GST pi was readily detected in a wide variety of normal and malignant tissues. The level of GST pi mRNA expression in normal tissues was heterogeneous, with lowest levels found in liver and the highest levels found in lung, esophagus, and placenta. GST pi was also variably expressed in human tumors, with the lowest relative levels occurring in lymphoma and breast cancer and the highest levels found in lung cancer and head and neck tumors. In addition, comparison of paired specimens from the same patient indicated that GST pi expression was increased in many tumors relative to matched normal tissue.

The use and success of cold coagulation for the treatment of high grade squamous cervical intra-epithelial neoplasia: a retrospective review.

OBJECTIVE: Cold coagulation is recognised as a viable, cost-effective and successful treatment for cervical intraepithelial neoplasia (CIN), being used less frequently than excisional treatments for high grade lesions. We set out to demonstrate successful long term follow-up of patient with high grade CIN treated with cold coagulation. STUDY DESIGN: We conducted a retrospective review over a one-year period of women with biopsy-proven CIN 2 and 3 who were treated with cold coagulation to the cervix, attending the colposcopy service of a large tertiary referral hospital. We examined follow-up cervical smear data for three years post treatment of low and high grade CIN, evaluated the success of treatment and re-treatment rates. RESULTS: 93 patients were included in our study, with 39 (41.9%) having CIN 1 and 54 (58.1%) diagnosed with CIN 2 or 3. Follow-up smears revealed low levels of recurrent high grade changes in both groups, with 31 (79.5%) of our CIN 1 group having a negative smear one year following treatment with cold coagulation, compared to 44 (81.1%) of patients with CIN 2 and 3. Successful primary treatment (i.e. no requirement for further treatment after 3 year follow-up) occurred in 33 (84.6%) of the CIN 1 group, and 42 (77.7%) of the CIN 2/3 group, demonstrating no statistical significance between re-treatment rates between both groups. CONCLUSIONS: This study demonstrates the effectiveness of cold coagulation for the treatment of high grade cervical intraepithelial neoplasia. High success rates, and low re-treatment rates confirm that this is an acceptable primary treatment for CIN 2 and 3.

1H-NMR spectroscopy can accurately quantitate the lipolysis and oxidation of cardiac triacylglycerols.

Triacylglycerol metabolism in isolated, perfused hearts from rats fed a diet containing 20% rapeseed oil (RSO) was studied using 1H-NMR spectroscopy. RSO-induced elevation in cardiac triacylglycerols is associated with an increase in the peak area of fatty acid 1H-NMR resonances. The ratio of methyl, gamma-methylene or methylene protons adjacent to a carbon-carbon double bond to the number of methylene protons in these hearts measured by 1H-NMR spectroscopy gives values similar to those derived from previously reported chemical analyses. In addition, the triacylglycerol content of these hearts determined by chemical analysis directly correlates with their content of 1H-NMR visible fatty acid resonances. This quantitative relationship allows the real-time measurement of the rates of cardiac triacylglycerol lipolysis using 1H-NMR spectroscopy. Rates of triacylglycerol lipolysis measured using 1H-NMR spectroscopy are similar to those previously measured by chemical methods. Triacylglycerol lipolysis measured using 1H-NMR spectroscopy occurs at a significantly faster rate in hearts perfused in the presence or absence of glucose when compared to hearts perfused with glucose and acetate or medium-chain fatty acids. Finally, the rate of triacylglycerol lipolysis in glucose perfused hearts is linearly related to work output. These results demonstrate that 1H-NMR spectroscopy can accurately quantitate triacylglycerol content and metabolism in the rapeseed oil-fed rat model. 1H-NMR spectroscopic or imaging techniques may be useful in the real-time evaluation of cardiac triacylglycerol content and metabolism.

Differences in arachidonic acid metabolism by human myelomonocytic cell lines.

The production of arachidonic acid metabolites by the HL60, ML3, and U937 human phagocyte cell lines was determined after incubation with interferon-gamma (IFN-gamma, 500 U/ml) or vehicle for 4 days. Cells were prelabeled with tritiated arachidonic acid, [3H]AA, for 4 h, and media supernatants were analyzed by high-performance liquid chromatography. None of the cell lines produced [3H]AA metabolites in large amounts during an unstimulated, basal release period (30 or 60 min). In response to 10 microM calcium ionophore A23187 incubation (30 min), undifferentiated and IFN-gamma-differentiated HL60 cells formed both cyclooxygenase products (thromboxane and prostaglandins) and lipoxygenase products (leukotrienes and hydroxyeicosatetraenoic acids). In contrast to the HL60 cells, IFN-gamma-differentiated U937 cells formed primarily cyclooxygenase products and undifferentiated and IFN-gamma-differentiated ML3 cells did not form any [3H]AA metabolites in response to A23187. These results indicate the need to be careful in selecting a cell line for use in a phagocyte assay system when cyclooxygenase and/or lipoxygenase products could influence the assay results.

Acute renal failure associated with mannitol intoxication. Report of a case.

Mannitol intoxication has been reported as a potentially life-threatening complication when the agent is used unrestrictedly in patients with established renal failure. We report a case of mannitol intoxication in which acute oliguric renal failure occurred without a known predisposing factor other than the intravenous infusion of massive quantities of mannitol.

Characterization of coliphage lambda hybrids carrying DNA fragments from Herpes simplex virus type 1 defective interfering particles.

We describe the characterization of 34 hybrid lambda bacteriophages carrying EcoRI fragments obtained from DNA of defective interfering particles of the Patton strain of Herpes simplex virus type 1 (HSV-1). All cloned fragments contained S region terminal repeat sequences (TRs) fused to unique HSV-1 DNA. Several fragments contained deletions and rearrangements not described previously for DNA of HSV-1 defective interfering particles. A model describing the generation of defective interfering DNA based on recombination events involving the terminal "a" sequence as presented.

Acetaldehyde (CH3CHO) production in rodent lung after exposure to metal-rich particles.

Epidemiological reports demonstrate an association between increased human morbidity and mortality with exposure to air pollution particulate matter (PM). Metal-catalyzed oxidative stress has been postulated to contribute to lung injury in response to PM exposure. We studied the effects of residual oil fly ash (ROFA), a component of ambient air PM, on the formation of lung carbonyls that are indicators of lipid peroxidation. Rats were instilled intratracheally with ROFA (62.5-1000 micrograms) and underwent lung lavage. Lavage fluid carbonyls were derivatized with 2,4-dinitrophenylhydrazine, and measured by high performance liquid chromatography with UV detection. Dose-dependent increases in a peak that eluted with the same retention time as the acetaldehyde (CH3CHO) derivative was observed in rats treated with ROFA 15 min after instillation (up to 25-fold greater than saline treated controls). The identification of CH3CHO was confirmed using gas chromatography-mass spectroscopy. ROFA-induced increases in other lavage fluid carbonyls were not seen. Increased CH3CHO in lavage fluid was observed as late as 8 h later. No increase in CH3CHO was observed in plasma from ROFA-treated rats. An increased formation of CH3CHO was observed in a human airway epithelial cell line incubated with ROFA suggesting a pulmonary source of CH3CHO production. Instillation of solutions of metals (iron, vanadium, nickel) contained in ROFA, or instillation of another ROFA-type particle containing primarily iron, also induced a specific increase in CH3CHO. These data support the hypothesis that metals were involved in the increased CH3CHO formation. Thus metals on PM may mediate lung responses through induction of lipid peroxidation and carbonyl formation.