A method for exposing rodents to resuspended particles using whole-body plethysmography

BACKGROUND: Epidemiological studies have reported increased risks of cardiopulmonary-related hospitalization and death in association with exposure to elevated levels of particulate matter (PM) across a wide range of urban areas. In response to these findings, researchers have conducted animal inhalation exposures aimed at reproducing the observed toxicologic effects. However, it is technically difficult to quantitate the actual amount of PM delivered to the lung in such studies, and dose is frequently estimated using default respiration parameters. Consequently, the interpretation of PM-induced effects in rodents exposed via whole-body inhalation is often compromised by the inability to determine deposited dose. To address this problem, we have developed an exposure system that merges the generation of dry, aerosolized particles with whole-body plethysmography (WBP), thus permitting inhalation exposures in the unrestrained rat while simultaneously obtaining data on pulmonary function. RESULTS: This system was validated using an oil combustion-derived particle (HP12) at three nominal concentrations (3, 12, and 13 mg/m(3)) for four consecutive exposure days (6 hr/day); a single 6-hour exposure to 13 mg/m(3 )of HP12 was also conducted. These results demonstrated that the system was both reliable and consistent over these exposure protocols, achieving average concentrations that were within 10% of the targeted concentration. In-line filters located on the exhaust outlets of individual WBP chambers showed relative agreement in HP12 mass for each day and were not statistically different when compared to one another (p = 0.16). Temperatures and relative humidities were also similar between chambers during PM and air exposures. Finally, detailed composition analyses of both HP12 filter and bulk samples showed that grinding and aerosolization did not change particle chemistry. CONCLUSION: The results of this study demonstrate that it is possible to expose rodents to resuspended, dry PM via whole-body inhalation while these animals are maintained in WBP chambers. This new methodology should significantly improve the ability to assess dosimetry under minimally stressful exposure conditions

Three Year Results on the Performance of Incinerator Residue in a Bituminous Base

DOT-FH-11-8027The use of incinerator residue as an aggregate in a bituminous base (termed littercrete) was studied. Test sections consisting of the experimental hot mixed littercrete base and a conventional hot mixed asphaltic concrete base (termed blackbase control) and topped with a conventional surface were placed on a city street in Houston, Texas. This report presents the results from observations and tests on cores during the first three years of in service performance. Results of the laboratory and field evaluations show that the littercrete section is performing in an excellent manner, almost identical with the conventional blackbase control section. The only distress that has occurred is minor cracking in both sections. This cracking is limited to the conventional wearing surface and has not progressed into the bases

Increased Nonconducted P-Wave Arrhythmias after a Single Oil Fly Ash Inhalation Exposure in Hypertensive Rats

Background: Exposure to combustion-derived fine particulate matter (PM) is associated with increased cardiovascular morbidity and mortality especially in individuals with cardiovascular disease, including hypertension. PM inhalation causes several adverse changes in cardiac function that are reflected in the electrocardiogram (ECG), including altered cardiac rhythm, myocardial ischemia, and reduced heart rate variability (HRV). The sensitivity and reliability of ECG-derived parameters as indicators of the cardiovascular toxicity of PM in rats are unclear. Objective: We hypothesized that spontaneously hypertensive (SH) rats are more susceptible to the development of PM-induced arrhythmia, altered ECG morphology, and reduced HRV than are Wistar Kyoto (WKY) rats, a related strain with normal blood pressure. Methods: We exposed rats once by nose-only inhalation for 4 hr to residual oil fly ash (ROFA), an emission source particle rich in transition metals, or to air and then sacrificed them 1 or 48 hr later. Results: ROFA-exposed SH rats developed nonconducted P-wave arrhythmias but no changes in ECG morphology or HRV. We found no ECG effects in ROFA-exposed WKY rats. ROFA-exposed SH rats also had greater pulmonary injury, neutrophil infiltration, and serum C-reactive protein than did ROFA-exposed WKY rats. Conclusions: These results suggest that cardiac arrhythmias may be an early sensitive indicator of the propensity for PM inhalation to modify cardiovascular function. Originally published Environmental Health Perspectives, Vol. 117, No. 5, May 200

Site 503: Eastern Equatorial Pacific

Our primary objective at Site 503 (Fig. 1) was to re- cover a complete, undisturbed Neogene and Quaternary section in the eastern equatorial Pacific. Site 503 is located near Site 83 in an area that contains an almost continuous pelagic record of the past 10 m.y. (Hays et al., 1972). Unfortunately, Site 83 was only spot-cored, and the recovered sediment is so badly disturbed by rotary drilling that most of the detailed record is lost. The section has an average sedimentation rate of 2.0 to 2.5 cm/k.y. with good-to-moderate preservation of all the major microfossil groups. We returned to Site 83 to core the same section, using the Hydraulic Piston Corer (HPC) to obtain an undisturbed, continuous section for high-resolution stratigraphic studies

Site 502: Colombia Basin, Western Caribbean

Our specific objective at Site 502 was to recover an undisturbed, complete section that could be used as a Neogene and Quaternary reference section. A complete record such as this would allow intercorrelations between (1) paleomagnetic stratigraphy, (2) calcareous biostratigraphy, (3) cyclic accumulation of sediment, (4) paleoceanographic changes, (5) oxygen and carbon isotope stratigraphies, (6) the chronology of Central American volcanism, (7) the timing and effects of the emergence of the Isthmus of Panama, and (8) the timing and effects of the initiation of Northern Hemisphere glaciation

Refinement of a 400-kb Critical Region Allows Genotypic Differentiation between Isolated Lissencephaly, Miller-Dieker Syndrome, and Other Phenotypes Secondary to Deletions of 17p13.3

Deletions of 17p13.3, including the LIS1 gene, result in the brain malformation lissencephaly, which is characterized by reduced gyration and cortical thickening; however, the phenotype can vary from isolated lissencephaly sequence (ILS) to Miller-Dieker syndrome (MDS). At the clinical level, these two phenotypes can be differentiated by the presence of significant dysmorphic facial features and a more severe grade of lissencephaly in MDS. Previous work has suggested that children with MDS have a larger deletion than those with ILS, but the precise boundaries of the MDS critical region and causative genes other than LIS1 have never been fully determined. We have completed a physical and transcriptional map of the 17p13.3 region from LIS1 to the telomere. Using fluorescence in situ hybridization, we have mapped the deletion size in 19 children with ILS, 11 children with MDS, and 4 children with 17p13.3 deletions not involving LIS1. We show that the critical region that differentiates ILS from MDS at the molecular level can be reduced to 400 kb. Using somatic cell hybrids from selected patients, we have identified eight genes that are consistently deleted in patients classified as having MDS. In addition, deletion of the genes CRK and 14-3-3ɛ delineates patients with the most severe lissencephaly grade. On the basis of recent functional data and the creation of a mouse model suggesting a role for 14-3-3ɛ in cortical development, we suggest that deletion of one or both of these genes in combination with deletion of LIS1 may contribute to the more severe form of lissencephaly seen only in patients with MDS

A Novel Redox Method for Rapid Production of Functional Bi-Specific Antibodies For Use in Early Pilot Studies

We demonstrate here a rapid alternative method for the production of functional bi-specific antibodies using the mild reducing agent 2-mercaptoethanesulfonic acid sodium salt (MESNA). Following reduction of a mixture of two monoclonal antibodies with MESNA to break inter heavy chain bonds, this solution is dialysed under oxidising conditions and antibodies are allowed to reform. During this reaction a mixture of antibodies is formed, including parental antibodies and bi-specific antibody. Bi-specific antibodies are purified over two sequential affinity columns. Following purification, bi-specificity of antibodies is determined in enzyme-linked immunosorbent assays and by flow cytometry. Using this redox method we have been successful in producing hybrid and same-species bi-specific antibodies in a time frame of 6–10 working days, making this production method a time saving alternative to the time-consuming traditional heterohybridoma technology for the production of bi-specific antibodies for use in early pilot studies. The use of both rat and mouse IgG antibodies forming a rat/mouse bi-specific antibody as well as producing a pure mouse bi-specific antibody and a pure rat bi-specific antibody demonstrates the flexibility of this production method

Techniques for Rehabilitating Pavements Without Overlays - A Systems Analysis Vol. 2 Appendixes

DOT-FH-11-9142The objective of the study was to determine the feasibility of a variety of innovative techniques for rehabilitating pavements without using thick overlays and to develop these techniques to the point where they could be implemented. A total of 39 potential techniques were identified. To determine their feasibility a systems decision analysis computer program was developed which utilizes utility theory to simultaneously consider 17 different decision criteria under four main attributes (Cost, Performance, Energy and Impact). Using this utility decision analysis program, a total of 19 techniques demonstrated the capability of solving certain problems better than currently used techniques. Included in the 19 promising techniques are a) use of rejuvenating agents for flexible pavements, b) horizontally-bored sleeper slab and joint restoration for rigid pavements, c) precast joint assemblies for rigid pavements. d) change the location of lane markings, and e) reworked surface of flexible pavement. For other specific problems the program indicated presently used techniques are better than any of the potential techniques. And finally. the program I revealed that 15 potential techniques did not show any promise at this time. Suggestions for further development, implementation and research have been made

Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats

Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O3) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O3 exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O3 at 0.25, 0.50, or 1.0 ppm, 6 h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm O3, 6 h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18 h post-exposure. O3 increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18 h-post second exposure. O3 increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O3. In conclusion, short-term O3 exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress–response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure