The etiology of neurodegenerative disorders is at present unknown. However, many of these disorders are associated with an increase in oxidative and inflammatory events. Although a small percentage of these disorders are familial cases linked to specific genetic defects, most are idiopathic. Thus, environmental factors are thought to play an important role in the onset and progression of such disorders. We have demonstrated that exposure (4 h, 5 days per week for 2 weeks) to concentrated airborne particulate matter increases inflammatory indices in brain of ovalbumin-sensitized BALB/c mice. Animals were divided into three exposure groups: filtered air (control), ultrafine particles, or fine and ultrafine particles. The levels of proinflammatory cytokines interleukin-1 alpha (IL-1alpha) and tumor necrosis factor alpha (TNF-alpha) were increased in brain tissue of mice exposed to particulate matter compared to that of control animals. Levels of the immune-related transcription factor NF-kappaB were also found to be substantially elevated in the brain of exposed groups compared with the control group. These data indicate that components of inhaled particulate matter may trigger a proinflammatory response in nervous tissue that could contribute to the pathophysiology of neurodegenerative diseases.

In support of predictions for inhaled particle deposition, morphometric measurements were taken on 20 replica airway casts of people aged 11 days to 21 years. Measurements of right upper lobe airway lengths, diameters, and branching angles were made such that a growth model suitable as input to predictive equations for particle deposition efficiency was obtained. The tracheobronchial airways growth was describable by linear regressions on body length. The length-todiameter ratio of growing airways did not change in any simple way as a function of airway generation. Airflow rates for a given state of physical activity for various ages were found from previously published data to be describable by linear regressions on body mass. Three states of physical exertion-low activity, light exertion, and heavy exertion-were used for modeling purposes. The computed particle deposition efficiencies indicate that under most circumstances smaller (younger) people will have greater tracheobronchial deposition efficiencies than larger (older) people. For example, tracheobronchial dose on a per kilogram body mass basis for 5-pmdiameter particles may be more than 6 times higher in the resting newborn than in the resting adult assuming equivalent deposition efficiencies above the larynx.Because little is known regarding age-related differ-(1913) published values for lengths and diameters (sagences in inhaled particle deposition, we have been inter-ittal and frontal) of the trachea and right and left main ested in developing mathematical predictions for particle bronchi for 12 children aged 1 month to 13 years, and a deposition in the tracheobronchial airways correspond-40-year-old adult. Engel's data show relatively rapid but ing to a range of ages. Such predictions are strongly decelerating growth of the measured structures up to dependent on airway anatomy, so measurements of the about age 7 years, but with only one child over age 10 growing airways were taken to develop a model upon years little can be said about growth after age 7. Also, which to base the mathematical predictions for depo-only two generations of airways were well described. sition.Although there is agreement on the sequence of events Although several investigators have provided quanti-during postnatal lung growth, many fundamental questative descriptions of the dimensions of adult human tions remain. There is general agreement (although perairways, few have described the manner in which these haps a lack of direct proof) that the full number of structures grow. Among the earliest morphometric bronchial airways are present at birth and that alveolarmodels for the complete adult tracheobronchial airways ization of bronchioles continues postnatally in a proxiwere those published by Weibel(1963). To generate these mal direction. Bronchial airway growth generally models, measurements from the trachea downward for parallels changes in stature, but there is confusion reabout 10 generations were made on a plastic replica cast garding details. This state of und...

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Wildlife refuges are sites of dense aggregations of wintering waterfowl. Refuge managers are concerned about local water-quality effects and the amount of birdborne nutrient load that might cause eutrophication in roosting ponds and(or) be exported to downstream systems. We initiated this research effort to test the hypothesis that daily feeding migrations by geese represented a significant source of nutrients to wetland systems at the Bosque del Apache National Wildlife Refuge in the middle Rio Grande River valley of New Mexico. We documented the role of geese in translocating nutrients through a combination of time budget and mass balance models for birds, bioassays of phytoplankton growth, and stable isotope methods that trace the source of nitrogen to food webs. Geese increased the nutrient loading rates in some wetland ponds by up to 40% for total nitrogen and 75% for total phosphorus. Bioassays revealed that nitrogen was consistently limiting to primary production by algae in the ponds. Chlorophyll levels increased in proportion to bird densities. Fish and crayfish from the ponds intensively used by birds had very low stable nitrogen signatures relative to those from the Rio Grande River. This result derived from the low 15 N in alfalfa and corn, which were the primary forage for birds, and accumulated through food webs in proportion to bird use of individual ponds as roosting areas. In general, the wetland ponds functioned efficiently in retaining the birdborne, allochthonous nutrient load and only modest amounts of the total nitrogen or phosphorus were exported downstream.Does the wild goose, reconnoitering the farmer's cornfield, bring something more than wild music from the lake, take something more than waste corn from his field?Aldo Leopold Lakes in relation to terrestrial life patterns Each autumn, hundreds of thousands of waterfowl migrate to winter refuges in southerly latitudes. In the southwestern U.S. winter months are spent near large river systems such as the Rio Grande. The riparian corridors in arid regions

Background: Menstrual cups have been available for decades, but their use is limited by bulky design and the need for multiple sizes. The Softcup Ò (Instead, Inc., San Diego, CA) is a simple single-size disposable over-thecounter (OTC) menstrual cup that compresses to tampon shape to facilitate insertion and can be worn during coitus. This report describes preclinical evaluation, clinical testing, and postmarketing monitoring of the Softcup. Methods: Preclinical testing complied with U.S. Food and Drug Administration (FDA) guidelines and used standard United States Pharmacopoeia methodologies for assessment of potential toxicity. Clinical testing enrolled 406 women in seven U.S. centers. A detailed written questionnaire assessed safety, acceptability, and effectiveness for menstrual collection. Study safety parameters included pelvic examinations, Pap smears, colposcopy, urinalysis, vaginal pH, wet mounts, gram stain, and vaginal microflora cultures. Postmarketing surveillance of over 100 million Softcups has been conducted by the manufacturer and by the FDA Medwatch system. Results: No toxicity or mutagenicity was observed in preclinical evaluations. In clinical testing, after three cycles of cup use, 37% of subjects rated the cup as better than, 29% as worse than, and 34% as equal to pads or tampons. The cup was preferred for comfort, dryness, and less odor. Cups received lower ratings for disposal and convenience. Eighty-one percent of enrolled women were able to insert and remove their first cup using only written instructions. Use difficulties resulting in study discontinuations included cramping (1%), leakage (1%), and improper fit (3%). No safety parameters were adversely affected. No significant health risks were reported during postmarketing surveillance.Conclusions: These results demonstrate that a single-size vaginal device has no significant health risks and is acceptable to many women without the need for fitting or other medical services.

Cigarette smoking (CS) is a major risk factor for vascular disease. The aim of this study was to quantitatively assess the influence of CS on mouse arteries. We studied the effect of short-term (6 wk) and long-term (16 wk) CS exposure on structural and mechanical properties of coronary arteries compared with that of control mice. We also examined the reversibility of the deleterious effects of CS on structural [e.g., wall thickness (WT)], mechanical (e.g., stiffness), and biochemical [e.g., nitric oxide (NO) by-products] properties with the cessation of CS. The left and right coronary arteries were cannulated in situ and mechanically distended. The stress, strain, elastic modulus, and WT of coronary arteries were determined. Western blot analysis was used to analyze endothelial NO synthase (eNOS) in the femoral and carotid arteries of the same mice, and NO by-products were determined by measuring the levels of nitrite. Our results show that the mean arterial pressure was increased by CS. Furthermore, CS significantly increased the elastic modulus, decreased stress and strain, and increased the WT and WT-to-radius ratio compared with those of control mice. The reduction of eNOS protein expression was found only after long-term CS exposure. Moreover, the NO metabolite was markedly decreased in CS mice after short- and long-term exposure of CS. These findings suggest that 16 wk of CS exposure can cause an irreversible deterioration of structural and elastic properties of mouse coronary arteries. The decrease in endothelium-derived NO in CS mice was seen to significantly correlate with the remodeling of arterial wall.

Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to iron oxide nanoparticles, micro and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat, human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles.

The purpose of this paper is to present a method for estimating particle doses that may be used to reconcile particle deposition doses used in in vitro toxicology studies with in vivo exposure levels. The focus is on the tracheobronchial (TB) tree of heavily exposed individuals. A review of the factors that influence inhaled particle deposition doses in environmental exposures leads to the identification of cases in which greater than average TB tree doses are received. Exercising individuals and those with chronic obstructive pulmonary disease not only inhale increased volumes of air but they also may have uneven ventilation that leads to greater than average particle deposition doses per unit of TB tree surface area. In addition, deposition hot spots, as occur at airway bifurcations, will greatly increase the particle exposures of target cells in the TB tree. Three particle exposure scenarios are proposed, and the average and local doses to the TB epithelium are calculated. When various factors that enhance particle doses (enhancement factors, or EFs) in vivo are considered, substantial particle doses may be justified for in vitro tissue culture studies that use TB target cells, such as epithelial cell cultures. The use of such EFs is intended to improve in vitro dosing with particles. Although the exposure of cells in vitro cannot fully replicate the complexity of in vivo exposures, it is possible to calculate toxicologically relevant doses that may define adverse health effects in potentially sensitive human populations. Local groups of TB cells in high-dose individuals are predicted to receive particle doses that are 3000-25,000 times higher than the doses averaged over the entire TB region.