Publications by authors named "Rudolph Jaeger"

6 Publications

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Inhalable curcumin: offering the potential for translation to imaging and treatment of Alzheimer's disease.

J Alzheimers Dis 2015 ;44(1):283-95

Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA Department of Radiology and Radiological Sciences, Vanderbilt School of Medicine, Nashville, TN, USA Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA Vanderbilt Institute of Chemical Biology, Nashville, TN, USA.

Curcumin is a promising compound that can be used as a theranostic agent to aid research in Alzheimer's disease. Beyond its ability to bind to amyloid plaques, the compound can also cross the blood-brain barrier. Presently, curcumin can be applied only to animal models, as the formulation needed for iv injection renders it unfit for human use. Here, we describe a novel technique to aerosolize a curcumin derivative, FMeC1, and facilitate its safe delivery to the brain. Aside from the translational applicability of this approach, a study in the 5XFAD mouse model suggested that inhalation exposure to an aerosolized FMeC1 modestly improved the distribution of the compound in the brain. Additionally, immunohistochemistry data confirms that following aerosol delivery, FMeC1 binds amyloid plaques expressed in the hippocampal areas and cortex.
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http://dx.doi.org/10.3233/JAD-140798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297252PMC
September 2015

Acute passive cigarette smoke exposure and inhaled human insulin (Exubera) pharmacokinetics.

Br J Clin Pharmacol 2008 Jun;65(6):864-70

Pfizer Global Research and Development, Groton, CT and Environmental Medicine Incorporated, Westwood, NJ, USA.

What Is Already Known About This Subject: Active cigarette smoking is associated with increased permeability of the pulmonary alveolar epithelium, resulting in faster absorption of inhaled drugs such as Exubera (EXU). Absorption of EXU is increased approximately twice to four times as much in chronic smokers compared with nonsmokers. The rate of clearance of radioaerosols such as technetium-labelled diethylenetriamine penta-acetic acid is decreased in response to passive smoke exposure.

What This Study Adds: Passive smoke exposure causes a decrease in lung permeability, an effect opposite to that of active smoking. Acute passive smoke exposure results in a decrease in EXU bioavailability and does not create a risk of hypoglycaemia. These results are consistent with previous studies of radioaerosol lung clearance. AIMS Relative to nonsmokers, the bioavailability of inhaled human insulin (Exubera(R); EXU) is markedly increased in chronic smokers. The pharmacokinetics of EXU following passive cigarette smoke exposure is unknown. METHODS In an open-label, crossover study, healthy nonsmoking volunteers received two treatments in randomized sequence separated by a 2-week wash-out: (i) EXU 3 mg with no passive smoke exposure and (ii) EXU 3 mg after passive smoke exposure (atmospheric nicotine levels 75-125 mug m(-3)) for 2 h. Blood samples were obtained at prespecified times up to 6 h after EXU administration.

Results: Twenty-seven subjects completed both study periods. Mean plasma insulin AUC(0-360) decreased by 17% [ratio 83%, 95% confidence interval (CI) 68.8, 99.5] and mean C(max) by 29% (ratio 71%, 95% CI 59.8, 83.1) after passive cigarette smoke exposure. The median (range) t(max) was 60 min (20-120 min) and 75 min (20-360 min) in the EXU with no exposure and EXU passive exposure groups, respectively. EXU was well tolerated.

Conclusions: Unlike active chronic smoking, acute passive cigarette smoke exposure modestly decreases EXU bioavailability and thus should not increase hypoglycaemia risk. These results are consistent with those from published literature involving technetium-labelled diethylenetriamine penta-acetic acid and suggest that passive cigarette smoke exposure causes an acute decrease in lung permeability vs. active smoking, which causes an increase in permeability.
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http://dx.doi.org/10.1111/j.1365-2125.2008.03122.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2485222PMC
June 2008

Distribution of lead in urban roadway grit and its association with elevated steel structures.

Chemosphere 2006 Dec 21;65(10):1762-71. Epub 2006 Jun 21.

Environmental Medicine Inc., 263 Center Avenue, Westwood, NJ 07675, USA.

In an effort to determine the source of exterior lead contamination, we investigated the concentration of lead in roadway grit along major thoroughfares in New York City and in certain areas under elevated steel structures supporting elevated rails. Such structures represent only one source of lead in roadway grit. While data revealed that the median lead concentration in roadway grit did not exceed the standard for a lead hazard in bare residential soil in any borough, the limit of 400 microg/g was exceeded 22%, 18%, 10.5%, and 7.7% of the time in Manhattan, Brooklyn, The Bronx, and Queens, respectively. The second part of the study revealed the presence of high concentrations of lead in roadway grit directly under elevated steel structures. The differences in the concentration of lead in roadway grit under steel structures in comparison to areas in NYC not near elevated rails was statistically significant. Of the eight sites studied from 225 total samples, the median roadway grit lead level was 340 ppm, while the level under steel structures was 1480 ppm. Preliminary efforts to determine particle size distribution revealed that 84% of the particles were in the range of 125-500 microm, but the highest concentration of lead was in the smallest fraction analyzed (<63 microm). Lead contamination of roadway grit from restoration of elevated painted steel structures is a public health problem as these lead particulates get re-suspended in the ambient environment and are wafted and tracked into residences.
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http://dx.doi.org/10.1016/j.chemosphere.2006.04.079DOI Listing
December 2006

An exterior and interior leaded dust deposition survey in New York City: results of a 2-year study.

Environ Res 2006 Feb 23;100(2):159-64. Epub 2005 Sep 23.

School of Health Sciences, Hunter College-CUNY, USA.

Environmental concentrations of leaded dust were monitored by weekly sample collection of interior and exterior settled dust that had accumulated due to atmospheric deposition. The weekly deposition amounts were measured and the cumulative rates of lead in dust that deposited on a weekly basis over 2 year's time were determined. The sampling analysis revealed that the median values of leaded dust for the interior plate (adjacent to the open window), unsheltered exterior plate, and the sheltered exterior plate were 4.8, 14.2, and 32.3 microg/feet2/week, respectively. The data supports the existence of a continuous source of deposited leaded dust in interior and exterior locations within New York City. Additional data from a control plate (interior plate with the window closed) demonstrate that the source of the interior lead deposition was from exterior (environmental) sources. Because of the ubiquitous nature of lead in our environment and the toxic threat of lead to the cognitive health of children, this data provides a framework for the understanding of environmental exposure to lead and its potential for continuing accumulation within an urban environment.
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http://dx.doi.org/10.1016/j.envres.2005.08.005DOI Listing
February 2006

A survey of spatially distributed exterior dust lead loadings in New York City.

Environ Res 2006 Feb 11;100(2):165-72. Epub 2005 Jul 11.

Hunter College-CUNY, School of Health Sciences, Westwood, NJ 07675, USA.

This work documents ambient lead dust deposition values (lead loading) for the boroughs of New York City in 2003-2004. Currently, no regulatory standards exist for exterior concentrations of lead in settled dust. This is in contrast to the clearance and risk assessment standards that exist for interior residential dust. The reported potential for neurobehavioral toxicity and adverse cognitive development in children due to lead exposure prompts public health concerns about undocumented lead sources. Such sources may include settled dust of outdoor origin. Dust sampling throughout the five boroughs of NYC was done from the top horizontal portion of pedestrian traffic control signals (PTCS) at selected street intersections along main thoroughfares. The data (n=214 samples) show that lead in dust varies within each borough with Brooklyn having the highest median concentration (730 microg/ft2), followed in descending order by Staten Island (452 microg/ft2), the Bronx (382 microg/ft2), Queens (198 microg/ft2) and finally, Manhattan (175 microg/ft2). When compared to the HUD/EPA indoor lead in dust standard of 40 microg/ft2, our data show that this value is exceeded in 86% of the samples taken. An effort was made to determine the source of the lead in the dust atop of the PTCS. The lead in the dust and the yellow signage paint (which contains lead) were compared using isotopic ratio analysis. Results showed that the lead-based paint chip samples from intact signage did not isotopically match the dust wipe samples taken from the same surface. We know that exterior dust containing lead contributes to interior dust lead loading. Therefore, settled leaded dust in the outdoor environment poses a risk for lead exposure to children living in urban areas, namely, areas with elevated childhood blood lead levels and background lead dust levels from a variety of unidentified sources.
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http://dx.doi.org/10.1016/j.envres.2005.05.001DOI Listing
February 2006

Infusion of di-2-ethylhexylphthalate for neonates: a review of potential health risk.

J Infus Nurs 2005 Jan-Feb;28(1):54-60

Environmental Medicine Inc., 163 Center Avenue, Westwood, NJ 07675, USA.

Plasticizers leach from polyvinyl chloride medical devices into infusion fluids. One plasticizer frequently found is di-2-ethylhexylphthalate. The Food and Drug Administration estimates that di-2-ethylhexylphthalate exposure exceeding a daily tolerable intake of 0.6 mg/kg per day may harm newborns, especially males. Exposure 20 times the tolerable intake or more may be given daily to certain infants, neonates, and premature infants in the neonatal intensive care unit. Currently, scant data exist on the exact dosage to this population. Furthermore, the exact potential for harm, either subtle or overt, is unknown or disputed. Thus, the recording of exposure history and "dose" in the medical record is warranted.
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http://dx.doi.org/10.1097/00129804-200501000-00007DOI Listing
April 2005
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