Stacey Waugh

Pulmonary and Cardiovascular Responses of Rats to Inhalation of Silver Nanoparticles

Exposure to wet aerosols generated during use of spray products containing silver (Ag) has not been evaluated. The goal was to assess the potential for cardiopulmonary toxicity following an acute inhalation of wet silver colloid. Rats were exposed by inhalation to a low concentration (100 μg/m3 ) using an undiluted commercial antimicrobial product (20 mg/L total silver; approximately 33 nm mean aerodynamic diameter [MAD]) or to a higher concentration (1000 μg/m3) using a suspension (200 mg/L total silver; approximately 39 nm MAD) synthesized to possess a similar size distribution of Ag nanoparticles for 5 h. Estimated lung burdens from deposition models were 0, 1.4, or 14 μg Ag/rat after exposure to control aerosol, low, and high doses, respectively. At 1 and 7 d postexposure, the following parameters were monitored: pulmonary inflammation, lung cell toxicity, alveolar air/blood barrier damage, alveolar macrophage activity, blood cell differentials, responsiveness of tail artery to vasoconstrictor or vasodilatory agents, and heart rate and blood pressure in response to isoproterenol or norepinephrine, respectively. Changes in pulmonary or cardiovascular parameters were absent or nonsignificant at 1 or 7 d postexposure with the exceptions of increased blood monocytes 1 d after high-dose Ag exposure and decreased dilation of tail artery after stimulation, as well as elevated heart rate in response to isoproterenol 1 d after low-dose Ag exposure, possibly due to bioavailable ionic Ag in the commercial product. In summary, short-term inhalation of nano-Ag did not produce apparent marked acute toxicity in this animal model.

Proapoptotic factor Bax is increased in satellite cells in the tibialis anterior muscles of old rats.

Aging impairs the ability of muscle to adapt to exercise or injury. The goal of this study was to determine whether age‐related changes in muscle adaptability could be the result of satellite cell apoptosis. Ten days after exposure to an injury protocol, estimates of edema in the exposed tibialis anterior muscles were higher in old (30 months) than young (3 months) rats, and isometric force levels were lower in old rats. Both young and old rats displayed an increase in MyoD labeling in the exposed muscle, indicating that injury induced satellite‐cell activation. However, there were more MyoD‐labeled cells that coexpressed the proapoptotic factor, Bax, in old than in young rats, suggesting that decrements in muscle recovery may be associated with an increase in satellite‐cell apoptosis. Based on these findings we conclude that reducing satellite‐cell apoptosis in aged animals may improve muscle recovery after injury. Muscle Nerve, 2006

Pulmonary and cardiovascular responses of rats to inhalation of a commercial antimicrobial spray containing titanium dioxide nanoparticles

Our laboratory has previously demonstrated that application of an antimicrobial spray product containing titanium dioxide (TiO2) generates an aerosol of titanium dioxide in the breathing zone of the applicator. The present report describes the design of an automated spray system and the characterization of the aerosol delivered to a whole body inhalation chamber. This system produced stable airborne levels of TiO2 particles with a median count size diameter of 110 nm. Rats were exposed to 314 mg/m3 min (low dose), 826 mg/m3 min (medium dose), and 3638 mg/m3 min (high dose) of TiO2 under the following conditions: 2.62 mg/m3 for 2 h, 1.72 mg/m3 4 h/day for 2 days, and 3.79 mg/m3 4 h/day for 4 days, respectively. Pulmonary (breathing rate, specific airway resistance, inflammation, and lung damage) and cardiovascular (the responsiveness of the tail artery to constrictor or dilatory agents) endpoints were monitored 24 h post-exposure. No significant pulmonary or cardiovascular changes were noted at low and middle dose levels. However, the high dose caused significant increases in breathing rate, pulmonary inflammation, and lung cell injury. Results suggest that occasional consumer use of this antimicrobial spray product should not be a hazard. However, extended exposure of workers routinely applying this product to surfaces should be avoided. During application, care should be taken to minimize exposure by working under well ventilated conditions and by employing respiratory protection as needed. It would be prudent to avoid exposure to children or those with pre-existing respiratory disease.

Characterization of frequency-dependent responses of the vascular system to repetitive vibration.

Objective: Occupational exposure to hand-transmitted vibration can result in damage to nerves and sensory loss. The goal of this study was to assess the frequency-dependent effects of repeated bouts of vibration on sensory nerve function and associated changes in nerves. Methods: The tails of rats were exposed to vibration at 62.5, 125, or 250 Hz (constant acceleration of 49 m/s2) for 10 days. The effects on sensory nerve function, nerve morphology, and transcript expression in ventral tail nerves were measured. Results: Vibration at all frequencies had effects on nerve function and physiology. However, the effects tended to be more prominent with exposure at 250 Hz. Conclusion: Exposure to vibration has detrimental effects on sensory nerve function and physiology. However, many of these changes are more prominent at 250-Hz exposure than at lower frequencies.

Acute effects of COREXIT EC9500A on cardiovascular functions in rats.

These studies characterized cardiovascular responses after an acute inhalation exposure to COREXIT EC9500A, the oil dispersant used in the Deepwater Horizon oil spill. Male Sprague-Dawley rats underwent a single 5-h inhalation exposure to COREXIT EC9500A (average exposure level 27.12 mg/m3) or air. On d 1 and 7 following the exposure, rats were implanted with indwelling catheters and changes in heart rate and blood pressure were assessed in response to increasing levels of adrenoreceptor agonists. A separate group of rats was euthanized at the same time points, ventral tail arteries were dissected, and vascular tone along with dose-dependent responses to vasoconstricting and dilating factors were assessed in vitro. Agonist-induced dose-dependent increases in heart rate and blood pressure were greater in COREXIT EC9500A-exposed than in air-exposed rats at 1 d but not 7 d after the exposure. COREXIT EC9500A exposure also induced a rise in basal tone and reduced responsiveness of tail arteries to acetylcholine-induced vasodilation at 1 d but not 7 d following the exposure. These findings demonstrate that an acute exposure to COREXIT EC9500A exerts transient effects on cardiovascular and peripheral vascular functions.

Acute vibration reduces Aβ nerve fiber sensitivity and alters gene expression in the ventral tail nerves of rats

Long‐term occupational exposure to hand–arm vibration can result in a permanent reduction in tactile sensitivity in exposed fingers and hands. Little is known about how vibration causes this reduction in sensitivity, and currently no testing procedures have been developed to monitor changes in sensory perception during ongoing exposures. We used a rat‐tail model of hand–arm vibration syndrome (HAVS) to determine whether changes in sensory nerve function could be detected after acute exposure to vibration. Nerve function was assessed using the current perception threshold (CPT) method. We also determined whether changes in nerve function were associated with changes in gene transcription. Our results demonstrate that the CPT method can be used to assess sensory nerve function repeatedly in rats and can detect transient decreases in the sensitivity of Aβ nerve fibers caused by acute exposure to vibration. This decrease in Aβ fiber sensitivity was associated with a reduction in expression of nitric oxide synthase‐1, and a modest increase in calcitonin gene–related peptide transcript levels in tail nerves 24 h after vibration exposure. These transient changes in sensory perception and transcript levels induced by acute vibration exposure may be indicators of more prolonged changes in peripheral nerve physiology. Muscle Nerve, 2007

The Effects of Impact Vibration on Peripheral Blood Vessels and Nerves

Research regarding the risk of developing hand-arm vibration syndrome after exposure to impact vibration has produced conflicting results. This study used an established animal model of vibration-induced dysfunction to determine how exposure to impact vibration affects peripheral blood vessels and nerves. The tails of male rats were exposed to a single bout of impact vibration (15 min exposure, at a dominant frequency of 30 Hz and an unweighted acceleration of approximately 345 m/s2) generated by a riveting hammer. Responsiveness of the ventral tail artery to adrenoreceptor-mediated vasoconstriction and acetylcholine-mediated re-dilation was measured ex vivo. Ventral tail nerves and nerve endings in the skin were assessed using morphological and immunohistochemical techniques. Impact vibration did not alter vascular responsiveness to any factors or affect trunk nerves. However, 4 days following exposure there was an increase in protein-gene product (PGP) 9.5 staining around hair follicles. A single exposure to impact vibration, with the exposure characteristics described above, affects peripheral nerves but not blood vessels.

Antivibration gloves: effects on vascular and sensorineural function, an animal model.

Anti-vibration gloves have been used to block the transmission of vibration from powered hand tools to the user, and to protect users from the negative health consequences associated with exposure to vibration. However, there are conflicting reports as to the efficacy of gloves in protecting workers. The goal of this study was to use a characterized animal model of vibration-induced peripheral vascular and nerve injury to determine whether antivibration materials reduced or inhibited the effects of vibration on these physiological symptoms. Rats were exposed to 4 h of tail vibration at 125 Hz with an acceleration 49 m/s2. The platform was either bare or covered with antivibrating glove material. Rats were tested for tactile sensitivity to applied pressure before and after vibration exposure. One day following the exposure, ventral tail arteries were assessed for sensitivity to vasodilating and vasoconstricting factors and nerves were examined histologically for early indicators of edema and inflammation. Ventral tail artery responses to an α2C-adrenoreceptor agonist were enhanced in arteries from vibration-exposed rats compared to controls, regardless of whether antivibration materials were used or not. Rats exposed to vibration were also less sensitive to pressure after exposure. These findings are consistent with experimental findings in humans suggesting that antivibration gloves may not provide protection against the adverse health consequences of vibration exposure in all conditions. Additional studies need to be done examining newer antivibration materials.

Long-term daily vibration exposure alters current perception threshold (CPT) sensitivity and myelinated axons in a rat-tail model of vibration-induced injury

ABSTRACT Repeated exposure to hand-transmitted vibration through the use of powered hand tools may result in pain and progressive reductions in tactile sensitivity. The goal of the present study was to use an established animal model of vibration-induced injury to characterize changes in sensory nerve function and cellular mechanisms associated with these alterations. Sensory nerve function was assessed weekly using the current perception threshold test and tail-flick analgesia test in male Sprague-Dawley rats exposed to 28 d of tail vibration. After 28 d of exposure, Aβ fiber sensitivity was reduced. This reduction in sensitivity was partly attributed to structural disruption of myelin. In addition, the decrease in sensitivity was also associated with a reduction in myelin basic protein and 2’,3’- cyclic nucleotide phosphodiasterase (CNPase) staining in tail nerves, and an increase in circulating calcitonin gene-related peptide (CGRP) concentrations. Changes in Aβ fiber sensitivity and CGRP concentrations may serve as early markers of vibration-induced injury in peripheral nerves. It is conceivable that these markers may be utilized to monitor sensorineural alterations in workers exposed to vibration to potentially prevent additional injury.

Recovery of Vascular Function After Exposure to a Single Bout of Segmental Vibration

Work rotation schedules may be used to reduce the negative effects of vibration on vascular function. This study determined how long it takes vascular function to recover after a single exposure to vibration in rats (125 Hz, acceleration 5g). The responsiveness of rat-tail arteries to the vasoconstricting factor UK14304, an α2C-adrenoreceptor agonist, and the vasodilating factor acetylcholine (ACh) were measured ex vivo 1, 2, 7, or 9 d after exposure to a single bout of vibration. Vasoconstriction induced by UK14304 returned to control levels after 1 d of recovery. However, re-dilation induced by ACh did not return to baseline until after 9 d of recovery. Exposure to vibration exerted prolonged effects on peripheral vascular function, and altered vascular responses to a subsequent exposure. To optimize the positive results of work rotation schedules, it is suggested that studies assessing recovery of vascular function after exposure to a single bout of vibration be performed in humans.