Kristine Krajnak

Work, Obesity, and Occupational Safety and Health

There is increasing evidence that obesity and overweight may be related, in part, to adverse work conditions. In particular, the risk of obesity may increase in high-demand, low-control work environments, and for those who work long hours. In addition, obesity may modify the risk for vibration-induced injury and certain occupational musculoskeletal disorders. We hypothesized that obesity may also be a co-risk factor for the development of occupational asthma and cardiovascular disease that and it may modify the workers response to occupational stress, immune response to chemical exposures, and risk of disease from occupational neurotoxins. We developed 5 conceptual models of the interrelationship of work, obesity, and occupational safety and health and highlighted the ethical, legal, and social issues related to fuller consideration of obesitys role in occupational health and safety.

Mitochondrial dysfunction and loss of Parkinson's disease-linked proteins contribute to neurotoxicity of manganese-containing welding fumes

Welding generates complex metal aerosols, inhalation of which is linked to adverse health effects among welders. An important health concern of welding fume (WF) exposure is neurological dysfunction akin to Parkinsons disease (PD), thought to be mediated by manganese (Mn) in the fumes. Also, there is a proposition that welding might accelerate the onset of PD. Our recent findings link the presence of Mn in the WF with dopaminergic neurotoxicity seen in rats exposed to manual metal arc-hard surfacing (MMA-HS) or gas metal arc-mild steel (GMA-MS) fumes. To elucidate the molecular mechanisms further, we investigated the association of PD-linked (Park) genes and mitochondrial function in causing dopaminergic abnormality. Repeated instillations of the two fumes at doses that mimic ∼1 to 5 yr of worker exposure resulted in selective brain accumulation of Mn. This accumulation caused impairment of mitochondrial function and loss of tyrosine hydroxylase (TH) protein, indicative of dopaminergic injury. A fascinating finding was the altered expression of Parkin (Park2), Uchl1 (Park5), and Dj1 (Park7) proteins in dopaminergic brain areas. A similar regimen of manganese chloride (MnCl(2)) also caused extensive loss of striatal TH, mitochondrial electron transport components, and Park proteins. As mutations in PARK genes have been linked to early-onset PD in humans, and because welding is implicated as a risk factor for parkinsonism, PARK genes might play a critical role in WF-mediated dopaminergic dysfunction. Whether these molecular alterations culminate in neurobehavioral and neuropathological deficits reminiscent of PD remains to be ascertained.

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.

Increased Oxidant Activity Mediates Vascular Dysfunction in Vibration Injury

Occupational exposure to hand-operated vibrating tools causes a spectrum of pathological changes in the vascular, neurological, and musculoskeletal systems described as the hand-arm vibration syndrome (HAVS). Experiments were performed to determine the effects of acute vibration on the function of digital arteries. Rats paws were exposed to a vibrating platform (4 h, 125 Hz, constant acceleration of 49 m/s2 root mean squared), and digital artery function was assessed subsequently in vitro using a pressure myograph system. Constriction to phenylephrine or 5-hydroxytryptamine was reduced in digital arteries from vibrated paws. However, after endothelium denudation, constriction to the agonists was no longer impaired in vibrated arteries. Inhibition of nitric-oxide synthase (NOS) with Nω-nitro-l-arginine methyl ester (l-NAME) increased constriction to phenylephrine or 5-hydroxytryptamine in vibrated but not control arteries and abolished the vibration-induced depression in constrictor responses. However, nitric oxide (NO) activity, determined using the NO-sensitive probe 4-amino-5-methylamino-2′, 7′-difluorofluorescein, was reduced in vibrated compared with control arteries. Endogenous levels of reactive oxygen species (ROS), determined using the ROS-sensitive probe 5-(and 6)-chloromethyl-2′,7′-dichlorodihydro-fluorescein, were increased in vibrated compared with control arteries. The increased ROS levels were abolished by l-NAME or by catalase, which degrades extracellular hydrogen peroxide. Catalase also increased constriction to phenylephrine or 5-hydroxytryptamine in vibrated but not control arteries and abolished the vibration-induced depression in constrictor responses. The results suggest that acute vibration causes vascular dysfunction in digital arteries by increasing ROS levels, which is probably mediated by uncoupling of endothelial NOS. Therefore, therapeutic strategies to inhibit ROS or augment NO activity may be beneficial in HAVS.

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

Three-Dimensional Finite Element Simulations of the Dynamic Response of a Fingertip to Vibration

Although excessive dynamic deformation of the soft tissues in the fingertip under vibration loading is thought to induce hand-arm vibration syndrome, the in vivo distributions of the dynamic stress/strain of the tissues in the fingertip under vibration conditions have not been studied because they cannot be measured experimentally. In the present study, we analyzed the dynamic responses of a fingertip to vibrations by extending our previously proposed three-dimensional finite element (FE) model. The FE model of the fingertip contains the essential anatomical structures of a finger, such as skin layers (dermis and epidermis), subcutaneous tissue, bone, and nail. Our analysis indicated that the fingertip has a major local resonance around 100 Hz and that the vibration displacement in the soft tissues under the nail bed is less than 10% of those in the finger pad for all precompression levels and vibration range. The resonant frequency of the fingertip was found to increase from 88 Hz to 125 Hz with the static precompression increasing from 0.5 mm to 2.0 mm. These results suggest that structural and functional changes in vascular function will likely initiate from the fingerpad, the location that undergoes the greatest deformation during vibration exposure. The current predictions are qualitatively consistent with the physiological data collected from workers with vibration white finger.

Current perception threshold and the HAVS Stockholm sensorineural scale

BACKGROUND It is important to determine which tests of sensorineural dysfunction identify the neurological damage from hand-arm vibration exposure. AIMS To examine the association between the hand-arm vibration syndrome (HAVS) Stockholm sensorineural scale stages and tests of peripheral neurological function including measurement of current perception threshold (CPT) and nerve conduction. METHODS All the subjects were men who were assessed for HAVS with a medical and occupational history and physical examination to determine the Stockholm stage, CPT testing at frequencies of 5, 250 and 2000 Hz for the median and ulnar nerves and measurement of nerve conduction carried out in a blinded fashion. RESULTS A total of 155 of the 157 recruited subjects agreed to take part in the study, a 99% participation rate. CPT was statistically significantly increased (P < 0.001) in both Stockholm sensorineural Stages 1 and > or =2 in comparison to Stage 0 for every frequency and nerve combination. However, CPT could not discriminate well between Stages 1 and > or =2. There was no association between median or ulnar neuropathy measured by nerve conduction and the Stockholm stages. Polychotomous multinomial logistic regression indicated that the CPT measurements at 2000 Hz, corresponding to damage to large myelinated nerve fibres, were most predictive of both Stockholm Stages 1 and > or =2 in comparison to Stage 0. CONCLUSIONS Neuropathy measured by nerve conduction was unrelated to the Stockholm scale stages. CPT was increased above Stage 0 but did not distinguish well between the higher stages of the Stockholm scale.