Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
Records 1-30 (of 47 Records) |
Query Trace: Krajnak K[original query] |
---|
Force-induced tissue compression alters circulating hormone levels and biomarkers of peripheral vascular and sensorineural dysfunction in an animal model of hand-arm vibration syndrome
Krajnak K , Waugh S , Warren C , Chapman P , Xu X , Welcome D , Hammer M , Richardson D , Dong R . J Toxicol Environ Health A 2024 1-21 Workers regularly using vibrating hand tools may develop a disorder referred to as hand-arm vibration syndrome (HAVS). HAVS is characterized by cold-induced vasospasms in the hands and fingers that result in blanching of the skin, loss of sensory function, pain, and reductions in manual dexterity. Exposure to vibration induces some of these symptoms. However, the soft tissues of the hands and fingers of workers are compressed as a result of the force generated when a worker grips a tool. The compression of these soft tissues might also contribute to the development of HAVS. The goal of this study was to use an established rat tail model to determine the mechanisms by which compression of the tail tissues affects (1) the ventral tail artery (VTA) and ventral tail nerves (VTN), (2) nerves and sensory receptors in the skin, (3) dorsal root ganglia (DRG), and (4) spinal cord. Tissue compression resulted in the following changes (1) circulating pituitary and steroid hormone concentrations, (2) expression of factors that modulate vascular function in the skin and tail artery, and (3) factors associated with nerve damage, DRG, and spinal cord. Some of these observed effects differed from those previously noted with vibration exposure. Based upon these findings, the effects of applied force and vibration are different. Studies examining the combination of these factors might provide data that may potentially be used to improve risk assessment and support revision of standards. |
Rat-tail models for studying hand-arm vibration syndrome: A comparison between living and cadaver rat tails
Warren CM , Xu XS , Jackson M , McKinney WG , Wu JZ , Welcome DE , Waugh S , Chapman P , Sinsel EW , Service S , Krajnak K , Dong RG . Vib 2024 7 (3) 722-737 Over-exposure of the hand-arm system to intense vibration and force over time may cause degeneration of the vascular, neurological, and musculoskeletal systems in the fingers. A novel animal model using rat tails has been developed to understand the health effects on human fingers exposed to vibration and force when operating powered hand tools or workpieces. The biodynamic responses, such as vibration stress, strain, and power absorption density, of the rat tails can be used to help evaluate the health effects related to vibration and force and to establish a dose-effect relationship. While the biodynamic responses of cadaver rat tails have been investigated, the objective of the current study was to determine whether the biodynamic responses of living rat tails are different from those of cadaver rat tails, and whether the biodynamic responses of both living and cadaver tails change with exposure duration. To make direct comparisons, the responses of both cadaver and living rat tails were examined on four different testing stations. The transfer function of each tail under a given contact force (2 N) was measured at each frequency in the one-third octave bands from 20 to 1000 Hz, and used to calculate the mechanical system parameters of the tails. The transfer functions were also measured at different exposure durations to determine the time dependency of the response. Differences were observed in the vibration biodynamic responses between living and cadaver tails, but the general trends were similar. The biodynamic responses of both cadaver and living rat tails varied with exposure duration. © 2024 by the authors. |
Quantification of mechanical behavior of rat tail under compression
Moore KD , Wu JZ , Krajnak K , Warren C , Dong RG . Biomed Mater Eng 2024 BACKGORUND: The development of vibration-induced finger disorders is likely associated with combined static and dynamic responses of the fingers to vibration exposure. To study the mechanism of the disorders, a new rat-tail model has been established to mimic the finger vibration and pressure exposures. However, the mechanical behavior of the tail during compression needs to be better understood to improve the model and its applications. OBJECTIVE: To investigate the static and time-dependent force responses of the rat tail during compression. METHODS: Compression tests were conducted on Sprague-Dawley cadaver rat tails using a micromechanical system at three deformation velocities and three deformation magnitudes. Contact-width and the time-histories of force and deformation were measured. Additionally, force-relaxation tests were conducted and a Prony series was used to model the force-relaxation behavior of the tail. RESULTS: The rat tails' force-deformation and stiffness-deformation relationships were strongly nonlinear and time-dependent. Force/stiffness increased with an increase in deformation and deformation velocity. The time-dependent force-relaxation characteristics of the tails can be well described using a Prony series. CONCULSIONS: We successfully quantified the static and time-dependent force responses of rat tails under compression. The identified mechanical behavior of the tail can help improve the rat-tail model and its applications. |
Exposure to emissions generated by 3-dimensional printing with polycarbonate: effects on peripheral vascular function, cardiac vascular morphology and expression of markers of oxidative stress in male rat cardiac tissue
Krajnak K , Farcas M , Richardson D , Hammer MA , Waugh S , McKinney W , Knepp A , Jackson M , Burns D , LeBouf R , Matheson J , Thomas T , Qian Y . J Toxicol Environ Health A 2024 1-19 Three-dimensional (3D) printing with polycarbonate (PC) plastic occurs in manufacturing settings, homes, and schools. Emissions generated during printing with PC stock and bisphenol-A (BPA), an endocrine disrupter in PC, may induce adverse health effects. Inhalation of 3D printer emissions, and changes in endocrine function may lead to cardiovascular dysfunction. The goal of this study was to determine whether there were any changes in markers of peripheral or cardiovascular dysfunction in animals exposed to PC-emissions. Male Sprague Dawley rats were exposed to PC-emissions generated by 3D printing for 1, 4, 8, 15 or 30 d. Exposure induced a reduction in the expression of the antioxidant catalase (Cat) and endothelial nitric oxide synthase (eNos). Endothelin and hypoxia-induced factor 1α transcripts increased after 30 d. Alterations in transcription were associated with elevations in immunostaining for estrogen and androgen receptors, nitrotyrosine, and vascular endothelial growth factor in cardiac arteries of PC-emission exposed animals. There was also a reduction eNOS immunostaining in cardiac arteries from rats exposed to PC-emissions. Histological analyses of heart sections revealed that exposure to PC-emissions resulted in vasoconstriction of cardiac arteries and thickening of the vascular smooth muscle wall, suggesting there was a prolonged vasoconstriction. These findings are consistent with studies showing that inhalation 3D-printer emissions affect cardiovascular function. Although BPA levels in animals were relatively low, exposure-induced changes in immunostaining for estrogen and androgen receptors in cardiac arteries suggest that changes in the action of steroid hormones may have contributed to the alterations in morphology and markers of cardiac function. |
Biological effects of diesel exhaust inhalation. III cardiovascular function
Krajnak K , Kan H , Thompson JA , McKinney W , Waugh S , South T , Burns D , Lebouf R , Cumpston J , Boots T , Fedan JS . Inhal Toxicol 2024 1-16 OBJECTIVE: Inhalation of diesel exhaust (DE) has been shown to be an occupational hazard in the transportation, mining, and gas and oil industries. DE also contributes to air pollution, and therefore, is a health hazard to the general public. Because of its effects on human health, changes have been made to diesel engines to reduce both the amounts of particulate matter and volatile fumes they generate. The goal of the current study was to examine the effects of inhalation of diesel exhaust. MATERIALS AND METHODS: The study presented here specifically examines the effects of exposure to 0.2 and 1.0 mg/m(3) DE or filtered air (6h/d for 4 d) on measures of peripheral and cardio-vascular function, and biomarkers of heart and kidney dysfunction in male rats. A Tier 2 engine used in oil and gas fracking operations was used to generate the diesel exhaust. RESULTS: Exposure to 0.2 mg/m(3) DE resulted in an increase in blood pressure 1d following the last exposure, and increases in dobutamine-induced cardiac output and stroke volume 1 and 27d after exposure. Changes in peripheral vascular responses to norepinephrine and acetylcholine were minimal as were changes in transcript expression in the heart and kidney. Exposure to 1.0 mg/m(3) DE did not result in major changes in blood pressure, measures of cardiac function, peripheral vascular function or transcript expression. DISCUSSION AND CONCLUSIONS: Based on the results of this study, we suggest that exposure to DE generated by a Tier 2 compliant diesel engine generates acute effects on biomarkers indicative of cardiovascular dysfunction. Recovery occurs quickly with most measures of vascular/cardiovascular function returning to baseline levels by 7d following exposure. |
Toxicological effects of inhaled crude oil vapor
Fedan JS , Thompson JA , Sager TM , Roberts JR , Joseph P , Krajnak K , Kan H , Sriram K , Weatherly LM , Anderson SE . Curr Environ Health Rep 2024 PURPOSE OF REVIEW: The purpose of this review is to assess the toxicological consequences of crude oil vapor (COV) exposure in the workplace through evaluation of the most current epidemiologic and laboratory-based studies in the literature. RECENT FINDINGS: Crude oil is a naturally occuring mixture of hydrocarbon deposits, inorganic and organic chemical compounds. Workers engaged in upstream processes of oil extraction are exposed to a number of risks and hazards, including getting crude oil on their skin or inhaling crude oil vapor. There have been several reports of workers who died as a result of inhalation of high levels of COV released upon opening thief hatches atop oil storage tanks. Although many investigations into the toxicity of specific hydrocarbons following inhalation during downstream oil processing have been conducted, there is a paucity of information on the potential toxicity of COV exposure itself. This review assesses current knowledge of the toxicological consequences of exposures to COV in the workplace. |
Applied force alters sensorineural and peripheral vascular function in a rat model of hand-arm vibration syndrome
Krajnak K , Warren C , Xu X , Chapman P , Waugh S , Boots T , Welcome D , Dong R . J Occup Environ Med 2023 OBJECTIVE: This study described the effects of applied force (grip) on vascular and sensorineural function in an animal model of hand-arm vibration syndrome (HAVS). METHODS: Rat tails were exposed to 0, 2 or 4 newtons (N) of applied force 4 hr/day for 10 days. Blood flow and sensitivity to transcutaneous electrical stimulation and pressure were measured. RESULTS: Applied force increased blood flow but reduced measures of arterial plasticity. Animals exposed to force tended to be more sensitive to 250 Hz electrical stimulation and pressure applied to the tail. CONCLUSIONS: Effects of applied force on blood flow and sensation are different than those of vibration. Studies examining co-exposures to force and vibration will provide data that can be used to determine how these factors affect risk of workers developing vascular and sensorineural dysfunction (i.e., HAVS). |
Inhalation of polycarbonate emissions generated during 3D printing processes affects neuroendocrine function in male rats
Krajnak K , Farcas M , McKinney W , Waugh S , Mandler K , Knepp A , Jackson M , Richardson D , Hammer M , Matheson J , Thomas T , Qian Y . J Toxicol Environ Health A 2023 86 (16) 1-22 Three-dimensional (3D) printing of manufactured goods has increased in the last 10 years. The increased use of this technology has resulted in questions regarding the influence of inhaling emissions generated during printing. The goal of this study was to determine if inhalation of particulate and/or toxic chemicals generated during printing with polycarbonate (PC) plastic affected the neuroendocrine system. Male rats were exposed to 3D-printer emissions (592 µg particulate/m(3) air) or filtered air for 4 h/day (d), 4 days/week and total exposures lengths were 1, 4, 8, 15 or 30 days. The effects of these exposures on hormone concentrations, and markers of function and/or injury in the olfactory bulb, hypothalamus and testes were measured after 1, 8 and 30 days exposure. Thirty days of exposure to 3D printer emissions resulted in reductions in thyroid stimulating hormone, follicle stimulating hormone and prolactin. These changes were accompanied by (1) elevation in markers of cell injury; (2) reductions in active mitochondria in the olfactory bulb, diminished gonadotropin releasing hormone cells and fibers as well as less tyrosine hydroxylase immunolabeled fibers in the arcuate nucleus; and (3) decrease in spermatogonium. Polycarbonate plastics may contain bisphenol A, and the effects of exposure to these 3D printer-generated emissions on neuroendocrine function are similar to those noted following exposure to bisphenol A. |
A novel rat-tail model for studying human finger vibration health effects
Dong RG , Warren C , Xu XS , Wu JZ , Welcome DE , Waugh S , Krajnak K . Proc Inst Mech Eng H 2023 237 (7) 9544119231181246 It has been hypothesized that the biodynamic responses of the human finger tissues to vibration are among the major stimuli that cause vibration health effects. Furthermore, the finger contact pressure can alter these effects. It is difficult to test these hypotheses using human subjects or existing animal models. The objective of this study was to develop a new rat-tail vibration model to investigate the combined effects of vibration and contact pressure and to identify their relationships with the biodynamic responses. Physically, the new exposure system was developed by adding a loading device to an existing rat-tail model. An analytical model of the rat-tail exposure system was proposed and used to formulate the methods for quantifying the biodynamic responses. A series of tests with six tails dissected from rat cadavers were conducted to test and evaluate the new model. The experimental and modeling results demonstrate that the new model behaves as predicted. Unlike the previous model, the vibration strain and stress of the rat tail does not depend primarily on the vibration response of the tail itself but on that of the loading device. This makes it possible to quantify and control the biodynamic responses conveniently and reliably by measuring the loading device response. This study also identified the basic characteristics of the tail biodynamic responses in the exposure system, which can be used to help design the experiments for studying vibration biological effects. |
Effects of whole-body vibration on reproductive physiology in a rat model of whole-body vibration
Krajnak K , Waugh S , Welcome D , Xu XS , Warren C , McKinney W , Dong RG . J Toxicol Environ Health A 2022 85 (23) 1-19 Findings from epidemiological studies suggest that occupational exposure to whole-body vibration (WBV) may increase the risk of miscarriage and contribute to a reduction in fertility rates in both men and women. However, workers exposed to WBV may also be exposed to other risk factors that contribute to reproductive dysfunction. The goal of this experiment was to examine the effects of WBV on reproductive physiology in a rat model. Male and female rats were exposed to WBV at the resonant frequency of the torso (31.5 Hz, 0.3 g amplitude) for 4 hr/day for 10 days. WBV exposure resulted in a significant reduction in number of developing follicles, and decrease in circulating estradiol concentrations, ovarian luteinizing hormone receptor protein levels, and marked changes in transcript levels for several factors involved in follicular development, cell cycle, and steroidogenesis. In males, WBV resulted in a significant reduction in spermatids and circulating prolactin levels, elevation in number of males having higher circulating testosterone concentrations, and marked alterations in levels of transcripts associated with oxidative stress, inflammation, and factors involved in regulating the cell cycle. Based upon these findings data indicate that occupational exposure to WBV contributes to adverse alterations in reproductive physiology in both genders that may lead to reduction in fertility. |
Biological effects of crude oil vapor. IV. Cardiovascular effects
Krajnak K , Russ KA , McKinney W , Waugh S , Zheng W , Kan H , Kashon ML , Cumpston J , Fedan JS . Toxicol Appl Pharmacol 2022 447 116071 Workers in the oil and gas extraction industry are at risk of inhaling volatile organic compounds. Epidemiological studies suggest oil vapor inhalation may affect cardiovascular health. Thus, in this hazard identification study we investigated the effects of inhalation of crude oil vapor (COV) on cardiovascular function. Male rats were exposed to air or COV (300ppm) for 6h (acute), or 6h/day 4 d/wk. 4 wk. (sub-chronic). The effects of COV inhalation were assessed 1, 28, and 90 d post-exposure. Acute exposure to COV resulted in a reduction in mean arterial and diastolic blood pressures 1 and 28 d after exposure, changes in nitrate-nitrite and H(2)O(2) levels, and in the expression of transcripts and proteins that regulate inflammation, vascular remodeling, and the synthesis of NO in the heart and kidneys. The sub-chronic exposure resulted in a reduced sensitivity to (1)-adrenoreceptor-mediated vasoconstriction in vitro 28 d post-exposure, and a reduction in oxidative stress in the heart. Sub-chronic COV exposure led to alterations in the expression of NO synthases and anti-oxidant enzymes, which regulate inflammation and oxidative stress in the heart and kidneys. There seems to be a balance between changes in the expression of transcripts associated with the generation of reactive oxygen species (ROS) and antioxidant enzymes. The ability of antioxidant enzymes to reduce or inhibit the effects of ROS may allow the cardiovascular system to adapt to acute COV exposures. However, sub-chronic exposures may result in longer-lasting negative health consequences on the cardiovascular system. |
High-fat western diet-consumption alters crystalline silica-induced serum adipokines, inflammatory cytokines and arterial blood flow in the F344 rat
Thompson JA , Krajnak K , Johnston RA , Kashon ML , McKinney W , Fedan JS . Toxicol Rep 2022 9 12-21 Adipose tissue (AT) plays a central role in the maintenance of whole-body energy homeostasis through release of adipokines. High-fat Western diet (HFWD)-consumption contributes to obesity, disruption of adipocyte metabolism, chronic systemic inflammation, and metabolic dysfunction (MetDys). MetDys is associated with impaired lung function, pulmonary hypertension, and asthma. Thirty-five percent of adults in the U.S. have MetDys, yet the impact of MetDys on susceptibility to occupational hazards is unknown. The aim of this study was to determine the potential of HFWD-consumption to alter inhaled crystalline silica dust-induced metabolic responses. Six-wk old male F344 rats were fed a HFWD (45 kcal % fat, sucrose 22.2 % by weight) or standard rat chow (STD, controls), and exposed to silica-inhalation (6 h/d, 5 d/wk, 39 d; Min-U-Sil 5®, 15 mg/m3) or filtered air. Indices of MetDys and systemic inflammation were measured at 0, 4, and 8 wk following cessation of silica exposure. At 8 wk post-exposure, silica reduced serum leptin and adiponectin levels, and increased arterial pulse frequency. HFWD-consumption induced weight gain, altered adipokines, liver, kidney, and pancreatic function, and increased tail artery blood flow. At 8 wk in HFWD + SIL-treated animals, the levels of serum pro-inflammatory cytokines (IFN-γ, CXCL-1, TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-10 and IL-13) were increased compared to STD + SIL but were less than HFWD + AIR-induced levels. In conclusion, consumption of a HFWD altered silica-induced metabolic responses and silica exposure disrupted AT endocrine function. These findings demonstrate previously unknown interactions between HFWD-consumption and occupational silica exposure. © 2021 The Authors |
A review of hand-arm vibration studies conducted by US NIOSH since 2000
Dong RG , Wu JZ , Xu XS , Welcome DE , Krajnak K . Vibration 2021 4 (2) 482-528 Studies on hand-transmitted vibration exposure, biodynamic responses, and biological effects were conducted by researchers at the Health Effects Laboratory Division (HELD) of the National Institute for Occupational Safety and Health (NIOSH) during the last 20 years. These studies are systematically reviewed in this report, along with the identification of areas where additional research is needed. The majority of the studies cover the following aspects: (i) the methods and techniques for measuring hand-transmitted vibration exposure; (ii) vibration biodynamics of the hand-arm system and the quantification of vibration exposure; (iii) biological effects of hand-transmitted vibration exposure; (iv) measurements of vibration-induced health effects; (iv) quantification of influencing biomechanical effects; and (v) intervention methods and technologies for controlling hand-transmitted vibration exposure. The major findings of the studies are summarized and discussed. |
Vibrotactile sensitivity testing for occupational and disease-induce peripheral neuropathies
Krajnak K . J Toxicol Environ Health B Crit Rev 2021 24 (4) 1-11 The International Standard Organization (ISO) standard 13091-1 describes methods and procedures for performing the vibrotactile perception threshold (VPT) testing to diagnose changes in tactile sensory function associated with occupational exposures. However, the VPT test also has been used in the diagnosis of peripheral neuropathies associated with a number of disorders. This review examines the VPT test, variations in procedures that have been used, as well as disorders and diseases in which this test has been reliable for the detection of sensory changes. Mechanisms potentially underlying the changes in VPTs are also discussed along with procedural and subject/patient factors that may affect the interpretation of test results. Based upon the review of the literature, there are also suggestions for where additional research might improve the administration of this test, depending upon the subject/patient population and interpretation of data. |
Biological effects of inhaled hydraulic fracturing sand dust. IX. Summary and significance
Anderson SE , Barger M , Batchelor TP , Bowers LN , Coyle J , Cumpston A , Cumpston JL , Cumpston JB , Dey RD , Dozier AK , Fedan JS , Friend S , Hubbs AF , Jackson M , Jefferson A , Joseph P , Kan H , Kashon ML , Knepp AK , Kodali V , Krajnak K , Leonard SS , Lin G , Long C , Lukomska E , Marrocco A , Marshall N , Mc Kinney W , Morris AM , Olgun NS , Park JH , Reynolds JS , Roberts JR , Russ KA , Sager TM , Shane H , Snawder JE , Sriram K , Thompson JA , Umbright CM , Waugh S , Zheng W . Toxicol Appl Pharmacol 2020 409 115330 An investigation into the potential toxicological effects of fracking sand dust (FSD), collected from unconventional gas drilling sites, has been undertaken, along with characterization of their chemical and biophysical properties. Using intratracheal instillation of nine FSDs in rats and a whole body 4-d inhalation model for one of the FSDs, i.e., FSD 8, and related in vivo and in vitro experiments, the effects of nine FSDs on the respiratory, cardiovascular and immune systems, brain and blood were reported in the preceding eight tandem papers. Here, a summary is given of the key observations made in the organ systems reported in the individual studies. The major finding that inhaled FSD 8 elicits responses in extra-pulmonary organ systems is unexpected, as is the observation that the pulmonary effects of inhaled FSD 8 are attenuated relative to forms of crystalline silica more frequently used in animal studies, i.e., MIN-U-SIL®. An attempt is made to understand the basis for the extra-pulmonary toxicity and comparatively attenuated pulmonary toxicity of FSD 8. |
Biological effects of inhaled hydraulic fracturing sand dust. VI. Cardiovascular effects
Krajnak K , Kan H , Russ KA , McKinney W , Waugh S , Zheng W , Kashon ML , Johnson C , Cumpston J , Fedan JS . Toxicol Appl Pharmacol 2020 406 115242 Hydraulic fracturing is used to access oil and natural gas reserves. This process involves the high-pressure injection of fluid to fracture shale. Fracking fluid contains approximately 95% water, chemicals and 4.5% fracking sand. Workers may be exposed to fracking sand dust (FSD) during the manipulation of the sand, and negative health consequences could occur if FSD is inhaled. In the absence of any information about its potential toxicity, a comprehensive rat animal model study (see Fedan, J.S., Toxicol Appl Pharmacol. 000, 000-000, 2020) was designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems. The goal of this study was to assess the effects of inhalation of one FSD, i.e., FSD 8, on factors and tissues that affect cardiovascular function. Male rats were exposed to 10 or 30 mg/m(3) FSD (6 h/d for 4 d) by whole body inhalation, with measurements made 1, 7 or 27 d post-exposure. One day following exposure to 10 mg/m(3) FSD the sensitivity to phenylephrine-induced vasoconstriction in tail arteries in vitro was increased. FSD exposure at both doses resulted in decreases in heart rate (HR), HR variability, and blood pressure in vivo. FSD induced changes in hydrogen peroxide concentrations and transcript levels for pro-inflammatory factors in heart tissues. In kidney, expression of proteins indicative of injury and remodeling was reduced after FSD exposure. When analyzed using regression analysis, changes in proteins involved in repair and remodeling were correlated. Thus, it appears that inhalation of FSD does have some prolonged effects on cardiovascular, and, possibly, renal function. The findings also provide information regarding potential mechanisms that may lead to these changes, and biomarkers that could be examined to monitor physiological changes that could be indicative of impending cardiovascular dysfunction. |
Frequency-dependent changes in mitochondrial number and generation of reactive oxygen species in a rat model of vibration-induced injury
Krajnak K . J Toxicol Environ Health A 2020 83 (1) 1-16 Regular use of vibrating hand tools results in cold-induced vasoconstriction, finger blanching, and a reduction in tactile sensitivity and manual dexterity. Depending upon the length and frequency, vibration induces regeneration, or dysfunction and apoptosis, inflammation and an increase in reactive oxygen species (ROS) levels. These changes may be associated with mitochondria, this study examined the effects of vibration on total and functional mitochondria number. Male rats were exposed to restraint or tail vibration at 62.5, 125, or 250 Hz. The frequency-dependent effects of vibration on mitochondrial number and generation of oxidative stress were examined. After 10 days of exposure at 125 Hz, ventral tail arteries (VTA) were constricted and there was an increase in mitochondrial number and intensity of ROS staining. In the skin, the influence of vibration on arterioles displayed a similar but insignificant response in VTA. There was also a reduction in the number of small nerves with exposure to vibration at 250 Hz, and a reduction in mitochondrial number in nerves in restrained and all vibrated conditions. There was a significant rise in the size of the sensory receptors with vibration at 125 Hz, and an elevation in ROS levels. Based upon these results, mitochondria number and activity are affected by vibration, especially at frequencies at or near resonance. The influence of vibration on the vascular system may either be adaptive or maladaptive. However, the effects on cutaneous nerves might be a precursor to loss of innervation and sensory function noted in workers exposed to vibration. |
Exposure to graphene nanoparticles induces changes in measures of vascular/renal function in a load and form-dependent manner in mice
Krajnak K , Waugh S , Stefaniak A , Schwegler-Berry D , Roach K , Barger M , Roberts J . J Toxicol Environ Health A 2019 82 (12) 1-16 Graphenes isolated from crystalline graphite are used in several industries. Employees working in the production of graphenes may be at risk of developing respiratory problems attributed to inhalation or contact with particulate matter (PM). However, graphene nanoparticles might also enter the circulation and accumulate in other organs. The aim of this study was to examine how different forms of graphene affect peripheral vascular functions, generation of reactive oxygen species (ROS) and changes in gene expression that may be indicative of cardiovascular and/or renal dysfunction. In the first investigation, different doses of graphene nanoplatelets were administered to mice via oropharyngeal aspiration. These effects were compared to those of dispersion medium (DM) and carbon black (CB). Gene expression alterations were observed in the heart for CB and graphene; however, only CB produced changes in peripheral vascular function. In the second study, oxidized forms of graphene were administered. Both oxidized forms increased the sensitivity of peripheral blood vessels to adrenoreceptor-mediated vasoconstriction and induced changes in ROS levels in the heart. Based upon the results of these investigations, exposure to graphene nanoparticles produced physiological and alterations in ROS and gene expression that may lead to cardiovascular dysfunction. Evidence indicates that the effects of these particles may be dependent upon dose and graphene form to which an individual may be exposed to. |
Can blood flow be used to monitor changes in peripheral vascular function that occur in response to segmental vibration exposure
Krajnak K , Waugh S , Sarkisian K . J Occup Environ Med 2019 61 (2) 162-167 OBJECTIVES: Laser Doppler blood flow measurements have been used for diagnosis or detection of peripheral vascular dysfunction. This study used a rat tail model of vibration-induced vascular injury to determine how laser Doppler measurements were affected by acute and repeated exposures to vibration, and to identify changes in the Doppler signal that were associated with the exposure. METHODS: Blood flow was measured immediately after a single exposure to vibration, or before vibration exposure on days 1, 5, 10, 15, and 20 of a 20 days exposure. RESULTS: After a single exposure to vibration, average tail blood flow was reduced. With 20 days of exposure, there was a reduction in the amplitude of the arterial pulse on days 10 to 20 in vibrated rats and days 15 to 20 in control rats. CONCLUSIONS: More detailed statistical analyses of laser Doppler data may be needed to identify early changes in peripheral circulation after exposure to vibration. |
Health effects associated with occupational exposure to hand-arm or whole body vibration
Krajnak K . J Toxicol Environ Health B Crit Rev 2018 21 (5) 1-15 Workers in a number of different occupational sectors are exposed to workplace vibration on a daily basis. This exposure may arise through the use of powered-hand tools or hand-transmitted vibration (HTV). Workers might also be exposed to whole body vibration (WBV) by driving delivery vehicles, earth moving equipment, or through use of tools that generate vibration at low dominant frequencies and high amplitudes, such as jackhammers. Occupational exposure to vibration has been associated with an increased risk of musculoskeletal pain in the back, neck, hands, shoulders, and hips. Occupational exposure may also contribute to the development of peripheral and cardiovascular disorders and gastrointestinal problems. In addition, there are more recent data suggesting that occupational exposure to vibration may enhance the risk of developing certain cancers. The aim of this review is to provide an assessment of the occupations where exposure to vibration is most prevalent, and a description of the adverse health effects associated with occupational exposure to vibration. This review will examine (1) various experimental methods used to measure and describe the characteristics of vibration generated by various tools and vehicles, (2) the etiology of vibration-induced disorders, and (3) how these data were employed to assess and improve intervention strategies and equipment that reduces the transmission of vibration to the body. Finally, there is a discussion of the research gaps that need to be investigated to further reduction in the incidence of vibration-induced illnesses and injuries. |
Acute vibration induces peripheral nerve sensitization in a rat tail model: Possible role of oxidative stress and inflammation
Pacurari M , Waugh S , Krajnak K . Neuroscience 2018 398 263-272 Prolonged occupational exposure to hand-held vibrating tools leads to pain and reductions in tactile sensitivity, grip strength and manual dexterity. The goal of the current study was to use a rat-tail vibration model to determine how vibration frequency influences factors related to nerve injury and dysfunction. Rats were exposed to restraint, or restraint plus tail vibration at 62.5 Hz or 250 Hz. Nerve function was assessed using the current perception threshold (CPT) test. Exposure to vibration at 62.5 and 250 Hz, resulted in a reduction in the CPT at 2000 and 250 Hz electrical stimulation (i.e. increased Abeta and Adelta, nerve fiber sensitivity). Vibration exposure at 250 Hz also resulted in an increased sensitivity of C-fibers to electrical stimulation and thermal nociception. These changes in nerve fiber sensitivity were associated with increased expression of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha in ventral tail nerves, and increases in circulating concentrations of IL-1 beta in rats exposed to 250 Hz vibration. There was an increase in glutathione, but no changes in other measures of oxidative activity in the peripheral nerve. However, measures of oxidative stress were increased in the dorsal root ganglia (DRG). These changes in pro-inflammatory factors and markers of oxidative stress in the peripheral nerve and DRG were associated with inflammation, and reductions in myelin basic protein and post-synaptic density protein (PSD)-95 gene expression, suggesting that vibration induced changes in sensory function may be the result of changes at the exposed nerve, the DRG and/or the spinal cord. |
Systemic effects of segmental vibration in an animal model of hand-arm vibration syndrome
Krajnak K , Waugh S . J Occup Environ Med 2018 60 (10) 886-895 OBJECTIVE: Epidemiology suggests that occupational exposure to hand-transmitted (segmental) vibration has local and systemic effects. This study used an animal model of segmental vibration to characterize the systemic effects of vibration. METHODS: Male Sprague Dawley rats were exposed to tail vibration for 10 days. Genes indicative of inflammation, oxidative stress, and cell cycle, along were measured in the heart, kidney, prostate and liver. RESULTS: Vibration increased oxidative stress and pro-inflammatory gene expression, and decreased anti-oxidant enzymes in heart tissue. In the prostate and liver, vibration resulted in changes in the expression of pro-inflammatory factors and genes involved in cell cycle regulation. CONCLUSIONS: These changes are consistent with epidemiological studies suggesting that segmental vibration has systemic effects. These effects may be mediated by changes in autonomic nervous system function, and/or inflammation and oxidative stress. |
Contact area affects frequency-dependent responses to vibration in the peripheral vascular and sensorineural systems
Krajnak K , Miller GR , Waugh S . J Toxicol Environ Health A 2017 81 1-14 Repetitive exposure to hand-transmitted vibration is associated with development of peripheral vascular and sensorineural dysfunctions. These disorders and symptoms associated with it are referred to as hand-arm vibration syndrome (HAVS). Although the symptoms of the disorder have been well characterized, the etiology and contribution of various exposure factors to development of the dysfunctions are not well understood. Previous studies performed using a rat-tail model of vibration demonstrated that vascular and peripheral nervous system adverse effects of vibration are frequency-dependent, with vibration frequencies at or near the resonant frequency producing the most severe injury. However, in these investigations, the amplitude of the exposed tissue was greater than amplitude typically noted in human fingers. To determine how contact with vibrating source and amplitude of the biodynamic response of the tissue affects the risk of injury occurring, this study compared the influence of frequency using different levels of restraint to assess how maintaining contact of the tail with vibrating source affects the transmission of vibration. Data demonstrated that for the most part, increasing the contact of the tail with the platform by restraining it with additional straps resulted in an enhancement in transmission of vibration signal and elevation in factors associated with vascular and peripheral nerve injury. In addition, there were also frequency-dependent effects, with exposure at 250 Hz generating greater effects than vibration at 62.5 Hz. These observations are consistent with studies in humans demonstrating that greater contact and exposure to frequencies near the resonant frequency pose the highest risk for generating peripheral vascular and sensorineural dysfunction. |
Effects of pulmonary exposure to chemically-distinct welding fumes on neuroendocrine markers of toxicity
Krajnak K , Sriram K , Johnson C , Roberts JR , Mercer R , Miller GR , Wirth O , Antonini JM . J Toxicol Environ Health A 2017 80 (5) 1-14 Exposure to welding fumes may result in disorders of the pulmonary, cardiovascular, and reproductive systems. Welders are also at a greater risk of developing symptoms similar to those seen in individuals with idiopathic Parkinson's disease. In welders, there are studies that suggest that alterations in circulating prolactin concentrations may be indicative of injury to the dopamine (DA) neurons in the substantia nigra. The goal of these studies was to use an established model of welding particulate exposure to mimic the effects of welding fume inhalation on reproductive functions. Since previous investigators suggested that changes in circulating prolactin may be an early marker of DA neuron injury, movement disorders, and reproductive dysfunction, prolactin, hypothalamic tyrosine hydroxylase (TH) levels (a marker of DA synthesis), and other measures of hypothalamic-pituitary-gonadal (HPG) function were measured after repetitive instillation of welding fume particulates generated by flux core arc-hard surfacing (FCA-HS), manual metal arc-hard surfacing (MMA-HS) or gas metal arc-mild steel (GMA-MS) welding, or manganese chloride (MnCl2). Exposure to welding fume particulate resulted in the accumulation of various metals in the pituitary and testes of rats, along with changes in hypothalamic TH and serum prolactin levels. Exposure to particulates with high concentrations of soluble manganese (Mn) appeared to exert the greatest influence on TH activity levels and serum prolactin concentrations. Thus, circulating prolactin levels may serve as a biomarker for welding fume/Mn-induced neurotoxicity. Other reproductive measures were collected, and these data were consistent with epidemiological findings that prolactin and testosterone may serve as biomarkers of welding particulate induced DA neuron and reproductive dysfunction. |
Transcriptional pathways altered in response to vibration in a model of hand-arm vibration syndrome
Waugh S , Kashon ML , Li S , Miller GR , Johnson C , Krajnak K . J Occup Environ Med 2016 58 (4) 344-50 OBJECTIVE: The aim of this study was to use an established model of vibration-induced injury to assess frequency-dependent changes in transcript expression in skin, artery, and nerve tissues. METHODS: Transcript expression in tissues from control and vibration-exposed rats (4 h/day for 10 days at 62.5, 125, or 250 Hz; 49 m/s, rms) was measured. Transcripts affected by vibration were used in bioinformatics analyses to identify molecular- and disease-related pathways associated with exposure to vibration. RESULTS: Analyses revealed that cancer-related pathways showed frequency-dependent changes in activation or inhibition. Most notably, the breast-related cancer-1 pathway was affected. Other pathways associated with breast cancer type 1 susceptibility protein related signaling, or associated with cancer and cell cycle/cell survivability were also affected. CONCLUSION: Occupational exposure to vibration may result in DNA damage and alterations in cell signaling pathways that have significant effects on cellular division. |
Changes in the expression of calcitonin gene-related peptide after exposure to injurious stretch-shortening contractions.
Johnson C , Miller GR , Baker BA , Hollander M , Kashon ML , Waugh S , Krajnak K . Exp Gerontol 2016 79 1-7 One of the factors that can result in musculoskeletal injuries, and time off work, is exposure to repetitive motion. The goal of this study was to determine if skeletal muscle injury induced by exposure to injurious stretch-shortening cycles (iSSCs), resulted in hyperalgesia in the hind limb and changes in calcitonin-gene related peptide (CGRP) immunolabeling in the dorsal root ganglia (DRG) in young and old male rats. METHODS: Young (3months) and old (30months) male Fisher 344xBN F1 rats were anesthetized with isoflurane and the left hind limbs were exposed to 15 sets of 10 SSCs. Control animals were exposed to a single bout of SSCs of equal intensity. Sensitivity to mechanical stimulation was assessed using von Frey filaments prior to beginning the experiment, and on days 2 and 9 following exposure to iSSCs. Rats were euthanized one, 3 or 10days after the exposure. The ipsilateral DRG were dissected from the L4-5 region of the spine, along with the left tibialis anterior (LTA) muscle. RESULTS: Rats exposed to iSSCs were more sensitive to mechanical stimulation than control rats 2days after the exposure, and showed a reduction in peak force 3days after exposure. Changes in sensitivity to pressure were not associated with increases in CGRP labeling in the DRG at 3days. However, 9days after exposure to iSSCs, old rats still displayed an increased sensitivity to mechanical stimulation, and this hyperalgesia was associated with an increase in CGRP immunolabeling in the DRG. Young rats exposed to iSSC did not display a change in CGRP immunolabeling and sensitivity to mechanical stimulation returned to control levels at 10days. CONCLUSIONS: These findings suggest that hyperalgesia seen shortly after exposure to iSSC is not influenced by CGRP levels. However, in cases where recovery from injury may be slower, as it is in older rats, CGRP may contribute to the maintenance of hyperalgesia. |
Factors affecting finger and hand pain in workers with HAVS
House R , Krajnak K , Jiang D . Occup Med (Lond) 2016 66 (4) 292-5 BACKGROUND: Pain and its management are important aspects of hand-arm vibration syndrome (HAVS). AIMS: To determine the factors associated with finger and hand pain in workers with HAVS and, specifically, to assess the impact of several neurological variables as well as the vascular component of HAVS, grip strength and age. METHODS: We assessed men with HAVS at a hospital occupational medicine clinic over 2 years. Subjects scored finger and hand pain separately using the Borg Scale (0-10). The possible predictors we evaluated included the Stockholm Neurological Scale (SNS) and Stockholm Vascular Scale (SVS) stages, current perception threshold (CPT), carpal tunnel syndrome (CTS), ulnar neuropathy, grip strength and age. We carried out nerve conduction testing to confirm the presence of CTS and ulnar neuropathy and measured CPT in the fingers at 2000 Hz, 250 Hz and 5 Hz corresponding to A-beta (large myelinated), A-delta (small myelinated) and C (unmyelinated) fibres, respectively. We calculated Spearman rank correlations to examine the relation between finger and hand pain and possible predictor variables. RESULTS: Among the 134 subjects, the median (25th-75th percentile) pain scores were 6 (4-8) for the fingers and 5 (1-7) for the hands. We found statistically significant correlations with finger pain for the SVS stage (r = 0.239; P < 0.01) and CTS (r = 0.184; P < 0.05). The only statistically significant correlation identified for hand pain was a negative correlation with grip strength (r = -0.185; P < 0.05). CONCLUSIONS: Management of finger and hand pain in HAVS should focus on the correlates we have identified. |
Long-term daily vibration exposure alters current perception threshold (CPT) sensitivity and myelinated axons in a rat-tail model of vibration-induced injury
Krajnak K , Raju SG , Miller GR , Johnson C , Waugh S , Kashon ML , Riley DA . J Toxicol Environ Health A 2016 79 (3) 1-11 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, Abeta 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 Abeta 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. |
The effects of repetitive vibration on sensorineural function: biomarkers of sensorineural injury in an animal model of metabolic syndrome
Kiedrowski M , Waugh S , Miller R , Johnson C , Krajnak K . Brain Res 2015 1627 216-24 Exposure to hand-transmitted vibration in the work-place can result in the loss of sensation and pain in workers. These effects may be exacerbated by pre-existing conditions such as diabetes or the presence of primary Raynaud's phenomena. The goal of these studies was to use an established model of vibration-induced injury in Zucker rats. Lean Zucker rats have a normal metabolic profile, while obese Zucker rats display symptoms of metabolic disorder or Type II diabetes. This study examined the effects of vibration in obese and lean rats. Zucker rats were exposed to 4h of vibration for 10 consecutive days at a frequency of 125Hz and acceleration of 49m/sec2 for 10 consecutive days. Sensory function was checked using transcutaneous electrical stimulation on days 1, 5 and 9 of the exposure. Once the study was complete the ventral tail nerves, dorsal root ganglia and spinal cord were dissected, and levels of various transcripts involved in sensorineural dysfunction were measured. Sensorineural dysfunction was assessed using transcutaneous electrical stimulation. Obese Zucker rats displayed very few changes in sensorineural function. However they did display significant changes in transcript levels for factors involved in synapse formation, peripheral nerve remodeling, and inflammation. The changes in transcript levels suggested that obese Zucker rats had some level of sensory nerve injury prior to exposure, and that exposure to vibration activated pathways involved in injury and re-innervation. |
Antivibration gloves: effects on vascular and sensorineural function, an animal model
Krajnak K , Waugh S , Johnson C , Miller RG , Welcome D , Xu X , Warren C , Sarkisian S , Andrew M , Dong RG . J Toxicol Environ Health A 2015 78 (9) 571-82 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/s(2). 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 alpha2C-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. |
- Page last reviewed:Feb 1, 2024
- Page last updated:Dec 02, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure