Effect of office chair design features on lumbar spine posture, muscle activity and perceived pain during prolonged sitting.

Chair design features are typically compared using multiple seats, which can lead to confounding effects. Using a single chair, configurable to four designs (control, lumbar support, seat pan tilt and scapular relief), we investigated the effect of chair design on spine posture and movement, muscle activity and perceived pain in a sample of 31 asymptomatic adults. A total of 39% of the population were classified as pain developers, having significantly higher peak pain levels across most body regions. The lumbar support and seat pan tilt condition resulted in more neutral spine and pelvic postures. Greater muscle activity was found in the seat pan condition and non-pain developers displayed lower spine muscle activation levels overall. Despite some improvements in spine posture, sitting-induced pain was present in the study sample at similar proportions to those reported previously. Future studies may consider investigating interventions targeted to sitting-induced pain developers as opposed to the general population. Practitioner summary: Four office chair configurations were tested. The lumbar support and seat pan tilt conditions resulted in the most neutral back posture but did not mitigate the clinically significant levels of sitting-induced pain experienced by a large portion of the tested sample. Future work should target interventions to these individuals.

The effect of lumbar spinal manipulation on biomechanical factors and perceived transient pain during prolonged sitting: a laboratory-controlled cross-sectional study.

BACKGROUND: Spinal manipulation has been shown to affect muscle activity, posture, and pain. To date, no studies have examined the effect of manipulation on biomechanical factors during sitting. Therefore, the purpose of this study was to investigate the immediate effect of lumbar spinal manipulation on trunk muscle activation, spine posture and movements, and perceived ratings of transient pain in asymptomatic adults during prolonged office sitting. METHODS: Twenty healthy adults were recruited for a single laboratory session that included a standardized office sitting/data entry protocol (120 min total, 3 blocks of 40 min). Data were collected between July and August 2012. The first block (baseline) was immediately followed by two experimental blocks. Prior to the start of each experimental block, participants were transferred to a therapy plinth and placed side lying (right side down), and a random presentation of either a control or high velocity low amplitude thrust directed at L4/L5 was delivered. Continuous measures of muscle activity, spine posture, and spine movements were recorded throughout the sitting trials. Perceived transient pain was measured by visual analogue scale at 10-min intervals (including immediately before and after the randomized maneuvers). RESULTS: There were no significant differences in spine or pelvic posture or perceived back pain following either the manipulation or control maneuvers. Significantly reduced muscle activity and increased shifts of the lumbar spine angle were identified in the block following manipulation compared to both baseline and post control blocks. CONCLUSIONS: Spinal manipulation does not appear to have an immediate impact on spine or pelvic posture in healthy adults but does appear to reduce muscle activity and increase spine movement during sitting. Future work should replicate this study with a larger population in a field setting. It may be worthwhile to explore the implication of reduced muscle activation and increased spine movements during prolonged sitting for office workers that receive manipulations or mobilizations during their workday.

Boston biorepository, recruitment and integrative network (BBRAIN): A resource for the Gulf War Illness scientific community.

AIMS: Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research. MAIN METHODS: BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid. KEY FINDINGS: To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received. SIGNIFICANCE: The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.

The effects of police duty belt and seat design changes on lumbar spine posture, driver contact pressure and discomfort.

Police officers spend large amounts of time performing duties within a police cruiser and report a high prevalence of musculoskeletal problems. This study evaluated the effects of driver seat and duty belt design on posture, pressure and discomfort. Ten male and 10 female university students attended two sessions involving simulated driving in a standard police seat (CV) and an active lumbar support (ALS) seat. Participants wore a full duty belt (FDB) or reduced duty belt (RDB) in each seat. Lumbar postures, driver-seat and driver-duty belt pressures and perceived discomfort were measured. Gender × Seat interactions were found for pelvic (p = 0.0001) and lumbar postures (p = 0.003). Females had more lumbar flexion than males and were more extended in the ALS seat (-9.8 ± 11.3°) than CV seat (-19.8 ± 9.6°). The FDB had greater seat pressure than the RDB (p < 0.0001), which corresponded to increased pelvis discomfort. This study supports the use of an ALS seat and RDB to reduce injury risk associated with prolonged sitting in police officers. PRACTITIONER SUMMARY: Police officers report a high prevalence of musculoskeletal problems to the lower back, associated with prolonged driving and further investigation is needed to reduce injury risk. This simulated driving study investigated seat and duty belt configuration on biomechanical measures and discomfort. Seat design had the greatest impact, regardless of gender and males benefited more from a reduced belt configuration.

Evaluation of the influence of mobile data terminal location on physical exposures during simulated police patrol activities.

Prolonged occupational police driving combined with use of an in-vehicle computer elicits awkward, sustained postures in a scenario that lacks the adjustability to accommodate many mobile officer anthropometries and job-specific components. Twenty participants performed simulated police patrol sessions at five mobile data terminal (MDT) locations and using two seats: standard police vehicle seat and modified seat designed for police use. An MDT location self-selected prior to the session reduced perceived discomfort by up to 50% in the low back (p < .0001) and 68% in the right shoulder (p < .0001) compared to other tested locations, including the most common currently used location recorded from a representative police force. Muscle activity was lowest at the self-selected and current MDT locations for all muscles, significantly so for posterior deltoid (p < .0001) and supraspinatus (p < .0001). The modified seat reduced low back discomfort from the standard seat by 28% (p < .0001). Combining a self-selected MDT location and modified driver seat generated lower discomfort and physical loading than the currently used configuration.

Trimethyltin-induced neurotoxicity: gene expression pathway analysis, q-RT-PCR and immunoblotting reveal early effects associated with hippocampal damage and gliosis.

Damage to the CNS results in a complex series of molecular and cellular changes involving the affected targets and the ensuing glial reaction. The initial gene expression events that underlie these cellular responses may serve as early biomarkers of neurotoxicity. Here, we examined gene expression profiles during the initial phase of hippocampal damage resulting from systemic exposure of rats to the organometallic neurotoxicant, trimethyltin (TMT, 8.0 mg/kg, i.p.). Using TMT as a neurodegeneration tool confers several advantages for evaluating molecular events associated with neural damage: 1) regional and cellular targets and time course of damage are known, 2) the blood-brain barrier is not compromised, which limits the contribution of blood-borne factors, e.g. immune, to neural injury responses and 3) known protein and mRNA signatures of TMT-induced neurotoxicity can be used as positive controls to validate novel expression events associated with exposure to this neurotoxicant. Using Affymetrix Gene Chip® to assess gene expression after TMT, combined with Ingenuity Pathway Analysis®, we observed changes consistent for genes known to be affected in hippocampus, while corresponding changes were not detected in cerebellum, a non-target region. In agreement with previous observations, limited changes in expression of inflammation-related genes were observed. Correlated expression profiles were found after exposure to TMT, including changes in gene ontologies associated with neurological disease, cellular assembly and maintenance, as well as signaling pathways associated with cellular stress, energy metabolism and glial activation. Selected gene changes were confirmed from each category by q-RT-PCR and immunoblot analysis. The canonical relationships identified implicate molecular pathways and processes relevant to detection of early stages of hippocampal damage in the TMT model. These observations provide new insight into early events associated with neuronal degeneration and associated glial activation that may serve as the basis for discovery and development of biomarkers of neurotoxicity.

A comparison of low back kinetic estimates obtained through posture matching, rigid link modeling and an EMG-assisted model.

This study examined errors introduced by a posture matching approach (3DMatch) relative to dynamic three-dimensional rigid link and EMG-assisted models. Eighty-eight lifting trials of various combinations of heights (floor, 0.67, 1.2 m), asymmetry (left, right and center) and mass (7.6 and 9.7 kg) were videotaped while spine postures, ground reaction forces, segment orientations and muscle activations were documented and used to estimate joint moments and forces (L5/S1). Posture matching over predicted peak and cumulative extension moment (p < 0.0001 for all variables). There was no difference between peak compression estimates obtained with posture matching or EMG-assisted approaches (p = 0.7987). Posture matching over predicted cumulative (p < 0.0001) compressive loading due to a bias in standing, however, individualized bias correction eliminated the differences. Therefore, posture matching provides a method to analyze industrial lifting exposures that will predict kinetic values similar to those of more sophisticated models, provided necessary corrections are applied.

Age exaggerates proinflammatory cytokine signaling and truncates signal transducers and activators of transcription 3 signaling following ischemic stroke in the rat.

Neuroinflammation is associated with glial activation following a variety of brain injuries, including stroke. While activation of perilesional astrocytes and microglia following ischemic brain injury is well documented, the influence of age on these cellular responses after stroke is unclear. This study investigated the influence of advanced age on neuronal degeneration, neuroinflammation, and glial activation in female Sprague-Dawley rats after reversible embolic occlusion of the middle cerebral artery (MCAO). Results indicate that in comparison to young adult rats (3 months), aged rats (18 months) showed enhanced neuronal degeneration, altered microglial response, and a markedly increased expression of proinflammatory cytokines/chemokines following MCAO. In addition, the time-course for activation of signal transducers and activators of transcription 3 (STAT3), the signaling mechanism that regulates astrocyte reactivity, was truncated in the aged rats after MCAO. Moreover, the expression of suppressor of cytokine signaling 3 (SOCS3), which is associated with termination of astrogliosis, was enhanced as a function of age after MCAO. These findings are suggestive of an enhanced proinflammatory response and a truncated astroglial response as a function of advanced age following MCAO. These data provide further evidence of the prominent role played by age in the molecular and cellular responses to ischemic stroke and suggest that astrocytes may represent targets for future therapies aimed at improving stroke outcome.

Biomechanical shoulder loads and postures in light automotive assembly workers: Comparison between shoulder pain/no pain groups.

BACKGROUND: The number of workplace shoulder compensation claims resulting from musculoskeletal disorders (MSDs) has decreased slightly in recent years, however the median number of days off work remains unchanged, which suggests an increase in injury severity. Little information is available regarding cumulative shoulder exposures, and there is no information on their impact on shoulder pain. METHODS: Seventy-nine automotive seat frame assembly workers completed a questionnaire about the prevalence and severity of shoulder pain and were videotaped performing assembly tasks. 3DMatch, a posture-matching software program, was used to calculate the peak and cumulative shoulder moments and forces by matching postures seen in the video with predetermined ranges of posture to be used in the biomechanical model. RESULTS: Of the 45.6% who reported shoulder pain, there was a mild correlation of pain severity with posterior shear of the shoulder. There were no significant differences in peak loads between Pain and No Pain groups; however, the No Pain group experienced significantly more cumulative caudal shear. CONCLUSION: Although there was no difference in percent time spent in different flexed postures between pain groups, those working some jobs may be at an increased risk of developing MSDs based on the amount of time spent in flexed postures, as well as the peak flexion moment acting on the shoulder.

Obesity and disability in the symptomatic Irish knee osteoarthritis population.

BACKGROUND: Osteoarthritis (OA) of the knee is a common disorder with significant social and financial implications. Obesity is the strongest modifiable risk factor of knee OA. There is little data on obesity in Irish knee OA populations and its relationship to other measures of disease severity. AIMS: In Beaumont Hospital, we have been collecting data on patients presenting with knee OA as part of a screening process for potential candidates for therapeutic exercise intervention studies. Here, we present data on the first 96 candidates screened during this process. RESULTS: The mean body mass index (BMI) of the group fell within the obese range (31); indeed, only 21% had a normal BMI. The vast majority of our patients had severe self-reported disability. In contrast, the distribution of radiographic severity of knee OA was more even. There was no significant relationship between radiographic severity and disability. BMI did predict disability but had a weak correlation. Radiographic severity did not correlate with BMI. CONCLUSION: Irish patients with knee OA referred for physiotherapy were very disabled, significantly obese and represent a challenging cohort of patients to treat.

Population variation in glial fibrillary acidic protein levels in brain ageing: relationship to Alzheimer-type pathology and dementia.

BACKGROUND: The cellular pathology of astrocytes in brain ageing and their role in modulating the brain's response to neurodegenerative pathology remain incompletely understood. METHODS: Using quantitative ELISA, we have investigated glial fibrillary acidic protein (GFAP) expression in the population-based neuropathology cohort of the Medical Research Council Cognitive Function and Ageing Study to determine: (1) the population variation in the astroglial hypertrophic response, (2) its relationship to the presence of Alzheimer-type pathology, and (3) its association with cognition. RESULTS: Increasing GFAP was found with increasing Braak stage, levels increasing even at early stages. Within Braak stages, GFAP did not differ between demented and non-demented individuals, but there was greater variance in GFAP in the demented. Possession of ApoE epsilon4 was associated with slightly increased GFAP levels (not significant) for given amyloid beta protein loads. CONCLUSION: In a population-based sample, increasing gliosis precedes development of Alzheimer lesions. Population variation in GFAP with varying Alzheimer lesion burdens suggests that they are not the only driver for astrogliosis. GFAP was not independently predictive of dementia, but the variation in astrocytic responses may be a factor modulating brain responses to neurodegenerative pathology.

Inter-rater reliability of output measures for a posture matching assessment approach: a pilot study with food service workers.

Despite the ongoing health problem of repetitive strain injuries, there are few tools currently available for ergonomic applications evaluating cumulative loading that have well-documented evidence of reliability and validity. The purpose of this study was to determine the inter-rater reliability of a posture matching based analysis tool (3DMatch, University of Waterloo) for predicting cumulative and peak spinal loads. A total of 30 food service workers were each videotaped for a 1-h period while performing typical work activities and a single work task was randomly selected from each for analysis by two raters. Inter-rater reliability was determined using intraclass correlation coefficients (ICC) model 2,1 and standard errors of measurement for cumulative and peak spinal and shoulder loading variables across all subjects. Overall, 85.5% of variables had moderate to excellent inter-rater reliability, with ICCs ranging from 0.30-0.99 for all cumulative and peak loading variables. 3DMatch was found to be a reliable ergonomic tool when more than one rater is involved.

Methodological considerations for the calculation of cumulative compression exposure of the lumbar spine: a sensitivity analysis on joint model and time standardization approaches.

Cumulative lumbar spine loading has attracted much attention as a factor associated with the development of low back pain. While evidence supports cumulative loading to be a plausible mechanism in explaining several workplace injuries, research establishing a threshold limit value (TLV) for cumulative spine loading has been challenging. The lack of a TLV or even a trend towards harmful cumulative load values may suggest that methodological considerations are greatly influencing the results. This paper examines the impact of different joint models (single muscle equivalent, an electromyography-based third order polynomial, a modified version of the polynomial and a hybrid approach) to determine cumulative spine compression, as well as the importance of time standardization in the calculation of a daily cumulative loading dose. Findings demonstrated that the polynomial predicted cumulative compression values were 43-53% higher than those with all other models tested and the single muscle equivalent predicted loads 18% higher than loads predicted using a modified polynomial. Profound differences between modelling approaches suggest that caution should be taken when selecting a muscle model to determine cumulative spine compressive loading. Time standardized cumulative compression values were found to be 28.3% greater than non-standardized estimates, illustrating the importance of selecting a standard time frame in the calculation of cumulative spine compression.

The effect of camera viewing angle on posture assessment repeatability and cumulative spinal loading.

Video-based task analysis in the workplace is often limited by equipment location and production line arrangement, therefore making it difficult to capture the motion in a single plane. The purpose of this study was to investigate the effects of camera placement on an observer's ability to accurately assess working postures in three dimensions and the resultant influence on the reliability and repeatability of calculated cumulative loading variables. Four video cameras were placed at viewing angles of 0 degrees, 45 degrees, 60 degrees and 90 degrees to the frontal plane, enabling the simultaneous collection of views of four lifting tasks (two symmetric and two asymmetric). A total of 11 participants were trained in the use of the 3DMatch 3-D posture matching software package (developed at the University of Waterloo) and were required to analyse 16 lifting trials. Four of the participants were randomly selected to return within 72 h and repeat the analysis protocol to test intra-observer repeatability. Posture matching agreement between camera views was higher when the body segments had a minimal range of motion during the task. There was no significant participant main effect; however, there was a significant (p < 0.05) task main effect. Intraclass correlation coefficients (ICC) were calculated to assess the between day reliability. Compression, reaction anterior shear and extension moment were all found to have excellent reliability (ICC > 0.75). Joint anterior shear and joint posterior shear both provided fair to good reliability (0.4 > ICC < 0.75). Overall, the impact of the camera viewing angle on an observer's ability to match working postural exposure was found to be small.

A threshold neurotoxic amphetamine exposure inhibits parietal cortex expression of synaptic plasticity-related genes.

Compulsive drug abuse has been conceptualized as a behavioral state where behavioral stimuli override normal decision making. Clinical studies of methamphetamine users have detailed decision making changes and imaging studies have found altered metabolism and activation in the parietal cortex. To examine the molecular effects of amphetamine (AMPH) on the parietal cortex, gene expression responses to amphetamine challenge (7.5 mg/kg) were examined in the parietal cortex of rats pretreated for nine days with either saline, non-neurotoxic amphetamine, or neurotoxic AMPH dosing regimens. The neurotoxic AMPH exposure [three doses of 7.5 mg/kg/day AMPH (6 h between doses), for nine days] produced histological signs of neurotoxicity in the parietal cortex while a non-neurotoxic dosing regimen (2.0 mg/kg/day x 3) did not. Neurotoxic AMPH pretreatment resulted in significantly diminished AMPH challenge-induced mRNA increases of activity-regulated cytoskeletal protein (ARC), nerve growth-factor inducible protein A (NGFI-A), and nerve growth-factor inducible protein B (NGFI-B) in the parietal cortex while neither saline pretreatment nor non-neurotoxic AMPH pretreatment did. This effect was specific to these genes as tissue plasminogen activator (t-PA), neuropeptide Y (NPY) and c-jun expression in response to AMPH challenge was unaltered or enhanced by amphetamine pretreatments. In the striatum, there were no differences between saline, neurotoxic AMPH, and non-neurotoxic AMPH pretreatments on ARC, NGFI-A or NGFI-B expression elicited by the AMPH challenge. These data indicate that the responsiveness of synaptic plasticity-related genes is sensitive to disruption specifically in the parietal cortex by threshold neurotoxic AMPH exposures.

Health effects of subchronic exposure to diesel-water-methanol emulsion emission.

The U.S. Environmental Protection Agency's National Ambient Air Quality Standards for ozone and particulate matter (PM) require urban non-attainment areas to implement pollution-reduction strategies for anthropogenic source emissions. The type of fuel shown to decrease combustion emissions components versus traditional diesel fuel, is the diesel emulsion. The Lubrizol Corporation, in conjunction with Lovelace Respiratory Research Institute and several subcontracting laboratories, recently conducted a health assessment of the combustion emissions of PuriNOx diesel fuel emulsion (diesel-water-methanol) in rodents. Combustion emissions from either of two, 2002 model Cummins 5.9L ISB engines, were diluted with charcoal-filtered air to exposure concentrations of 125, 250 and 500 microg total PM/m3. The engines were operated on a continuous, repeating, heavy-duty certification cycle (U.S. Code of Federal Regulations, Title 40, Chapter I) using Rotella-T 15W-40 engine oil. Nitrogen oxide (NO) and PM were reduced when engines were operated on PuriNOx versus California Air Resources Board diesel fuel under these conditions. Male and female F344 rats were housed in Hazleton H2000 exposure chambers and exposed to exhaust atmospheres 6 h/day, five days/week for the first 11 weeks and seven days/week thereafter. Exposures ranged from 61 to 73 days depending on the treatment group. Indicators of general toxicity (body weight, organ weight, clinical pathology and histopathology), neurotoxicity (glial fibrillary acidic protein assay), genotoxicity (Ames assay, micronucleus, sister chromatid exchange), and reproduction and development were measured. Overall, effects observed were mild. Emulsion combustion emissions were not associated with neurotoxicity, reproductive/developmental toxicity, or in vivo genotoxicity. Small decreases in serum cholesterol in the 500-microg/m3 exposure group were observed. PM accumulation within alveolar macrophages was evident in all exposure groups. The latter findings are consistent with normal physiological responses to particle inhalation. Other statistically significant effects were present in some measured parameters of other exposed groups, but were not clearly attributed to emissions exposure. Positive mutagenic responses in several strains of Salmonella typhimurium were observed subsequent to treatment with emulsion emissions subfractions. Based on the cholesterol results, it can be concluded that the 250-microg/m3 exposure level was the no observed effect level. In general, biological findings in exposed rats and bacteria were consistent with exposure to petroleum diesel exhaust in the F344 rat and Ames assays.

The effects of lumbar massage on muscle fatigue, muscle oxygenation, low back discomfort, and driver performance during prolonged driving.

An increasing dependence of society on automobiles for both work and leisure and the corresponding increase in time spent seated in the car has been correlated with a greater risk of low back pain and absence from work (Porter and Gyi 2002). This study examined the effects of three types of lumbar massage units on seating comfort, muscle fatigue, muscle oxygenation, muscle blood flow and driving performance during a 1 h simulated driving task. Electromyographic (EMG) signals were recorded from the right and left thoracic and lumbar erector spinae musculature. Average EMG (AEMG), mean power frequency (MPF), gaps and amplitude probability distribution function (APDF) parameters were analysed from the three massage seats and compared to a control seat. Near infrared spectroscopy (NIRS) and skin temperature from the right thoracic and lumbar erector spinae were used as an indication of muscle oxygenation and blood flow throughout the driving task. Ratings of perceived discomfort were used to assess driver discomfort, and driving performance was assessed by calculating mean lap times for the duration of each driving trial. The results showed statistically significant increases in skin temperature compared with the control seat after 60 min of driving. The NIRS results reflected these trends although the results were not statistically significant. AEMG and MPF measures showed no significant differences between the seats. MPF measures were found to increase over time, effects attributed to increases in muscle temperature. Gaps and APDF analyses revealed greater rest times and lower activation levels, respectively, with the control seat, which could result in increased loading of passive structures. This study demonstrated the beneficial effects of lumbar massage systems in increasing muscle blood flow and oxygenation. Although EMG parameters were not significantly different, the trends support the significant blood flow results. Future research should include longer driving times and adjustments in EMG measures to account for the effects of increasing muscle temperature on AEMG and MPF measures.

Health effects of subchronic exposure to diesel-water emulsion emission.

The U.S. Environmental Protection Agency (EPA) National Ambient Air Quality Standards for ozone and particulate matter are requiring urban nonattainment areas to implement pollution-reduction strategies for anthropogenic source emissions. A type of fuel shown to decrease combustion emissions components versus traditional diesel fuels is the diesel-water emulsion. The Lubrizol Corporation in conjunction with Lovelace Respiratory Research Institute and several subcontracting laboratories recently conducted a rodent health assessment of inhaled combustion emissions of PuriNO(x) diesel fuel emulsion. Combustion emissions from either of two 2001 model Cummins 5.9-L ISB engines were diluted with charcoal-filtered air to exposure concentrations of 100, 200, and 400 microg total particulate matter/m(3). The engines were operated on a continuously repeating, heavy-duty certification cycle (U.S. Code of Federal Regulations, Title 40, Chapter I) using Rotella-T 15W-40 engine oil. Nitrogen oxide and particulate matter were reduced when engines were operated on PuriNO(x) versus California Air Resources Board diesel fuel under these conditions. Male and female F344 rats were housed in Hazleton H2000 exposure chambers and exposed to exhaust atmospheres 6 h/day, 5 days/wk for the first 11 wk and 7 days/wk threafter. Exposures ranged from 58 to 70 days, depending on the treatment group. Indicators of general toxicity (body weight, organ weight, clinical pathology, and histopathology), neurotoxicity (glial fibrillary acidic protein assay), genotoxicity (Ames assay, micronucleus, sister chromatid exchange), and reproduction and development were measured. Overall, effects observed were mild. Emulsion combustion emissions were not associated with neurotoxicity, reproductive/developmental toxicity, or in vivo genotoxicity. Small decreases in serum cholesterol and small increases in platelet values in some groups of exposed animals were observed. Particulate matter accumulation within alveolar macrophages was evident in all exposure groups. These findings are consistent with normal physiological responses to particle inhalation. Other statistically significant effects were present in some measured parameters of other exposed groups but were not clearly attributed to emissions exposure. Positive mutagenic responses in several strains of Salmonella typhimurium were observed subsequent to treatment with emulsion emissions subfractions. Based on the cholesterol and platelet results, it can be concluded that the 100 microg/m(3) exposure level was the no-observed-effect level. In general, biological findings in diesel emulsion emission-exposed animals and bacteria were consistent with exposure to petroleum diesel exhaust in the F344 rat and Ames assays.

Aging, stress and the hippocampus.

Functional loss often occurs in many body systems (e.g., endocrine, cognitive, motor) with the passage of years, but there is great individual variation in the degree of compromise shown. The current focus on brain aging will continue because demographic trends indicate that the average lifespan will show a continued increase. There is increasing emphasis on understanding how aging contributes to a decline in brain functions, cognition being a prime example. This is due in part to the fact that dementias and other losses in brain function that sometimes accompany aging cause an obvious decline in the quality of life and these deficits are of more concern as the number of elderly increase. Stress also is a ubiquitous aspect of life and there is now a greater interest in understanding the role of stress and the stress response in brain aging. The key role of the hippocampus and its related brain structures in cognition, as well as in the feedback control of the response to stress, have made this brain area a logical focus of investigation for those interested in the impact of stress on brain aging. Here, we describe how the hippocampus changes with age and we examine the idea that age-related changes in the secretion patterns of the hypothalamic-pituitary adrenal (HPA) axis can contribute to aging of this structure. We also examine the proposal that stress, perhaps due to compromised HPA axis function, can contribute to hippocampal aging through exposure to excessive levels of glucocorticoids. The aging hippocampus does not appear to suffer a generalized loss of cells or synapses, although atrophy of the structure may occur in humans. Thus, age-related cognitive impairments are likely related to other neurobiological alterations that could include changes in the signaling, information encoding, plasticity, electrophysiological or neurochemical properties of neurons or glia. Although excessive levels of glucocorticoids are able to interfere with cognition, as well as hippocampal neuronal integrity, and aging is sometimes accompanied by an increase in these steroids because of inadequate feedback control of the HPA axis, none of these are a foregone consequence of aging. The general preservation of cells and the plastic potential of the hippocampus provide a focus for the development of pharmacological, nutritive or lifestyle strategies to combat age-related declines in the hippocampus as well as other brain areas.

Effects of aging and stress on hippocampal structure and function.

Aging is often simply defined as the decline in various body systems and functions (eg, endocrine, cognitive, motor, etc) that occur with the passage of time, although the degree of deterioration can vary greatly across individuals. Increases in average life span have brought a greater focus on brain aging. There is an emphasis on understanding how aging contributes to a decline in brain functions (eg, cognition) because such a decline adversely affects the quality of life. The hippocampus is a key brain structure for cognition and the feedback control of the stress response. Herein we describe how the hippocampus changes with age and we examine the idea that age-related changes in the secretory patterns of the hypothalamic-pituitary adrenal (HPA) axis can contribute to hippocampal aging. We also examine the proposal that cumulative stress, perhaps due to compromised HPA axis function, can contribute to hippocampal aging by subjecting it to exposure to excessive levels of glucocorticoids. The aging hippocampus does not appear to suffer a generalized loss of cells or synapses, although atrophy of the structure may occur in humans. Thus, age-related cognitive impairments are likely related to other neurobiological alterations that could include changes in the signaling, information encoding, and plastic, electrophysiological, or neurochemical properties of neurons or glia. Dysfunction of the HPA axis sometimes occurs with aging, and while excessive glucocorticoids can disrupt cognition as well as hippocampal neuronal integrity, these are not an inevitable consequence of aging. The general preservation of cells and the plastic potential of the hippocampus provide a focus for the development of pharmacological, nutritional, or life-style strategies to combat age-related declines.