Health and motivation as mediators of the effects of job demands, job control, job support, and role conflicts at work and home on sickness presenteeism and absenteeism.

PURPOSE: The first objective was to contribute to a better understanding of the contrasting and paradoxical results in studies of work environment factors and sickness presence and sickness absence. A second objective was to examine if, and under what conditions, employees choose to replace sickness absence with sickness presence, i.e., so-called substitution. METHODS: The study utilizes a large body of cross-sectional questionnaire data (n = 130,161) gathered in Sweden from 2002 to 2007 in connection with a comprehensive health promotion initiative. Health and motivation were analyzed as mediators of the effects of five job factors, job control, job support, job demand, role conflict and "work to family conflict" on sickness presence and absence. RESULTS: The results concerning job demands indicate substitution in that increased job demands are associated with increased presenteeism and reduced absenteeism. The direct effect of higher job support was increased absenteeism, but via the health and motivation paths, the total effect of more social support was health-promoting and associated with a reduction in sickness absence and sickness presence. High job control emerged as the most pronounced health-promoting factor, reducing sickness presenteeism as well as absenteeism. More role conflicts and work-to-family conflicts were directly and indirectly associated with decreased health and increased absenteeism as well as presenteeism. earlier research. CONCLUSION: The mediation analyzes shed light on some of the paradoxes in research on sickness presenteeism and sickness absenteeism, especially regarding job demands and job support. The substitution effect is important for workplace policy and occupational health practice.

Sick leave among people in paid work after age 65: A Swedish population-based study covering 1995, 2000, 2005 and 2010.

AIMS: Extending working life into older age groups is discussed in many countries. However, there is no knowledge about how this affects rates of sick leave. The aim of this work was to investigate rates of sick leave among people in paid work after retirement age and if such rates have changed over time. METHODS: Swedish nationwide register data on people aged >65 years and living in Sweden in 1995, 2000, 2005 and 2010 were analysed. All people with a sufficiently high work income to be eligible for public sick leave benefits were included. The proportions in paid work and compensated rates of sick leave for people aged 66-70 and ≥71 were analysed by sex, educational level, country of birth, living area, and employment type and sector. RESULTS: The percentage of people in paid work at ages 66-70 years increased from <10% in 1995 to 24% in 2010 and among those aged ≥71 years from 2.7% in 1995 to 3.5% in 2010. The rates of sick leave among working people aged 66-70 years were 3.3% in 1995 and 2.4% in 2010 and for people aged ≥71 years the rates of sick leave were 2.2% in 1995 and 0.2% in 2010. Women had higher rates of sick leave than men in 2005 and 2010, but lower in 1995 and 2000. In 2010, the rates of sick leave were similar between employees and the self-employed, and higher among employees in the public sector than among employees in the private sector. CONCLUSIONS: Rates of sick leave among workers aged >65 years were lower in 2010 than in 1995, despite much higher rates of labour market participation in 2010.

Outcome of three screening questions for temporomandibular disorders (3Q/TMD) on clinical decision-making.

Patients with temporomandibular disorders (TMD) seem to go undetected and not adequately managed within dentistry. To identify these patients, three screening questions (3Q/TMD) have been introduced within dentistry in parts of Sweden. It is not known whether 3Q/TMD affects the clinical decision-making for these patients. The aim of this study was to evaluate the outcome of 3Q/TMD on the clinical decision-making and to analyse whether gender, age and the fee system the individual was assigned to were related to prescribed TMD treatment. This cohort study was carried out within the Public Dental Health service in Västerbotten, Sweden. As part of the routine dental check-up, a health declaration including 3Q/TMD was completed. The study population was randomly selected based on their 3Q/TMD answers. In total, 300 individuals with an affirmative answer to any of the 3Q/TMD, and 500 individuals with all negative answers were selected. The 3Q/TMD includes questions on weekly jaw-face-temple pain (Q1), pain on function (Q2) and catching/locking of the jaw (Q3). The 3Q/TMD was analysed in relation to prescribed treatment assessed from dental records. There was significantly more treatment performed or recommended for 3Q-positives (21·5%), compared to 3Q-negatives (2·2%) (P < 0·001). The odds ratio for TMD-related treatment for 3Q-positives versus 3Q-negatives was 12·1 (95% CI: 6·3-23·4). Although affirmative answers to the 3Q/TMD was related to TMD treatment, the majority of individuals with a screen positive still did not, according to dental records, receive assessment or treatment. Further studies are needed to better understand the clinical decision-making process for patients with TMD.

Validity of three screening questions (3Q/TMD) in relation to the DC/TMD.

Temporomandibular disorders (TMD) are common but seem to be largely undetected within general dental care. To improve dentists' awareness of these symptoms, three screening questions (3Q/TMD) have been introduced. Our aim was to validate 3Q/TMD in relation to the diagnostic criteria for TMD (DC/TMD), while taking into account the severity level of the symptoms. The study population consisted of 7831 individuals 20-69 years old, who had their routine dental check-up at the Public Dental Health Service in Västerbotten, Sweden. All patients answered a health declaration, including the 3Q/TMD regarding frequent temporomandibular pain, pain on movement and catching/locking of the jaw. All 3Q-positives (at least one affirmative) were invited for examination in randomised order. For each 3Q-positive, a matched 3Q-negative was invited. In total, 152 3Q-positives and 148 3Q-negatives participated. At examination, participants answered 3Q/TMD a second time, before they were examined and diagnosed according to DC/TMD. To determine symptom's severity, the Graded Chronic Pain Scale and Jaw Functional Limitation Scale-20 (JFLS-20) were used. In total, 74% of 3Q-positives and 16% of 3Q-negatives met the criteria for DC/TMD pain or dysfunction (disc displacements with reduction and degenerative joint disorder were excluded). Fifty-five per cent of 3Q-positives had a TMD diagnosis and CPI score ≥3 or a JFLS-20 score ≥5, compared to 4% of 3Q-negatives. The results show that the 3Q/TMD is an applicable, cost-effective and valid tool for screening a general adult population to recognise patients in need of further TMD examination and management.

Pain and Disability in the Jaw and Neck Region following Whiplash Trauma.

The relationship between whiplash trauma and chronic orofacial pain is unclear, especially with regard to the time elapsed from trauma to development of orofacial pain. The aim was to analyze prevalence of jaw pain and disability, as well as the relationship between pain and disability in the jaw and neck regions in the early nonchronic stage after whiplash trauma. In this case-control study, 70 individuals (40 women, 30 men, mean age 35.5 y) who visited an emergency department with neck pain following a car accident were examined within 3 wk of trauma (group 1) and compared with 70 individuals (42 women, 28 men, mean age 33.8 y), who declined to attend a clinical examination but agreed to fill in questionnaires (group 2). The 2 case groups were compared with a matched control group of 70 individuals (42 women, 28 men, mean age 37.6 y) without a history of neck trauma. All participants completed questionnaires regarding jaw pain and dysfunction, rating pain intensity in jaw and neck regions on the Numerical Rating Scale, the Neck Disability Index, and Jaw Disability Checklist. Compared with controls, individuals with a recent whiplash trauma reported more jaw pain and dysfunction. Furthermore, there was a moderate positive correlation between jaw and neck pain ratings for group 1 (r = 0.61, P < 0.0001) and group 2 (r = 0.59, P < 0.0001). In the logistic regression analysis, cases showed higher odds ratios (range, 6.1 to 40.8) for jaw and neck pain and disability compared with controls. Taken together, the results show that individuals with a recent whiplash trauma report more jaw pain and disability compared with controls without a history of neck trauma. Furthermore, the correlation between jaw and neck pain intensity implies that intensity of neck pain in the acute stage after whiplash trauma might be a possible risk factor also for development of chronic orofacial pain.

Temporomandibular pain and jaw dysfunction at different ages covering the lifespan--A population based study.

BACKGROUND: Temporomandibular pain and jaw dysfunction can have a negative effect on daily life, but these conditions are not well recognized in the health care systems. The general aim was to examine the cross-sectional prevalence of frequent temporomandibular pain and jaw dysfunction in men and women across the lifespan. METHODS: The analysis was based on data from 137,718 individuals (mean age 35 years, SD 22.7) who answered three questions (3Q/TMD) included in the digital health declaration in the Public Dental Health care in the county of Västerbotten, Sweden; Q1: 'Do you have pain in your temple, face, jaw or jaw joint once a week or more?'; Q2: 'Does it hurt once a week or more when you open your mouth or chew?'; and Q3: 'Does your jaw lock or become stuck once a week or more?' RESULTS: The prevalence of frequent temporomandibular pain (Q1) was 5.2% among women and 1.8% among men (p < 0.0001). The prevalence of frequent pain on jaw movement (Q2) was 2.5% among women and 0.9% among men (p < 0.0001). The prevalence of frequent locking of the jaw (Q3) was 2.7% among women and 1.2% among men (p < 0.0001). CONCLUSIONS: The study shows that the cross-sectional prevalence of temporomandibular pain and jaw dysfunction varies during the lifespan. For men and women, respectively, symptoms increase during adolescence, peak in middle age and then gradually diminish. The prevalence of these symptoms is significantly higher among women except from the first and last decades of a 100-year lifespan.

Associations between health and combinations of sickness presence and absence.

BACKGROUND: The association between sickness presence (SP), sickness absence (SA) and health is not well known although research on these phenomena has grown in recent years. AIMS: To identify the health outcomes of different combinations of self-reported SP and SA while controlling for background and work-related factors. METHODS: The study group was a representative three-wave sample of 1886 employed individuals from the Swedish Working Life Cohort, gathered in 2004-2006. Block-wise multiple logistic regression analyses were conducted for combinations of self-reported SP and SA, using controls for background, work-related and previous health factors. RESULTS: The crude odds ratios showed that health and mental well-being were most negatively affected in the group with high SP and SA in the preceding year. When differences in individual background, health and work-related factors were controlled for, distinct significant odds ratios remained. The odds ratios for negative health outcomes were between 1.49 (95% CI: 1.02-2.18) and 2.64 (95% CI: 1.81-3.85) higher among those with both high SP and high SA than those with both low SP and low SA. However, the study also indicated that individuals with high SP and low SA showed the highest odds ratios for poor mental well-being. CONCLUSIONS: The results showed that combinations of frequent self-rated SP and SA are related to negative values in the four measured aspects of self-reported health 1 year later. Occupational medicine practitioners should therefore be concerned particularly with employees who report frequently occurring SP and SA.

Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase-1 mutant mouse in vivo: evidence for increased persistent inward currents.

AIM: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a preferential loss of motor neurones. Previous publications using in vitro neonatal preparations suggest an increased excitability of motor neurones in various superoxide dismutase-1 (SOD1) mutant mice models of ALS which may contribute to excitotoxicity of the motor neurones. METHODS: Using intracellular recording, we tested this hypothesis in vivo in the adult presymptomatic G127insTGGG (G127X) SOD1 mutant mouse model of ALS. RESULTS: At resting membrane potentials the basic intrinsic properties of lumbar motor neurones in the adult presymptomatic G127X mutant are not significantly different from those of wild type. However, at more depolarized membrane potentials, motor neurones in the G127X SOD1 mutants can sustain higher frequency firing, showing less spike frequency adaption (SFA) and with persistent inward currents (PICs) being activated at lower firing frequencies and being more pronounced. CONCLUSION: We demonstrated that, in vivo, at resting membrane potential, spinal motor neurones of the adult G127X mice do not show an increased excitability. However, when depolarized they show evidence of an increased PIC and less SFA which may contribute to excitotoxicity of these neurones as the disease progresses.

Work status, work hours and health in women with and without children.

OBJECTIVES: The authors studied self-reported health in women with and without children in relation to their work status (employed, student, job seeker or homemaker), work hours and having an employed partner. METHODS: The study group comprised of 6515 women born in 1960-1979 who were interviewed in one of the Swedish Surveys of Living Conditions in 1994-2003. Self-rated health, fatigue and symptoms of anxiety were analysed. RESULTS: Having children increased the odds of poor self-rated health and fatigue in employed women, female students and job seekers. The presence of a working partner marginally buffered the effects. In dual-earner couples, mothers reported anxiety symptoms less often than women without children. Few women were homemakers (5.8%). The odds of poor self-rated health and fatigue increased with increasing number of children in employed women, and in women working 40 h or more. Poor self-rated health was also associated with the number of children in students. Many mothers wished to reduce their working hours, suggesting time stress was a factor in their impaired health. The associations between having children and health symptoms were not exclusively attributed to having young children. CONCLUSIONS: Having children may contribute to fatigue and poor self-rated health particularly in women working 40 h or more per week. Student mothers and job seeking mothers were also at increased risk of poor self-rated health. The results should be noted by Swedish policy-makers. Also countries aiming for economic and gender equality should consider factors that may facilitate successful merging of work and family life.

Meta-analysis of vascular endothelial growth factor variations in amyotrophic lateral sclerosis: increased susceptibility in male carriers of the -2578AA genotype.

BACKGROUND: Targeted delivery of the angiogenic factor, vascular endothelial growth factor (VEGF), to motor neurons prolongs survival in rodent models of amyotrophic lateral sclerosis (ALS), while mice expressing reduced VEGF concentrations develop motor neuron degeneration reminiscent of ALS, raising the question whether VEGF contributes to the pathogenesis of ALS. An initial association study reported that VEGF haplotypes conferred increased susceptibility to ALS in humans, but later studies challenged this initial finding. METHODS AND FINDINGS: A meta-analysis was undertaken to critically reappraise whether any of the three common VEGF gene variations (-2578C/A, -1154G/A and -634G/C) increase the risk of ALS. Over 7000 subjects from eight European and three American populations were included in the analysis. Pooled odds ratios were calculated using fixed-effects and random-effects models, and four potential sources of heterogeneity (location of disease onset, gender, age at disease onset and disease duration) were assessed. After correction, none of the genotypes or haplotypes was significantly associated with ALS. Subgroup analysis by gender revealed, however, that the -2578AA genotype, which lowers VEGF expression, increased the risk of ALS in males (OR = 1.46 males vs females; 95% CI = 1.19 to 1.80; p = 7.8 10E-5), even after correction for publication bias and multiple testing. CONCLUSIONS: This meta-analysis does not support the original conclusion that VEGF haplotypes increase the risk of ALS in humans, but the significant association of the low-VEGF -2578AA genotype with increased susceptibility to ALS in males reappraises the link between reduced VEGF concentrations and ALS, as originally revealed by the fortuitous mouse genetic studies.

Gene expression of 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase in relation to androstenone, testosterone, and estrone sulphate in gonadally intact male and castrated pigs.

Androstenone is one of the main compounds responsible for boar taint, and 3beta-hydroxysteroid dehydrogenase (3betaHSD) might be involved in its metabolism. In this study, the gene expression of 3betaHSD and 17beta-hydroxysteroid dehydrogenase (17betaHSD) were determined by real-time PCR analysis and related to the concentrations of androstenone, testosterone, and estrone sulphate (E1S). The experiments were performed on gonadally intact male pigs classified based on high or low fat androstenone concentrations, as predetermined by HPLC, as well as on immunocastrated and surgically castrated male pigs. The male pigs with high androstenone concentrations in fat had low 3betaHSD gene expression in liver and testis. Moreover, the 17betaHSD gene expression in liver, but not in testis, varied negatively with fat androstenone concentrations. Immunocastrated and surgically castrated male pigs had nondetectable concentrations of fat androstenone and plasma testosterone and E1S, and the castration procedure induced a significant increase of 3betaHSD and 17betaHSD gene expression. The mRNA expression was generally much greater from the 3betaHSD than from the 17betaHSD gene. Furthermore, fat androstenone was negatively correlated with liver 3betaHSD gene expression (Pearson correlation, r = -0.69; P < 0.05), and the 17betaHSD gene expression in liver was negatively correlated with plasma E1S (r = -0.95; P < 0.001), indicating an important role of liver 17betaHSD in the estrogen metabolism of gonadally intact male pigs. Another strong correlation was found between 3betaHSD and 17betaHSD gene expression in liver of the gonadally intact male pigs (r = 0.86; P < 0.01), possibly reflecting similar regulation mechanisms of these genes.

Clinicopathological phenotype of ALS with a novel G72C SOD1 gene mutation mimicking a myopathy.

A 71-year-old woman with a family history of amyotrophic lateral sclerosis (ALS) was investigated for symmetrical, proximal limb and abdominal muscle weakness. Initial examination showed mild proximal muscle weakness in the arms and legs, slightly elevated serum creatine kinase (CK) level, and normal electromyographic (EMG) findings. A myopathy was the presumed diagnosis. Over the next year, weakness became severe and tendon reflexes became unelicitable; no upper motor signs were present. EMG then showed acute and chronic denervation and a muscle biopsy showed target fibers and grouped atrophy. DNA analysis revealed a G72C CuZn-superoxide dismutase (SOD1) mutation. Fasciculations were absent throughout the disease. The patient died 53 months after symptom onset and autopsy revealed loss of lower motor neurons (LMN) and SOD1-positive inclusions. This case expands the phenotypic spectrum of ALS associated with SOD1 mutations to include presenting features that mimic a myopathy.

Fibre composition of human intrinsic tongue muscles.

The muscle fibre composition of three human intrinsic tongue muscles, the longitudinalis, verticalis and transversus, was investigated in four anterior to posterior regions of the tongue using morphological and enzyme- and immunohistochemical techniques. All three muscles typically contained type I, IIA and IM/IIC fibres. Type I fibres expressed slow myosin heavy chain (MyHC), type II fibres fast MyHC, mainly fast A MyHC, whereas type IM/IIC coexpressed slow and fast MyHCs. Type II fibres were in the majority (60%), but regional differences in proportion and diameter of fibre types were obvious. The anterior region of the tongue contained a predominance of relatively small type II fibres (71%), in contrast to the posterior region which instead showed a majority of larger type I and type IM/IIC fibres (66%). In general, the fibre diameter was larger in the posterior region. This muscle fibre composition of the tongue differs from those of limb, orofacial and masticatory muscles, probably reflecting genotypic as well as phenotypic functional specialization in oral function. The predominance of type II fibres and the regional differences in fibre composition, together with intricate muscle structure, suggest generally fast and flexible actions in positioning and shaping the tongue, during vital tasks such as mastication, swallowing, respiration and speech.

Amelioration of antigen-induced arthritis in rats by transfer of extracellular superoxide dismutase and catalase genes.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), while antioxidant enzymes, such as extracellular superoxide dismutase (EC-SOD) and catalase, block radical-induced events. The present study tested if the ex vivo transfer of EC-SOD and catalase genes alone or in combination in the knee joint of rats with monoarticular antigen-induced arthritis (AIA) was anti-inflammatory, and examined the potential mechanisms involved. Synoviocytes isolated from female Wistar rats were immortalized with a retroviral vector SUV19.5. These cells were permanently transfected with an EC-SOD expression plasmid (pEC-SODZeo) or a catalase expression plasmid (pCatalaseZeo) to create cells overexpressing EC-SOD or catalase, as measured by RT-PCR and Western blots. The cells were engrafted in knee joints of animals at the time of the induction of AIA. Three gene transfer groups, an EC-SOD group, a catalase group and a combined therapy group (EC-SOD and catalase) were included in these experiments. Animals in the control group were engrafted with synoviocytes transfected with the plasmid pZeoSV2 without an insert. Clinical and histological assessments were performed, as well as tissue measurements of SOD, catalase and gelatinase activities. Ex vivo gene transfer of EC-SOD and catalase into rat knee joints produced about a six- to seven-fold increase in EC-SOD activity and a two- to three-fold increase in catalase activity compared with the control animals. Rats treated with cells overexpressing EC-SOD, catalase or a combination of EC-SOD and catalase showed significant suppression of knee joint swelling, decreased infiltration of inflammatory cells within the synovial membrane and reduced gelatinase activity in knee joints, compared with animals receiving cells transfected with the plasmid alone. No statistically significant difference was found between the groups treated with cells overexpressing EC-SOD, catalase or a combination of both. Gene therapy involving the local intra-articular overexpression of two antioxidant enzymes, EC-SOD and catalase, was anti-inflammatory in AIA. One mechanism appears to be the suppression of gelatinase activities by both EC-SOD and catalase.

Molecular characterization and mutational screening of the PRKAG3 gene in the horse.

The PRKAG3 gene encodes a muscle-specific isoform of the regulatory gamma subunit of AMP-activated protein kinase (AMPK). A major part of the coding PRKAG3 sequence was isolated from horse muscle cDNA using reverse-transcriptase (RT)-PCR analysis. Horse-specific primers were used to amplify genomic fragments containing 12 exons. Comparative sequence analysis of horse, pig, mouse, human, Fugu, and zebrafish was performed to establish the exon/intron organization of horse PRKAG3 and to study the homology among different isoforms of AMPK gamma genes in vertebrates. The results showed conclusively that the three different isoforms (gamma1, gamma2, and gamma3) were established already in bony fishes. Seven single nucleotide polymorphisms (SNPs), five causing amino acid substitutions, were identified in a screening across horse breeds with widely different phenotypes as regards muscle development and intended performance. The screening of a major part of the PRKAG3 coding sequence in a small case/control material of horses affected with polysaccharide storage myopathy did not reveal any mutation that was exclusively associated with this muscle storage disease. The breed comparison revealed several potentially interesting SNPs. One of these (Pro258Leu) occurs at a residue that is highly conserved among AMPK gamma genes. In an SNP screening, the variant allele was only found in horse breeds that can be classified as heavy (Belgian) or moderately heavy (North Swedish Trotter, Fjord, and Swedish Warmblood) but not in light horse breeds selected for speed or racing performance (Standardbred, Thoroughbred, and Quarter horse) or in ponies (Icelandic horses and Shetland pony). The results will facilitate future studies of the possible functional significance of PRKAG3 polymorphisms in horses.

Melanocortin-4 receptor (MC4R) genotypes have no major effect on fatness in a Large White x Wild Boar intercross.

The melanocortin-4 receptor (MC4R), a G-protein coupled receptor, is implicated in mediating the effect of leptin on food intake and energy balance. A previous candidate gene study reported an association between an MC4R missense mutation (Asp298Asn) and fatness, growth and feed intake in pigs. To assess this association further, we analysed the segregation of this missense mutation in relation to variation in fatness traits using a Wild Boar x Large White intercross. The Wild Boar and Large White founders were homozygous for different MC4R alleles. The MC4R was assigned to the expected region on pig chromosome 1. The statistical evaluation did not reveal any indication of a significant effect on fatness related traits in this pedigree.

Increased ozone-induced airway neutrophilic inflammation in extracellular-superoxide dismutase null mice.

Extracellular-superoxide dismutase (EC-SOD) exists primarily in the tissue interstitium and the lung contains particularly large amounts of the enzyme. To determine the roles of EC-SOD and extracellularly formed superoxide radicals in the pulmonary response to the common air pollutant ozone, wild-type mice and mice lacking EC-SOD were exposed to 1.5 ppm ozone for 48 h. The exposure resulted in a marked neutrophilic inflammatory reaction observed both in the bronchoalveolar lavage fluid (BALF) and by histopathology of the lungs, which was much stronger in the mice lacking EC-SOD. Unlike the wild-type mice, the null mutants also showed increased levels of interleukin-6 in the BALF. The ozone exposure also resulted in increased airway mucosal permeability and cell damage as indicated by increased protein and lactate dehydrogenase in the BALF. There was, however, no difference between the two groups of mice.The results suggest that extracellular superoxide radicals are important inflammatory mediators in the pulmonary response to ozone, but in the present model, the radical and the infiltrating neutrophils contributed little to the pulmonary injury The data, together with previous findings, support a role for EC-SOD as a modulator of inflammatory reactions.

Corneal endothelial integrity in mice lacking extracellular superoxide dismutase.

PURPOSE: To evaluate corneal endothelial morphology in mice without secreted extracellular superoxide dismutase (SOD) in normal ageing and in a lipopolysaccharide (LPS)-induced inflammation model and to measure the contents of SOD isoenzymes in the mouse cornea and the superoxide radical concentrations in corneas with and without extracellular SOD. METHODS: The central corneal endothelium of wild-type and extracellular SOD-null mice were studied in micrographs at eight different ages and after a unilateral intravitreal injection of LPS, with the contralateral eye serving as the control. The activities of the SOD isoenzymes in the mouse cornea were determined with a direct assay, the superoxide radical concentration was assessed by lucigenin-induced chemiluminescence, and the extracellular SOD distribution was mapped with immunohistochemistry. RESULTS: The activities of the cytosolic Cu- and Zn-containing SOD, the mitochondrial Mn-containing SOD and extracellular SOD were 4300, 15, and 340 U/g wet weight, respectively. Extracellular SOD was found in the epithelium, stroma, and endothelium. The concentration of extracellular superoxide radicals was doubled in extracellular SOD-null corneas, and the endothelial cell density decreased more with age in extracellular SOD-null than in wild-type control corneas. In the LPS-induced inflammation model, the cell density decreased more, and the cells became more irregular in extracellular SOD-null than in wild-type corneas. CONCLUSIONS: In the mouse cornea, absence of extracellular SOD leads to a higher concentration of extracellular superoxide radicals, an enhancement in the spontaneous age-related loss of endothelial cells, and an increased susceptibility to acute inflammatory endothelial damage. Extracellular SOD is likely to have a protective role in the corneal endothelium.

Differences in basal airway antioxidant concentrations are not predictive of individual responsiveness to ozone: a comparison of healthy and mild asthmatic subjects.

The air pollutant ozone induces both airway inflammation and restrictions in lung function. These responses have been proposed to arise as a consequence of the oxidizing nature of ozone, depleting endogenous antioxidant defenses with ensuing tissue injury. In this study we examined the impact of an environmentally relevant ozone challenge on the antioxidant defenses present at the surface of the lung in two groups known to have profound differences in their antioxidant defense network: healthy control (HC) and mild asthmatic (MA) subjects. We hypothesized that baseline differences in antioxidant concentrations within the respiratory tract lining fluid (RTLF), as well as induced responses, would predict the magnitude of individual responsiveness. We observed a significant loss of ascorbate (ASC) from proximal (-45.1%, p <.01) and distal RTLFs (-11.7%, p <.05) in healthy subjects 6 h after the end of the ozone challenge. This was associated (Rs, -0.71, p <.01) with increased glutathione disulphide (GSSG) in these compartments (p =.01 and p <.05). Corresponding responses were not seen in asthmatics, where basal ASC concentrations were significantly lower (p <.01) and associated with elevated concentrations of GSSG (p <.05). In neither group was any evidence of lipid oxidation seen following ozone. Despite differences in antioxidant levels and response, the magnitude of ozone-induced neutrophilia (+20.6%, p <.01 [HC] vs. +15.2%, p =.01 [MA]) and decrements in FEV(1) (-8.0%, p <.01 [HC] vs. -3.2%, p <.05 [MA]) did not differ between the two groups. These data demonstrate significant differences between the interaction of ozone with RTLF antioxidants in MA and HC subjects. These responses and variations in basal antioxidant defense were not, however, useful predictive markers of group or individual responsiveness to ozone.