High serum arginase I levels in asthma: its correlation with high-sensitivity C-reactive protein.

BACKGROUND: Much attention has been directed to the induction of arginase I in the lung of asthmatic mice. However, there is no agreement on the changes of serum arginase activity in asthmatic patients among previous studies. OBJECTIVES: The aim of this study was to evaluate the clinical relevance of serum arginase I in asthmatic patients. METHODS: Serum arginase I was examined cross-sectionally in non-smoking asthmatic patients (n = 23) and healthy individuals (n = 30) using enzyme-linked immunosorbent assay (ELISA) and its correlations with several clinical parameters were investigated. RESULTS: Serum levels of arginase I were significantly increased in asthmatic patients (mean ± SD 67.4 ± 41.0 ng/mL) compared with healthy controls (27.2 ± 12.9 ng/mL). In healthy controls, a difference in arginase I levels was not observed between sex groups but was observed between age groups. In asthmatic patients, serum arginase I levels were not different between groups of age, sex, and inhalation steroid therapy but were different between groups of atopic status. Non-atopic asthmatic patients revealed significantly high serum arginase I levels compared with atopic asthmatic patients and healthy controls although no difference was observed between atopic asthmatic patients and healthy controls. Spearman's correlation analysis showed that serum arginase I level had a significant negative correlation with age and a positive correlation with red blood cell numbers in healthy controls, whereas in asthmatic patients, it had significant positive correlations with alanine aminotransferase (ALT), high-sensitivity C-reactive protein (hs-CRP) and a negative correlation with immunoglobulin-E (IgE). CONCLUSIONS: High serum arginase I levels in asthmatic patients may be associated with airway inflammation in non-atopic asthma.

The relationship between joint pain and climate conditions in Japan.

This study aimed to determine whether there was any association between the regional climate and the proportion of people with joint pain. Regional climate data between 1971 and 2000 were obtained from the Japan Meteorological Agency. The variables used in the cluster analysis included sunlight hours, amount of precipitation, number of days with precipitation, and temperature. The regional proportion of people with joint pain was obtained from the National Survey for Health in 2001. After performing a cluster analysis, one-way ANOVA and Welch's test were used to determine whether the climate characteristics of the clusters were significantly different. Within each cluster, stepwise multiple linear regression analyses were performed. We found that sunlight hours showed a direct, negative association with the proportion of people with joint pain (adjusted R2=0.532, p=0.016) in cluster 1, which was characterized as the region with the fewest total hours of sunlight, less precipitation, a modest number of rainy days, and low temperature. In the other clusters, the regional female population rate (cluster 2) and the senior population rate (cluster 3, 4) were the primary predictors. We concluded that the degree of exposure to sunlight may play a crucial role in prevention of joint pain. This finding should encourage people to set aside some time for staying outdoors in their daily lives.

Direct inhibition of arginase attenuated airway allergic reactions and inflammation in a Dermatophagoides farinae-induced NC/Nga mouse model.

The expression of arginase I has been a focus of research into the pathogenesis of experimental asthma, because arginase deprives nitric oxide synthase (NOS) of arginine and therefore participates in the attenuation of bronchodilators such as nitric oxide (NO). The present study used an intranasal mite-induced NC/Nga mouse model of asthma to investigate the contribution of arginase to the asthma pathogenesis, using an arginase inhibitor, N(omega)-hydroxy-nor-l-arginine (nor-NOHA). The treatment with nor-NOHA inhibited the increase in airway hyperresponsiveness (AHR) and the number of eosinophils in bronchoalveolar lavage fluid. NOx levels in the lung were elevated despite suppressed NOS2 mRNA expression. Accompanied by the attenuated activity of arginase, the expression of arginase I at both the mRNA and protein level was downregulated. The levels of mRNA for T helper 2 cytokines such as IL-4, IL-5, and IL-13, and for chemotactants such as eotaxin-1 and eotaxin-2, were reduced. Moreover, the accumulation of inflammatory cells and the ratio of goblet cells in the bronchiole were decreased. The study concluded that the depletion of NO caused by arginase contributes to AHR and inflammation, and direct administration of an arginase inhibitor to the airway may be beneficial and could be of use in treating asthma due to its anti-inflammatory and airway-relaxing effects, although it is not clear whether the anti-inflammatory effect is direct or indirect.

The role of catalase in pulmonary fibrosis.

BACKGROUND: Catalase is preferentially expressed in bronchiolar and alveolar epithelial cells, and acts as an endogenous antioxidant enzyme in normal lungs. We thus postulated epithelial damage would be associated with a functional deficiency of catalase during the development of lung fibrosis. METHODS: The present study evaluates the expression of catalase mRNA and protein in human interstitial pneumonias and in mouse bleomycin-induced lung injury. We examined the degree of bleomycin-induced inflammation and fibrosis in the mice with lowered catalase activity. RESULTS: In humans, catalase was decreased at the levels of activity, protein content and mRNA expression in fibrotic lungs (n = 12) compared to control lungs (n = 10). Immunohistochemistry revealed a decrease in catalase in bronchiolar epithelium and abnormal re-epithelialization in fibrotic areas. In C57BL/6J mice, catalase activity was suppressed along with downregulation of catalase mRNA in whole lung homogenates after bleomycin administration. In acatalasemic mice, neutrophilic inflammation was prolonged until 14 days, and there was a higher degree of lung fibrosis in association with a higher level of transforming growth factor-ß expression and total collagen content following bleomycin treatment compared to wild-type mice. CONCLUSIONS: Taken together, these findings demonstrate diminished catalase expression and activity in human pulmonary fibrosis and suggest the protective role of catalase against bleomycin-induced inflammation and subsequent fibrosis.

Relationship between indoor chemical concentrations and subjective symptoms associated with sick building syndrome in newly built houses in Japan.

OBJECTIVES: This study explored possible associations between chemical substances and sick building syndrome (SBS)-type symptoms of residents living in new houses in Japan. METHODS: We randomly sampled 5,709 newly built conventional homes. In the end, 1,479 residents in 425 households completed a questionnaire survey and agreed to environmental monitoring for indoor aldehydes and volatile organic compounds (VOCs) to be conducted in their homes. If the residents had complained about at least one SBS-related symptom, they were classified as suffering from SBS. Multiple logistic regression analysis was used to select predictive chemical factors of SBS symptoms. RESULTS: About 14% of the subjects suffered from SBS. Many aldehydes and VOCs were associated factors of optical, nasal, and gular symptoms in univariate analysis. After adjustment for other possible risk factors, formaldehyde dose-dependently showed to be a significant risk factor for SBS. Several chemicals had tendency to be associated with SBS symptoms. CONCLUSIONS: Chemicals detected in Japanese newly built houses tend to increase the risk of subjective symptoms in residents suffering from SBS.

Evaluation of pyrogallol-induced cytotoxicity in catalase-mutant escherichia coli and mutagenicity in Salmonella typhimurium.

We evaluated pyrogallol cytotoxicity using Escherichia coli strains that express mammalian catalase gene derived from catalase mutant mice (Cs(b)) and wild-type (Cs(a)), and pyrogallol mutagenicity by Ames test. Pyrogallol was more toxic to Cs(b) rather than to Cs(a) (p < 0.05), while catalase, superoxide dismutase and ascorbic acid decrease the toxic effect. Pyrogallol also showed mutagenic effect (mutagenic index = 3.8 for 10 micromol pyrogallol/plate) while ascorbic acid (19.4% reduction, p < 0.001) and naringin (35.1% reduction, p < 0.001) played a protective role against it. Pyrogallol cytotoxicity and mutagenicity seem to be attributable, at least in part, to reactive oxygen species formation. This study also suggests that newly established catalase mutant E. coli is probably useful in hazard identification of oxidative chemicals.

Nationwide study of sick house syndrome: comparison of indoor environment of newly built dwellings between Sapporo city and Southern areas including those in Honshu and Kyushu.

OBJECTIVES: The aims of this study are to evaluate the associations between residential factors and sick house syndrome (SHS) in a cold region and in a temperate region in Japan. METHODS: A questionnaire survey was conducted on dwellings aged within 7 years from 2003 to 2004 in Sapporo and 'Honshu and northern Kyushu' including Fukushima, Aichi, Osaka, Okayama, and Kitakyushu. The questionnaire consisted of questions about the characteristics of dwellings, manner of living, and health problems of occupants. SHS was identified from the 'yes' responses to the questions on the five items on nasal, throat and respiratory, eyes, skin, and general symptoms that appeared frequently or sometimes at home and improved upon leaving the home. RESULTS: The dwellings with the SHS problem, where at least one inhabitant reported any symptoms of SHS, were 4.7% in Sapporo City and 3.3% in Honshu and northern Kyushu. Regarding ventilation, the principal method was the enforced ventilation in Sapporo and ventilation from open windows in Honshu and northern Kyushu. The sums of five signs of dampness were 0.8 +/- 1.0 in Sapporo and 1.3 +/- 1.0 in Honshu and northern Kyushu. The elevated scores were accompanied by the increased percentage of SHS in both groups. Condensation on both window panes and walls was strongly associated with SHS. CONCLUSIONS: Differences were found in the ventilation method and in the dampness state between Sapporo and Honshu and northern Kyushu. In both groups, the dampness state was associated with SHS.

Relationship of psychological factors with physical activity stage of change in prime-and middle-aged Japanese.

The present study aimed to investigate the status of physical activity and the differences in psychological factors associated with physical activity from the perspective of transtheoretical model stages between prime- and middle-aged Japanese. The study involved 375 prime-aged volunteers (175 men, 200 women) and 557 middle-aged volunteers (247 men, 310 women) living in Kuse, a town in Okayama Prefecture, Japan. We found that the prime-aged men at the preparation stage had significantly higher self-efficacy scores than at the contemplation stage (p<0.01). Middle-aged men had significantly higher self-efficacy scores at the contemplation stage than at the precontemplation stage (p<0.001). Middle-aged women, meanwhile, had significantly higher self-efficacy scores at the maintenance stage than at the action stage (p<0.01), and at the contemplation stage than at the precontemplation stage (p<0.001). The present findings provide valuable information about the differences in psychological factors affecting physical activity between prime-aged and middle-aged community-dwelling Japanese. This information may be useful to health professionals as they develop effective community-based intervention programs for target populations.

Preparation and Characterization of a Polyclonal Antibody against Brominated Protein.

(Di)bromotyrosine is formed by the specific reaction of eosinophil peroxidase and can be used as an eosinophil activation marker. In the present study, an antibody for (di)bromotyrosine in proteins was prepared to investigate the pathogenesis of eosinophil-related diseases such as allergic responses. A rabbit polyclonal antibody was raised against brominated keyhole limpet hemocyanin. The specificity of the antiserum was investigated with an enzyme-linked immunosorbent assay (ELISA). The antiserum recognized brominated bovine serum albumin (BSA) and dibromotyrosine-conjugated BSA. The antiserum also reacted with chlorinated BSA and di-iodotyrosine-conjugated BSA. Moreover, the specificity of the antiserum was investigated using competitive ELISA. Dibromotyrosine and di-iodotyrosine inhibited the recognition of brominated BSA by the antiserum. However, the recognition of brominated BSA by the antiserum was not inhibited by bromotyrosine, chlorotyrosine, iodotyrosine, nitrotyrosine, aminotyrosine, phosphotyrosine, or tyrosine. These results suggested that the epitope of the antiserum is dihalogenated tyrosine. Immunohistochemically, the antiserum stained brominated rat eosinophils but not chlorinated or nitrated eosinophils. In conclusion, an antiserum for dihalogenated protein was prepared. It is expected that the antiserum will be useful for the analysis of the pathogenesis of allergic diseases such as asthma and atopic dermatitis.

Oxidative stress biomarkers and lifestyles in Japanese healthy people.

The urinary concentrations of 8-isoprostane and 8-hydroxy-2'-deoxyguanosine (8-OHdG), which are biomarkers of oxidative stress, were measured in 677 Japanese people without any diseases, and their correlations with lifestyle facotrs, lifestyle-related blood biochemical parameters, and dietary intake of antioxidative vitamins were investigated. The mean urinary concentration of 8-isoprostane and 8-OHdG was 0.58 ng/mg creatinine and 8.43 ng/mg creatinine, respectively. Mean urinary 8-isoprostane was significantly different in terms of age, gender, smoking and alcohol consumption but not different in terms of body mass index (BMI) and exercise. By multiple regression analysis, urinary 8-isoprostane was significantly influenced by smoking and age. On the other hand, mean urinary 8-OHdG showed differences only by age group. Multiple regression analysis revealed that urinary 8-OHdG was significantly influenced by age, smoking, body weight, levels of high-sensitivity C-reactive protein (Hs-CRP) and low density lipoprotein-cholesterol in females, although it was significantly influenced by body weight in males. The present study shows that urinary 8-isoprostane is associated with lipid peroxidation related-lifestyles such as smoking, and urinary 8-OHdG is associated with arteriosclerosis related-factors such as Hs-CRP. Our findings suggest that 8-isoprostane and 8-OHdG appear to be prospective biomarkers for early prediction of lifestyle related-disease risk at the population level.

Symptom definitions for SBS (sick building syndrome) in residential dwellings.

The potential risk factors for sick building syndrome (SBS) in newly built dwellings were investigated. Two different definitions for SBS were used, a narrow definition (symptoms related to home environment and continuously occurring in the last 3 months were regarded as positive) and another relatively broad definition (symptoms related to home environment and either continuously or sporadically occurring in the last 3 months were regarded as positive). With both definitions indoor air chemicals, especially TVOC, and high stress during work were found to be significantly associated with SBS symptoms. Allergic history was more associated with narrow-sense symptoms and odor perception with broad-sense symptoms. The results indicate that the broad definition be preferred to find more potential risk factors.

Association between serum gamma-glutamyltransferase and oxidative stress related factors.

BACKGROUND/AIMS: To investigate the main factors correlated with the serum gamma-glutamyltransferase activity. METHODOLOGY: We measured serum gamma-glutamyltransferase activity in 248 healthy Japanese people and determined its correlations with serum antioxidants, other plasma or serum factors, urinary 8-hydroxydeoxyguanine, and lifestyle factors. RESULTS: The mean serum gamma-glutamyltransferase activity was 29 IU/L. Gamma-glutamyltransferase activities of males and persons older than 45 years were significantly higher than each counterpart. Gamma-glutamyltransferase levels increased significantly with the number of cigarettes smoked per day and the frequency of alcohol consumption except for the persons who did not take alcohol. Additionally, gamma-glutamyltransferase significantly correlated with urinary 8-hydroxydeoxyguanine, and with more blood factors including serum tocopherols, carotenoids, antioxidative enzymes, lipid peroxide, and free fatty acids than urinary 8-hydroxydeoxyguanine did. In multiple regression analyses, gamma-glutamyltransferase had significant associations with retinol, 8-hydroxydeoxyguanine, docosahexaenoic acid, and cigarette smoking. CONCLUSIONS: Our present findings support the hypothesis that gamma-glutamyltransferase can be used as a marker related with oxidative stress.

Development of a new assay for evaluation of l-3,4-dihydroxyphenylalanine cytotoxicity in catalase-mutant Escherichia coli.

The present study aimed to assess whether a newly constructed, catalase-deficient Escherichia coli strain that express mammalian catalase gene could be used to identify oxidative stress-generating chemicals. We tested l-3,4-dihydroxyphenylalanine (l-DOPA), a well-known agent that induces reactive oxygen species. We found that l-DOPA exposure reduced the survival of catalase-mutant E. coli in a dose-dependent manner, especially in the strains with lower catalase activities, implying the usefulness of these strains in assessment of oxidative chemicals.

The half-life of Ascaris lumbricoides prevalence in Japanese school children.

In the present study, we examined the dynamic of school-health-based parasite control and the related socio-economic influences. This is an ecological study based on data from 46 prefectures in Japan. The exponential decay of Ascaris lumbricoides prevalence was calculated by iterative least-squares method. Pearson's correlation and multiple linear regression model analysis were performed to assess the associations between the prevalence of Ascaris lumbricoides in Japanese school children and socio-economic variables such as the prefecture income per capita, the percentage of primary industry, the population density per 1 km2, the diffusion rate of population under water supply, and the percentage of upper secondary school enrollment. The results indicated that the parasite carrier rate was higher in younger students. The half-life of Ascaris lumbricoides prevalence was approximately 3 years with significant variation among prefectures. Multiple regression analyses showed that the decrease of infection in elementary and lower secondary school children had a significant positive association with primary industry and a significant negative association with prefecture income per capita. The school-health-based parasite intervention differs by prefecture and has changed over time according to the respective prefectural stage of economic development.

Effects of mask fitness and worker education on the prevention of occupational dust exposure.

To decrease the incidence of pneumoconiosis, we examined dust protective mask performance and its relation to pulmonary function as well as the effects of worker education on the proper wearing of masks. One hundred and seventy-eight workers from 15 factories subject to dust exposure participated in this study. All participants were interviewed to obtain relevant personal information and underwent both a mask leakage and a pulmonary function test. The mask leakage was expressed as a percentage, with under 10% leakage indicating that the dust protective mask worked efficiently. In addition, 23 workers from 2 factories were educated on how to wear masks properly. The average mask leakage was 24.3%, and 58% of workers wore ineffective masks. Though pulmonary function was almost normal, the percent vital capacity (%VC) tended to be lower depending on the mask leakage. Mask education, which was very easy and took only a short time, dramatically decreased average mask leakage from 32.1% to 10.5% (p0.001). Educating workers to wear masks properly might prevent the worsening of pulmonary function in response to dust exposure. Appropriate mask fitness by education could be useful in preventing the development of pneumoconiosis.

Disposition of protein-bound 3-nitrotyrosine in rat plasma analysed by a novel protocol for HPLC-ECD.

3-Nitrotyrosine (NTyr) is considered as a biomarker of the generation of reactive nitrogen species (RNS). However, it is still difficult to determine its concentration in biological samples. To develop a reliable and high-throughput method, we optimized the conditions for high performance liquid chromatography and electrochemical detection (HPLC-ECD). The best separation of NTyr was achieved using a highly acidic mobile phase (pH 2.5). The concentration of protein-bound NTyr in plasma protein was 593.6 +/- 53.8 fmol/mg in rats treated with lipopolysaccharide (LPS) and 114.4 +/- 27.6 fmol/mg in control. After intravenous administration of in vitro-nitrated plasma protein, NTyr concentration decreased; the half-life was 63.4 +/- 16.8 h. Consistently, protein-bound NTyr concentration in plasma after LPS treatment declined gradually, but was detectable for 1 week. Our protocol is reproducible and suitable for analysing multiple clinical samples to study RNS production in vivo.

Clinical application of Clostridium botulinum type A neurotoxin purified by a simple procedure for patients with urinary incontinence caused by refractory destrusor overactivity.

Type A neurotoxin of Clostridium botulinum was purified by a simple procedure using a lactose gel column. This procedure was previously reported for type B neurotoxin. Hemagglutinin-positive toxins (19S and 16S) were bound to the column under acid conditions, and the neurotoxin alone was dissociated from these hemagglutinin-positive toxins by changing the pH of the column to an alkaline condition. The toxicity of this purified toxin preparation was retained for at least 1 year at -30 degrees C by supplementing it with either 0.1% albumin or 0.05% albumin plus 1% trehalose. This preparation was used to treat 18 patients with urinary incontinence caused by refractory idiopathic and neurogenic detrusor overactivity; 16 of the patients showed excellent improvement. Improvements started within 1 week after injection in most cases and lasted 3-12 months [corrected]

Unmetabolized VOCs in urine as biomarkers of low level exposure in indoor environments.

This study aimed to test the possible use of unmetabolized volatile organic compounds (VOCs) in urine as biomarkers of low-level indoor environmental exposure. Twenty-four subjects in 13 dwellings in a prefecture of Japan participated in this study. Air samples of the breathing zone were collected in the living room and bedroom, along with spot urine samples (before bedtime and first morning voids). Toluene, ethylbenzene, xylene isomers, styrene and p-dichlorobenzene in the air and urine samples were measured by gas chromatography/mass spectrometry. For the 21 subjects without solvent exposure at work, there were significant correlations between the time-weighted average air concentrations in the bedroom and morning urinary concentrations for toluene, o-xylene, total xylene and p-dichlorobenzene (correlation coefficients of 0.54, 0.61, 0.56 and 0.84, respectively). Multiple linear regression analysis showed only air VOCs in the bedroom influenced the morning urinary VOC concentrations. We concluded that unmetabolized VOCs in the urine can provide a reliable biological indicator for air VOC exposures in non-occupational environments.

The effects of caregiving resources on the incidence of depression over one year in family caregivers of disabled elderly.

The purpose of the study was to investigate the over-time effects of physical, psychological and social resources on the incidence of depression in family caregivers of the disabled elderly. Data were collected twice at a one-year interval from 1,141 primary caregivers of a disabled older person in an urban area of Japan using a self-reported questionnaire survey. The questionnaire included physical health as an indicator of physical resources, caregiving satisfaction and intention to care as indicators of psychological resources, and instrumental and emotional support network and formal home care service utilization as indicators of social resources. The mental health outcome measure was the General Health Questionnaire 12-item version (GHQ-12). Complete data on 235 non-depressed female caregivers were separated into 3 groups according to the relationship type (wife, daughter and daughter-in-law) and analyzed separately. Multivariate logistic regression models controlling for duration of caregiving, care-recipient's gender, ADL dependency and behavioral problems demonstrated that significant predictors of depression were caregiving satisfaction and intention to care in wives, caregiving satisfaction in daughters, and physical health and emotional support network in daughters-in-law. Noteworthy, intention to care increased the risk of depression in wives, while decreasing the risk of depression in daughters-in-law. The findings indicate that the effects of caregivers' resources on mental health may differ by relationship type.

Biochemical characterization of reactive nitrogen species by eosinophil peroxidase in tyrosine nitration.

It is well known that eosinophils are involved in tyrosine nitration. In this study, we evaluated tyrosine nitration by rat eosinophils isolated from peritoneal fluid and constituent eosinophils in the stomach. Rat peritoneal eosinophils activated with 1 microM phorbol myristate acetate (PMA) and 50 microM NO2- showed immunostaining for nitrotyrosine only in smaller cells, despite the fact that eosinophils are capable of producing superoxide (O2*-) Free tyrosine nitrating capacity after incubation with PMA and NO2- was 4-fold higher in eosinophils than in neutrophils. Catalase and alpha- and gamma-tocopherol inhibited free tyrosine nitration by reactive nitrogen species from eosinophils but not that by peroxynitrite. Superoxide dismutase augmented free tyrosine nitration by activated eosinophils and peroxynitrite. The concentration of nitric oxide released from eosinophils was relatively low (0.32 microM/10(6) cells/h) and did not contribute to the formation of nitrotyrosine. On the other hand, most constituent eosinophils constituent in the rat stomach stimulated by PMA and NO2- showed tyrosine nitration capacity. These results suggest that intact cells other than apoptotic-like eosinophils eluted in the intraperitoneal cavity could not generate reactive species responsible for nitration by a peroxidase-dependent mechanism. In contrast, normal eosinophils in the stomach were capable of nitration, suggesting that the characteristics of eosinophils in gastric mucosa are different from those eluted in the peritoneal cavity.