The effect of mask fit test on the association between the concentration of metals in biological samples and the results of time-weighted average personal exposure: A study on Japanese male welders.

OBJECTIVES: The mask fit test confirms whether the wearing condition of the wearer's face and the facepiece of the respirators are used appropriately. This study aimed to examine whether the results of the mask fit test affect the association between the concentration of metals related to welding fumes in biological samples and the results of time-weighted average (TWA) personal exposures. METHODS: A total of 94 male welders were recruited. Blood and urine samples were obtained from all participants to measure the metal exposure levels. Using personal exposure measurements, the 8-h TWA (8 h-TWA) of respirable dust, TWA of respirable Mn, and 8-h TWA of respirable Mn were calculated. The mask fit test was performed using the quantitative method specified in the Japanese Industrial Standard T8150:2021. RESULTS: Fifty-four participants (57%) passed the mask fit test. Only in the Fail group of the mask fit test, it was observed that blood Mn concentrations be positively associated with the results of TWA personal exposure after adjusting for multivariate factors (8-h TWA of respirable dust; coefficient, 0.066; standard error (SE), 0.028; P = 0.018, TWA of respirable Mn: coefficient, 0.048; SE, 0.020; P = 0.019, 8 h-TWA of respirable Mn: coefficient, 0.041; SE, 0.020; P = 0.041). CONCLUSIONS: The results clarify that welders with high concentrations of welding fumes in their breathing air zone are exposed to dust and Mn if there is leaking air owing to the lack of fitness between respirators and the wearer's face when using human samples in Japan.

Associations between welding fume exposure and neurological function in Japanese male welders and non-welders.

OBJECTIVES: There are some studies reporting the association between (manganese [Mn]) exposure to welding fume and neurological dysfunction. This study examined the relationship between Mn exposure and neurological behavior in Japanese male welders and non-welders using biological samples, which to date has not been assessed in Japan. METHODS: A total of 94 male welders and 95 male non-welders who worked in the same factories were recruited. The blood and urine samples were obtained from all the participants to measure Mn exposure levels. Neurological function tests were also conducted with all participants. The sampling of the breathing air zone using a personal sampler was measured for welders only. RESULTS: The odds ratios (ORs) for the Working Memory Index (WMI) scores were significantly higher among all participants in the low blood Mn concentration group than those in the high blood Mn concentration group (OR, 2.77; 95% confidence interval [CI], 1.24, 6.19; P = .013). The association of WMI scores and blood Mn levels in welders had the highest OR (OR, 3.73; 95% CI, 1.04, 13.38; P = .043). Although not statistically significant, a mild relationship between WMI scores and blood Mn levels was observed in non-welders (OR, 2.09; 95% CI, 0.63, 6.94; P = .227). CONCLUSIONS: The results revealed a significant positive relationship between blood Mn and neurological dysfunction in welders. Furthermore, non-welders at the same factories may be secondarily exposed to welding fumes. Further research is needed to clarify this possibility.

Evaluation of chemical-specific IgG antibodies in male workers from a urethane foam factory.

BACKGROUND: Plastic resins are complex chemicals that contain toluene diisocyanate (TDI) and/or trimellitic anhydride (TMA), which cause occupational allergies (OA), including respiratory allergies. Serum IgGs against TDI and TMA have been suggested as potential markers of the exposure status and as exploring cause of OA. Although TDI-specific IgG has been examined for suspected OA, TMA-specific IgG is not commonly evaluated in a urethane foam factory. This study therefore investigated both TDI- and TMA-specific IgGs in suspected OA patients and to evaluate the usefulness of the measurement of multiple chemical-specific IgG measurement for practical monitoring. METHODS: Blood samples were collected from two male workers who developed respiratory allergies supposedly caused by occupational exposure to TDI and/or TMA for the presence of TDI- and TMA-specific IgGs. In addition, blood samples from 75 male workers from a urethane foam factory, along with 87 male control subjects, were collected in 2014 and tested for the same IgGs in 2014. The presence and levels of TDI- and TMA-specific serum IgGs were measured using dot blot assays. RESULTS: We found that controls had mean concentrations of TDI- and TMA-specific IgGs of 0.98 and 2.10 µg/mL, respectively. In the two workers with respiratory allergies, the TDI-specific IgG concentrations were 15.6 and 9.51 µg/mL, and TMA-specific IgG concentrations were 4.56 and 14.4 µg/mL, which are clearly higher than those in controls. Mean concentrations of TDI- and TMA-specific IgGs in the factory workers were 1.89 and 2.41 µg/mL, respectively, and are significantly higher than those of the controls (P < 0.001 and P < 0.026 for TDI- and TMA-specific IgGs, respectively). CONCLUSION: The workers suspected of OA showed an evidently high level of TDI- and TMA-specific IgG, and these levels in workers at the urethane foam factory were also significantly higher than those in controls. In conclusion, the measurement of TDI- and TMA-specific IgG among workers using plastic resins is helpful to monitor their exposure status.

Changes of Working Responsibilities and Intentions of Industrial Physicians (Graduates of University of Occupational and Environmental Health, Japan) in a Comparison Between 2001, 2008 and 2015 Questionnaire Analyses.

For the purpose of understanding the current conditions of the duties of industrial physicians and the consciousness of graduates of the University of Occupational and Environmental Health, Japan (UOEH) engaged in industry, we performed a questionnaire survey in July, 2001 and July, 2008 and reported the results (J UOEH 2009 31: 281-91). A similar survey was carried out in July, 2015. We dispatched the questionnaire to industrial physicians and physicians in occupational health organizations who had graduated from UOEH and got the replies. The investigation asked about their career, their activities, and how they thought about their duties. We compared the three years and got the following results: 1) The ratio of respondents who were satisfied with the salary or official post was 38.3, 48.1, 65.4% in each investigation, respectively. 2) The ratio of the respondents whose official post and rank would not be promoted in the future was 25.3, 28.4, 32.3%, respectively. 3) The ratio of respondents satisfied with the relationship with the superior and the industrial health staff was 70.8, 80.3, 86.1%, respectively. The investigation performed every seven years since July, 2001 showed that the ratio of the graduates of UOEH whose official post and rank would not be promoted in the future had gradually increased, while the ratio of graduates who were satisfied with the relationship with the superior and the industrial health staff had also gradually increased.

Comparison of IgG against plastic resin in workers with and without chemical dermatitis.

BACKGROUND: There are many chemical sensitizers which cause allergy in the surrounding environment. However, the identification of substances causing allergy is difficult. We developed a new method to detect IgG which reacts against many kinds of chemical-human serum albumin (HSA) adducts at the same time. In this study, the diagnostic significance of the IgG was studied among workers of a company where a mass outbreak of chemical dermatitis had occurred after changing a plastic resin to a new one. METHODS: Eleven workers who handled the new plastic resin and suffered from dermatitis (case) and 9 workers who also handled the same resin in the same company but were free from dermatitis (control) were the subjects. Immunological dot blotting was carried out to detect serum IgG using originally prepared diagnostic antigens, comprising a mixture of HSA and the plastic resin or its components under various conditions. RESULTS: IgG against the plastic resin in use was detected in all workers who suffered from dermatitis. The prevalence of the IgG against the plastic resin was significantly higher in workers with than in those without dermatitis. On the other hand, IgG against its components (bisphenol A diglycidyl ether, m-xylylenediamine and butyl 2,3-epoxypropyl ether) was detected in a few workers with dermatitis. DISCUSSION: This suggests that IgG against chemical-HSA adduct reflects not only exposure but also causative chemicals of dermatitis. Our method to use a material itself as a hapten is practical and useful in the occupational field. CONCLUSION: It is suggested that IgG against chemicals is a useful marker of chemicals inducing dermatitis.

ALDH2 Deficiency Promotes Ethanol-Induced Gut Barrier Dysfunction and Fatty Liver in Mice.

BACKGROUND: Acetaldehyde, the toxic ethanol (EtOH) metabolite, disrupts intestinal epithelial barrier function. Aldehyde dehydrogenase (ALDH) detoxifies acetaldehyde into acetate. Subpopulations of Asians and Native Americans show polymorphism with loss-of-function mutations in ALDH2. We evaluated the effect of ALDH2 deficiency on EtOH-induced disruption of intestinal epithelial tight junctions and adherens junctions, gut barrier dysfunction, and liver injury. METHODS: Wild-type and ALDH2-deficient mice were fed EtOH (1 to 6%) in Lieber-DeCarli diet for 4 weeks. Gut permeability in vivo was measured by plasma-to-luminal flux of FITC-inulin, tight junction and adherens junction integrity was analyzed by confocal microscopy, and liver injury was assessed by the analysis of plasma transaminase activity, histopathology, and liver triglyceride. RESULTS: EtOH feeding elevated colonic mucosal acetaldehyde, which was significantly greater in ALDH2-deficient mice. ALDH2(-/-) mice showed a drastic reduction in the EtOH diet intake. Therefore, this study was continued only in wild-type and ALDH2(+/-) mice. EtOH feeding elevated mucosal inulin permeability in distal colon, but not in proximal colon, ileum, or jejunum of wild-type mice. In ALDH2(+/-) mice, EtOH-induced inulin permeability in distal colon was not only higher than that in wild-type mice, but inulin permeability was also elevated in the proximal colon, ileum, and jejunum. Greater inulin permeability in distal colon of ALDH2(+/-) mice was associated with a more severe redistribution of tight junction and adherens junction proteins from the intercellular junctions. In ALDH2(+/-) mice, but not in wild-type mice, EtOH feeding caused a loss of junctional distribution of tight junction and adherens junction proteins in the ileum. Histopathology, plasma transaminases, and liver triglyceride analyses showed that EtOH-induced liver damage was significantly greater in ALDH2(+/-) mice compared to wild-type mice. CONCLUSIONS: These data demonstrate that ALDH2 deficiency enhances EtOH-induced disruption of intestinal epithelial tight junctions, barrier dysfunction, and liver damage.

[University of Occupational and Environmental Health, Japan: 2013 alumni physician statistics].

The University of Occupational and Environmental Health, Japan (UOEH) is a publically funded medical school for occupational health physician and researchers. All students are funded through six years of medical school and commit to a nine-year health services of occupational medicine after graduation. Between 1984 and 2013, the number of physicians graduating from UOEH was 2,875. Of these, 473 were medical residents in our postgraduate residency programs and 526 were occupational health physicians affiliated with different companies. A total of 252 graduates became UOEH research/teaching staff, 219 obtained employment as physicians at Rousai hospital (hospital operated by Japan Labour Health and Welfare Organization), and 84 entered industrial hygiene and health check organizations. UOEH alumni are distributed throughout Japan in large workplaces/ business establishments. Many physicians continued in their job after the nine-year obligation, thus contributing to the increasing number of occupational health physicians during recent decades. We suggest that funding and postgraduate residency programs contribute to the increasing numbers of physicians, but further analysis needs to be done.

Effect of Korean pear (Pyruspyrifolia cv. Shingo) juice on hangover severity following alcohol consumption.

Korean pear has been used as a traditional prophylactic agent for alcohol hangover. However, its mechanism was not investigated in human yet. Therefore, we performed a randomized single blind crossover trial with 14 healthy young men to examine effects of Korean pear juice on alcohol hangover. All subjects consumed 540 ml of spirits (alcohol conc. 20.1 v/v%) after 30 min from the intervention, i.e. placebo or Korean pear juice treatment. Blood and urine specimens were collected in time-courses (9 time-points for 15 h after alcohol consumption). The total and average of hangover severity were alleviated to 16% and 21% by Korean pear juice at 15 h after the alcohol consumption, respectively (ps<0.05). Particularly, 'trouble concentrating' was significantly improved by the pear juice treatment (p<0.05). Impaired memory, and sensitivity to light and sound were significantly improved by Korean pear juice among the subjects with ALDH2*1/*1 or ALDH2*1/*2 genotypes (ps<0.05) but not in the subjects with ALDH2*2/*2 genotype. In addition, the pear juice treatment lowered levels of blood alcohol (p<0.01). Therefore, Korean pear juice may alleviate alcohol-hangover and its detoxification of alcohol seems to be modified by the genetic variation of ALDH2.

Disruption of aldehyde dehydrogenase 2 gene results in altered cortical bone structure and increased cortical bone mineral density in the femoral diaphysis of mice.

INTRODUCTION: Aldehyde dehydrogenase 2 (ALDH2) degrades acetaldehyde produced by the metabolism of alcohol. The inactive ALDH2 phenotype is prevalent in East Asians, and an association between this ALDH2 polymorphism and osteoporosis has been reported. In our previous study, we found that alcohol consumption results in decreased trabecular bone volume in aldh2 knockout (aldh2(-/-)) mice compared with the volume in wild-type (aldh2(+/+)) mice. However, the effect of aldh2 gene on the skeletal phenotype in the absence of alcohol consumption remains unknown. The aim of this study was to clarify the effect of aldh2 disruption on femoral bone structure and dynamics in aldh2-disrupted mice in the absence of alcohol consumption. MATERIALS AND METHODS: We examined aldh2(-/-) and aldh2(+/+) mice at the ages of 4, 8 and 12weeks. The femoral bone length and bone mineral density (BMD) were measured using peripheral quantitative computed tomography. The mechanical strength was assessed by the three-point bending test at 12weeks, and cortical bone histomorphometry at the femur diaphysis was performed at all three time points. Osteogenic activities in aldh2(-/-) and aldh2(+/+) mice were assessed by osteoblast culture from calvariae of the neonatal mice. Bilateral femoral and tibial bones containing no bone marrow cells of 8-week-old mice were used for analysis of mRNA expression. In addition, mRNA expression in aldh2(-/-) and aldh2(+/+) mice after tail suspension or climbing exercise for 7days from 8weeks was analyzed to clarify the response to mechanical loading. RESULTS: At 12weeks, there were no significant differences in femoral bone length, trabecular BMD in the distal metaphyses of the femurs, or mechanical strength between aldh2(-/-) and aldh2(+/)(+) mice, whereas cortical BMD and cortical thickness were significantly increased and cross-sectional area and bone marrow area were significantly decreased in the femoral diaphysis of aldh2(-/-) mice relative to the corresponding values in aldh2(+/+) mice. At 8weeks, bone formation rate and mineral apposition rate on the periosteal and endocortical surfaces were significantly increased in aldh2(-/-) mice relative to the rates in aldh(+/+) mice. Calvarial osteoblast culture study revealed that the percentage of alkaline phosphatase stained cells was significantly higher in aldh2(-/-) mice compared to that in aldh(+/+) mice. Quantitative real-time RT-PCR revealed a significant increase in the expressions of bmp2, osterix, runx2, and col1a1 mRNA in aldh2(-/-) mice, along with an increase in the expression of wnt5a mRNA and the lrp5/sost mRNA ratio. The mRNA expressions of bmp2, osterix, runx2 and pthr in aldh2(-/-) mice were significantly decreased after climbing exercise compared to those in the control, although the mRNA expressions of bmp2, osterix, runx2 were not significantly decreased and pthr mRNA expression was increased in aldh(+/+) mice after climbing exercise. CONCLUSION: Our results show that disruption of aldh2 gene resulted in altered cortical bone structure and dynamics in mice. Cross-sectional area was decreased. Cortical BMD was increased owing to the promotion of cortical bone formation on the periosteal and endocortical surfaces of the femoral diaphysis. The possible mechanisms underlying altered cortical bone structure in aldh2(-/-) mice were gene-related higher osteogenic activity of osteoblasts and weakened osteogenice response to mechanical loading in growth period.

[Turnover of full-time occupational physicians in Japan in the period 2002-2008: a component model survey].

OBJECTIVE: Recently, the number of occupational physicians has greatly increased compared to other types of physician in Japan, and the number of unfilled job vacancies remains high, suggesting a higher turnover of occupational physicians. Job turnover and seniority are important indices for measuring the balance of vacancies and applicants, as well as for improving occupational health services; however, job turnover and career moves of occupational physicians are currently not known. METHOD: Based on a component model study of physicians, dentists and pharmacists, we made a component model of 4 levels (national, prefectural, urban, and municipal levels) and estimated the turnover and regional migration of occupational physicians. As a reference for the component models, we used the 2008/2006 cross-tabulation data of each type of physician published by the Ministry of Health, Labour and Welfare. RESULTS: The municipality level component model fitted the data best. The increase in occupational physicians for the 2 yr was 283-348, and the decrease was 202-222, indicating that 55-65% of occupational physicians quit their post within 2 yr. CONCLUSIONS: The propensity for short tenure is observed not only in occupational medicine, but also in emergency and rehabilitation medicine. It is suspected that 80% of new occupational physicians, except those graduating from the University of Occupational and Environmental Health, quit their positions within two years. This is a remarkably short tenure period compared to the 5.6 yr average seniority of physicians reported in the Basic Survey of Wage Structure. The reasons for the high job turnover of occupational physicians are thought to be unrelated to income or license renewal. We need to survey the actual reasons for the short tenure of occupational physicians to provide insights into lifetime education and career organization of occupational physicians.

The effect of ethanol on the formation of N2-ethylidene-dG adducts in mice: implications for alcohol-related carcinogenicity of the oral cavity and esophagus.

The present study aimed to experimentally confirm that long-term alcohol drinking causes a high risk of oral and esophageal cancer in aldehyde dehydrogenase 2 (ALDH2)-deficient individuals. Aldh2 knockout mice, an animal model of ALDH2-deficiency, were treated with 8% ethanol for 14 months. Levels of acetaldehyde-derived DNA adducts were increased in esophagus, tongue and submandibular gland. Our finding that a lack of Aldh2 leads to more DNA damage after chronic ethanol treatment in mice supports epidemiological findings on the carcinogenicity of alcohol in ALDH2-deficient individuals who drink chronically.

Reduced bone formation in alcohol-induced osteopenia is associated with elevated p21 expression in bone marrow cells in aldehyde dehydrogenase 2-disrupted mice.

INTRODUCTION: High consumption of alcohol is one of the risk factors for osteoporosis. Approximately 45% of Chinese and Japanese individuals have the inactive aldehyde dehydrogenase 2 (Aldh2) phenotype. The absence of the ALDH2*2 allele is found to adversely influence the risk of osteoporosis. The aim of this study is to clarify the effects of alcohol consumption on osteoblast differentiation in bone marrow and trabecular bone formation in Aldh2-disrupted mice. MATERIALS AND METHODS: Seven-week-old male Aldh2 knockout mice (Aldh2(-/-)) and wild-type (Aldh2(+/+)) mice were fed with water (groups Aldh2(-/-)/Wa and Aldh2(+/+)/Wa) or with 5% ethanol (groups Aldh2(-/-)/Al and Aldh2(+/+)/Al) for 4 weeks. At the age of 12 weeks, bone histomorphometry was performed at the secondary spongiosa of the tibias. Bone marrow cells from the bilateral femurs and tibias were used for mRNA expression analysis. RESULTS: Histomorphometrical study revealed that trabecular bone was significantly reduced in the Aldh2(-/-)/Al group compared with that in the Aldh2(-/-)/Wa and Aldh2(+/+)/Wa groups. Bone formation rate was significantly decreased in Aldh2(-/-)/Al compared with the other three groups. Quantitative RT-PCR revealed a significant decrease in type I collagen, osterix, osteopontin, and osteocalcin mRNA expressions in Aldh2(-/-)/Al compared with Aldh2(-/-)/Wa. In bone marrow cell cultures, mineralized nodule formation in Aldh2(-/-)/Al was significantly decreased compared with that in Aldh2(+/+)/Wa and Aldh2(-/-)/Wa, while PAK18, a p21-activated kinase inhibitor, recovered the decreased mineralized nodule formation in Aldh2(-/-)/Al. CONCLUSION: Alcohol consumption suppressed the differentiation and mineralization of osteoblasts and then reduced trabecular bone formation and bone volume in association with the elevated p21 expression in bone marrow cells, especially in aldehyde dehydrogenase 2-disrupted mice.

Formation of acetaldehyde-derived DNA adducts due to alcohol exposure.

Epidemiological studies have identified chronic alcohol consumption as a significant risk factor for cancers of the upper aerodigestive tract, including the oral cavity, pharynx, larynx and esophagus, and for cancer of the liver. Ingested ethanol is mainly oxidized by the enzymes alcohol dehydrogenase (ADH), cytochrome P-450 2E1 (CYP2E1), and catalase to form acetaldehyde, which is subsequently oxidized by aldehyde dehydrogenase 2 (ALDH2) to produce acetate. Polymorphisms of the genes which encode enzymes for ethanol metabolism affect the ethanol/acetaldehyde oxidizing capacity. ADH1B*2 allele (ADH1B, one of the enzyme in ADH family) is commonly observed in Asian population, has much higher enzymatic activity than ADH1B*1 allele. Otherwise, approximately 40% of Japanese have single nucleotide polymorphisms (SNPs) of the ALDH2 gene. The ALDH2 *2 allele encodes a protein with an amino acid change from glutamate to lysine (derived from the ALDH2*1 allele) and devoid of enzymatic activity. Neither the homozygote (ALDH2*2/*2) nor heterozygote (ALDH2*1/*2) is able to metabolize acetaldehyde promptly. Acetaldehyde is a genotoxic compound that reacts with DNA to form primarily a Schiff base N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dG) adduct, which may be converted by reducing agents to N(2)-ethyl-2'-deoxyguanosine (N(2)-ethyl-dG) in vivo, and strongly blocked translesion DNA synthesis. Several studies have demonstrated a relationship between ALDH2 genotypes and the development of certain types of cancer. On the other hand, the drinking of alcohol induces the expression of CYP2E1, resulting in an increase in reactive oxygen species (ROS) and oxidative DNA damage. This review covers the combined effects of alcohol and ALDH2 polymorphisms on cancer risk. Studies show that ALDH2*1/*2 heterozygotes who habitually consume alcohol have higher rates of cancer than ALDH2*1/*1 homozygotes. Moreover, they support that chronic alcohol consumption contributes to formation of various DNA adducts. Although some DNA adducts formation is demonstrated to be an initiation step of carcinogenesis, it is still unclear that whether these alcohol-related DNA adducts are true factors or initiators of cancer. Future studies are needed to better characterize and to validate the roles of these DNA adducts in human study.

Effects of acetaldehyde inhalation in mitochondrial aldehyde dehydrogenase deficient mice (Aldh2-/-).

Human body might be exposed to acetaldehyde from smoking or occupational environment, which is known to be associated with cancer through the formation of DNA adducts, in particular, N2-ethylidene-2'- deoxyguanosine (N2-ethylidene-dG). Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that contribute to the detoxification of acetaldehyde in human body. In this study, wild type (Aldh2+/+) and Aldh2KO (Aldh2-/-) mice were exposed to the air containing 0, 125, 500 ppm acetaldehyde for 2 weeks. After inhalation, levels of N2- ethylidene-dG in the chromosomal DNA were analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS). N2-ethylidene-dG levels in livers of Aldh2-/- mice were always lower than those of Aldh2+/+ mice, suggesting that Aldh2 deficiency might cause the induction of acetaldehyde metabolizing enzymes in the liver such as P450s. The differences between Aldh2-/- and Aldh2+/+ mice were greater in the order of nasal epithelium > lung > dorsal skin, suggesting that nasal epithelium and lung are the major target sites for acetaldehyde. Acetaldehyde inhalation may cause a high risk in nasal epithelium and lung cancers for individuals with inactive ALDH2.

[Necessary number of dedicated industrial physicians in Japan: evaluated from the establishment and enterprise census].

The required number of dedicated industrial physicians has been enacted by the Ministry of Health, Labour and Welfare in Japan. However, the number of workplaces requiring an appointment of industrial physicians is unknown, because of the lack of official publication from the Ministry of Health, Labor and Welfare. The Bureau of Statistics in the Ministry of Internal Affairs and Communications has published the Establishment and Enterprise Census. Based on this statistical data, we estimated the minimal necessary number of dedicated industrial physicians in Japan. There are 1,228 workplaces where 1,000 workers or more are regularly employed. Considering that the number of hazardous workplaces where 500-999 workers are regularly employed is around 1,500, it is estimated that at least 2,000-2,500 dedicated industrial physicians are required in Japan.

Characteristics of aldehyde dehydrogenase 2 (Aldh2) knockout mice.

Acetaldehyde is an intermediate of ethanol oxidation. It covalently binds to DNA, and is known as a carcinogen. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes acetaldehyde. Approximately 45% of Chinese and Japanese individuals have the inactive ALDH2 genotypes (ALDH2*2/*2 and ALDH2*1/*2), and Aldh2 knockout mice appear to be a valid animal model for humans with inactive ALDH2. This review gives an overview of published studies on Aldh2 knockout mice, which were treated with ethanol or acetaldehyde. According to these studies, it was found that Aldh2 -/- mice (Aldh2 knockout mice) are more susceptible to ethanol and acetaldehyde-induced toxicity than Aldh2 +/+ mice (wild type mice). When mice were fed with ethanol, the mortality was increased. When they were exposed to atmospheres containing acetaldehyde, the Aldh2 -/- mice showed more severe toxic symptoms, like weight loss and higher blood acetaldehyde levels, as compared with the Aldh2 +/+ mice. Thus, ethanol and acetaldehyde treatment affects Aldh2 knockout mice more than wild type mice. Based on these findings, it is suggested that ethanol consumption and acetaldehyde inhalation are inferred to pose a higher risk to ALDH2-inactive humans. These results also support that ALDH2-deficient humans who habitually consume alcohol have a higher rate of cancer than humans with functional ALDH2.

[Changes of working responsibilities and intentions of industrial physicians who are graduates of University of Occupational and Environmental Health, Japan, in 2001 and 2008 questionnaire analyses].

To investigate the working responsibilities and intentions of industrial physicians who are graduates of University of Occupational and Environmental Health, Japan (UOEH), we performed a questionnaire survey in 2008 and compared the results with those of 2001. To industrial physicians belonging to a company or occupational health organization, we dispatched a questionnaire and asked them to return it with an answer. The items to investigate included their careers and working activities and their intentions to their responsibilities. We obtained the following results. 1. The dissatisfaction with salary and official position was mostly reduced to 24.7% from 29.2% and 19.7% from 29.9%. 2. The practical duty of medical examination of workers and the subsequent management was decreased to 51.5% from 74.7%, while mental health support and the advice on severe health issues such as excess work death were increased to 85.6% from 54.5% and 32.4% from 22.1%. 3. Concerning the working status of industrial physicians, the ratio of the answer of "The industrial physician duties are not positively evaluated by his or her company" was decreased to 23.1% from 32.5%. The investigation of 2008 revealed that the situation of UOEH graduated industrial physicians was substantially improved concerning the dissatisfaction with salary and official position, as compared with the study of 7 years before.

Cholinergic alterations following alcohol exposure in the frontal cortex of Aldh2-deficient mice models.

We investigated the effects of alcohol (EtOH) and acetaldehyde (ACe) on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the frontal cortex of Aldh2-/- (KO) mice. KO mice were used as models of Aldh2-deficient humans to examine ACe effects. Brain samples were analyzed at 40 and 120 min after 2- and 4-g/kg intraperitoneal EtOH administration by RT-PCR and Western blot. Wild-type (WT) mice exhibited a remarkable decrease in ChAT and AChE mRNA expression at both time points only after 4-g/kg EtOH treatment compared with the naive control, whereas KO mice showed a considerable reduction in cholinergic markers after 2- and 4-g/kg EtOH treatment. The 4-g/kg EtOH-induced decrease in ChAT and AChE RNA expression at both time points was significantly greater than that in obtained with the administration of 2-g/kg at 40 min in WT mice. KO mice showed a significant difference in ChAT mRNA at 40 min between the EtOH groups. The findings regarding the ChAT mRNA levels are consistent with the results of Western blot in both types of mice, with some exceptions. EtOH-induced ChAT and AChE expression in KO mice was significantly lower than that in WT mice. This genotype effect occurred mostly at 40 min after EtOH dosing. Only ACe was quantified in the brains of KO mice, whereas EtOH was detected in both types of mice in vivo. These results suggest that EtOH and ACe combined or high EtOH alone alters cholinergic markers expression via changes in presynaptic and postsynaptic processes in the mice frontal cortex, thus indicating that central cholinergic neurons may be sensitive to EtOH and ACe.

Hazardous environmental factors enhance impairment of liver function in HBV and HCV hepatitis.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) often cause chronic liver disease. We hypothesized that environmental factors adversely impact the liver function in workers with these types of hepatitis. We used liver function tests including aspartate aminotransferase, alanine aminotransferase, and g -glutamyltransferase to evaluate whether hazardous work conditions increase the incidence of chronic liver disease among HBV and HCV infected workers. Organic solvent, night work, visual display terminals, dust, lead, vibrations, and ionizing radiation all led to increased impairment of liver function in patients with hepatitis as compared to the control group that were not exposed to such agents. Therefore, hazardous working conditions have to be carefully considered in the progress of chronic liver disease in workers infected with HBV and HCV.

Application of tryptophan fluorescence to assess sensitizing potentials of chemicals.

There are too many chemical substances around our living space. However, the toxicity of most of them has not been reported, especially regarding their sensitizing potentials. We aimed to develop a simple in vitro method to quantitatively predict the sensitizing potentials of chemicals by measuring the fluorescence of chemical-human serum albumin (HSA) complexes. HSA was treated with test chemicals and then analyzed by tryptophan fluorescence and protein concentration measurement. Four commonly designated sensitizers, two possible sensitizers, and two nonsensitizers were examined using the tryptophan fluorescence assay. HSA fluorescence at 280 nm excitation and 340 nm emission was reduced by toluene 2,4-diisocyanate (TDI), dose dependently. The addition of TDI immediately reduced the fluorescence, and it was stable for 6 h to 21 days after treatment, with a slight decrease. The reduction of HSA fluorescence by chemicals was in the order: commonly designated sensitizers > possible sensitizers > nonsensitizers. Chemical treatment at 0.05 and 0.5 mM led to optimal separation among the three groups. o-Phthalaldehyde (OPA), which has not been evaluated regarding its sensitization potential by any of the authorized organizations, reduced HSA fluorescence as much as the commonly designated sensitizer at final concentrations of the chemical of 0.05 and 0.5 mM. According to our method, OPA is evaluated as a commonly designated sensitizer. The treatment of all test chemicals did not lead to marked differences in the total protein concentrations by either the Lowry or the Bradford method. The assay utilizing tryptophan fluorescence loss of HSA after chemical treatment is a promising method to evaluate the sensitizing potentials of chemicals.