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Objectives: We aimed to develop a method to determine workers' personal exposure levels to N‐(phosphonomethyl)glycine (glyphosate) for their risk assessments. Methods: The proposed method was assessed as follows: recovery, stability of samples on storage, method limit of quantification, and reproducibility. Glyphosate in air was sampled using an air‐sampling cassette containing a glass fiber filter. Ultrapure water was used to extract glyphosate from sampler filters. After derivation with 9‐fluorenylmethyloxycarbonyl chloride, samples were analyzed by high‐performance liquid chromatography using a fluorescence detector. Results: Spiked samples indicated an overall recovery of 101%. After 7 days of storage at 4°C, recoveries were approximately 100%. The method limit of quantification was 0.060 μg/sample. Relative standard deviations representing overall reproducibility, defined as precision, were 1.4%–1.8%. Conclusions: The method developed in this study allows 4‐h personal exposure monitoring of glyphosate at 0.250–500 μg/m3. Thus, this method can be used to estimate worker exposure to glyphosate. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to develop and validate a simple and reliable gas chromatography‐mass spectrometry (GC‐MS) method to simultaneously determine urinary 1‐naphthol (1‐NAP) and 2‐naphthol (2‐NAP) for biological monitoring of occupational exposure to naphthalene. Methods: NAPs were derivatized in situ with acetic anhydride after enzymatic hydrolysis, extracted with n‐hexane, and analyzed using GC‐MS. Validation of the proposed method was conducted in accordance with US Food and Drug Administration guidance. A final validation was performed by analyzing a ClinChek®‐Control for phenolic compounds. Results: The linearity of calibration curves was indicated by a high correlation coefficient (>0.999) in the concentration range 1‐100 μg/L for each NAP. The limits of detection and quantification for each NAP were 0.30 and 1.00 μg/L, respectively. The recovery was 90.8%‐98.1%. The intraday and interday accuracies, expressed as the deviation from the nominal value, were 92.2%‐99.9% and 93.4%‐99.9%, respectively. The intraday and interday precision, expressed as the relative standard deviation, was 0.3%‐3.9% and 0.4%‐4.1%, respectively. The ClinChek® values obtained using our method were sufficiently accurate. Conclusions: The proposed method is simple, reliable, and appropriate for routine analyses, and is useful for biological monitoring of naphthalene exposure in occupational health practice. [ABSTRACT FROM AUTHOR]

Acetoaceto- o -toluidide (AAOT) is made from ortho -toluidine (OTD) and is used for the synthesis of pigments. A report of occupational urinary bladder carcinomas in Japanese workers chronically exposed to OTD and AAOT has recently been published. OTD is a well-known human urinary bladder carcinogen; however, little is known about the toxicity and the carcinogenicity of AAOT. The aim of the present study is to evaluate the toxic effects of AAOT on urinary bladder epithelium. In vitro, the cytotoxicities of AAOT and OTD were evaluated in rat (MYP3) and human (1T1) urothelial cells. The LC50 of AAOT was higher than that of OTD in both MYP cells and 1T1 cells. In vivo, 6-week-old male and female F344 rats were fed diets supplemented with 0%, 1.5%, or 3% AAOT for 4 weeks. Incidences of simple hyperplasia, cell proliferative activity, and γ-H2AX expression, which is a novel marker for the prediction of carcinogenicity, were significantly increased in a dose-dependent manner in the bladder urothelium of male and female rats administered AAOT. Furthermore, in male and female rats administered AAOT, the major urine metabolite of AAOT was OTD. These results demonstrate that AAOT has proliferation-enhancing activity and suggest that OTD metabolized from AAOT may play a pivotal role in the deleterious effects of AAOT in rats. The results of the present study also indicate that AAOT, like other carcinogenic aromatic amines, is likely to be a human bladder carcinogen. [ABSTRACT FROM AUTHOR]

1,2-dichloropropane (1,2-DCP) was reclassified recently by IARC as a Group 1 carcinogen based on epidemiological studies on an outbreak of cholangiocarcinoma in offset-printing workers exposed to 1,2-DCP in Japan. However, the underlying mechanism of 1,2-DCP-induced cholangiocarcinoma remains obscure. A previous whole-genome mutation analysis of cholangiocarcinoma of 4 cases exposed to 1,2-DCP suggested the involvement of activation-induced cytidine deaminase (AID), based on specific signatures of mutation patterns. The objective of the present study is to determine whether exposure to 1,2-DCP induces expression of AID in human cholangiocytes. Human MMNK-1 cholangiocytes, differentiated THP-1 macrophages, and co-cultures of MMNK-1/THP-1 cells were exposed to 1,2-DCP at different concentrations and time intervals. The mRNA expression levels of AID and related genes were quantified by real-time PCR. Protein expression was measured by immunostaining. Alkaline Comet assay was performed to examine DNA damage. The results showed that 1,2-DCP alone did not change AID expression in MMNK-1 cholangiocytes. 1,2-DCP significantly increased pro-inflammatory cytokine TNF-α expression in THP-1 macrophages. TNF-α treatment upregulated expression of AID, NF-κB, and IκB in MMNK-1 cholangiocytes. SN50, a NF-κB inhibitor, significantly downregulated TNF-α-induced AID expression, suggesting the involvement of NF-κB pathway in TNF-α-induced AID expression. Exposure to 1,2-DCP significantly increased AID expression in MMNK-1 cholangiocytes co-cultured with THP-1 macrophages. Comet assay showed that 1,2-DCP-induced DNA damage in MMNK-1 cholangiocytes, as indicated by increased tail DNA% and tail moment, was enhanced when co-cultured with macrophages. The results suggest that inflammatory response of macrophages and consequent aberrant AID expression or DNA damage in the cholangiocytes underlie the mechanism of 1,2-DCP-induced cholangiocarcinoma in humans. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the relationship between cumulative exposure to 1,2-dichloropropane (1,2-DCP) and incidence risk of cholangiocarcinoma among workers in the offset proof-printing section of a small printing company in Osaka, Japan.Methods: We identified 95 workers of a printing company (78 men and 17 women) who had been exposed to 1,2-DCP between 1987 and 2006, and calculated the standardised incidence ratio (SIR) of cholangiocarcinoma from 1987 to 2012. We estimated cumulative exposure to 1,2-DCP and calculated SIRs in four exposure categories. We also calculated incidence rate ratios (RRs) adjusted by sex, age, calendar year and dichloromethane (DCM) exposure for three exposure categories using Poisson regression analysis.Results: Cumulative exposures to 1,2-DCP ranged from 32 to 3433 ppm-years (mean, 851 ppm-years) and the SIR was 1171 (95% CI 682 to 1875). In the analysis of the four exposure categories, SIRs increased significantly in the three highest exposure categories, but not in the lowest category. Adjusted RRs in the middle and high exposure categories were 14.9 (95% CI 4.1 to 54.3) and 17.1 (95% CI 3.8 to 76.2), respectively, in the analysis without lag time, and were 11.4 (95% CI 3.3 to 39.6) and 32.4 (95% CI 6.4 to 163.9), respectively, in the analysis with a 5-year lag. The trend analysis revealed a significant increase in RR in association with increasing cumulative exposure to 1,2-DCP. DCM exposure was not significantly associated with the development of cholangiocarcinoma.Conclusions: The present study demonstrated an exposure-response relationship between exposure to 1,2-DCP and the development of cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to establish an efficient strategy for screening and surveillance for occupational cholangiocarcinoma. Methods: We evaluated the consecutive changes in laboratory findings during regular health examinations and in abdominal ultrasonography findings before the diagnosis of occupational cholangiocarcinoma in nine patients. The results of laboratory tests and abdominal ultrasonography at the time of diagnosis were also examined. Results: In all patients, the serum γ-glutamyl transpeptidase (γ-GTP) activity increased several years before the diagnosis of cholangiocarcinoma. The serum alanine aminotransferase (ALT) activity also increased several years before the diagnosis, following an increase in the serum aspartate aminotransferase (AST) activity in most patients. Abdominal ultrasonography before the diagnosis revealed regional dilatation of the bile ducts, which continued to enlarge. At the time of diagnosis, the γ-GTP, AST, and ALT activities were increased in nine, seven, and seven patients, respectively. The regional dilatation of bile ducts without tumor-induced stenosis, dilated bile ducts due to tumor-induced stenosis, space-occupying lesions, and/or lymph node swelling were observed. The serum concentrations of carbohydrate antigen 19-9 (CA 19-9) and/or carcinoembryonic antigen (CEA) were increased in all patients. Conclusions: Regular health examinations with a combination of ultrasonography and laboratory tests including the γ-GTP, AST, ALT, CA 19-9, and CEA levels are useful for screening and surveillance for occupational cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Objective: To examine cross-sectionally whether intraabdominal fat area (IAFA), i.e., visceral fat, and liver fat assessed by computed tomography (CT) are independently associated with hyperuricemia.Methods: Subjects were 801 Japanese men not taking antidiabetic, antihypertensive, or urate-lowering medications, without any history of renal disease, cardiovascular disease, or cancer, and with serum creatinine <1.5 mg/dl. Abdominal, thoracic, and thigh fat areas were measured by CT. Total fat area (TFA) was the sum of these fat areas. Total subcutaneous fat area (TSFA) was TFA minus IAFA. Liver fat was assessed by liver-to-spleen (L/S) ratio measured by CT. Hyperuricemia was defined as serum uric acid level >7.0 mg/dl. Its association with adiposity was tested using logistic regression.Results: The prevalence of hyperuricemia was 19.6% (157 men). Both greater IAFA and lower L/S ratio were independently associated with hyperuricemia in models that simultaneously included IAFA and L/S ratio: multiple-adjusted odds ratios of hyperuricemia for quintiles 3, 4, and 5 of IAFA were 2.16 (95% confidence interval [95% CI] 1.02-4.59), 2.41 (95% CI 1.13-5.16), and 4.00 (95% CI 1.81-8.85), respectively, compared to quintile 1, and the L/S ratios for quintiles 3, 2, and 1 were 2.34 (95% CI 1.16-4.75), 2.15 (95% CI 1.06-4.34), and 2.79 (95% CI 1.35-5.76), respectively, compared to quintile 5. Both IAFA and L/S ratio remained significant even after adjusting for abdominal subcutaneous fat area, TFA, TSFA, body mass index, or waist circumference. Of all fat measurements, IAFA had the strongest association with hyperuricemia by Akaike's information criteria.Conclusion: Greater amounts of both visceral fat and liver fat were independently associated with hyperuricemia. [ABSTRACT FROM AUTHOR]

Background/Aims: The association between alcohol consumption and the risk of chronic kidney disease (CKD) has been reported. What is not known is whether drinking pattern combined with the weekly frequency of alcohol consumption and the quantity per drinking day is associated with the risk of CKD. Methods: We enrolled 9,112 Japanese nondiabetic men aged 40 to 55 years with absence of proteinuria, an estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73 m2 or higher, and not on antihypertensive medications at baseline. CKD was defined if eGFR was <60 ml/min/1.73 m2. The weekly frequency classification was nondrinkers, 1-3 drinking days/week, or 4-7 drinking days/week. The quantity consumed per drinking day was classified as 0.1-23.0 g ethanol/drinking day, 23.1-46.0 g ethanol/drinking day, 46.1-69.0 g ethanol/drinking day, and ≥69.1 g ethanol/drinking day. Results: During the 79,099 person-years, 1,253 subjects developed CKD. Compared to nondrinkers, those who consumed 23.1-46.0 or 46.1-69.0 g ethanol/drinking day on 4-7 drinking days/week had a decreased risk of CKD (multiple-adjusted hazard ratio (HR) 0.62 (0.52-0.74) and 0.76 (0.59-0.97), respectively). The association between the quantity per drinking day and the incidence of CKD was U-shaped among each category of the weekly frequency. HRs within similar categories of quantity per drinking day were lower in the 4-7 drinking days/week group than in the 1-3 drinking days/week group. Conclusion: Among middle-aged Japanese men, the people who drank middle-range quantity, specifically who drank 4-7 days/week, had lower risk of CKD than nondrinkers. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective Butyrylcholinesterase is synthesized in the liver. The serum butyrylcholinesterase level has been cross-sectionally reported to be higher in patients with diabetes, hyperlipidaemia, obesity and fatty liver than in those without them. It is not known whether serum butyrylcholinesterase is associated with the risk of future type 2 diabetes. Design A prospective cohort study. Participants A total of 8470 Japanese men aged 40-55 years without type 2 diabetes at baseline. Measurements Type 2 diabetes was diagnosed if a fasting plasma glucose ( FPG) level was ≥7·0 mmol/l, if a HbA1c level was ≥6·5% or if participants were taking oral hypoglycaemic medication or insulin. Results During the 42 227 person-years of follow-up, 868 cases had developed type 2 diabetes. Serum butyrylcholinesterase was significantly positively correlated with body mass index ( BMI), FPG, alanine aminotransferase ( ALT), γ-glutamyltransferase ( GGT) and triglycerides ( TG), whereas negatively with high-density lipoprotein ( HDL) cholesterol. In Cox proportional hazards models, after adjusting for age, BMI, FPG, alcohol consumption, smoking habit, walk to work, regular leisure-time physical activity and family history of diabetes, the highest quartile (398-806 IU/l) of serum butyrylcholinesterase increased the risk of type 2 diabetes compared with the lowest quartile (56-311 IU/l) [hazard ratio ( HR) 1·41 (95% confidence interval ( CI), 1·14-1·74)]. After further adjusting for ALT and GGT, this association remained [ HR 1·40 (95% CI, 1·13-1·73)]. Furthermore, this association was significant independent of TG and HDL cholesterol. Conclusions Elevated serum butyrylcholinesterase was independently associated with an increased risk of future type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim: The prevalence of underweight women, who have an increased risk for small-for-gestational-age (SGA) birth, is increasing in Japan. We examined the associations of pre-pregnancy body mass index and gestational weight gain (GWG) with SGA birth among Japanese women. Material and Methods: We conducted a prospective cohort study of 1391 women who delivered full-term singleton babies. SGA was defined as below the 10th percentile of birthweight at each gestational age, baby sex, and parity. We calculated the 5th percentile of birthweight in the same way for another threshold for SGA. According to pre-pregnancy body mass index, we divided the participants into three groups: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), and overweight and obese (≥25.0 kg/m2). Results: SGA birth was observed most frequently among the underweight group (13.8%). Underweight was associated with an increased risk of SGA birth. The multiple-adjusted odds ratio for underweight was 1.96 (95% confidence interval, 1.23-3.11) compared with normal weight. Sufficient GWG reduced the incidence and the multiple-adjusted odds ratio for 1-kg increase of GWG was 0.86 (0.81-0.92). The same tendency was observed for the delivery of infants below the 5th birthweight percentile. Women with underweight and normal weight who had 9.0 kg or less of GWG had a significantly higher risk of SGA birth than women with normal weight who had 9.1-11.0 kg of GWG. Conclusions: Underweight and poor GWG were associated with a higher incidence of SGA birth. However, the incidence of SGA birth among underweight women was not increased significantly if they had sufficient GWG. [ABSTRACT FROM AUTHOR]

Tonsillectomy is being frequently used in Japan, while Western nephrologists are more reluctant to adopt tonsillectomy as a treatment for IgAN…(In this issue of NDT) Isseki et al. report the outcome of 200 Japanese patients with biopsy-proven IgAN followed in mean for up to 7 years after renal biopsy.Background Indication of tonsillectomy in IgA nephropathy is controversial. The purpose of this study was to examine the efficacy of tonsillectomy on remission and progression of IgA nephropathy. Methods We conducted a single-center 7-year historical cohort study in 200 patients with biopsy-proven IgA nephropathy. Study outcomes were clinical remission defined as disappearance of urine abnormalities at two consecutive visits, glomerular filtration rate (GFR) decline defined as 30% GFR decrease from baseline and GFR slope during the follow-up. Results Seventy of the 200 patients received tonsillectomy. Tonsillectomy was associated with increased incidence of clinical remission (P + 0.01, log-rank test) and decreased incidence of GFR decline (P = 0.01, log-rank test). After adjustment for age and gender, hazard ratios in tonsillectomy were 3.90 (95% confidence interval 2.46–6.18) for clinical remission and 0.14 (0.02–1.03) for GFR decline. After further adjustment for laboratory (baseline mean arterial pressure, GFR, 24-h proteinuria and hematuria score), histological (mesangial score, segmental sclerosis or adhesion, endocapillary proliferation and interstitial fibrosis) or treatment variables (steroid and renin–angiotensin system inhibitors), similar results were obtained in each model. Even after exclusion of 69 steroid-treated patients, results did not change. GFR slopes in tonsillectomy and non-tonsillectomy groups were 0.60 ± 3.65 and − 1.64 ± 2.59 mL/min/1.73 m2/year, respectively. In the multiple regression model, tonsillectomy prevented GFR decline during the follow-up period (regression coefficient 2.00, P = 0.01). Conclusion Tonsillectomy was associated with a favorable renal outcome of IgA nephropathy in terms of clinical remission and delayed renal deterioration even in non-steroid-treated patients. [ABSTRACT FROM PUBLISHER]

Background Moderate alcohol consumption is associated with a decreased risk of type 2 diabetes. However, the relationship between drinking patterns, such as the weekly frequency of alcohol consumption and the quantity per drinking day, and the incidence of type 2 diabetes has not been sufficiently addressed. Methods Study participants included 10 631 Japanese men aged 40e55 years without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was $7.0 mmol/l or if participants were taking diabetes medications. Data on alcohol consumption were obtained from questionnaires. Results During the 37 172 person-years of follow-up, we confirmed 878 cases of type 2 diabetes. Frequent alcohol consumption was associated with a low risk of type 2 diabetes. Compared to non-drinkers, the multiple-adjusted HR for those who drank 4e7 days weekly was 0.76 (95% CI, 0.63 to 0.92). To assess the association between drinking pattern and type 2 diabetes, we examined the joint association of the weekly frequency and the quantity per drinking day with type 2 diabetes. Men who consumed 0.1e2.0 or 2.1e4.0 US standard drinks per drinking day on 4e7 days weekly had a lower risk of type 2 diabetes (HR 0.74, 95% CI 0.58 to 0.95; HR 0.74, 95% CI 0.60 to 0.91, respectively) compared to non-drinkers. Conclusions More frequent alcohol consumption lowered the risk of type 2 diabetes. Light to moderate alcohol consumption per drinking day on 4e7 days weekly lowered the risk of type 2 diabetes compared to non-drinkers. [ABSTRACT FROM AUTHOR]

Objectives: Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content. Methods: The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry. Results : The median iAs concentration in drinking water was 55 μgAs/L (range <0.5-332 μgAs/L). Speciation analysis revealed the presence of arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid in urine samples with medians (range) of 16.8 (7.7-32.3), 1.8 (<0.5-3.3), 13.7 (5.6-25.0), and 88.6 μgAs/L (47.9-153.4 μgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water. Conclusions: All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration. [ABSTRACT FROM AUTHOR]

Background/Aims: No prospective studies have estimated the association between white blood cell (WBC) count and the risk of proteinuria. We prospectively examined the relationships of WBC count, as a marker of inflammation, with two outcomes: proteinuria and low estimated glomerular filtration rate (eGFR). Methods: We enrolled 10,008 Japanese men aged 40-55 years who had neither proteinuria nor low eGFR and were not taking antihypertensive medications at entry. Proteinuria was defined as 1+ or higher on urine dipstick. Low eGFR was defined if eGFR was <60 ml/min/1.73 m2. Results: During the 49,644 person-years of follow-up, 1,557 cases of proteinuria were confirmed. After adjusting for age, body mass index, fasting plasma glucose, systolic blood pressure, diastolic blood pressure, antidiabetic medications, alcohol consumption, smoking, regular leisure-time physical activity and eGFR, the highest quintile (≥7.51 × 103/μl) of WBC count was independently associated with an increased risk of incidence of proteinuria [HR: 1.45 (95% CI: 1.23-1.73)] compared with the lowest quintile (≤4.80 × 103/μl). On the other hand, during 52,833 person-years, we confirmed 439 cases of low eGFR. In multivariate models, there was no association between WBC count and low eGFR. Conclusion: Elevated WBC count was independently associated with an increased risk of proteinuria, but not low eGFR. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Dimethylarsinous acid (DMAIII) induced tetraploidy and multinucleation in V79 cells. While the highest yield of tetraploids and multinucleated cells was at 1.25 μM of DMAIII, the mitotic index was highest at DMAIII 2.5 μM due to mitotic arrest. Mitosis was not observed at 5 μM. We observed V79 cells treated with DMAIII and visualized with rhodamine-phalloidin. Abnormal actin location was observed in the dividing cells which were treated with DMAIII and visualized with rhodamine-phalloidin. These findings suggested strongly that DMAIII inhibits not only formation of the normal mitotic spindle but cytokinesis and induces the formation of multinuclear cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE--It has been reported that moderate alcohol consumption decreased the risk of type 2 diabetes but that elevated liver enzymes increased it. The comparative importance of alcohol consumption and liver enzymes as predictors of type 2 diabetes remains unconfirmed. RESEARCH DESIGN AND METHODS--The participants included 8,576 Japanese men, aged 40-55 years, without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was ≥126 mg/dl or if participants were taking oral hypoglycemic medications or insulin. RESULTS--During the 4-year follow-up period, we confirmed 878 cases. In multivariate models, moderate daily alcohol consumption (16.4-42.6 g ethanol/day) decreased the risk of type 2 diabetes, and higher levels of γ-glutamyhransferase (GGT) and alanine aminotransferase (ALT) increased the risk. In joint analyses of alcohol consumption and liver enzymes, moderate drinkers with the lowest tertile of GGT had the lowest risk of type 2 diabetes. Compared with them, nondrinkers with the highest GGT had the highest risk of type 2 diabetes (odds ratio 3.18 [95% CI 1.75-5.76]). At every level of GGT, moderate or heavy alcohol drinkers (≥42.7 g ethanol/day) had a lower risk of type 2 diabetes than nondrinkers. The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT. CONCLUSIONS--GGT, ALT, and daily alcohol consumption were independently associated with the risk of type 2 diabetes. Nondrinkers with the highest GGT or ALT had a high risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Formaldehyde is a carcinogen to which humans are exposed daily, but few methods are available to quantify formaldehyde in biological samples. We developed a simple, sensitive and rapid technique for the quantification of formaldehyde in urine by derivatization with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine, using a headspace sampler coupled to a gas chromatograph equipped with an electron capture detector. The detection limit was 1.08 µg/L. The overall recovery of formaldehyde spiked in urine was 99%. The concentration of formaldehyde in urine obtained from healthy volunteers ranged from 56.85 to 144.57 µg/L. This method can be used successfully to measure formaldehyde in urine. [ABSTRACT FROM AUTHOR]

In order to identify potential genotoxicant(s) in recycled paperboard, samples were fractionated using multiple liquid/liquid extraction, and gel permeation chromatography, and analysed by gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. The rec -assay was used as an indicator of genotoxicity. Genotoxicants in the recycled paperboard were identified as dehydroabietic acid (DHA) and abietic acid (AA). DHA and AA were detected in two out of five virgin products, and in all seven recycled products for food-contact use. Total amounts of DHA and AA were 240 and 990&ThickSpace;µg/g in the virgin products and 200-990&ThickSpace;µg/g in the recycled products. A good correlation was observed in the total amount of DHA and AA content determined in paper products and DNA-damaging activity. Moreover, genotoxic effects in paper products showed a good match with standard compounds, indicating that the genotoxic effects of these paper products was mostly attributable to DHA and AA. [ABSTRACT FROM AUTHOR]

There is abundant epidemiological evidence that arsenic is an environmental carcinogen related to human cancers of the skin, lung, liver and urinary bladder, in particular. Dimethylarsinic acid (DMA) has also been reported to act as a carcinogen/or a promoter in rat models. To elucidate molecular mechanisms, we conducted an 18 month carcinogenicity study of DMA in p53 heterozygous (+/–) knockout mice, which are susceptible to early spontaneous development of various types of tumors, and wild-type (+/+) C57BL/6J mice. Totals of 88–90 males, 7–8 weeks of age, were divided into three groups each administered 0, 50 or 200 p.p.m. DMA in their drinking water for 18 months. Mice that were found moribund or died before the end of the study were autopsied to evaluate the tumor induction levels, as well as those killed at the end. Both p53+/– knockout and wild-type mice demonstrated spontaneous tumor development, but lesions were more prevalent in the knockout case. Carcinogenic effect of DMA was evident by significant early induction of tumors in both treated p53+/– knockout and wild-type mice, significant increase of the tumor multiplicity in 200 p.p.m.-treated p53+/– knockout mice, and by significant increase in the incidence and multiplicity of tumors (malignant lymphomas) in the treated wild-type mice. By the end of 80 weeks, tumor induction, particularly malignant lymphomas and sarcomas, were similar in treated and control p53+/– knockout mice. No evidence for organ-tumor specificity of DMA was obtained. Molecular analysis using PCR–SSCP techniques revealed no p53 mutations in lymphomas from either p53+/– knockout or wild-type mice. In conclusion, DMA primarily exerted its carcinogenic effect on spontaneous development of tumors with both of the animal genotypes investigated here. [ABSTRACT FROM PUBLISHER]

Arsenic is a well-documented human carcinogen, and contamination with this heavy metal is of global concern, presenting a major issue in environmental health. However, the mechanism by which arsenic induces cancer is unknown, in large part due to the lack of an appropriate animal model. In the present set of experiments, we focused on dimethylarsinic acid (DMA), a major metabolite of arsenic in most mammals including humans. We provide, for the first time, the full data, including detailed pathology, of the carcinogenicity of DMA in male F344 rats in a 2-year bioassay, along with the first assessment of the genetic alteration patterns in the induced rat urinary bladder tumors. Additionally, to test the hypothesis that reactive oxygen species (ROS) may play a role in DMA carcinogenesis, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation in urinary bladder was examined. In experiment 1, a total of 144 male F344 rats at 10 weeks of age were randomly divided into four groups that received DMA at concentrations of 0, 12.5, 50 and 200 p.p.m. in the drinking water, respectively, for 104 weeks. From weeks 97–104, urinary bladder tumors were observed in 8 of 31 and 12 of 31 rats in groups treated with 50 and 200 p.p.m. DMA, respectively, and the preneoplastic lesion, papillary or nodular hyperplasias (PN hyperplasia), was noted in 12 and 14 rats, respectively. DMA treatment did not cause tumors in other organs and no urinary bladder tumors or preneoplastic lesions were evident in the 0 and 12.5 p.p.m.-treated groups. Urinary levels of arsenicals increased significantly in a dose-responsive manner except for arsenobetaine (AsBe). DMA and trimethylarsine oxide (TMAO) were the major compounds detected in the urine, with small amounts of monomethylarsonic acid (MMA) and tetramethylarsonium (TeMa) also detected. Significantly increased 5-bromo-2′-deoxyuridine (BrdU) labeling indices were observed in the morphologically normal epithelium of the groups treated with 50 and 200 p.p.m. DMA. Mutation analysis showed that DMA-induced rat urinary bladder tumors had a low rate of H-ras mutations (2 of 20, 10%). No alterations of the p53, K-ras or β-catenin genes were detected. Only one TCC (6%) demonstrated nuclear accumulation of p53 protein by immunohistochemistry. In 16 of 18 (89%) of the TTCs and 3 of 4 (75%) of the papillomas, decreased p27kip1 expression could be demonstrated. Cyclin D1 overexpression was observed in 26 of 47 (55%) PN hyperplasias, 3 of 4 (75%) papillomas, and 10 of 18 (56%) TCCs. As a molecular marker of oxidative stress, increased COX-2 expression was noted in 17 of 18 (94%) TCCs, 4 of 4 (100%) papillomas, and 39 of 47 (83%) PN hyperplasias. In experiment 2, 8-OHdG formation in urinary bladder was significantly increased after treatment with 200 p.p.m. DMA in the drinking water for 2 weeks compared with the controls. The studies demonstrated DMA to be a carcinogen for the rat urinary bladder and suggested that DMA exposure may be relevant to the carcinogenic risk of inorganic arsenic in humans. Diverse genetic alterations observed in DMA-induced urinary bladder tumors imply that multiple genes are involved in stages of DMA-induced tumor development. Furthermore, generation of ROS is likely to play an important role in the early stages of DMA carcinogenesis. [ABSTRACT FROM PUBLISHER]

Presents a study which investigated the relationship between daily alcohol consumption and the risk of type 2 diabetes in a large Japanese cohort. Research design and methods; Results; Conclusions.

Presents information on a study regarding the effect of impaired fasting glucose (IFG) in increasing the risk of hypertension on Japanese cohorts during 1980 and 1990. Diagnosis of diabetes, IFG and hypertension; Biochemical measurements and clinical characteristics of the study; Result and discussion.

The article presents a study on detecting the urinary N-acetyl-glucosaminidase (NAG) activity as the only biochemical indicator reacting at an early stage of lead nephrosis. The study examined and measured microglobulin concentrations in 99 male lead solder factory and lead refinery workers. The study shows the substantial indications that lead exposure to workers causes a functional alteration in their renal tubules.

The article presents a study on the genotoxicity of organic and inorganic arsenic compounds in the cells of Chinese hamster. The study used V79 cells which came from the Chinese hamster diploid and lung cells and human peripheral blood to analyze the said genotoxicity. Results show that the dimethylarsenic acid (DMA) of the said compounds induces mitotic arrest and tetraploids.

The article presents a study on the effects of sulfate, calcium, and magnesium on the toxicity of Daphnia similis on potassium dichromate The study uses various methods such as conducting static acute toxicity tests on the collected samples of daphnia similis, and exposing them to 1.25-fold dilution concentrations. Results show the decrease on the toxicity of potassium dichromate on Daphnia similis after expositing it on various chemicals.

The metabolism of arsenic compounds in rats was studied by comparing urinary metabolites of arsenic compounds administered for 1 wk or 7 mo. Male F344/DuCrj rats were given 100 mg As/L as monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), trimethylarsine oxide (TMAO), or arsenobetaine (AsBe), or 10 mg As/L as arsenite \[As(III)] via drinking water for 7 mo. Urine was collected by forced urination after 1 wk or 7 mo. Arsenic metabolites in urine were analyzed by ion chromatography with inductively coupled plasma mass spectrometry. In the case of As(III) ingestion, a small portion of all arsenic excreted in urine (about 6% ) was excreted in inorganic form, while most arsenic was excreted as methylated arsenic metabolites. Following MMA treatments for 1 wk or 7 mo, the predominant products excreted were unchanged MMA and DMA accompanied by small amounts of TMAO and tetramethylarsonium (TeMA). In the case of DMA treatment the urinary compounds found were mainly the parent DMA and TMAO with minute amounts of TeMA. TMAO was methylated to TeMA to a slight extent after 1 wk and 7 mo of administration, although most TMAO was excreted in the form of unchanged TMAO. AsBe was predominantly eliminated in urine without any transformation. Two unidentified metabolites were detected in urine after 7 mo of arsenic species exposure; the amounts of these metabolites increased in the order DMA > MMA > TMAO with only small quantities of these detected in the As(III)-treated group. These results suggest that these unidentified metabolites are formed during a demethylation process, and not during methylation. Our findings indicate that long-term exposure to As(III), MMA, or DMA decreases the proportion of TMAO elimination in urine and increases that of DMA, M-1, and M-2, and that further methylation to TMAO to TeMA does occur to a slight extent following long-term exposure to arsenical compounds in rats. [ABSTRACT FROM AUTHOR]

Arsenicals are epidemiologically significant chemicals in relation to induction of urinary bladder cancer in man. In the present study, we investigated the dose-dependent promotion potential of dimethylarsinic acid (DMA), a major metabolite of inorganic arsenicals in mammals, for rat urinary bladder carcinogenesis. In experiment 1, 6-week-old male F344 rats were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks and then given one of several concentrations of DMA in their drinking water (groups 1–6: 0, 2, 10, 25, 50 and 100 p.p.m.) for 32 weeks. The development of preneoplastic lesions and tumors (papillomas and carcinomas) in the urinary bladder was enhanced by treatment with DMA in a dose-dependent manner. A significant increase in multiplicity of tumors (papillomas and carcinomas) was observed even at a low concentration of DMA (10 p.p.m.). On the other hand, no preneoplastic lesions and tumors were observed in the rats treated with DMA alone. In experiment 2, different concentrations of DMA (groups 1–4: 0, 10, 25 and 100 p.p.m.) in drinking water were administered to the rats for 8 weeks without prior initiation by BBN. A significant increase in the 5-bromo-2'-deoxyuridine labeling index and alteration of the surfaces of the urinary bladder epithelial cells, as revealed by scanning electron microscopy, provided evidence of a dose-dependent increase in cell proliferation due to the DMA treatment. These results suggest that DMA has the potential to promote rat urinary bladder carcinogenesis and one of the mechanisms involved is its stimulation of cell proliferation in the urinary bladder epithelium. [ABSTRACT FROM PUBLISHER]

Objective: We prospectively assessed whether the combined measurements of fasting plasma glucose (FPG) and A1C were effective for predicting type 2 diabetes.Research Design and Methods: Study participants included 6,736 nondiabetic Japanese men aged 40-55 years. Type 2 diabetes was diagnosed in those who had an FPG >or=126 mg/dl or who were being treated with an oral antidiabetic agent or insulin. The models including FPG, A1C, and both were compared using the area under the receiver operating characteristic (AUROC) curves.Results: During the 4-year follow-up period, we confirmed 659 diabetes cases. In multivariate analysis, both FPG and A1C were independently associated with the risk of type 2 diabetes. The model including both FPG and A1C had a greater AUROC curve than that including FPG alone (0.853 vs. 0.818; P < 0.001) or A1C alone (0.853 vs. 0.771; P < 0.001).Conclusions: The combined measurement of FPG and A1C was effective for predicting type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- We prospectively assessed whether the combined measurements of fasting plasma glucose (FPG) and A1C were effective for predicting type 2 diabetes. RESEARCH DESIGN AND METHODS-- Study participants included 6,736 nondiabetic Japanese men aged 40-55 years. Type 2 diabetes was diagnosed in those who had an FPG ≥126 mg/dl or who were being treated with an oral antidiabetic agent or insulin. The models including FPG, A1C, and both were compared using the area under the receiver operating characteristic (AUROC) curves. RESULTS -- During the 4-year follow-up period, we confirmed 659 diabetes cases. In multivariate analysis, both FPG and A1C were independently associated with the risk of type 2 diabetes. The model including both FPG and A1C had a greater AUROC curve than that including FPG alone (0.853 vs. 0.818; P < 0.001) or A1C alone (0.853 vs. 0.771; P < 0.001). CONCLUSIONS -- The combined measurement of FPG and A1C was effective for predicting type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes.Research Design and Methods: The study participants were nondiabetic Japanese men (n = 8,570) aged 40-55 years at entry. Type 2 diabetes was diagnosed if fasting plasma glucose was >or=126 mg/dl or if participants were taking oral hypoglycemic medication or insulin.Results: During the 4-year follow-up period, 877 men developed type 2 diabetes. Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44-2.54) compared with those who had levels between 0.71 and 0.80 mg/dl.Conclusions: Lower serum creatinine increased the risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes. RESEARCH DESIGN AND METHODS-- The study participants were nondiabetic Japanese men (n = 8,570) aged 40-55 years at entry. Type 2 diabetes was diagnosed if fasting plasma glucose was ≥ 126 mg/dl or if participants were taking oral hypoglycemic medication or insulin. RESULTS-- During the 4-year follow-up period, 877 men developed type 2 diabetes. Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44-2.54) compared with those who had levels between 0.71 and 0.80 mg/dl. CONCLUSIONS -- Lower serum creatinine increased the risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article discusses a study on the relationship between walking to work and the development of type 2 diabetes in Japanese men. It mentions that studies revealed that physical activity is effective in preventing diabetes. Men were examined based on their leisure-time physical activity, smoking habits and alcohol intake. The result of the study provided evidence that duration of the walk going to work has an independent effect on the risk of type 2 diabetes.