The present cohort study examined how lifestyle, household environment, and caries activity test score of Japanese children at age 1.5 years affected their dental caries incidence at age 3. Inclusion criteria were 1.5-year-old children with no dental caries. Dental examinations were performed for 33,655 children who participated in routine dental examinations at 1.5 years of age, and the exam was repeated approximately 21 months later (at age 3) at the Kobe City Public Health Center in Japan. After excluding 622 children who had caries at age 1.5 and 1831 children with missing lifestyle and household environment data in the questionnaires, the final data analysis was performed on a total of 31,202 children (16,052 boys, 15,150 girls).The multivariate logistic regression analysis indicated a strong association of the consumption of sugar-sweetened beverages/snacks, less frequent tooth brushing by the parents, lack of fluoride varnish, family history of smoking, with the risk of developing dental caries. A child’s late bedtime is also one of the major risk factors for dental caries development. Further investigation is needed to examine whether the short duration or the irregularity of the sleep-wake cycle would affect early childhood oral health and whether there is a relationship between late bedtime and late night snack intake.

To evaluate the effect of airborne particulate matter 2.5 (PM2.5) in winter on airway inflammation, water-soluble supernatant (Sup) and water-insoluble precipitate (Pre) in PM2.5 were inoculated in NC/Nga mice with high sensitivity to mite allergens. Sup with aluminum oxide was injected intraperitoneally for sensitization. Five days later, Sup, Pre or both Sup and Pre were inoculated via the nasal route five times for more sensitization and a challenge inoculation on the 11th day in NC/Nga mice. On the 12th day, mice were examined for airway hyperresponsiveness (AHR), BALF cell count and IL-1β concentration, mRNA expression of Th1 and Th2 cytokines, chemokines such as eotaxin 1 and eotaxin 2, inflammasomal complex molecules such as IL-1β, caspase 1 and the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) in lung tissue as well as histopathology. The synergistic effect of Sup and Pre was observed in terms of increases in AHR, BALF cells, the mRNA expression of IL-13, eotaxin1 and IL-1β, and the IL-1β concentration in BALF. Intracellular deposits of insoluble particulates were observed in macrophages around inflammatory granulation of the mouse group treated with Sup and Pre. These results suggest that PM2.5 can induce airway hyperresponsiveness in mice with genetically high sensitivity to mite allergens by an inflammasome-associated mechanism and synergistic action of insoluble particulates and soluble components.

Changes in the expression of arginase and their association with nitrosative stress were investigated using an asthmatic model previously established in NC/Nga mice with mite extract. Mite crude extract (100 microg/day) from Dermatophagoides farinae was administered intranasally for 5 consecutive days (day 0-4), and a single challenge was performed on day 11. On day 12, upregulation of the mRNA expression of inducible types of nitric oxide synthase (iNOS) and increases in immunohistochemical staining for iNOS and nitrotyrosine were observed. However, the level of nitrite + nitrate was unchanged. An increase in enzymatic activity, upregulation of mRNA expression, and immunostaining for arginase I was detected in the lung tissue and serum. Moreover, increases in both arginase I and II were revealed by immunoblotting. Goblet cell hyperplasia in bronchial epithelial cells and increasing collagen synthesis around the bronchus were also observed. These results suggested that an increase in arginase may lead to decreased availability of arginine for nitric oxide synthase and may contribute to the remodeling of the lung.

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 -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 antiinflammatory and airway-relaxing effects, although it is not clear whether the anti-inflammatory effect is direct or indirect. experimental asthma; arginase inhibitor; nor-NOHA

: Inhalation exposure of guaranteed reagent grade trichloroethylene was performed in female ICR mice and female SD rats at 50, 150 and 450 ppm for 7 hours a day, 5 days a week, for 104 weeks followed by an observation period of 3 weeks. Tumors were distributed mainly in the hematopoietic systems, lungs and mammary glands in the mice, and in the pituitary glands and mammary glands in the rats, while several types of tumors were observed in other organs at low incidences. The average number of lung tumors per mouse in mice exposed to 150 ppm or 450 ppm was more than 3-fold the incidence in control mice. The incidences of pulmonary adenocarcinomas in mice exposed to 150 ppm and 450 ppm were 16% and 15%, respectively, which was significantly (p<0.05) higher than that of the controls (2%). No significant differences in the incidences of other types of tumors, tumors of specific organs by site of origin or numbers of animals with tumors were recognized between the controls and dosed groups of mice and rats.

1. The use of everted sacs of the small intestine as an enzyme source for studying the metabolism of xenobiotics by cytochrome P450 (P450, CYP) enzymes and UDP-glucuronosyltransferases has been investigated. 2. Most of the drug oxidation activities for testosterone, bufuralol, ethoxyresorufin and 7-ethoxycoumarin resided in the upper part of the everted sacs and in intestinal microsomes. Testosterone 6 beta-hydroxylase activities in the everted sacs were about two times higher than those in the intestinal microsomes. By freezing and thawing treatment, the testosterone 6 beta- and 16 alpha-hydroxylase activities of the everted sacs were considerably decreased, and those of the intestinal microsomes were abolished. 3. Microsomal testosterone 6 beta-hydroxylation, bufuralol 1'-hydroxylation, and pentoxyresorufin and ethoxyresorufin O-dealkylation were inhibited by ketoconazole, quinine, metyrapone and alpha-naphthoflavone respectively. Immunoreactive proteins using anti-CYP2B1 and anti-CYP3A2 antibodies were detected in the upper and middle parts of the rat small intestine. 4. Except for morphine 3-glucuronidation, glucuronidation activities in intestinal microsomes or everted sacs were not dependent on the intestinal region. The lower part of the everted sacs exhibited about 10 times higher morphine-3-glucuronidation activities compared with those of the upper part. The glucuronidation activities of 4-nitrophenol in the everted sacs were 10 times higher than those in microsomes. 5. These results demonstrated that the upper part of rat small intestine serves as the major site for intestinal P450-mediated first-pass metabolism. CYP3A enzymes in rat intestinal microsomes may not be stable but probably play an important role in drug oxidations. The high activity of glucuronidation in the rat small intestine should also be considered in terms of drug metabolism.

Although cigarette smoking is known to be an important risk factor for renal disease, the mechanism by which smoking induces progressive renal disease in a healthy population has not been established. We hypothesized that oxidative stress (measured as 8-iso-prostaglandin F 2a , 8-iso-PGF2a), inflammation (highly sensitive C-reactive protein (CRP), hs-CRP) and nitric oxide may be associated with an alteration in the estimated glomerular filtration rate (eGFR) and proteinuria in otherwise healthy smokers. A total of 649 eligible subjects were classified according to their smoking status. Plasma NOx was measured using ozone-based chemiluminescence, urinary 8-iso-PGF2a was measured using enzyme immunoassay and serum hs-CRP was measured using a latex aggregation nephelometry method. The levels of 8-iso-PGF2a and hs-CRP increased in current smokers (P¼0.001 and P¼0.029, respectively), although there was not an increase in the NOx level. The prevalence of a high eGFR increased in light smokers (odds ratio (OR) 1.15 (95% confidence interval (CI), 0.61-2.17)) and heavy smokers (OR 2.33 (95% CI, 1.06-5.10)) when compared with non-and past smokers (P for trend¼0.024). The multivariable-adjusted mean values of the eGFR in current smokers, reported from the lowest to the highest quintiles of hs-CRP levels, were 82.1, 85.1, 86.4 and 88.5 ml per min per 1.73 m 2 (P for trend¼0.027). The mean values of proteinuria were 28.6, 34.6, 37.2 and 39.5 mg g À1 creatinine (P for trend¼0.003). The correlation coefficient between hs-CRP and eGFR was increased significantly (P¼0.03) across non-(r¼0.03), past (r¼À0.17), light (r¼0.13) and heavy smokers (r¼0.31). In conclusion, cigarette smoking is a risk factor for renal function alteration in healthy smokers and is characterized by a high eGFR and a high urinary protein associated with an increase in the hs-CRP. This finding suggests that hs-CRP may help mediate the alteration of renal function in smokers.

Determination of various important parameters of coagulation and fibrinolysis, clinical characteristics, and levels of serum lipid were compared in 193 patients with NIDDM and 50 control subjects. Levels of fibrinogen, tissue factor pathway inhibitor (TFPI), thrombin-anti-thrombin complex, and plasminogen activator inhibitor 1 in plasma increased significantly in the diabetic patients. Levels of TFPI correlated significantly with levels of total cholesterol. In the patients with coronary heart disease or cerebral infarction, levels of lipoprotein(a) increased significantly. From these results, we have concluded that there is a thrombotic tendency or at least an imbalance between the hemostatic and thrombosis-protecting system in diabetic patients, especially in patients with angiopathy.