Spatio-temporal trends in caries: A study on children in Berlin-Mitte.

BACKGROUND: Significant inequalities in caries distribution among children in Germany have been reported, but small-scale areas remain understudied. AIM: To examine spatio-temporal trends in children's dental caries at the small-area level in Berlin-Mitte. DESIGN: Routinely collected data from Berlin's annual Health Examination Surveys were used, which also include information on age, sex, country of origin, and residential area. The study population consists of 14,866 children aged 5 to 7 between 2006 and 2014 in the district of Berlin-Mitte. Outcome variables are the dmft (decayed, missing, and filled teeth), the presence of any caries experience, untreated caries, and caries risk. The outcomes are summarized descriptively and graphically presented for 10 quarters and 41 communities within Berlin-Mitte. RESULTS: Relevant gaps in children's dental caries were discovered between the quarters of Mitte. Three quarters in the northeast part of Mitte have consistently indicated the lowest oral health status in all four outcomes, and children having high caries risk have been increasingly concentrating in this area over time. Despite the continuous improvements in the southern part, the averages in total of Mitte for all outcomes have risen. CONCLUSION: Our findings confirm the spatiotemporally mounting disparities in children's oral health between the quarters in Berlin-Mitte and that particular quarters need urgent attention. The small-area approach made it easier and more effective to reveal the spatial distribution of children's dental caries at the local level. The small-area analysis should be strongly encouraged in future caries research to narrow the inequalities in children's oral health.

Sox4 stimulates ß-catenin activity through induction of CK2.

ß-catenin is a key component of the Wnt signaling pathway and the abnormal accumulation of ß-catenin is characteristic of various types of cancer. Here we demonstrate that overexpression of Sox4 enhances ß-catenin/TCF activity by increasing the stability of ß-catenin. Sox4 increased the protein level of ß-catenin and its target gene cyclin D1 in a dose-dependent manner. An siRNA experiment for Sox4 also demonstrated that Sox4 increases the protein levels of ß-catenin and thus activates the Wnt signaling pathway. We found that induction of ß-catenin/TCF activity by Sox4 is caused by stabilization of the ß-catenin protein, but not by induction of ß-catenin transcription. We further demonstrate that the increased level of ß-catenin is caused by induction of CK2. In light of recent evidence that Sox4 expression is activated in the colon and in other tumors with ß-catenin dysregulation, our findings suggest that Sox4 acts as an agonist of Wnt signaling in cancer cells.

Data mining approach to model the diagnostic service management.

Korea has National Health Insurance Program operated by the government-owned National Health Insurance Corporation, and diagnostic services are provided every two year for the insured and their family members. Developing a customer relationship management (CRM) system using data mining technology would be useful to improve the performance of diagnostic service programs. Under these circumstances, this study developed a model for diagnostic service management taking into account the characteristics of subjects using a data mining approach. This study could be further used to develop an automated CRM system contributing to the increase in the rate of receiving diagnostic services.

Repression by oxidative stress of iNOS and cytokine gene induction in macrophages results from AP-1 and NF-kappaB inhibition mediated by B cell translocation gene-1 activation.

Previously, we reported that oxidative stress caused by sulfur amino acid deficiency (SD) induces B cell translocation gene-1 (Btg-1), which belongs to the Apro family, in hepatocytes. In view of the impairment of immune function by protein restriction that causes SD, this study investigated whether SD or other oxidative stress inhibits iNOS and cytokine expression and induces Btg-1 in macrophages and explored the causal relationship of Btg-1 induction and repression of the genes. When macrophages were incubated in sulfur amino acid-deprived medium, lipopolysaccharide induction of iNOS, TNFalpha, IL-1beta, and IL-6 was significantly decreased compared to control. Because AP-1 and NF-kappaB are the common transcription factors that regulate the genes encoding iNOS and cytokines, we examined AP-1 and NF-kappaB DNA binding activities and transactivation of the iNOS gene containing the DNA binding elements. Induction of the reporter gene pGL-miNOS-1588 comprising the -1.6 kb iNOS promoter in lipopolysaccharide-activated macrophages was inhibited 30-70% by SD or treatment with pro-oxidants, including tert-butylhydroxyquinone, buthionine sulfoximine, and 3-morpholinosydnonimine. Oxidative stress increased Btg-1 mRNA. SD-induced oxidative stress activated Btg-1 in macrophages, as evidenced by nuclear translocation of endogenous or green fluorescent protein-tagged Btg-1, which localized in the cytoplasm in the resting state. Expression of Btg-1 inhibited lipopolysaccharide-inducible AP-1 and NF-kappaB activities, repressing transactivation of the target gene pGL-miNOS-1588. These results provide evidence that oxidative stress induced by SD or pro-oxidants inhibits the expression of iNOS and cytokines in macrophages with Btg-1 activation and that the gene repression by oxidative stress may result from Btg-1-mediated inhibition of AP-1 and NF-kappaB activities.

Pharmacokinetics of theophylline in diabetes mellitus rats: induction of CYP1A2 and CYP2E1 on 1,3-dimethyluric acid formation.

Pharmacokinetic parameters of theophylline and one of its metabolites, 1,3-dimethyluric acid (1,3-DMU), were compared after intravenous and oral administration of aminophylline, 5mg/kg as theophylline, to diabetes mellitus rats induced by alloxan (DMIA) or streptozotocin (DMIS), and their respective control rats. In DMIA and DMIS rats, expression of CYP1A2 and 2E1 increased approximately three times. Theophylline was metabolized to 1,3-DMU by CYP1A2 and 2E1 in rats. Hence, it was expected that formation of 1,3-DMU increased in DMIA or DMIS rats. This was proven by the following results. First, after intravenous administration of theophylline, the AUC of 1,3-DMU was significantly greater in DMIA (110% increase) or DMIS (47.4% increase) rats. Second, the AUC of theophylline was significantly smaller in DMIA (26.1% decrease) or DMIS (30.1% decrease) rats because of significantly faster time-averaged total body clearance in DMIA (34.8% increase) or DMIS (42.7% increase) rats. Third, based on in vitro hepatic microsomal studies, intrinsic 1,3-DMU formation clearances were significantly faster in DMIA (20.4% increase) or DMIS (30.7% increase) rats than respective control rats. Similar results (AUC values of theophylline and 1,3-DMU) were also obtained after oral administration.

Inhibition of lipopolysaccharide-inducible nitric oxide synthase, TNF-alpha and COX-2 expression by sauchinone effects on I-kappaBalpha phosphorylation, C/EBP and AP-1 activation.

1. Sauchinone, a lignan isolated from Saururus chinensis (Saururaceae), is a diastereomeric lignan with cytoprotective and antioxidant activities in cultured hepatocytes. The effects of sauchinone on the inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha) and cyclooxygenase 2 (COX-2) gene expression and on the activation of transcription factors, nuclear factor-kappaB (NF-kappaB), CCAAT/enhancer-binding protein (C/EBP), activator protein-1 (AP-1) and cAMP-response element-binding protein (CREB) were determined in Raw264.7 cells as part of the studies on its anti-inflammatory effects. 2. Expression of the iNOS, TNF-alpha and COX-2 genes was assessed by Northern and Western blot analyses. NO production was monitored by chemiluminescence detection using a NO analyzer. To identify the transcriptional factors affected by sauchinone, the extents of NF-kappaB, C/EBP, AP-1 and CREB activation were measured. Activation of the transcription factors was monitored by gel mobility shift assay, whereas p65 and I-kappaBalpha were analyzed by immunocytochemical and immunoblot analyses. 3. Sauchinone inhibited the induction of iNOS, TNF-alpha and COX-2 by lipopolysaccharide (LPS) (IC50

Effects of acute renal failure on the pharmacokinetics of chlorzoxazone in rats.

The purpose of this study is to report the changes of CYP2E1, CYP1A2, CYP2B1/2, CYP2C11, CYP3A23, and CYP3A2 expression and pharmacokinetics and tissue distribution of chlorzoxazone (CZX) and 6-hydroxychlorzoxazone (OH-CZX) in rats with acute renal failure induced by uranyl nitrate (U-ARF), and the role of CYP3A23 and CYP3A2 in the formation of OH-CZX in rats with U-ARF. In rats with U-ARF, CYP2C11 decreased to 20% of control, whereas CYP2E1 and CYP3A23 increased 2.3 and 4 times, respectively, compared with control. But expression of CYP1A2 and CYP2B1/2 was not changed by U-ARF. After i.v. administration of CZX at a dose of 20 mg/kg to rats with U-ARF, the areas under the plasma concentration-time curve from time 0 to time infinity (AUCs) of CZX and OH-CZX were significantly smaller and greater, respectively, than those in control rats. In rats with U-ARF, CZX was below the detection limit at 120 min in all rat tissues studied, whereas it was detected in all tissues of control rats at both 30 and 120 min. However, in control rats, OH-CZX was below the detection limit at both 30 and 120 min in all rat tissues except kidney, whereas it was detected in all tissues of rats with U-ARF at both 30 and 120 min. Based on results from supporting experiments with DDT and 2,2-bis(4-chlorophenyl)1,1-dichloroethylene treatment of rats, the contribution of CYP3A23 and CYP3A2 to the enhanced formation of OH-CZX in rats with U-ARF is likely to be negligible.

Identification of genes enhanced by protein-calorie malnutrition by differential display polymerase chain reaction (expression of fibrinogen B beta chain, B cell translocation gene 1 and thyroid hormone responsive protein genes).

Protein-calorie malnutrition (PCM), as one of global health problems, arises during protein and/or energy deficit due to disease and nutritional inadequacy. Previously, we showed that PCM elicited oxidative stress with activation of the phase II detoxifying gene expression, which was reversed by cysteine supplementation. As part of the attempts to identify the cellular adaptive responses and the associated gene expression during PCM, the current study was initiated to analyze the genes differentially expressed in the rat during PCM. Among 1,916 bands amplified, 85 putative differentially amplified bands were enhanced by PCM in the liver, while the expression of 64 bands was suppressed. Northern and/or reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that PCM increased the expression of fibrinogen B beta chain, B cell translocation gene I (BTGI) and thyroid hormone responsive protein (THRP) mRNAs. The increase in the hepatic fibrinogen B beta chain mRNA was not prevented by cysteine supplementation, whereas cysteine decreased the enhancement in the rGSTA2 and microsomal epoxide hydrolase mRNA expression. Cysteine was also active in reversing the increase in BTG1 mRNA during PCM. This was supported by the increase in BTG1 mRNA in H4IIE cells exposed to sulfur amino acid-deprived medium. Northern blot analysis revealed that THRP, highly expressed in the brain in a tissue-specific manner, was induced by PCM and that cysteine supplementation abolished the THRP induction. Conversely, the level of hepatic albumin mRNA was markedly decreased by PCM, which was partially restored by cysteine supplementation. Differential display RT-PCR analysis allowed us to identify the genes that are responsive to oxidative stress during PCM and to characterize the differential role of cysteine on the expression of the fibrinogen B beta chain, BTG1 and THRP genes as a homeostatic adaptive response during protein deficiency.