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Aims To test the hypothesis that 1-h plasma glucose in an oral glucose tolerance test is a better predictor of the development of diabetes than 2-h plasma glucose, independently of indices of insulin secretion or action in Japanese adults. Methods A historical cohort study was conducted in 1445 Japanese workers who did not have diabetes. The association between 1-h plasma glucose and the development of Type 2 diabetes was analysed. Results Overall, 95 of the study participants developed Type 2 diabetes during a mean follow-up of 4.5 years. The area under the receiver-operating characteristic curve for 1-h plasma glucose for future diabetes [0.88 (95% CI 0.84-0.91)] was greater than that for 2-h plasma glucose [0.79 (95% CI 0.74-0.84)], and for insulinogenic [0.73 (95% CI 0.68-0.78)] and disposition indices [0.79 (95% CI 0.74-0.84); P < 0.05]. Compared with the first quartile, the hazard ratio for future diabetes in the fourth quartile of 1-h plasma glucose was 42.5 [95% CI 5.7-315.2 ( P < 0.05)] and the hazard ratio in the fourth quartile of 2-h plasma glucose was 4.4 [95% CI 1.8-10.8 ( P < 0.05)], after adjustments for covariates including fasting plasma glucose. The significance of the elevated hazard ratio in the fourth quartile of 1-h plasma glucose was maintained after adjustments for 2-h plasma glucose, insulinogenic index or disposition index, whereas the elevation of the hazard ratio in the fourth quartile of 2-h plasma glucose was diminished and was no longer significant after adjustments for 1-h plasma glucose. Conclusions One-hour plasma glucose had a greater association with the future development of Type 2 diabetes than did 2-h plasma glucose, independently of oral glucose tolerance test-derived indices of insulin action in a Japanese population. [ABSTRACT FROM AUTHOR]

Aims: Mineralocorticoid receptor (MR) blockade is an effective treatment for hypertension and diabetic nephropathy. There are no data on the effects of MR blockade on diabetic peripheral neuropathy (DPN). The aim of this study was to determine whether MRs are present in the peripheral nerves and to investigate the effectiveness of MR blockade on DPN in streptozotocin (STZ)-induced diabetic rats. Methods: Expression of MR protein and messenger RNA (mRNA) was examined in the peripheral nerves using Western blot analysis and RT-PCR. We next studied the effects of the selective MR antagonist eplerenone and the angiotensin II receptor blocker candesartan on motor and sensory nerve conduction velocity (NCV), morphometric changes and cyclooxygenase-2 (COX-2) gene and NF- κB protein expression in the peripheral nerves of STZ-induced diabetic rats. Results: Expression of MR protein and mRNA in peripheral nerves was equal to that in the kidney. Motor NCV was significantly improved by 8 weeks of treatment with either eplerenone (39.1 ± 1.2 m/s) or candesartan (46.4 ± 6.8 m/s) compared with control diabetic rats (33.7 ± 2.0 m/s) (p < 0.05). Sensory NCV was also improved by treatment with candesartan or eplerenone in diabetic rats. Eplerenone and candesartan caused significant improvement in mean myelin fibre area and mean myelin area compared with control diabetic rats (p < 0.05). COX-2 mRNA and NF- κB protein were significantly elevated in the peripheral nerves of diabetic rats compared with control rats, and treatment with eplerenone or candesartan reduced these changes in gene expression (p < 0.05). Conclusion: MR blockade may have neuroprotective effects on DPN. [ABSTRACT FROM AUTHOR]

Objective To determine the usefulness of colour Doppler ultrasonography (CDUS) in detecting prostate cancer, by comparing CDUS with grey-scale transrectal ultrasonography (TRUS) and magnetic resonance imaging (MRI). Patients and methods In all, 278 patients who underwent prostate biopsies because of an abnormal digital rectal examination, elevated prostate specific antigen levels, and/or abnormal TRUS between May 1998 and November 1999 were evaluated. The diagnostic accuracies of TRUS, CDUS, MRI and combinations of these imaging techniques in detecting prostate cancer were compared, based on the biopsy results. Results Carcinoma was detected in 233 of 1696 specimens, and 87 patients were diagnosed with prostate cancer. For each detected cancer site, the sensitivity of CDUS was lower than those of other imaging techniques, but CDUS had high a specificity and positive predictive value. The combination of grey-scale TRUS and CDUS or MRI improved the sensitivity and negative predictive value. The specificity and positive predictive value of the combination of grey-scale TRUS and MRI were less than those for grey-scale TRUS alone, while those for the combination of grey-scale TRUS and CDUS were higher than those for grey-scale TRUS alone. Five tumours were isoechoic but seen as hypervascular lesions with CDUS. Conclusion CDUS provides information useful for detecting prostate cancer when used in combination with grey-scale TRUS, and should be included in the routine examination for prostate cancer. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated a novel cytokine with osteoclastopoietic activity. Topics covered include the use of a human squamous cancer of the maxilla which caused marked leukocytosis and hypercalcemia with an increased osteoclastic bone resorption in nude mice. Also cited is the need for further research on the role of the particular cytokine in alveolar bone loss in periodontal disease.

Introduction: Recent studies have reported a relationship between periodontitis and obesity; however, the mechanisms of obesity's effects on periodontitis are not well understood. On the other hand, microRNAs (miRNAs) are known to play key roles in the post-transcriptional regulation gene expression by suppressing translation and protein synthesis. We examined the association between obesity-related miRNAs and gene expression in gingival tissue using miRNA-messenger RNA (mRNA) pairing analysis in an obese rat model., Methods: Sixteen male Wistar rats aged 8 weeks old were divided into two groups: the control group was fed a normal powdered food for 8 weeks, and the obesity group was fed a high-fat diet for 8 weeks. Distance from the cement-enamel junction to the alveolar bone crest of the first molars was measured. miRNA microarray analysis was performed on samples of serum and gingival tissue; the resulting data were used to calculate fold changes in miRNA levels in the obesity group relative to the control group, and miRNA-mRNA pairing analysis was performed to identify mRNAs potentially targeted by miRNAs of interest., Results: Alveolar bone loss in the obesity group exceeded that in the control group (p = .017). miRNA-mRNA pairing analysis identified an association between 4 miRNAs (miR-759, miR-9a-3p, miR-203b-3p, and miR-878) that were differentially expressed in the obesity and control groups and 7 genes (Ly86, Arid5b, Rgs18, Mlana, P2ry13, Kif1b, and Myt1) expressed in gingival tissue., Conclusion: This study revealed that several miRNAs play an important role in the mechanism of periodontal disease progression induced by the obesity., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: DNA methylation is believed to be maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not stable. We demonstrate that stimulatory signals can change the DNA methylation status around transcription factor binding sites and a transcription start site and activate expression of the aldosterone synthase gene ( CYP11B2 )., Methods and Results: DNA methylation of CYP11B2 was analyzed in aldosterone-producing adenomas, nonfunctioning adrenal adenomas, and adrenal glands and compared with the gene expression levels. CpG dinucleotides in the CYP11B2 promoter were found to be hypormethylated in tissues with high expression, but not in those with low expression, of CYP11B2 . Methylation of the CYP11B2 promoter fused to a reporter gene decreased transcriptional activity. Methylation of recognition sequences of transcription factors, including CREB1, NGFIB (NR4A1), and NURR1 (NR4A2) diminished their DNA-binding activity. A methylated-CpG-binding protein MECP2 interacted directly with the methylated CYP11B2 promoter. In rats, low salt intake led to upregulation of CYP11B2 expression and DNA hypomethylation in the adrenal gland. Treatment with angiotensin II type 1 receptor antagonist decreased CYP11B2 expression and led to DNA hypermethylation., Conclusions: DNA demethylation may switch the phenotype of CYP11B2 expression from an inactive to an active state and regulate aldosterone biosynthesis., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the generation/function of bone forming and resorbing cells. Aging also decreases connexin43 (Cx43) expression in bone; and osteocytic Cx43 deletion partially mimics the skeletal phenotype of old mice. Particularly, aging and Cx43 deletion increase osteocyte apoptosis, and osteoclast number and bone resorption on endocortical bone surfaces. We examined herein the molecular signaling events responsible for osteocyte apoptosis and osteoclast recruitment triggered by aging and Cx43 deficiency. Cx43-silenced MLO-Y4 osteocytic (Cx43 def ) cells undergo spontaneous cell death in culture through caspase-3 activation and exhibit increased levels of apoptosis-related genes, and only transfection of Cx43 constructs able to form gap junction channels reverses Cx43 def cell death. Cx43 def cells and bones from old mice exhibit reduced levels of the pro-survival microRNA miR21 and, consistently, increased levels of the miR21 target phosphatase and tensin homolog (PTEN) and reduced phosphorylated Akt, whereas PTEN inhibition reduces Cx43 def cell apoptosis. miR21 reduction is sufficient to induce apoptosis of Cx43-expressing cells and miR21 deletion in miR21 fl/fl bones increases apoptosis-related gene expression, whereas a miR21 mimic prevents Cx43 def cell apoptosis, demonstrating that miR21 lies downstream of Cx43. Cx43 def cells release more osteoclastogenic cytokines [receptor activator of NFκB ligand (RANKL)/high-mobility group box-1 (HMGB1)], and caspase-3 inhibition prevents RANKL/HMGB1 release and the increased osteoclastogenesis induced by conditioned media from Cx43 def cells, which is blocked by antagonizing HMGB1-RAGE interaction. These findings identify a novel Cx43/miR21/HMGB1/RANKL pathway involved in preventing osteocyte apoptosis that also controls osteoclast formation/recruitment and is impaired with aging., (© 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Aim: Studies demonstrated that periodontitis modulates microRNA (miRNAs) expression rates in periodontal tissue. However, the relationship between periodontitis and miRNAs profile in circulation remains unclear. In this study, we investigated the effects of periodontitis on serum miRNAs profile in a rat model., Material and Methods: Male Wistar rats (n = 32, 8 weeks old) were divided into four groups of eight rats each. The control groups received no treatment for 2 or 4 weeks. In the other two groups, periodontitis was ligature induced for 2 or 4 weeks. Serum miRNAs expression profiles of each group were compared., Results: Ligation around teeth induced periodontal inflammation at 2 weeks and periodontal tissue destruction at 4 weeks. Microarray results showed that 25 miRNAs were expressed with a <0.5 or >2 difference between the control and periodontitis groups at 4 weeks. Results of real-time PCR revealed that the periodontitis group up-regulated expression rates of serum miR-207 and miR-495 at 2 weeks, and miR-376b-3p at 4 weeks (p < 0.05)., Conclusion: Serum miRNAs (miR-207, miR-495, and miR-376b-3p) could be valuable biomarkers for periodontitis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The purpose of this prospective cohort study was to investigate whether body mass index (BMI) and oral health behaviour are related to changes in periodontal status in Japanese university students., Materials and Methods: Students (n = 224) who were interested in receiving oral health examinations before entering university and before graduation were included in the analysis. Subjects were investigated regarding the correlations of oral health behaviours and increases in BMI with the percentage of bleeding on probing (%BOP) and Community Periodontal Index (CPI) scores as indicators of changes in periodontal status., Results: The risk of increased %BOP was associated with the non-use of dental floss (adjusted odds ratio [OR]: 3.11; 95% confidence interval [CI]: 1.31-7.37; p < 0.05), whereas the risk of increased CPI score was associated with increases in BMI (OR: 1.95; 95% CI: 1.05-3.65; p < 0.05) and simplified oral hygiene index score (OR: 2.28; 95% CI: 1.23-4.22; p < 0.01)., Conclusion: Increases in BMI were associated with worsening of periodontal status, defined as increased CPI score in Japanese university students, whereas lack of inter-dental cleaning was associated with exacerbated gingival bleeding., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The exposure of blood to hemodialysis membranes results in numerous phenomena and/or complications in hemodialyzed patients, which have an influence on the quality of life (QOL) of those patients. A vitamin E-modified regenerated cellulose membrane (E-membrane) was developed to act as a scavenger for reactive oxygen species causing complications in hemodialysis patients. Neopterin (NEOP) is a metabolite derived from guanosine triphosphate with the production and release of NEOP being induced in monocytes and macrophages by cytokines such as interferon-gamma (IFN-gamma). Serum neopterin levels are shown to be a reactive marker of bioincompatibility of dialysis membranes in hemodialysis patients. The following report evaluates the usefulness of serum NEOP as a marker for the biocompatibility of the E-membrane hemodialyzer in a clinical study. In the clinical study, where extracorporeal ultrafiltration strategies with E-membranes were employed, the serum levels of NEOP were lower than those in patients using cellulose triacetate membranes (C-membranes). In the long-term evaluation of the biocompatibility of E- and C-membranes, the increase of serum neopterin levels in the C-membrane was higher than those in the E-membrane. In conclusion, the evaluation of serum neopterin levels during hemodialysis shows that the E-membrane has a good biocompatibility in hemodialyzed patients.

1. 11 beta-Hydroxysteroid dehydrogenase (11-HSD) activity in mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was determined and expressed as the percentage conversion of [3H]-corticosterone to [3H]-11-dehydrocorticosterone. 2. 11-HSD activity was significantly decreased in mesenteric arteries of both 4 and 9 week old SHR (8.4 +/- 0.8%, 5.0 +/- 1.5%, respectively) compared with WKY rats (12.4 +/- 0.6%, 15.8 +/- 0.7%, respectively; P < 0.05). 3. Total RNA from rat vascular smooth muscle cells (VSMC) and endothelial cells (EC) were prepared with selective precipitation in 3 mol/L LiCl/6 mol/L urea. The expression of 11-HSD mRNA was confirmed in the rat VSMC but its mRNA expression was not detected in EC, using northern blot analysis. 4. The results in this study indicate that 11-HSD in the vascular wall may play a role in the pathogenesis of hypertension in SHR.