Association of Increased Indoleamine 2, 3‐Dioxygenase With Impaired Natural Killer Cell Activity in Hemodialysis Patients

Indoleamine 2, 3‐dioxygenase (IDO) suppresses adaptive immune response. However, there was no study to examine whether IDO activity is associated with immune parameters in dialysis patients. In this study, we estimated serum IDO activity by the kynurenine/tryptophan ratio (KTR), and compared KTR with natural killer (NK) cell activity, soluble interleukin‐2 receptor (sIL‐2R) and serum levels of trace elements such as selenium (Se) and zinc (Zn) that affect T‐cell function in 28 hemodialysis (HD) patients (age: 72 ± 13 years old, time on HD: 79 ± 89 months). NK cell activity was decreased in 35.7% of the patients. KTR values were almost 10‐times higher in HD patients (380.81 ± 385.46 mM/M) than those in the referred controls (32.9 ± 9.10 mM/M). KTR was lower in patients with impaired NK cell activity than those without (279 ± 111 vs. 565 ± 603 mM/M, P = 0.07). There was no relationship between KTR and sIL‐2R and Zn, while KTR was significantly and negatively correlated with serum Se levels that can impair cellular immunity (r = ?0.41, P < 0.05). Our findings suggest that increased IDO activity with Se deficiency may be associated with impaired NK cell function in HD patients.     

Impacts of Recombinant Human Erythropoietin Treatment During Predialysis Periods on the Progression of Chronic Kidney Disease in a Large‐Scale Cohort Study (Co‐JET study)

The effect of recombinant human erythropoietin (rHuEPO) treatment on the progression of chronic kidney disease (CKD) has not been fully evaluated in Japan. We therefore retrospectively evaluated this in a sub‐cohort of a prospective multicenter study to investigate optimal hemoglobin (Hb) level of CKD patients on hemodialysis (HD) treated with rHuEPO; Japan Erythropoietin Treatment Study for Target Hb and Survival (JET study). Effect of rHuEPO treatment during predialysis period to delay initiation of HD was retrospectively assessed in 2434 patients from the JET study comparing groups with and without rHuEPO treatment. The assessment was done by Cox proportional hazards regression analysis and inverse probability‐weighted (IPW) analysis to adjust for time‐dependent confounders. The weights used in the IPW analysis were calculated using a logistic model that included baseline confounders and time‐dependent variables. During the predialysis period, 71.7% (1746 patients) were treated with rHuEPO (mean Hb level of 8.7 g/dL at initiation of rHuEPO treatment). Covariates significantly associated with initiation of rHuEPO treatment were Hb level, serum creatinine level, age, diabetes, cardiac insufficiency, and hypertension. The adjusted hazard ratio for time until HD initiation under rHuEPO treatment was 0.272 (95% CI, 0.223–0.331; P < 0.001) in the Cox analysis and 0.63 (95% CI, 0.53–0.76; P < 0.0001) in the IPW analysis. This retrospective study suggests that rHuEPO treatment during the predialysis period has preventive effects on the progression of CKD although further prospective investigation on the efficacy is needed.     

Objective assessment of internal stress in children during dental treatment by analysis of autonomic nervous activity

International Journal of Paediatric Dentistry 2012; 22: 331–341 Aims. The aim of this study was to assess the internal stress of children during dental treatment based on autonomic nerve activity and facial muscle activity. Methods. We recorded the electrocardiogram of children during the treatment of composite resin restoration and analysed autonomic nerve activity by means of power spectral analysis of heart rate variability. Simultaneously, electromyography (EMG) activity of the corrugator muscle was recorded in children during dental treatment, and the relationship between sympathetic nerve activity and corrugator EMG activity was analysed. Results. In all subjects, the mean sympathetic nerve activity was significantly higher during oral examination and after treatment compared with pre‐treatment. Depending on the sympathetic nerve responses to the other treatment procedures, the subjects could be classified into two groups: the stress group and the nonstress group. Sympathetic nerve activity was significantly higher during infiltration anaesthesia and cavity preparation compared with pre‐treatment activity in the stress group, whereas it was consistently lower than the pre‐treatment levels during most treatment procedures in the nonstress group. The mean amplitudes of the averaged corrugator muscle EMG during dental treatment did not differ between the stress and nonstress groups. Conclusion. The present results suggest that the measurement of autonomic nervous activity, especially sympathetic nervous activity, is quite useful in assessing the internal stress of children, even when no expressed sign of unease are present during dental treatment.     

Correlations between pentraxin 3 or cytokine levels in gingival crevicular fluid and clinical parameters of chronic periodontitis

The gingival crevicular fluid (GCF) contains various biomarkers, such as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α), and IL-10, among others. These cytokines have been reported to correlate with gingival inflammation and periodontal status. Therefore, the analysis of GCF may be useful for the diagnosis of periodontal status. Pentraxin 3 (PTX3) is the first identified long pentraxin, and is released by several cell types in response to proinflammatory signals. The aim of this study was to determine the levels of IL-1β, IL-6, IL-8, TNF-α, IL-10 and PTX3 in GCF from diseased and healthy sites in patients with chronic periodontitis. Cross-sectional clinical data were obtained from 50 patients with chronic periodontitis. GCF samples were collected with paper strips from one periodontal diseased site and one periodontally healthy site per subject. The levels of IL-1β, IL-6, IL-8, IL-10 and TNF-α were determined using a multiplexed bead immunoassay, and the PTX3 level was measured using an enzyme-linked immunosorbent assay. Mean clinical parameters were significantly higher at diseased sites (P < 0.01) as compared to healthy sites, and the mean levels of PTX3, IL-1β, IL-6, IL-8, IL-10 and TNF-α were higher in diseased sites (P < 0.01) than in healthy sites. There were strong correlations between PTX3 or IL-1β and periodontal status. These results suggest that GCF PTX3 levels might be useful as a diagnostic marker for periodontal disease.     

Repair processes of experimental root fractures in rat molars examined by histopathological techniques and 3D micro-CT imaging

AimsThe purpose of this study was to investigate the repair processes of experimental intra-alveolar root fractures of immature rat molars with histopathological techniques and 3-dimensional micro-computed X-ray tomography (3D micro-CT) imaging.MethodsTwelve left upper first molars of 4-week-old rats were dislocated toward the palate with modified Hoe's pliers at a load of 900 g for 20 s, and repositioned. After 1 or 2 weeks, the maxillae were dissected and scanned with micro CT for 3D micro-CT imaging. After standard histological preparation, buccolingual serial sections of the maxillae were stained with hematoxylin and eosin or Masson–Goldner stain and observed by light microscopy. Subsequently, we examined the identified root fracture lesions by 3D micro-CT imaging and histopathological sections.ResultsWe identified 6 intra-alveolar vertical incomplete fracture lines in the mesial roots. Histopathological findings showed that newly differentiated odontoblast-like cells had formed immature reparative dentin on the pulpal side of the fracture line at 1 postoperative week, and deposited reparative dentin with a tubular structure at 2 weeks. While surface resorption and granulation-tissue formation occurred on the periodontal side of the fracture line, the narrow fracture line remained unchanged, and the surface resorption lacunae were partly covered with cementum at postoperative 2 weeks.ConclusionsRoot-fracture investigation requires a combination of histopathological observation and 3D-CT imaging. Intra-alveolar fractured root repair accompanied by tubular reparative dentin formation at the pulpal side, and the deposition of cementum at the periodontal side, may occur when the fracture line is too narrow for the formation of granulation tissue.