The inter‐rater reliability of the Japanese version of the Inventory of Depressive Symptomatology, Clinician version

The Inventory of Depressive Symptomatology, clinician version (IDS‐C), was developed by Rush et al. to evaluate the severity of major depressive episodes. The aim of the present study was to establish the inter‐rater reliability of the Japanese version of the IDS‐C. A total of 16 subjects with DSM‐IV major depressive episode were evaluated. Two psychiatrists, who had completed a training session for evaluating the IDS‐C before starting this reliability study, attended systematic interview sessions with each subject to evaluate the IDS‐C independently, using the Japanese version of the structured interview guide for combined rating of the IDS‐C and the Hamilton Depression Rating Scale. The severity of the 30 IDS‐C items assessed by the two raters ranged from 0 to 4 for 27 items and from 0 to 3 for 3 items. The analysis of variance intra‐class correlation inter‐rater reliability values for the individual scale items ranged from 0.874 to 1.000. The present results suggest that the Japanese version of the IDS‐C is a potentially useful rating instrument with high inter‐rater reliability for measuring the severity of depressive symptoms in the hands of psychiatrists with sufficient evaluation training.     

Drug-drug interaction study to assess the effects of multiple-dose pitavastatin on steady-state warfarin in healthy adult volunteers

Warfarin, an antagonist of vitamin K, which inhibits clotting factor synthesis, is prescribed for thrombosis prophylaxis and treatment and is known to have a narrow therapeutic range. Pitavastatin is a potent HMG-CoA reductase inhibitor. In this study, the influence of multiple-dose pitavastatin (4 mg once daily) on steady-state warfarin pharmacodynamic and pharmacokinetic profiles was investigated in 24 healthy male participants whose international normalized ratio (INR) was maintained by individualized doses of warfarin. The ratio of the least squares mean of prothrombin time and INR was 0.989 (90% confidence interval [CI], 0.955-1.023) and 0.993 (0.956-1.209), respectively (test: warfarin + pitavastatin; reference: warfarin only). The geometric mean ratios of C(max) and AUC were 1.034 (90% CI, 0.994-1.075) and 1.066 (1.035-1.099), respectively, for R-warfarin and 1.033 (0.995-1.073) and 1.058 (1.026-1.092), respectively, for S-warfarin. Warfarin pharmacodynamic profiles and pharmacokinetic profiles did not differ between the warfarin monotherapy and the coadministration of pitavastatin and warfarin. No drug-drug interaction between pitavastatin and warfarin was demonstrated.     

Differential ability of periodontopathic bacteria to modulate invasion of human gingival epithelial cells by Porphyromonas gingivalis

Periodontitis is a polymicrobial infection caused by selected gram-negative bacteria including Porphyromonas gingivalis. Host cell invasion by P. gingivalis has been proposed as a possible mechanism of pathogenesis in periodontitis. The aim of the present study was to assess the influence of periodontopathogens on P. gingivalis invasion of gingival epithelial cells in polymicrobial infection. P. gingivalis was tested for its ability to invade a human gingival epithelial cell line Ca9-22 in co-infection with periodontopathogens, using an antibiotic protection assay. Among the pathogens tested, only Fusobacterium nucleatum demonstrated the ability to significantly promote P. gingivalis invasion (P < 0.01). This increased invasion was confirmed by confocal scanning laser microscopy utilizing a dual labeling technique. In contrast, co-infection with Aggregatibacter actinomycetemcomitans or Tannerella forsythia attenuated P. gingivalis invasion. The fusobacterial enhancement of host cell invasion was not observed in co-incubation with other periodontopathogens tested. These results suggested that complex synergistic or antagonistic physiologic mechanisms are intimately involved in host cell invasion by P. gingivalis in polymicrobial infection.     

Hyperbilirubinemia-related behavioral and neuropathological changes in rats: A possible schizophrenia animal model

Background

Patients with schizophrenia show a significantly higher frequency of hyperbilirubinemia than patients suffering from other psychiatric disorders and the general healthy population. We examined the hyperbilirubinemia on behavioral and neuropathological changes in rats as a possible animal model of schizophrenia.

Methods

Gunn rats with severe hyperbilirubinemia (j/j), Gunn rats without severe hyperbilirubinemia (+/j), and Wistar rats were examined by open-field, social interaction, and prepulse inhibition tests. TUNEL, AgNOR and Ki-67 were also assayed on paraffin-embedded brain sections of these rats.

Results

Compared to Wistar rats, both Gunn j/j and +/j rats showed hyperlocomotion, high sniffing scores, and low defecation scores. They showed significantly more aggressive behaviors and impaired prepulse inhibition. The numbers of Ki-67-labeled cells and AgNOR were lower and the number of TUNEL-positive cells was higher than that of Wistar rats.

Conclusions

These results might support the neurodevelopmental hypothesis of schizophrenia. Both Gunn j/j and +/j rats may be a useful animal model and provide clues to the role of hyperbilirubinemia in schizophrenia.     

Predictors of the usefulness of duloxetine for chemotherapy-induced peripheral neuropathy

Duloxetine is an effective therapeutic agent for chemotherapy-induced peripheral neuropathy (CIPN). However, predictors of duloxetine response have not been adequately explored. Therefore, this retrospective study was performed to identify predictive factors of duloxetine response in CIPN patients to guide future strategies to improve the quality of life of patients undergoing chemotherapy. The participants were 74 cancer patients who were given duloxetine for relief of CIPN at our institute between October 2010 and January 2016. Variables were extracted from clinical records for regression analysis of factors related to relief of CIPN. We evaluated the effect of duloxetine 2 weeks after administration. Groups were categorized according to degree of improvement: poor, effective, and very effective. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the usefulness of duloxetine. Threshold measures were examined using a receiver operating characteristic analysis (ROC) curve. Body height [odds ratio (OR) 0.943, 95% confidence interval (CI) 0.889–0.997; P = 0.0387], history of docetaxel use (OR 0.084, 95% Cl 0.009–0.814; P = 0.0325), and site of symptom (upper limb) (OR 3.848, 95% Cl 1.072–13.807; P = 0.0387) were significant factors related to the effect of duloxetine. ROC curve analysis of the poor effect group indicated a threshold for body height of >171.4 cm (area under the curve [AUC] = 0.61). In conclusion, body height (low), history of docetaxel use (less), and site of symptom (upper limb) were shown to be predictive factors for the usefulness of duloxetine for CIPN in patients undergoing chemotherapy.