Abstract-Although cAMP is an important second messenger that plays a pivotal role in the regulation of platelet aggregation and dilatation of blood vessels, little is known about the action of cAMP on the growth of vascular smooth muscle cells (VSMCs). Thus, we initially studied the effects of cAMP accumulation by using various cAMP stimulants, including a phosphodiesterase type 3 inhibitor (cilostazol) on human aortic VSMC growth. Accumulation of cAMP inhibited the platelet-derived growth factor (PDGF)-stimulated VSMC growth in a dose-dependent manner (PϽ0.01), whereas PDGF significantly stimulated the growth of human VSMCs. Thus, we focused on the role of cell cycle regulatory genes, especially on a negative regulator, an anti-oncogene, p53. The protein of p53 was potentiated by cilostazol as well as forskolin and 8-bromo-cAMP, whereas PDGF decreased p53 expression. Upregulation of p53 protein by cAMP was further confirmed by the observation that the decrease in p21, a p53-inducible protein, by PDGF was significantly attenuated by cilostazol in a dose-dependent manner (PϽ0.01). These results revealed that accumulation of cAMP inhibited VSMC proliferation, which was at least in part due to an increase in p53-p21 expression. Because p53 and p21 have been reported to induce apoptosis, we examined apoptotic cells for cAMP accumulation. Incubation of VSMCs with cilostazol resulted in a significant increase in apoptotic cells in a dose-dependent manner compared with vehicle treatment as assessed by nuclear chromatic morphology (PϽ0.01); forskolin also stimulated apoptotic cells. Consistent with nuclear staining, DNA fragmentation in VSMCs treated with forskolin as well as 8-bromo-cAMP and cilostazol was significantly increased compared with DNA fragmentation in VSMCs treated with vehicle, whereas PDGF significantly decreased the rate of DNA fragmentation (PϽ0.01

Aim Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. Methods Four hundred thirteen out of 461 psychiatrists attended two 1‐day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants’ clinical knowledge of the treatment guidelines using self‐completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants’ demographics and their clinical knowledge scores. Results The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. Conclusion Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants’ clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders.

Background Guideline for Pharmacological Therapy for Schizophrenia was published by the Japanese Society of Neuropsychopharmacology in 2015. “Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)” project aimed to standardize medical practice using quality indicators (QIs) as indices to evaluate the quality of medical practice. In this study, we have reported the quality indicator values of prescription before the beginning of the guideline lectures in the EGUIDE project to ascertain the baseline status of treating patients with schizophrenia. Methods A cross‐sectional, retrospective case record survey was conducted, involving 1164 patients with schizophrenia at the time of discharge. We checked all types and dosage of psychotropic drugs. Results Forty‐three percent of patients had antipsychotic polypharmacy, and substantial concomitant medication was observed (antidepressants; 8%, mood stabilizers: 37%, anxiolytics or hypnotics: 68%). Conclusions In the results obtained in this study, we plant to report changes in the effectiveness of education in the EGUIDE project near the future.

According to past analyses of prescription and treatment patterns for major depressive disorder (MDD), the majority of MDD patients in Japan have not been treated according to the recommended guidelines. 1 In this context, the Japanese Society of Mood Disorders published the 'Treatment Guidelines for Major Depressive Disorders' (GL) in 2012, and the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' project was launched in 2016, which aimed to standardize medical practice using quality indicators (QI) as indices for the quality of medical practice. 2, 3 The present study was a cross-sectional, retrospective study conducted in a total of 84 institutions (36 university hospitals, 23 national/

We report the case of a 31-year-old man who had mild traumatic brain injury as a result of an accident at the age of 24 years. Seven years after the trauma, at the age of 31 years, he had a lower verbal intelligence quotient than performance intelligence quotient by the Wechsler Adult Intelligence Scale - Revised, and frontal lobe dysfunction, for example, difficulty in maintaining or changing the set as revealed by the Wisconsin Card Sorting Test Keio Version. Conventional brain magnetic resonance imaging had not shown any abnormalities. Abnormal brain areas were detected on magnetic resonance diffusion tensor imaging. On tractography, some fibres from the corpus callosum towards the frontal cortex were noted to be lacking in the left hemisphere compared with the right. The tractography results may explain the patient's lowered verbal intelligence quotient and focal left frontal lobe dysfunction. Diffusion tensor imaging is therefore helpful in detecting lesions in mild traumatic brain injury with diffuse axonal injury.