Promising role of D-amino acids in irritable bowel syndrome

Irritable bowel syndrome (IBS) is an important health care concern. Alterations in the microbiota of the gut-brain axis may be linked to the pathophysiology of IBS. Some dietary intake could contribute to produce various metabolites including D-amino acids by the fermentation by the gut microbiota. D-amino acids are the enantiomeric counterparts of L-amino acids, in general, which could play key roles in cellular physiological processes against various oxidative stresses. Therefore, the presence of D-amino acids has been shown to be linked to the protection of several organs in the body. In particular, the gut microbiota could play significant roles in the stability of emotion via the action of D-amino acids. Here, we would like to shed light on the roles of D-amino acids, which could be used for the treatment of IBS.     

Guidelines for standardizing cleansing and disinfection of gastrointestinal endoscopes

As part of the activities toward standardizing endoscopy procedures, the Japan Gastroenterological Endoscopy Society has prepared guidelines for cleansing and disinfection of gastrointestinal endoscopes. The environment of gastrointestinal endoscopy differs between Japan and advanced Western countries. In advanced Western countries, gastrointestinal endoscopy is performed almost exclusively at specialized facilities, where strict provisions are observed for cleansing and disinfecting endoscopes. In Japan, however, gastrointestinal endoscopy is performed even in small clinics, and the annual number of gastrointestinal endoscopy cases is enormous. In addition, the method for cleansing and disinfecting endoscopes differs among hospitals. Although there is a distinct lack of evidence for how gastrointestinal endoscopes are cleaned and disinfected, it is necessary to standardize the method for doing so to advance the field of endoscopic medicine.     

Spontaneous recovery of fear differs among early – late adolescent and adult male mice

Adolescence is a vulnerable period for developing anxiety-related mental disorders such as post-traumatic stress disorder (PTSD), which requires a long-term course of therapy when a traumatic event has been experienced during childhood. However, the biological mechanism underlying these age-dependent characteristics remains unclear. In the present study, we used early adolescent, late adolescent and adult (4-, 8-, and 15-week old) male mice to examine age differences in fear memory, fear extinction, and spontaneous recovery of fear. We also measured the activation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus (dHip) and the basolateral amygdala (BLA) following a spontaneous recovery test. Our major findings were as follows: (1) early adolescent and adult mice did not recover the fear response; only late adolescent mice recovered the fear response. (2) The ERK2 in the dHip was more activated after the spontaneous recovery test in late adolescent mice than in adult mice, and the ERK2 in the BLA was more activated after the spontaneous recovery test in adult mice than in late adolescent mice. These results suggest that there exists a unique period in which spontaneous recovery occurs and that these late adolescent behavioral signatures may be related to alteration in the ERK2 phosphorylation in the dHip and BLA.     

Risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia

Objective

The purpose of this study was to identify the risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia (FCD).

History and Profile of Diagnosis Procedure Combination (DPC): Development of a Real Data Collection System for Acute Inpatient Care in Japan

DPC, which is an acronym for “Diagnosis Procedure Combination,” is a patient classification method developed in Japan for inpatients in the acute phase of illness. It was developed as a measuring tool intended to make acute inpatient care transparent, aiming at standardization of Japanese medical care, as well as evaluation and improvement of its quality. Subsequently, this classification method came to be used in the Japanese medical service reimbursement system for acute inpatient care and appropriate allocation of medical resources. Furthermore, it has recently contributed to the development and maintenance of an appropriate medical care provision system at a regional level, which is accomplished based on DPC data used for patient classification. In this paper, we first provide an overview of DPC. Next, we will look back at over 15 years of DPC history; in particular, we will explore how DPC has been refined to become an appropriate medical service reimbursement system. Finally, we will introduce an outline of DPC-related research, starting with research using DPC data.Key words: Diagnosis Procedure Combination (DPC), DPC-based Per-Diem Payment System (DPC/PDPS), patient classification system, health policy, Japan     

Repair of DNA damage induced by the novel nucleoside analogue CNDAG through homologous recombination

We postulate that the deoxyguanosine analogue CNDAG [9-(2-C-cyano-2-deoxy-1-β-d-arabino-pentofuranosyl)guanine] likely causes a single-strand break after incorporation into DNA, similar to the action of its cytosine congener CNDAC, and that subsequent DNA replication across the unrepaired nick would generate a double-strand break. This study aimed at identifying cellular responses and repair mechanisms for CNDAG prodrugs, 2-amino-9-(2-C-cyano-2-deoxy-1-β-d-arabino-pentofuranosyl)-6-methoxy purine (6-OMe) and 9-(2-C-cyano-2-deoxy-1-β-d-arabino-pentofuranosyl)-2,6-diaminopurine (6-NH2). Each compound is a substrate for adenosine deaminase, the action of which generates CNDAG. Growth inhibition assay, clonogenic survival assay, immunoblotting, and cytogenetic analyses (chromosomal aberrations and sister chromatid exchanges) were used to investigate the impact of CNDAG on cell lines. The 6-NH2 derivative was selectively potent in T cell malignant cell lines. Both prodrugs caused increased phosphorylation of ATM and its downstream substrates Chk1, Chk2, SMC1, NBS1, and H2AX, indicating activation of ATM-dependent DNA damage response pathways. In contrast, there was no increase in phosphorylation of DNA-PKcs, which participates in repair of double-strand breaks by non-homologous end-joining. Deficiency in ATM, RAD51D, XRCC3, BRCA2, and XPF, but not DNA-PK or p53, conferred significant clonogenic sensitivity to CNDAG or the prodrugs. Moreover, hamster cells lacking XPF acquired remarkably more chromosomal aberrations after incubation for two cell cycle times with CNDAG 6-NH2, compared to the wild type. Furthermore, CNDAG 6-NH2 induced greater levels of sister chromatid exchanges in wild-type cells exposed for two cycles than those for one cycle, consistent with increased double-strand breaks after a second S phase. CNDAG-induced double-strand breaks are repaired mainly through homologous recombination.