Rhythm-control strategy with oral cilostazol for refractory protein-losing enteropathy and sinus node dysfunction after the Fontan operation: A case report.

Despite recent advances in therapeutic approaches, treatment for patients with refractory protein-losing enteropathy (PLE) after undergoing the Fontan procedure remains a challenge for clinicians. In this report, we present a Fontan patient in whom oral cilostazol improved PLE with a restored atrial rhythm. We report on a 13-year-old girl with double-outlet right ventricle, ventricular septal defect, l-transposition of the great arteries, and left ventricle hypoplasia. After the Fontan procedure at 16 months of age, she developed PLE at the age of 2 years. As medical treatments such as diuretics, enalapril, heparin, stent implantation for left pulmonary artery, and oral steroids did not lead to remission, intermittent albumin administration was needed. She had ectopic atrial and junctional rhythms, and cardiac catheterization revealed that the junctional rhythm decreased cardiac output and increased central venous pressure. We therefore started her on cilostazol and succeeded in the maintenance of atrial rhythm, resulting in increased serum albumin, globulin, electrolytes, and nutritional status markers with suppression of bowel inflammation. This patient finally was taken off the steroid and returned to a normal school and home life. Oral cilostazol is a possible therapeutic strategy for refractory PLE, as it improves hemodynamics in Fontan patients with sinus node dysfunction. Learning objective: We present a Fontan patient in whom oral cilostazol for maintaining atrial rhythm improved protein-losing enteropathy (PLE) without any side effects. The junctional rhythm disappeared after the initiation of cilostazol, which suggested that cilostazol stimulated a dominant pacemaker even if the pacemaker was an ectopic focus in the atrium. Oral cilostazol is a possible therapeutic strategy for refractory PLE. We also propose oral cilostazol as a bridging therapy prior to pacemaker implantation.

Tuberculosis screening using a T-cell interferon-γ release assay in Japanese medical students and non-Japanese international students.

Screening of medical students and international students for tuberculosis (TB) at the time of admission is a key strategy to control and prevent the spread of infection on university campus and teaching hospitals because of the high risk of exposure to TB patients. The Mycobacterium tuberculosis antigen-specific T-cell interferon-γ release assays (IGRAs) are specific latent tuberculosis detection methods used in such groups. Currently, in Japan, there are no guidelines and no baseline data on IGRAs to evaluate the risk of TB in these high-risk groups. In order to evaluate TB risk at the time of admission in university campus and medical schools in Japan, a retrospective study was conducted. A total of 969 students (585 Japanese students and 384 international students) were screened for TB using the IGRAs at the time of admission. Eight Japanese students (0.9%) were positive for IGRAs, but none were diagnosed with active TB at the follow-up. In contrast, 30 international students (7.8%) were positive for IGRAs, including two students diagnosed with active TB during follow up. Positive ratio of IGRAs in international students was significantly higher than that of medical students at the time of admission. Here we propose a standard approach for TB screening with IGRAs at the time of admission for medical students and international students in Japan.

Diphenylpropynone derivatives as probes for imaging ß-amyloid plaques in Alzheimer's brains.

A new series of diphenylpropynone (DPP) derivatives for use in vivo to image ß-amyloid (Aß) plaques in the brain of patients with Alzheimer's disease (AD) were synthesized and characterized. Binding experiments in vitro revealed high affinity for Aß (1-42) aggregates at a K(i) value ranging from 6 to 326 nM. Furthermore, specific labeling of plaques was observed in sections of brain tissue from Tg2576 transgenic mice stained using one of the compounds, 1. In biodistribution experiments with normal mice, [(125)I]1 displayed moderate uptake (1.55%ID/g at 2 min) and clearance from the brain with time (0.76 ID/g at 60 min). Taken together, DPP can serve as a new molecular scaffold for developing novel Aß imaging agents by introducing appropriate substituted groups.

Fluoro-pegylated chalcones as positron emission tomography probes for in vivo imaging of beta-amyloid plaques in Alzheimer's disease.

This paper describes the synthesis and biological evaluation of fluoro-pegylated (FPEG) chalcones for the imaging of beta-amyloid (Abeta) plaques in patients with Alzheimer's disease (AD). FPEG chalcone derivatives were prepared by the aldol condensation reaction. In binding experiments conducted in vitro using Abeta(1-42) aggregates, the FPEG chalcone derivatives having a dimethylamino group showed higher Ki values (20-50 nM) than those having a monomethylamino or a primary amine group. When the biodistribution of 11C-labeled FPEG chalcone derivatives having a dimethyamino group was examined in normal mice, all four derivatives were found to display sufficient uptake for imaging Abeta plaques in the brain. 18F-labeled 7c also showed good uptake by and clearance from the brain, although a slight difference between the 11C and 18F tracers was observed. When the labeling of Abeta plaques was carried out using brain sections of AD model mice and an AD patient, the FPEG chalcone derivative 7c intensely labeled Abeta plaques. Taken together, the results suggest 7c to be a useful candidate PET tracer for detecting Abeta plaques in the brain of patients with AD.

18F-labeled flavones for in vivo imaging of beta-amyloid plaques in Alzheimer's brains.

In vivo imaging of beta-amyloid (Abeta) aggregates in the brain may lead to early detection of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of treatment. The purpose of this study was to develop novel (18)F-labeled amyloid-imaging probes based on flavones as a core structure. Fluoropegylated (FPEG) flavone derivatives were designed and synthesized. The affinity of the derivatives for Abeta aggregates varied from 5 to 321nM. In brain sections of AD model mice, FPEG flavones with the dimethylamino group intensely stained beta-amyloid plaques. In biodistrubution experiments using normal mice, they displayed high uptake in the brain ranging from 2.9 to 4.2%ID/g at 2 min postinjection. The radioactivity washed out from the brain rapidly (1.3-2.0%ID/g at 30 min), which is highly desirable for beta-amyloid imaging agents. FPEG flavones may be potential PET imaging agents for beta-amyloid plaques in Alzheimer's brains.

Low dose effects of bisphenol A on sexual differentiation of the brain and behavior in rats.

There is an endocrinological concern that environmental endocrine disrupters (EEDs) may influence sexual differentiation. Bisphenol A (BPA), one of EEDs, is released from polycarbonate plastics, and has been detected in the human umbilical cord. In this study, we examined the effect of BPA on the sexual differentiation of open-field behavior and the sexually dimorphic nuclei in the brain in the offspring of rats exposed to BPA during the fetal and suckling periods at a dosage below the human tolerable daily intake (TDI) level. In the control group, females were more active in the open field and had a larger locus coeruleus (LC) volume than males. BPA abolished and inverted the sex differences of the open-field behavior and the LC volume, respectively, without affecting the reproductive system. We also compared the effects of estrogenic compounds, diethylstilbestrol (DES) and resveratrol (RVT), to that of BPA because of their structural similarities. DES affected the open-field behavior, LC volume and reproductive system, while RVT affected the LC volume and the reproductive system. These results suggest that the brain is highly sensitive to BPA at a dosage below TDI and that the disrupting effects of BPA on sexual differentiation may vary from those of RVT and DES.