Humanin derivative, HNG, enhances neurotransmitter release.

BACKGROUND: Humanin (HN) is an endogenous 24-residue peptide that was first identified as a protective factor against neuronal death in Alzheimer's disease (AD). We previously demonstrated that the highly potent HN derivative HNG (HN with substitution of Gly for Ser14) ameliorated cognitive impairment in AD mouse models. Despite the accumulating evidence on the antagonizing effects of HN against cognitive deficits, the mechanisms behind these effects remain to be elucidated. METHODS: The extracellular fluid in the hippocampus of wild-type young mice was collected by microdialysis and the amounts of neurotransmitters were measured. The kinetic analysis of exocytosis was performed by amperometry using neuroendocrine cells. RESULTS: The hippocampal acetylcholine (ACh) levels were increased by intraperitoneal injection of HNG. HNG did not affect the physical activities of the mice but modestly improved their object memory. In a neuronal cell model, rat pheochromocytoma PC12 cells, HNG enhanced ACh-induced dopamine release. HNG increased ACh-induced secretory events and vesicular quantal size in primary neuroendocrine cells. CONCLUSIONS: These findings suggest that HN directly enhances regulated exocytosis in neurons, which can contribute to the improvement of cognitive functions. GENERAL SIGNIFICANCE: The regulator of exocytosis is a novel physiological role of HN, which provides a molecular clue for HN's effects on brain functions under health and disease.

Endoscopic Transpapillary Gallbladder Drainage for Acute Cholecystitis After Biliary Self-Expandable Metal Stent Placement.

BACKGROUND: Endoscopic transpapillary gallbladder drainage (ETGBD) for acute cholecystitis (AC) after self-expandable metal stent (SEMS) placement is technically challenging and there are no reports about its outcome in a several cases. This study aims to assess the outcomes of ETGBD for AC after SEMS placement. METHODS: Between April 2011 and April 2019, 314 patients underwent SEMS placement for biliary stricture. Among them, 12 of 21 patients who developed AC after SEMS placement underwent ETGBD. In general, ETGBD was performed after SEMS removal in cases in which a covered SEMS was previously placed or with the SEMS kept in place in cases in which an uncovered SEMS was previously placed. When the orifice of the cystic duct overlapped the uncovered SEMS, ETGBD was performed through the mesh of the SEMS. RESULTS: Among the 12 patients who underwent ETGBD, the previously placed SEMS was in the distal (n=8) or perihilar (n=4) bile duct. The type of SEMS placed in the distal bile duct was covered in 7 (fully covered: 6, partially covered: 1) and uncovered in 1, whereas that in the perihilar bile duct was uncovered for all. The technical success rate of ETGBD was 83.3% (10/12), and that according to the previous SEMS placement site was 75.0% (6/8) for the distal bile duct and 100% (4/4) for the perihilar bile duct. In the technically successful, the clinical success rate for AC was 90.0% (9/10). The rate of adverse event was 16.7% (2/12) (stent kink: 1, tube self-removal: 1). CONCLUSIONS: ETGBD can have relatively good outcomes for AC after SEMS placement.

A rare case of Epstein-Barr virus-positive mucocutaneous ulcer that developed into an intestinal obstruction: a case report.

BACKGROUND: Epstein-Barr virus-positive mucocutaneous ulcer (EBV-MCU) is a new category of mature B-cell neoplasms. Ulcers occur in the oropharyngeal mucosa, skin, and gastrointestinal tract. The onset of EBV-MCU is suggested to be related to the decreased immunity of the patient, the causes of which include the use of immunosuppressive agents and aging. EBV-MCU may regress spontaneously and it often has a benign course after the dose reduction or discontinuation of immunosuppressive agents or during follow-up. Here, we report the case of a patient who required surgical resection for the intestinal obstruction arising from EBV-MCU. CASE PRESENTATION: A Japanese elderly male visited our hospital with chief complaints of a palpable mass and dull pain in the left upper quadrant, loss of appetite, and weight loss. Although abdominal computed tomography and total colonoscopy (TCS) revealed a tumor with circumferential ulcer in the transverse colon, histopathological analysis of a biopsy specimen of this lesion showed only nonspecific inflammation. Because the tumor spontaneously regressed during the time he underwent tests to obtain a second opinion from another hospital, TCS was reperformed on the patient. TCS revealed that the tumor decreased in size and the inflammatory changes in the surrounding mucosa tended to improve; however, tightening of the surrounding mucosa due to scarring was observed. Another histopathological analysis of a biopsy specimen showed widespread erosion of the mucosa and the formation of granulation tissue with marked infiltration of various inflammatory cells into the mucosal tissue of the large intestine. Moreover, some of the B-lymphocyte antigen CD20-positive B cells were also positive for EBV-encoded small RNA-1, suggesting the possibility of EBV-MCU. Later, the tumor developed into an intestinal obstruction; thus, the transverse colon was resected. Histopathological analysis of the resected specimen demonstrated scattered Hodgkin and Reed-Sternberg-like multinucleated large B cells in addition to EBER-1-positive cells. The patient was finally diagnosed as having EBV-MCU. CONCLUSIONS: This is the first report of a case of EBV-MCU that developed into an intestinal obstruction requiring surgical resection. It is necessary to consider the possibility of EBV-MCU when examining an ulcerative or tumorous lesion in the gastrointestinal tract.

Endoscopic Sphincterotomy before Fully Covered Metal Stent Placement Is Not Required for Distal Malignant Biliary Stricture due to a Pancreatic Head Tumor.

BACKGROUND/AIMS: Endoscopic sphincterotomy (EST) is often performed before fully covered self-expandable metal stent (FCSEMS) placement in order to prevent pancreatitis. However, it is not clear whether EST prevents pancreatitis or affects other adverse events (AEs). This study is conducted to evaluate the necessity of EST before FCSEMS placement for distal malignant biliary strictures due to a pancreatic head tumor. METHODS: This study included 68 patients who underwent FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor. Treatment outcomes and AEs were retrospectively compared between 32 patients with EST before FCSEMS placement (EST group) and 36 patients without EST (non-EST group). RESULTS: The success rates of drainage for the EST and non-EST groups were 100% and 97.2%, respectively (P = 0.95). The incidence of pancreatitis in the EST and non-EST groups was 3.1% and 0%, respectively (P = 0.95). The incidence of hyperamylasemia in the EST and non-EST groups was 12.5% and 13.9%, respectively (P = 0.85). The incidence of all AEs in the EST and non-EST groups was 15.6% (pancreatitis: 1, cholecystitis: 2, and stent migration: 2) and 13.9% (cholecystitis: 3, stent migration: 2), respectively (P = 0.89). CONCLUSIONS: EST before FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor does not affect the successful drainage and incidence of adverse events. The necessity of EST to prevent pancreatitis before FCSEMS placement was deemed low.

Efficacy of Combined Thrombomodulin and Antithrombin in Anticoagulant Therapy for Acute Cholangitis-induced Disseminated Intravascular Coagulation.

Objective The efficacy and safety of concomitant use of antithrombin (AT) with recombinant human soluble thrombomodulin (rTM) for acute cholangitis-induced disseminated intravascular coagulation (AC-induced DIC) remains unclear. This study was conducted to investigate the efficacy of AT combined with rTM as anticoagulant therapy for AC-induced DIC. Methods One hundred patients with AC-induced DIC received anticoagulant therapy using rTM from April 2010 to December 2017. Of the 83 patients treated with rTM immediately after the diagnosis of DIC, excluding those who had not undergone biliary drainage or who had malignancies or a serum AT III level >70%, 56 patients were studied. Outcomes and adverse events (AEs) were retrospectively compared between the 16 patients treated with rTM alone (rTM group) and the 40 patients treated with rTM and AT (rTM+AT group). Results Patients' background characteristics did not differ markedly, except for a significantly higher serum D-dimer level in the rTM group than in the rTM+AT group (p=0.038). The DIC resolution rates on day 9 were 100% and 95.1% in the rTM and rTM+AT groups, respectively (p=0.909). The mean DIC scores were significantly lower in the rTM group than in the rTM+AT group on days 3 (p=0.012), 5 (p<0.001), 7 (p=0.033), and 9 (p=0.007). The incidence of AEs was 6.3% and 10.0% (p=0.941), and the in-hospital mortality rates was 0% and 5.0% (p=0.909) in the rTM and rTM+AT groups, respectively. Conclusion The concomitant use of AT with anticoagulant therapy using rTM for AC-induced DIC may not help improve the treatment outcome.

Diagnostic Ability of Endoscopic Bile Cytology Using a Newly Designed Biliary Scraper for Biliary Strictures.

BACKGROUND: A new device with metallic wires for scrape cytology was developed. AIMS: To compare the diagnostic performance of scrape cytology and conventional cytology during endoscopic retrograde cholangiopancreatography for biliary strictures. METHODS: A total of 420 cases with biliary stricture underwent transpapillary bile cytology. Among them, there are 79 cases with scrape cytology using the new device (scrape group) and 341 cases with conventional cytology (control group). Seventy-two and 174 cases underwent biliary biopsy at the same time as bile cytology in the scrape and control group, respectively. RESULTS: The sensitivity for malignancy of bile cytology in the scrape and control group was 41.2% [pancreatic cancer (PC): 23.1%, biliary cancer (BC): 52.5%] and 27.1% (PC: 16.3%, BC: 38.0%), respectively (P = 0.023). When analyzed PC and BC, respectively, there was no significant difference between the two groups. In the both groups, the sensitivity was significantly higher for BC than PC. In the scrape group, there was no difference in the sensitivity between cytology and biopsy [39.7% (PC: 17.4%, BC: 55.3%)], but in the control group, a significantly lower sensitivity was observed with cytology than biopsy (36.4% (PC: 19.7%, BC: 50.0%)) (P = 0.046). When analyzed PC and BC, respectively, there was no significant difference between cytology and biopsy. The sensitivity of combined cytology and biopsy was 55.6% (PC: 30.4%, BC: 71.1%) in the scrape group and 47.0% (PC: 24.6%, BC: 64.3%) in the control group. CONCLUSION: Scrape bile cytology for biliary strictures may be superior to conventional cytology.

Efficacy and Safety of Single-Session Endoscopic Stone Removal for Acute Cholangitis Associated with Choledocholithiasis.

Background/Aims: In early endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis due to choledocholithiasis, it is unclear that single-session stone removal can be safely performed. We examined the efficacy and safety of early single-session stone removal for mild-to-moderate acute cholangitis associated with choledocholithiasis. Methods: Among patients with mild-to-moderate acute cholangitis associated with choledocholithiasis who underwent early ERCP (n = 167), we retrospectively compared the removal group (patients who underwent single-session stone removal; n = 78) with the drainage group (patients who underwent biliary drainage alone; n = 89) and examined the effectiveness and safety of single-session stone removal by early ERCP. Results: The patients in the removal group had significantly fewer and smaller stones compared with those in the drainage group. The single-session complete stone removal rate was 85.9% in the removal group. The complication rate in early ERCP was 11.5% in the removal group and 10.1% in the drainage group, with no significant difference (P = 0.963). On comparing patients who underwent early endoscopic sphincterotomy (EST) with those who underwent elective EST after cholangitis had improved, the post-EST bleeding rates were 6.8% and 2.7%, respectively, with no significant difference (P = 0.600). The mean duration of hospitalization was 11.9 days for the removal group and 19.9 days for the drainage group, indicating a shorter stay for the removal group (P < 0.001). In multiple linear regression analysis, stone removal in early ERCP, number of stones, and C-reactive protein level were significant predictors of hospitalization period. Conclusions: Single-session stone removal for mild-to-moderate acute cholangitis can be safely performed. It is useful from the perspective of shorter hospital stay.

Post-Embryonic Development and Genital-Complex Formation in Three Species of Polyclad Flatworms.

Without the establishment of effective culturing systems, little can be known about the late developmental stages of polyclad flatworms. Here, we report a laboratory culturing system for three polyclad species: Comoplana pusilla, Notocomplana koreana, and Pseudostylochus obscurus, and we describe changes in their morphology from hatching to reproductive maturity. These species hatch out as lobe-less larvae with four eyespots, but the number of eyespots increases in later development. Cross-like and triangularly shaped larvae are observed in N. koreana and P. obscurus, respectively. After settlement, a pale area appears on the body of juveniles and then develops into the copulatory complexes. All three species could be successfully reared on brine shrimp, but only C. pusilla and N. koreana achieved reproductive maturation in such a culturing system. In P. obscurus, switching the food to the gastropod Monodonta labio induced sexual maturation.

A low cost light diffuser made of metal coil.

We proposed a low cost flexible light diffuser made of metal coil to obtain an appropriate light dose against certain laser therapies in narrow bending organs. We investigated experimentally the diffusion light dose of prototype coils made of stainless steel (sus304). We measured the diffusion light intensity of the prototype coils along the irradiation direction and the circumferential direction with the various pitch distances of the prototype coils and numerical aperture (NA) of laser light beam as the characteristic parameters of the light diffusion. We measured the temperature elevation of the prototype coils to study the waste energy of these prototype coils. The FWHM on the light intensity along the prototype coils marked up to 12.8mm with the constant pitch distance of 0.09 mm and the fiber output light NA of 0.038. The FWHM on the light intensity was improved to 13.7 mm with the composite pitch distance coils of which the pitch distances were 0.09 mm in the proximate and 0.18 mm in the distal. Since the efficiency of the diffusion irradiation against the fiber output was typically 7.7% in the prototype coils of which the surface reflectance was 50%, approximately 90% of the laser light energy was transferred to the temperature elevation. We estimated the practical diffusion efficiency around 75% using the high reflection of the prototype coils surface up to 90%.