Cell‐type‐dependent action potentials and voltage‐gated currents in mouse fungiform taste buds

Taste receptor cells fire action potentials in response to taste substances to trigger non‐exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole‐cell recordings, and subsequently we identified their cell types immunologically with cell‐type markers, an IP₃ receptor (IP₃R3) for type II cells and a SNARE protein (SNAP‐25) for type III cells. Cells not immunoreactive to these antibodies were examined as non‐IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non‐IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na⁺ current density was similar in type II cells and type III cells, but it was significantly smaller in non‐IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non‐IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA‐sensitive current density and TEA‐insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed.     

Histological features of primary tumors after induction or high-dose chemotherapy in high-risk neuroblastoma

Purpose

In the recent years in Japan, an increasing number of patients with neuroblastoma (NB) are being treated by the “delayed local treatment (DL)” policy, undergoing surgery after the completion of high-dose chemotherapy with hematopoietic stem cell rescue (HDC). We reviewed the histopathological findings of second-look operations, including those of patients treated with DL.

Patients

From 1998 to 2013, 26 patients with high-risk NB underwent radical operation following chemotherapy. Surgery was performed after induction chemotherapy in 17 cases (standard; STD), whereas 9 cases completed induction chemotherapy and HDC before undergoing tumor resection (DL). The amount of necrosis and the degree of differentiation within the post-treatment tumor were assessed.

Results

Eighty-eight percent of the tumors showed necrosis in more than 1/3 of the specimen. Two DL cases showed complete disappearance of viable tumor cells. Amount of necrosis did not affect the prognosis of the patient. Tumors with immature, poorly differentiated phenotypes showed an extremely aggressive thereafter. Though not statistically proven, ¹²³I-MIBG (metaiodobenzylguanidine) uptake may be correlated with the amount of viable cells remaining within the tumor, but not with the degree of differentiation.

Conclusions

Our results support the previous reports advocating that tumors that sustain unfavorable histology after chemotherapy behave aggressively thereafter.     

Primary orbital neuroblastoma in a 1‐month‐old boy

Neuroblastoma is a malignant tumor predominantly occurring in children and usually arising from the adrenal gland or sympathetic ganglia. We describe a neuroblastoma in a 1‐month‐old boy arising from his left orbital cavity. This tumor was refractory to chemotherapy or radiotherapy, requiring enucleation of the left eye for complete removal of the intraorbital tumor. Thereafter, he received high‐dose chemotherapy followed by autologous peripheral blood stem cell transplantation, and has been in complete remission for 3 years. Unlike neuroblastomas arising from the adrenal gland or sympathetic ganglia, primary orbital neuroblastoma may be refractory even in early infancy.     

Indications and techniques of biliary drainage for acute cholangitis in updated Tokyo Guidelines 2018

The Tokyo Guidelines 2013 (TG13) include new topics in the biliary drainage section. From these topics, we describe the indications and new techniques of biliary drainage for acute cholangitis with videos. Recently, many novel studies and case series have been published across the world, thus TG13 need to be updated regarding the indications and selection of biliary drainage based on published data. Herein, we describe the latest updated TG13 on biliary drainage in acute cholangitis with meta‐analysis. The present study showed that endoscopic transpapillary biliary drainage regardless of the use of nasobiliary drainage or biliary stenting, should be selected as the first‐line therapy for acute cholangitis. In acute cholangitis, endoscopic sphincterotomy (EST) is not routinely required for biliary drainage alone because of the concern of post‐EST bleeding. In case of concomitant bile duct stones, stone removal following EST at a single session may be considered in patients with mild or moderate acute cholangitis except in patients under anticoagulant therapy or with coagulopathy. We recommend the removal of difficult stones at two sessions after drainage in patients with a large stone or multiple stones. In patients with potential coagulopathy, endoscopic papillary dilation can be a better technique than EST for stone removal. Presently, balloon enteroscopy‐assisted endoscopic retrograde cholangiopancreatography (BE‐ERCP) is used as the first‐line therapy for biliary drainage in patients with surgically altered anatomy where BE‐ERCP expertise is present. However, the technical success rate is not always high. Thus, several studies have revealed that endoscopic ultrasonography‐guided biliary drainage (EUS‐BD) can be one of the second‐line therapies in failed BE‐ERCP as an alternative to percutaneous transhepatic biliary drainage where EUS‐BD expertise is present.     

Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos)

Although the diagnostic and severity grading criteria on the 2013 Tokyo Guidelines (TG13) are used worldwide as the primary standard for management of acute cholangitis (AC), they need to be validated through implementation and assessment in actual clinical practice. Here, we conduct a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for AC and propose TG18 criteria. While there is little evidence evaluating the TG13 criteria, they were validated through a large‐scale case series study in Japan and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate of AC based on the TG13 diagnostic criteria was higher than that based on the TG07 criteria, and that 30‐day mortality in patients with a higher severity based on the TG13 severity grading criteria was significantly higher. Furthermore, a comparison of patients treated with early or urgent biliary drainage versus patients not treated this way showed no difference in 30‐day mortality among patients with Grade I or Grade III AC, but significantly lower 30‐day mortality in patients with Grade II AC who were treated with early or urgent biliary drainage. This suggests that the TG13 severity grading criteria can be used to identify Grade II patients whose prognoses may be improved through biliary drainage. The TG13 severity grading criteria may therefore be useful as an indicator for biliary drainage as well as a predictive factor when assessing the patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can provide results quickly, are minimally invasive for the patients, and are inexpensive. We recommend that the TG13 criteria be adopted in the TG18 guidelines and used as standard practice in the clinical setting. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.     

Utility of a Score for Predicting Glomerular Filtration Rate Overestimation in Patients with Cardiovascular and Renal Diseases and Their Risk Factors

Objective We recently reported a novel score for the detection of glomerular filtration rate (GFR) overestimation using a creatinine-based equation. We examined the utility of this score in patients with cardiovascular/renal diseases and diabetes mellitus. Methods We enrolled 1,425 patients (65±15 years old; 37% women) who were admitted to our hospital for the management of cardiovascular and renal diseases and their risk factors. Overestimation of the GFR (OE) was defined as a creatinine-based GFR (eGFRcre) ≥120% of the cystatin C-based estimated GFR. The OE score was calculated as the sum of the scores for the body weight, hemoglobin concentration, and blood urea nitrogen (BUN)/serum creatinine (Scr), totaling 1 point if the body weight was <63.0 kg in men or <42.0 kg in women, 1 point if the hemoglobin concentration was <12.4 g/dL in men or <11.0 g/dL in women, and 1 point if the BUN/Scr was >26.5. Results The proportion of patients with OE was 14.2%. The score predicted OE with a sensitivity of 70.8% and a specificity of 99.6%, and the sensitivity was increased in patients ≥75 years old (88.3%) and decreased in diabetics (58.6%). When patients were divided into subgroups by the total score, the frequencies of OE were 8% (59/754), 14% (72/502), 38% (58/151), and 72% (13/18) in patients with scores of 0, 1, 2, and 3, respectively. Conclusion The OE score is useful for detecting elderly cases of cardiovascular and renal diseases in which eGFRcre overestimates the GFR, although its utility is limited in diabetics.     

Analysis of sodium generation by sodium oxide decomposition on corrosion resistance materials: a new approach towards sodium redox water-splitting cycle

In this study, the investigation of materials with corrosion resistance was carried out to prevent side reactions caused by sodium oxide (Na₂O) in the Na-redox thermochemical water splitting cycle, and essential operational conditions for sodium (Na) generation from Na₂O were also investigated. Thermal desorption spectroscopy and X-ray diffraction techniques at altered conditions were mainly used for the experimental investigation. Numerous types of materials were tested to find materials with high resistance towards corrosion and to understand essential thermal decomposition processes of Na₂O. In addition, under different temperatures and pressure conditions, the thermodynamic calculation of Gibbs free energy was performed to obtain experimental results. As a result, a Ti alloy showed significant resistance towards the corrosive reaction by Na₂O. The obtained experimental and simulated results support the direct decomposition of Na₂O to form Na and O₂ below 600 °C under low partial pressure conditions. The optimized conditions for Na generation with the Ti alloy sample can be used for low temperature water splitting.

In this study, investigation of materials with corrosion resistance was carried out to prevent side reactions by sodium oxide (Na₂O) in the Na-redox cycle, and essential operational conditions for Na generation from Na₂O were investigated.