Effect of orexin-A on post-ischemic glucose intolerance and neuronal damage

Orexin-A is a newly identified neuropeptide expressed in the lateral areas of the hypothalamus that plays a role in various physiological functions, including regulation of glucose metabolism. We have previously reported that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage. Therefore, the aim of this study was to determine the effects of orexin-A on the development of post-ischemic glucose intolerance and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Neuronal damage was estimated by histological and behavioral analysis after MCAO. Intracerebroventricular administration of orexin-A (2.5, 25, or 250 pmol/mouse) significantly and dose-dependently suppressed the development of post-ischemic glucose intolerance on day 1 after MCAO and neuronal damage on day 3 after MCAO. In the liver and skeletal muscle, the expression levels of insulin receptor were decreased, whereas those of gluconeogenic enzymes were increased on day 1 after MCAO. Furthermore, these expressions were completely recovered to normal levels by orexin-A and were reversed by the administration of SB334867, a specific orexin-1 receptor antagonist. These results suggest that regulation of post-ischemic glucose intolerance by orexin-A suppressed cerebral ischemic neuronal damage.     

Phase IIb study of pembrolizumab combined with S‐1 + oxaliplatin or S‐1 + cisplatin as first‐line chemotherapy for gastric cancer

The KEYNOTE‐659 study evaluated the efficacy and safety of first‐line pembrolizumab plus S‐1 and oxaliplatin (SOX) (cohort 1) or S‐1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open‐label phase IIb study enrolled patients with advanced programmed death‐ligand 1 (PD‐L1)‐positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)‐negative G/GEJ adenocarcinoma. The primary end‐point was the objective response rate (ORR). Other end‐points were duration of response (DOR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow‐up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment‐related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD‐L1‐positive, HER2‐negative G/GEJ adenocarcinoma.     

IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells

Neurokinin 2 receptor (NK2R), a G protein‐coupled receptor for neurokinin A (NKA), a tachykinin family member, regulates various physiological functions including pain response, relaxation of smooth muscle, dilation of blood vessels, and vascular permeability. However, the precise role and regulation of NK2R expression in cancer cells have not been fully elucidated. In this study, we found that high NK2R gene expression was correlated with the poor survival of colorectal cancer patients, and Interferon (IFN‐α/β) stimulation significantly enhanced NK2R gene expression level of colon cancer cells in a Janus kinas 1/2 (JAK 1/2)‐dependent manner. NKA stimulation augmented viability/proliferation and phosphorylation of Extracellular‐signal‐regulated kinase 1/2 (ERK1/2) levels of IFN‐α/β‐treated colon cancer cells and NK2R blockade by using a selective antagonist reduced the proliferation in vitro. Administration of an NK2R antagonist alone or combined with polyinosinic‐polycytidylic acid, a synthetic analog of double‐stranded RNA, to CT26‐bearing mice significantly suppressed tumorigenesis. NK2R‐overexpressing CT26 cells showed enhanced tumorigenesis and metastatic colonization in both lung and liver after the inoculation into mice. These findings indicate that IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells, suggesting that NK2R blockade may be a promising strategy for colon cancers.     

Predicting outcome of one-step total hysteroscopic resection of sessile submucous myoma

STUDY OBJECTIVE: To analyze variables for successful 1-step hysteroscopic myomectomies of sessile submucous myomas. DESIGN: Retrospective case-control study. (Canadian Task Force classification II-2). SETTING: Single operator's practice in a university hospital and its related hospitals. PATIENTS: Twenty-eight patients with sessile submucous myomas and menorrhagia, infertility, or both. INTERVENTIONS: Our strategy for hysteroscopic myomectomy is as follows. First, we scraped and/or vaporized intrauterine dome of myoma until top of myoma was even with level of wall of cavity. Next, the remnant intramural node was squeezed by uterine contractions induced by prostaglandin F2alpha injection. Finally, the newly raised myoma dome was sectioned or vaporized electrosurgically only within the space of the intrauterine cavity and/or was separated mechanically from healthy myometrium without electrosurgery. MEASUREMENTS AND MAIN RESULTS: Submucous myomas in 16 (57.1%) patients were completely removed after 1 surgery. By logistic regression analysis, thickness of outer myometrial layer of myoma node (OR 3.06, p = .02), myoma size (OR 0.86, p = .04), and intramural extension degree (OR 0.91, p = .03) were significantly associated with outcome of complete resection. CONCLUSION: Thickness of outer myometrial layer of myoma node, myoma size, and intramural extension degree predicted outcome of 1-step hysteroscopic myomectomy. The chance of performing successful surgery increased with increased thickness of outer myometrial layer of myoma, and decreased with larger myomas and greater degrees of intramural extension.     

The Impact of Purple-Flesh Potato (Solanum tuberosum L.) cv. “Shadow Queen” on Minor Health Complaints in Healthy Adults: A Randomized,Double-Blind,Placebo-Controlled Study

The purple-flesh potato (Solanum tuberosum L.) cultivar “Shadow Queen” (SQ) naturally contains anthocyanins. This randomized, double-blind, placebo-controlled study determines whether ingesting purple potatoes increases the number of mesenchymal stem cells (MSC) and improves stress response, a minor health complaint in healthy adults (registration number: UMIN000038876). A total of 15 healthy subjects (ages: 50–70 years) with minor health complaints were randomly assigned to one of two groups. For 8 weeks, the placebo group received placebo potatoes cv. “Haruka” and the test group received test potato cv. SQ containing 45 mg anthocyanin. The MSC count and several stress responses were analyzed at weeks 0 and 8 of the intake periods. The ingestion of a SQ potato did not affect the MSC count but markedly improved psychological stress response, irritability, and depression as minor health complaints compared with “Haruka”. No adverse effects were noted. Hence, an 8-week intake of SQ could improve stress responses.     

Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia

European Archives of Psychiatry and Clinical Neuroscience - Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the...     

MR imaging of primary malignant lymphoma of the pancreas

Pancreatic lymphoma is rare and is usually found as a large pancreatic mass. We report the case of a small 2-cm pancreatic lymphoma in a 54-year-old woman that had its histological origin in the pancreatic parenchyma. The mass showed homogeneously high signal-intensity on T2-weighted images and low signal-intensity on T1-weighted images. The infiltrative nature and hypovascularity in early-phase dynamic contrast study without encasement of arteries and veins were well demonstrated by MR imaging and were consistent with malignant lymphoma.