Inhibiting glutamine metabolism has been proposed as a potential treatment strategy for improving non-alcoholic steatohepatitis (NASH). However, effective methods for assessing dynamic metabolic responses during interventions targeting glutaminolysis have not yet emerged. Here, we developed a positron emission tomography (PET) imaging platform using l-[5-¹¹C]glutamine ([¹¹C]Gln) and evaluated its efficacy in NASH mice undergoing metabolic therapy with bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES), a glutaminase 1 (GLS1) inhibitor that intervenes in the first and rate-limiting step of glutaminolysis. PET imaging with [¹¹C]Gln effectively delineated the pharmacokinetics of l-glutamine, capturing its temporal-spatial pattern of action within the body. Furthermore, [¹¹C]Gln PET imaging revealed a significant increase in hepatic uptake in methionine and choline deficient (MCD)-fed NASH mice, whereas systemic therapeutic interventions with BPTES reduced the hepatic avidity of [¹¹C]Gln in MCD-fed mice. This reduction in [¹¹C]Gln uptake correlated with a decrease in GLS1 burden and improvements in liver damage, indicating the efficacy of BPTES in mitigating NASH-related metabolic abnormalities. These results suggest that [¹¹C]Gln PET imaging can serve as a noninvasive diagnostic platform for whole-body, real-time tracking of responses of glutaminolysis to GLS1 manipulation in NASH, and it may be a valuable tool for the clinical management of patients with NASH undergoing glutaminolysis-based metabolic therapy.

Psoriasis vulgaris is a chronic intractable disease characterized by systemic demarcated erythema and rashes with silvery-white scales. Tumor necrosis factor (TNF) α inhibitors, one of the biological agents, are new therapeutic options for psoriasis vulgaris. However, the number of cases of paradoxical reactions has been increasing in psoriasis patients treated with TNF α inhibitors. Here, we show a successful case indicating the efficacy of Kampo formulas for treating an infliximab-associated paradoxical reaction. The patient was an 83-year-old man. He was diagnosed with psoriasis vulgaris at the age of 69. While receiving infliximab injection and topical steroids, he presented and was admitted to our hospital after painful erythema appeared on his trunk and limbs. He was diagnosed with a paradoxical reaction related to infliximab. We identified the patient’s painful edematous erythema and systemic coldness. Therefore, we stopped infliximab and started to administer eppikajutsubutokadaio. His erythema and other symptoms gradually improved, and he was discharged on the 11th day of hospitalization. Eppikajutsubutokadaio has potential efficacy for psoriasis vulgaris with TNF α inhibitor-associated paradoxical reaction.

Objective: In this study, we conducted a questionnaire survey of hospital pharmacists throughout Japan with the aim of identifying the most-requested in-hospital preparations and off-label use drugs, and exploring the possibility of commercializing them.Methods: The Commercialization Study Group of the Japanese Society of Hospital Pharmacists conducted a questionnaire survey on the Japanese Society of Hospital Pharmacists website targeting hospital pharmacists who are members of the Japanese Society of Hospital Pharmacists. The period of the survey was from February 1, 2019 until January 21, 2020. In the questionnaire, the respondents wrote specific product names (generic names), specifications, and dosage forms that they would like to see improved and made commercially available in a free-text format. In addition, respondents chose their reasons for wanting the product to be improved or made commercially available from a list.Results: A total of 1,627 drugs were requested to be made commercially available. After duplicates and insufficient descriptions were excluded, the total was 553. The drugs that were most frequently requested were Levothyroxine suppositories, followed by Mohs’ ointment and Ulinastatin vaginal suppositories.Discussion: This survey identified certain drugs that pharmacists want to be commercialized and the specific reasons why. In-hospital preparations not only benefit patients whose diseases are becoming more complex and difficult to treat with existing prescription drugs, but also enable pharmacists to demonstrate their abilities. We believe that the commercialization of these important in-hospital preparations and off-label drugs will help avoid various risks associated with dispensing them and enhance the pharmacy profession. For this reason, pharmaceutical drug companies should conduct further surveys on the actual use of and literature research on the efficacy and safety of the drugs that were ranked high on the questionnaire and start considering their commercialization.

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified

OBJECTIVE: We conducted a retrospective, multi-institutional, collaborative study to accumulate cases of neuroendocrine carcinoma of the endometrium, to clarify its clinicopathologic features, treatment, prognosis and prognostic factors to collate findings to establish future individualized treatment regimens. To our knowledge, this is the largest case study and the first study to statistically analyze the prognosis of this disease. METHODS: At medical institutions participating in the Kansai Clinical Oncology Group/Intergroup, cases diagnosed at a central pathologic review as neuroendocrine carcinoma of the endometrium between 1995 and 2014 were enrolled. We retrospectively analyzed the clinicopathologic features, treatment, prognosis and prognostic factors of this disease. RESULTS: A total of 65 cases were registered from 18 medical institutions in Japan. Of these, 42 (64.6%) cases were diagnosed as neuroendocrine carcinoma of the endometrium based on the central pathological review and thus included in the study. Advanced International Federation of Gynecology and Obstetrics stages (stage III and IV) and pure type small cell neuroendocrine carcinoma cases had a significantly worse prognosis. Upon multivariate analysis, only histologic subtypes and surgery were significant prognostic factors. Pure type cases had a significantly worse prognosis compared to mixed type cases and complete surgery cases had a significantly better prognosis compared to cases with no or incomplete surgery. CONCLUSION: Our findings suggest that complete surgery improves the prognosis of neuroendocrine carcinoma of the endometrium. Even among cases with advanced disease stages, if complete surgery is expected to be achieved, clinicians should consider curative surgery to improve the prognosis of neuroendocrine carcinoma of the endometrium.
Carcinoma, Large Cell ; Carcinoma, Neuroendocrine ; Carcinoma, Small Cell ; Endometrial Neoplasms ; Endometrium ; Female ; Gynecology ; Japan ; Medical Oncology ; Multivariate Analysis ; Obstetrics ; Prognosis ; Retrospective Studies

Adipose triglyceride lipase (ATGL) catalyzes the first step of triglyceride hydrolysis. The gene mutations cause neutral lipid storage disease with myopathy (NLSDM) and/or triglyceride deposit cardiomyovasculopathy (TGCV) . Here we give the first report on rehabilitation of a patient with NLSDM and TGCV. The 62-years-old patient was admitted to our hospital for rehabilitation for skeletal myopathy and rehabilitation for cardiac dysfunction (NYHA class Ⅲ , ejection fraction 20%) . He complaint of dyspnea during the activity of daily life and exercise torelance was low. Our rehabilitation program consisted of physical therapy, occupational therapy, nutrition and cardiac education. We had paid a special attention to the intensity of exercise (aerobic training and resistance training) due to the low cardiac function, energy dysfunction and myopathy. After rehabilitation for two months, muscle strength had increased and 6MWT, ATVO₂ had improved. Importantly, the reduction of dyspnea on exertion as well as the increase in exercise capacity are considered to have led to improvement of quality of life.

A Valsalva aneurysm filled with thrombi can be difficult to diagnose, because it mimics a cardiac tumor. Both cardiac magnetic resonance imaging (MRI) and transesophageal echocardiogram (TEE) were performed on a patient who showed a low-echoic mass located between the atrial septum and the non-coronary sinus. Based on MRI findings allowing tissue characterization and the accurate location of the mass and the TEE findings of an irregular surface of the mass and a partial defect in the edge of the non-coronary sinus, we diagnosed the mass as a thrombosed Valsalva aneurysm that had perforated the inter-atrial septum. The operative findings coincided with the preoperative diagnosis. Both MRI and TEE are useful for diagnosing this condition.
Aneurysm ; Atrial Septum ; Echocardiography ; Heart Neoplasms ; Humans ; Magnetic Resonance Imaging ; Sinus of Valsalva

A 77-year-old woman with a medical history of myocardial infarction had a medical check-up at a local clinic. She reported sensation of abdominal distension which had appeared 6 months previously. Computed tomography demonstrated a very large ovarian tumor concomitant with an abdominal aortic aneurysm with a maximum diameter of 68 mm, and she was referred to our hospital. We performed a simultaneous extirpation of the ovarian tumor and abdominal aneurysm prosthetic graft replacement. The patient was discharged 13 days postoperatively after an uneventful postoperative course. The histopathological diagnosis of the ovarian tumor was mucinous cystadenoma. We reviewed the surgical procedures for similar cases of concomitant disease, and found that reports of surgical cases of simultaneous huge ovarian tumor extirpation and abdominal aneurysm prosthetic graft replacement are rare.

Since the Infection Control Team (ICT) was organized in 1999, our hospital has been engaged in evidence-based operations against nosocomial infections. The ICT's major activities included guidance in preventive measures against infections, surveillance involving continuous environmental monitoring, proposition as regards prescription of antibacterial medicines, and consultation with clinicians about prophylaxis. The team comprising physicians, nurses, pharmacists and clinical laboratory technicians has made expert propositions to clinicians. To be concrete, the team members, with the liaison clerk playing a central role, met with physicians in charge or with other staff members of the hospital, studied the infection cases in question, and presented the study findings to the clinicians. Fundamentally, therefore, it is not that the ICT intervenes in the affairs of the clinical department by way of directions but that it presents clinicians with the ideas gained through discussion between ICT members and physicians and other hospital staffers. While cementing a relationship of mutual trust between hospital employees, the ICT is expected to engage in nosocomial infection prevention activities by joining forces transdeoartmentally.
Clinical ; Hospitals ; Infection Control ; seconds ; Prophylactic

The effects of exercise and dietary therapy on the prevention of diabetic nephropathy (DN) were compared. Thirty-two male OLETF rats were divided into four groups (Ex, Diet, Sed, Pre) . Fourteen LETO rats served as the normal controls. Therapy was conducted for 10 weeks from age 22 to 31 weeks. The Ex group was trained by voluntary exercise, and the Diet group had a restricted food intake resulting in the same BW as that of the Ex group. The Ex developed a significant increase in urinary albumin excretion compared to the Diet group, although significantly less than the Sed group. Blood pressure in the Ex group showed a tendency to be higher during therapy. BW and serum lipids were significantly reduced, and glucose intolerance was improved in both the Ex and Diet groups. There were no differences in the metabolic indices between the Ex and Diet groups. The Ex group showed a significantly heavier kidney weight and a tendency for enlargement of the glomerular area and volume. The protective effect of DN through improvement of the metabolic dis-order by exercise might be offset by exercise-induced renal loads. Control of exercise intensity and blood pressure appear to be important as well as the improvement of glucose intolerance and lipid metabolisms in exercise therapy to prevent an occurrence and development of DN.