Objective: Extract from cultured Lentinula edodes mycelia (L.E.M.) is a food ingredient possessing various pharmacologic actions such as immunomodulatory properties, antitumor and hepatoprotective effects. In Japan, it has been used as a health food for 30 years or more.
In the present study to evaluate the safety of L.E.M., a genotoxicity study and acute toxicity study were conducted. In addition, the inhibitory effect of drug-metabolizing enzyme by L.E.M. was tested in vitro, to gain insight on the interaction with medicines.
Methods: The genotoxicity study was performed using a bacterial reverse mutation assay and a in vivo mammalian bone marrow cell chromosomal mutation assay. The acute toxicity study was performed using a single-dose oral toxicity test in rats. Inhibitory activity of cytochrome P-450 3A4 (CYP3A4), one of the most important drug-metabolizing enzymes, by L.E.M. was tested using a baculovirus-expressed system.
Results: In the genotoxicity study, mutagenicity was negative for both bacterial reverse mutation assay and in vivo mammalian bone marrow cell chromosomal mutation assay. In the acute toxicity study, no toxic symptoms were observed by single dose oral administration of L.E.M. at a dose of 10,000 mg/kg BW in rats. This implies LD₅₀>10,000 mg/kg BW. No inhibitory activity of CYP3A4 by L.E.M. was observed at in the in vitro screening system to investigate drug-L.E.M. interaction.
Conclusion: It is believed L.E.M. is a safety ingredient for foods used in complementary and alternative medicine, since it was toxicologically safe and showed no inhibitory activity of CYP3A4 in the studies conducted.

In the present study, we investigated the effect of heat stress on disuse atrophy from changes in the muscle protein levels of desmin and calpain. Wistar strain female rats (6-8 months old) were randomly assigned to two experimental groups: control (C) and heat stress (H). One hindlimb of all animals was immobilized in plantar flexion with plaster. Before immobilization, animals in H group were placed in a heat chamber (42°C for 60 min). Following 6 days of immobilization, the soleus muscles were removed and analyzed. Although immobilization resulted in significant muscle atrophy in all experimental animals, the soleus weight-to-body weight ratio in immobilized limbs of H group was significantly higher compared to that of C group. Expression of desmin and HSP72 in the atrophied soleus muscle from C group was significantly lower compared with the contralateral muscle; but this was not the case in H group. Further, in C group, the ratio of autolyzed calpains I increased significantly in the atrophied muscle compared to the contralateral muscle. These results show that the effect of heat stress on disuse skeletal muscle atrophy is attributed to the decreasing degradation of desmin by suppressing the activation of calpain.

A 66-year-old man with an unknown medical history developed chest pain and a diagnosis of acute myocardial infarction (AMI) was given by his physician. Percutaneous coronary intervention was performed in the left anterior descending artery. Echocardiography revealed ventricular septal perforation (VSP) ; therefore, the patient was transferred to our hospital. After admission, his platelet count dropped rapidly during heparin administration, and left ventricular thrombosis and deep vein thrombosis were noted, raising a suspicion of heparin-induced thrombocytopenia (HIT). To establish cardiopulmonary bypass, argatroban alone was insufficient to prolong the Powered by Editorial Manager^® and ProduXion Manager^® from the Aries Systems Corporation activated clotting time (ACT) ; thus, nafamostat mesilate was also used for coronary artery bypass grafting and surgical repair of VSP. It took many hours to normalize the ACT, requiring re-exploration for excessive bleeding. On the 37th postoperative day, the patient was transferred to another hospital. We performed cardiac surgical procedures using argatroban in a patient who developed HIT during the course of VSP following AMI ; however, we had difficulty in controlling the ACT. Since, to the best of our knowledge, there are no previous studies reporting surgical case of VSP complicated by HIT, we present this case with a review of the relevant literature.

The purpose of this study was to examine the effects of combination of a heat stress and astaxanthin supplementation, known as a potent anti-oxidative nutrient, on muscle protein degradation and disuse muscle atrophy. Fifty-two male Wistar rats (261.7±1.17 g) were divided into five groups: control (Cont, n=10), suspension (Sus, n=11), heat stress and suspension (Heat, n=10), astaxanthin and suspension (Ax, n=10), and heat stress, astaxanthin and suspension (H+A, n=11). There were no significant differences in Cu,Zn-SOD, cathepsin L and caspase-3 levels among the Heat, Ax and H+A groups in the soleus and plantaris muscles. Although levels of calpain 2 and ubiquitinated protein in the myofibrillar fraction in the soleus muscle were not significantly different among the Heat, Ax and H+A groups, levels in the H+A group were significantly (p<0.05) lower than Sus. Concerning atrophied plantaris muscles, the H+A group significantly (p<0.05) suppressed the expression of calpain 1 in the myofibrillar fraction, but there were no marked changes of proteolytic indexes. These data indicate that the combination of the heat stress and astaxanthin supplementation could be effective in inhibiting muscle protein degradation in disuse atrophy of the soleus.

The case was a 27-year-old woman with a history of Turner syndrome. The patient underwent ascending-descending aorta bypass for aortic coarctation 6 years previously and underwent subsequent follow-up on an outpatient basis. She consulted our department because of fever, chest pain and headache as the main complaints. Age-indeterminate type A aortic dissection was found on computed tomography, and she was admitted to the hospital on the same day. Echocardiography also revealed an enlarged aortic root and bicuspid aortic valve. Aortic root replacement and total arch replacement were performed, and her postoperative course was favorable. It is reported that in cases of Turner syndrome with aortic coarctation, aortic aneurysm and aortic dissection are likely to occur due to the vulnerability of the aortic wall. We encountered a patient with Turner syndrome who underwent ascending-descending aorta bypass for adult aortic coarctation and subsequently developed type A aortic dissection, underwent aortic root and total arch replacement, and rehabilitated after surgery, as well as provide bibliographic considerations.

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

BACKGROUND: Internal medicine (IM) doctors in Japan play the role of primary care physicians; however, the shortage of rural physicians continues. This study aims to elucidate the association of age, sex, board certification, type of work, and main clinical work with the retention or migration of IM doctors to rural areas. METHODS: This retrospective cohort study included 82,363 IM doctors in 2010, extracted from the national census data of medical doctors. The explanatory variables were age, sex, type of work, primary clinical work, and changes in board certification status. The outcome was retention or migration to rural areas. The first tertile of population density (PD) of municipalities defined as rural area. After stratifying the baseline ruralities as rural or non-rural areas, the odds ratios (ORs) of the explanatory variables were calculated using generalized estimation equations. The analyses were also performed after age stratification (<39, 40-59, ≥60 years old). RESULTS: Among the rural areas, women had a significantly higher OR for retention, but obtaining board certification of IM subspecialties had a significantly lower OR. Among the non-rural areas, physicians who answered that their main work was IM without specific subspecialty and general had a significantly higher OR, but obtaining and maintaining board certification for IM subspecialties had a significantly lower OR for migration to rural areas. After age stratification, the higher OR of women for rural retention was significant only among those aged 40-59 years. Those aged under 40 and 40-59 years in the non-rural areas, who answered that their main work was IM without specific subspecialty had a significantly higher OR for migration to rural areas, and those aged 40-59 years in the rural areas who answered the same had a higher OR for rural retention. CONCLUSIONS Obtaining and maintaining board certification of IM subspecialties are possible inhibiting factors for rural work, and IM doctors whose main work involves subspecialties tend to work in non-rural areas. Once rural work begins, more middle-aged female IM doctors continued rural work compared to male doctors.
Middle Aged ; Humans ; Male ; Female ; Retrospective Studies ; East Asian People ; Certification ; Physicians ; Internal Medicine

Pulmonary thromboembolism (PTE) is a life-threatening disease, and in severe cases is required surgical treatment. Emergency pulmonary embolectomy using retrograde pulmonary perfusion (RPP) as an adjunct was successfully performed in 2 patients suffering from massive acute PTE. After removal of the pulmonary thrombus via incision of the pulmonary artery trunk, RPP via the right upper pulmonary vein was performed, which enabled the removal of residual thrombotic material and air from the peripheral branches of pulmonary arteries.

The Trail Making Test (TMT) is a widely used measure of attention impairment. The time needed to complete the TMT (TMT score) is longer with greater impairment of attention in patients with brain diseases. TMT score becomes large in a proportion of patients with minor ischemic stroke. The Japanese version of the TMT- (TMT-J) was published in 2019. The purpose of this study was to clarify serial changes in TMT-J scores in patients with minor ischemic stroke. We retrospectively reviewed the TMT-J scores in those patients who completed the test both 8-14 days and 29-35 days after stroke onset. On initial evaluation, 1 of 21 patients could not complete TMT-J Part A. TMT-J Part A scores had a mean of 67 s and were abnormally large in 45% of the 20 patients who completed this part. Two of these 20 patients could not complete TMT-J Part B. TMT-J Part B scores had a mean of 135 s and were abnormally large in 61% of the 18 patients who completed this part. On second evaluation, scores on Part A and Part B improved in 76% and 73% of patients, respectively. This study demonstrated that abnormal TMT-J scores 8-14 days after onset of minor ischemic stroke improved over time in most patients.

We examined the effect of a combination of astaxanthin (AX) supplementation, repeated heat stress, and intermittent reloading (IR) on satellite cells in unloaded rat soleus muscles. Forty-nine male Wistar rats (8-week-old) were divided into control, hind-limb unweighting (HU), IR during HU, IR with AX supplementation, IR with repeated heat stress (41.0-41.5 °C for 30 min), and IR with AX supplementation and repeated heat stress groups. After the experimental period, the antigravitational soleus muscle was analyzed using an immunohistochemical technique. Our results revealed that the combination of dietary AX supplementation and heat stress resulted in protection against disuse muscle atrophy in the soleus muscle. This protective effect may be partially due to a higher satellite cell number in the atrophied soleus muscle in the IR/AX/heat stress group compared with the numbers found in the other groups. We concluded that the combination treatment with dietary AX supplementation and repeated heat stress attenuates soleus muscle atrophy, in part by increasing the number of satellite cells.
Animals ; Body Weight ; Dietary Supplements ; Fibrinolytic Agents/pharmacology* ; Heat-Shock Response ; Hindlimb ; Hot Temperature ; Immunohistochemistry ; Male ; Muscle, Skeletal ; Muscular Atrophy/drug therapy* ; Oxidative Stress ; Rats ; Rats, Wistar ; Satellite Cells, Skeletal Muscle/cytology* ; Xanthophylls/pharmacology*