Glycogenic hepatopathy following attempted suicide by long-acting insulin overdose in patient with type 1 diabetes

Patients with poorly controlled insulin-dependent type 1 or type 2 diabetes rarely present with glycogenic hepatopathy, which is characterized by hepatomegaly and liver enzyme abnormalities. Glycogenic hepatopathy occurs as a consequence of excessive accumulation of glycogen in hepatocytes caused by insulin. We report a young male patient with type 1 diabetes mellitus who developed glycogenic hepatopathy following a suicide attempt by insulin overdose via subcutaneous injection. The patient's medication/nutrition compliance and adherence to insulin were poorly controlled due to comorbid schizophrenia. Our patient required a large amount of continuous glucose to maintain euglycemia for persistent intractable hypoglycemia induced by overdose of long-acting insulin. On admission day 4, the patient presented elevated transaminases, hepatomegaly, and lactic acidosis. Computed tomography revealed swollen liver parenchyma with a diffusely high absorption. The patient gradually recovered without any medical intervention except for adequate control of blood sugar and was moved to a psychiatric ward on day 8 for schizophrenia management. This report may help emergency physicians be aware of the common symptoms, clinical course, and pathophysiology of glycogenic hepatopathy. Doctors should include glycogenic hepatopathy in the differential diagnosis of abnormal liver enzymes and hepatomegaly for those with poorly controlled insulin-dependent diabetes mellitus or unstable blood sugar levels due to insulin overdose like our patient

Pivotal role of Sirt6 in the crosstalk among ageing, metabolic syndrome and osteoarthritis

AbstractOsteoarthritis (OA) is a chronic degenerative joint disorder commonly associated with metabolic syndrome. As ageing and obesity has a great impact on the initiation/severity of OA, herein we sought to investigate the involvement of Sirt6 in the crosstalk between ageing and metabolic syndrome/OA. Sirt6 haploinsufficiency in mice promoted the expression of inflammatory cytokines in the IPFP. Enhanced inflammation of the IPFP in the aged Sirt6 ± HFD group was paralleled with accelerated OA change, including osteophyte growth and chondrocyte hypertrophy. Conversely, mesenchyme-specific Sirt6-deficient mice revealed both attenuated chondrocyte hypertrophy and proteoglycan synthesis, although chondrocyte senescence was enhanced as shown in the aged WT mice. Thus Sirt6 has key roles in the relationship among ageing, metabolic syndrome, and OA

Clinical Safety Assessment of Autologous Freeze-Drying Platelet-Rich Plasma for Bone Regeneration in Maxillary Sinus Floor Augmentation: A Pilot Study

The purpose of this clinical study is to evaluate the safety and preliminary efficacy of autologous freeze-drying platelet-rich plasma (FD-PRP) on bone regeneration in maxillary sinus floor augmentation as a preliminary pilot study. Five patients that required sinus floor augmentation to facilitate the placement of dental implants participated in this clinical study. The PRP was prepared from the autologous peripheral blood and was lyophilized and stored at −20 °C for 4 weeks before surgery. At surgery, triple-concentrated FD-PRP (x3FD-PRP) mixed with synthetic bone grafting materials was rehydrated following the transplantation into the sinus floor. The primary outcome was a safety verification of x3FD-PRP, evaluated in terms of the clinical course and consecutive blood tests. The secondary outcome was clinical efficacy focused on bone regeneration in sinus floor augmentation evaluated by radiographic examination and implant stability. There were no adverse events, such as systemic complications, excessive inflammatory reactions, severe infection, or local site healing complications, besides those on the usual course associated with surgery. Vertical augmented height was maintained, and the initial stability of implants was achieved post-operatively in 6 months. The results obtained in this study suggest that x3FD-PRP can be used safely for bone engineering in clinical practice. Further studies are required to draw a conclusion concerning the efficacy of x3FD-PRP since this was a pilot study with a single arm and a small sample size

Research Project on the Design for the Optimum Disclosure System Volume 2: Sustainable Growth of Japanese Companies and the Direction of Non-financial Information Disclosure (Japanese)

For quite some time there has been a debate surrounding the issue requiring companies to disclose not only financial information but also non-financial information, as shown in recent efforts for enhanced business reporting (EBR). This discussion paper explores non-financial information in three aspects: social and environmental information, intellectual capital information, and risk information, and it also examines the extent and reasons for the disclosure of non-financial information. In addition, the question about the media is also discussed with consideration to the trend for integrated reporting and XBRL. Ultimately, non-financial information should fuse with financial information and evolve to become integrated reporting. XBRL can only realize its potential if both non-financial information and financial information are integrated. However, there are many obstacles for realizing integrated reporting at one time. Therefore, to stimulate a change in investor behavior and company behavior, as argued by some international organizations such as IIFC, there is an urgent demand for extended reporting that integrates information on sustainability and information on intellectual capital as a source of company competitive advantage. For such non-financial information, there is a necessity to discuss questions related to an expansion in management's disclosure responsibility, as well as the corresponding judgment in auditing. There is also a necessity to discuss questions concerning how to reduce the cost of auditing and how to construct an assurance system that helps to improve the reliability of information and to limit the overextension of non-financial information.

Effect of Cetraxate, a Mucosal Protective Agent, on Gastric Mucosal Blood Flow and Gastric Clarithromycin Concentration in Nicotine-treated Rats

Our previous study demonstrated that combination treatment with cetraxate plus omeprazole, amoxicillin, and clarithromycin is effective for the eradication of Helicobacter pylon in smokers. To evaluate the effect of cetraxate on gastric mucosal blood flow (GMBF) and the gastric concentration of clarithromycin in nicotine-treated rats, 10 rats were divided into two groups given nicotine with or without cetraxate, and GMBF was measured by laser Doppler blood flowmetry. Another 36 rats were divided into three groups (control, nicotine, and nicotine + cetraxate). Clarithromycin was administered intraduodenally and nicotine was administered after 30 minutes, with cetraxate being given 30 minutes later. The gastric mucosal clarithromycin concentration was measured. After cetraxate administration, GMBF increased significantly in the nicotine + cetraxate group compared with the nicotine group (p<0.05). The mucosal clarithromycin concentration increased in the nicotine + cetraxate group compared with the nicotine group, but the difference was not significant. Our results indicate that cetraxate increased GMBF in nicotine-treated rats

Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy

ObjectivesWe sought to explore the relationship between a Tcap gene (TCAP)abnormality and cardiomyopathy.BackgroundHypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) cause severe heart failure and sudden death. Recent genetic investigations have revealed that mutations of genes encoding Z-disc components, including titin and muscle LIM protein (MLP), are the primary cause of both HCM and DCM. The Z-disc plays a role in establishing the mechanical coupling of sarcomeric contraction and stretching, with the titin/Tcap/MLP complex serving as a mechanical stretch sensor. Tcap interacts with the calsarcin, which tethers the calcineurin to the Z-disc.MethodsThe TCAPwas analyzed in 346 patients with HCM (236 familial and 110 sporadic cases) and 136 patients with DCM (34 familial and 102 sporadic cases). Two different in vitro qualitative assays—yeast two-hybrid and glutathion S-transferase pull-down competition—were performed in order to investigate functional changes in Tcap's interaction with MLP, titin, and calsarcin-1 caused by the identified mutations and a reported DCM-associated mutation, R87Q.ResultsTwo TCAPmutations, T137I and R153H, were found in patients with HCM, and another TCAPmutation, E132Q, was identified in a patient with DCM. It was demonstrated by the qualitative assays that the HCM-associated mutations augment the ability of Tcap to interact with titin and calsarcin-1, whereas the DCM-associated mutations impair the interaction of Tcap with MLP, titin, and calsarcin-1.ConclusionsThese observations suggest that the difference in clinical phenotype (HCM or DCM) may be correlated with the property of altered binding among the Z-disc components

Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies: Possible association with malignancy

Objectives: Myositis-specific autoantibodies (MSAs) are useful tools for identifying clinically homogeneous subsets and predicting prognosis of patients with idiopathic inflammatory myopathies (IIM) including polymyositis (PM) and dermatomyositis (DM). Recent studies have shown that anti-NXP2 antibody (Ab) is a major MSA in juvenile dermatomyositis (JDM). In this study the frequencies and clinical associations of anti-NXP2 Ab were evaluated in adult patients with IIM. Methods: Clinical data and serum samples were collected from 507 adult Japanese patients with IIM (445 with DM and 62 with PM). Eleven patients with JDM, 108 with systemic lupus erythematosus, 433 with systemic sclerosis and 124 with idiopathic pulmonary fibrosis were assessed as disease controls. Serum was examined for anti-NXP2 Ab by immunoprecipitation and western blotting using polyclonal anti-NXP2 Ab. Results: Seven patients (1.6%) with adult DM and one (1.6%) with adult PM were positive for anti-NXP2 Ab. Except for two patients with JDM, none of the disease controls were positive for this autoantibody. Among eight adult patients with IIM, three had internal malignancies within 3 years of diagnosis of IIM. Another patient with DM also had a metastatic cancer at the diagnosis. All of the carcinomas were at an advanced stage (stage IIIb-IV). Conclusions: While less common than in juvenile IIM, anti-NXP2 Ab was found in adult IIM. Anti-NXP2 Ab may be associated with adult IIM with malignancy

Procyanidin B3 Prevents Articular Cartilage Degeneration and Heterotopic Cartilage Formation in a Mouse Surgical Osteoarthritis Model

Osteoarthritis (OA) is a common disease in the elderly due to an imbalance in cartilage degradation and synthesis. Heterotopic ossification (HO) occurs when ectopic masses of endochondral bone form within the soft tissues around the joints and is triggered by inflammation of the soft tissues. Procyanidin B3 (B3) is a procyanidin dimer that is widely studied due to its high abundance in the human diet and antioxidant activity. Here, we evaluated the role of B3 isolated from grape seeds in the maintenance of chondrocytes in vitro and in vivo. We observed that B3 inhibited H2O2-induced apoptosis in primary chondrocytes, suppressed H2O2- or IL-1ß−induced nitric oxide synthase (iNOS) production, and prevented IL-1ß−induced suppression of chondrocyte differentiation marker gene expression in primary chondrocytes. Moreover, B3 treatment enhanced the early differentiation of ATDC5 cells. To examine whether B3 prevents cartilage destruction in vivo, OA was surgically induced in C57BL/6J mice followed by oral administration of B3 or vehicle control. Daily oral B3 administration protected articular cartilage from OA and prevented chondrocyte apoptosis in surgically-induced OA joints. Furthermore, B3 administration prevented heterotopic cartilage formation near the surgical region. iNOS protein expression was enhanced in the synovial tissues and the pseudocapsule around the surgical region in OA mice fed a control diet, but was reduced in mice that received B3. Together, these data indicated that in the OA model, B3 prevented OA progression and heterotopic cartilage formation, at least in a part through the suppression of iNOS. These results support the potential therapeutic benefits of B3 for treatment of human OA and heterotopic ossification