Thiamine prevents obesity and obesity-associated metabolic disorders in OLETF rats

We previously found that thiamine mitigates metabolic disorders in spontaneously hypertensive rats, harboring defects in glucose and fatty acid metabolism. Mutation of thiamine transporter gene SLC19A2 is linked to type 2 diabetes mellitus. The current study extends our hypothesis that thiamine intervention may impact metabolic abnormalities in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, exhibiting obesity and metabolic disorders similar to human metabolic syndrome. Male OLETF rats (4 wk old) were given free access to water containing either 0.2% or 0% of thiamine for 21 and 51 wk. At the end of treatment, blood parameters and cardiac functions were analyzed. After sacrifice, organs weights, histological findings, and hepatic pyruvate dehydrogenase (PDH) activity in the liver were evaluated. Thiamine intervention averted obesity and prevented metabolic disorders in OLETF rats which accompanied mitigation of reduced lipid oxidation and increased hepatic PDH activity. Histological evaluation revealed that thiamine alleviated adipocyte hypertrophy, steatosis in the liver, heart, and skeletal muscle, sinusoidal fibrosis with formation of basement membranes (called pseudocapillarization) which accompanied significantly reduced expression of laminin β1 and nidogen-1 mRNA, interstitial fibrosis in the heart and kidney, fatty degeneration in the pancreas, thickening of the basement membrane of the vasculature, and glomerulopathy and mononuclear cell infiltration in the kidney. Cardiac and renal functions were preserved in thiamine treatment. Thiamine has a potential to prevent obesity and metabolic disorders in OLETF rats.     

Pro- vs anti-stenotic capacities of type-I vs type-II human induced pluripotent-derived endothelial cells

AIM: To verify in vivo relevance of the categorization of human vascular endothelial cells (VECs) into type-I (pro-proliferative) and type-II (anti-proliferative). METHODS: Endothelial layers of murine femoral arteries were removed by wire injury (WI) operation, a common technique to induce arteriostenosis. Type-I and type-II VECs produced from human induced pluripotent stem cells (iPSCs), whose characters were previously determined by their effects on the proliferation of vascular smooth muscle cells in in vitro co-culture experiments, were mixed with Matrigel^® Matrix. The mixtures were injected into subcutaneous spaces around WI-operated femoral arteries for the transplanted human iPSC-derived VECs (iPSdECs) to take a route to the luminal surface via vasa vasorum, a nutrient microvessel for larger arteries. Histologies of the femoral arteries were examined over time. The presence of human iPSdECs was checked by immunostaining studies using an antibody that specifically recognizes human VECs. Degrees of stenosis of the femoral arteries were calculated after three weeks. To determine the optimal experimental condition, xenotransplantation experiments were performed under various conditions using immunocompromised mice as well as immunocompetent mice with or without administration of immunosuppressants. RESULTS: Because immunocompromised mice showed unexpected resistance to WI-induced arteriostenosis, we performed xenotransplantation experiments using immunocompetent mice along with immunosuppressant administrations. After one week, luminal surfaces of the WI-operated arteries were completely covered by human iPSdECs, showing the efficacy of our novel transplantation technique. After three weeks, type-I-iPSdECs-transplanted arteries underwent total stenosis, while type-II-iPSdECs-transplanted arteries remained intact. However, untransplanted arteries of immunosuppressant-treated mice also remained intact by unknown reasons. We found that transplanted human VECs had already been replaced by murine endothelial cells by this time, indicating that a transient existence of human type-II-iPSdECs on arterial luminal surfaces can sufficiently prevent the development of stenosis. Thus, we re-performed xenotransplantation experiments using immunocompetent mice without administrating immunosuppressants and found that arteriostenosis was accelerated or prevented by transplantation of type-I or type-II iPSdECs, respectively. Similar results were obtained from the experiments using human embryonic stem cell-derived VECs at early passages (i.e., type-II) and late passages (i.e., type-I). CONCLUSION: Pro- and anti-stenosis capacities of type-I and type-II human iPSdECs were verified, respectively, promising a therapeutic application of allogenic iPSdECs.     

Trimethoprim‐sulfamethoxazole compared with benzathine penicillin for treatment of impetigo in Aboriginal children: A pilot randomised controlled trial

We conducted a pilot randomized controlled trial comparing trimethoprim‐sulfamethoxazole to benzathine penicillin for treatment of impetigo in Aboriginal children. Treatment was successful in 7 of 7 children treated with trimethoprim‐sulfamethoxazole and 5 of 6 treated with benzathine penicillin. Trimethoprim‐sulfamethoxazole achieved microbiological clearance and healing of sores from which β‐hemolytic streptococci and community‐associated methicillin‐resistant Staphylococcus aureus were initially cultured.     

Clinicopathologic study of intraductal papillary-mucinous tumors and mucinous cystic tumors of the pancreas

BACKGROUND/AIMS: We analyzed clinicopathologic and imaging findings of intraductal papillary-mucinous tumors (IPMTs) and mucinous cystic tumors (MCTs) of the pancreas to evaluate the difference between IPMTs and MCTs, and to identify the signs indicative of malignancy in IPMTs. METHODOLOGY: Clinicopathological features of 20 patients with IPMT and six patients with MCT of the pancreas were studied. RESULTS: The patients with IPMT comprised 16 males and four females with a mean age of 62.9 years. Eighty percent of IPMTs were located in the pancreatic head, and the mean tumor size was 38.6mm. Recurrence was observed in one patient, who died of IPM adenocarcinoma. In contrast, all patients with MCT were females, with a mean age of 53.0 years. None of the MCTs arose in the pancreatic head, and the mean tumor size was 42.7mm. One patient died of MC adenocarcinoma, but all of the others survived without recurrence. The difference in gender, location of the tumor, and connection to the pancreatic duct reached statistical significance between IPMTs and MCTs. A significant connection to the pancreatic duct and high level of serum carbohydrate antigen 19-9 (CA19-9) was observed in the adenocarcinoma and moderate dysplasia groups of IPMT. CONCLUSIONS: The main duct type and an elevation of serum CA19-9 level suggested malignancy in IPMTs.     

Production of infectious hepatitis C virus particles in three-dimensional cultures of the cell line carrying the genome-length dicistronic viral RNA of genotype 1b

We show that a dicistronic hepatitis C virus (HCV) genome of genotype 1b supports the production and secretion of infectious HCV particles in two independent three-dimensional (3D) culture systems, the radial-flow bioreactor and the thermoreversible gelation polymer (TGP), but not in monolayer cultures. Immunoreactive enveloped particles, which are 50-60 nm in diameter and are surrounded by membrane-like structures, are observed in the culture medium as well as at the endoplasmic reticulum membranes and in dilated cytoplasmic cisternae in spheroids of Huh-7 cells. Infection of HCV particles is neutralized by anti-E2 antibody or patient sera that interfere with E2 binding to human cells. Finally, the utility of the 3D-TGP culture system for the evaluation of antiviral drugs is shown. We conclude that the replicon-based 3D culture system allows the production of infectious HCV particles. This system is a valuable tool in studies of HCV morphogenesis in a natural host cell environment.     

Iodine-131-metaiodobenzylguanidine therapy with reduced-intensity allogeneic stem cell transplantation in recurrent neuroblastoma

Neuroblastoma is the most common extracranial solid tumor of childhood, and iodine-131-metaiodobenzylguanidine (MIBG) therapy is a new approach for grade IV neuroblastoma. We describe the case history of a 3-year-old girl with recurrent neuroblastoma who received MIBG therapy with reduced-intensity allogeneic stem cell transplantation (RIST) because of an extensive bone marrow involvement. The post-transplant course was uneventful and complete chimerism was obtained. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. The patient remained in remission for 3 months after RIST until the second relapse. MIBG therapy combined with RIST warrants further trials.