Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

Direct insertion of an ultra‐slim upper endoscope for cholangioscopy in patients undergoing choledochoduodenostomy

Direct peroral cholangioscopy (POC) using an ultra‐slim upper endoscope is one modality of POC for intraductal endoscopic evaluation and treatment of the bile duct. Choledochoduodenostomy (CDS) is one modality of biliary bypass surgery that provides a new route to the bile duct. We carried out direct POC using an ultra‐slim upper endoscope without the use of accessories in 10 patients (four sump syndromes, three bile duct strictures and three intrahepatic duct stones) previously undergoing surgical CDS. Direct POC was successful in all patients. The use of an intraductal balloon catheter was required in one patient for advancement of the endoscope into the bile duct. Distal bile ducts with sump syndromes were cleared using baskets and water irrigation under direct POC. Cholangiocarcinoma was diagnosed in one patient with hilar bile duct stricture after cholangioscopic evaluation and a targeting forceps biopsy under direct POC. Intrahepatic duct stones were successfully extracted after intraductal fragmentation under direct POC. Oozing bleeding occurred during intraductal lithotripsy but stopped spontaneously. Direct POC using an ultra‐slim upper endoscope without the assistance of accessories can easily be carried out in patients undergoing CDS.     

Epidemiologic Characteristics of Work-related Eye Injuries and Risk Factors Associated with Severe Eye Injuries: A Registry-based Multicentre Study

ABSTRACT

Purpose

Work-related eye injuries have been reported with a variety of epidemiologic and clinical characteristics. We aimed to identify epidemiologic characteristics of work-related eye injuries and risk factors associated with severe injury in a large metropolitan city.     

Erythema induratum of Bazin in a 10‐year‐old boy

Erythema induratum of Bazin (EIB) is a form of tuberculid resulting from hypersensitivity to tuberculosis antigen. EIB occurs most commonly in middle‐aged women and is not typically seen in children. Here, we present a rare case of EIB, presenting as a chronic nodular panniculitis, in a 10‐year‐old Korean boy.     

Dorsal suspension for Morton’s neuroma: A comparison with neurectomy

BackgroundThe purpose of this study was to investigate and compare the clinical outcomes of dorsal suspension with those of neurectomy for the treatment of Morton’s neuroma.MethodsWe conducted a retrospective study of dorsal suspension and neurectomy group. The dorsal suspension was performed by dorsal transposition of neuroma over the dorsal transverse ligament after neurolysis. The visual analog scale (VAS), the Foot and Ankle Ability Measure (FAAM), postoperative satisfaction, and complications were evaluated.ResultsBoth groups reported significant pain relief, and there were no significant differences between the groups with respect to postoperative pain. The postoperative FAAM outcomes showed no significant between-group differences. Satisfaction analysis showed ‘excellent’ and ‘good’ results in the dorsal suspension and neurectomy groups (95% and 77.7%, respectively). Complications of numbness and paresthesia reported in the dorsal suspension group (5% and 5%, respectively) were significantly fewer than those of neurectomy group (61.1% and 33.3%, respectively) (both, p < .05).ConclusionsWith its favorable results, dorsal suspension can be another operative option for the treatment of Morton’s neuroma.Level of Evidence: Level III, retrospective comparative case series.     

Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.