Marliolide Derivative Induces Melanosome Degradation via Nrf2/p62-Mediated Autophagy.

Nuclear factor erythroid 2-related factor 2 (Nrf2), which is linked to autophagy regulation and melanogenesis regulation, is activated by marliolide. In this study, we investigated the effect of a marliolide derivative on melanosome degradation through the autophagy pathway. The effect of the marliolide derivative on melanosome degradation was investigated in α-melanocyte stimulating hormone (α-MSH)-treated melanocytes, melanosome-incorporated keratinocyte, and ultraviolet (UV)B-exposed HRM-2 mice (melanin-possessing hairless mice). The marliolide derivative, 5-methyl-3-tetradecylidene-dihydro-furan-2-one (DMF02), decreased melanin pigmentation by melanosome degradation in α-MSH-treated melanocytes and melanosome-incorporated keratinocytes, evidenced by premelanosome protein (PMEL) expression, but did not affect melanogenesis-associated proteins. The UVB-induced hyperpigmentation in HRM-2 mice was also reduced by a topical application of DMF02. DMF02 activated Nrf2 and induced autophagy in vivo, evidenced by decreased PMEL in microtubule-associated proteins 1A/1B light chain 3B (LC3)-II-expressed areas. DMF02 also induced melanosome degradation via autophagy in vitro, and DMF02-induced melanosome degradation was recovered by chloroquine (CQ), which is a lysosomal inhibitor. In addition, Nrf2 silencing by siRNA attenuated the DMF02-induced melanosome degradation via the suppression of p62. DMF02 induced melanosome degradation in melanocytes and keratinocytes by regulating autophagy via Nrf2-p62 activation. Therefore, Nrf2 activator could be a promising therapeutic agent for reducing hyperpigmentation.

Pharmacokinetic Properties of Moracin C in Mice.

Moracin C from Morus alba fruits, also known as the mulberry, has been proven to exhibit inhibitory activities against lipoxygenase enzymes, TNF-α and interleukin-1ß secretion, and proprotein convertase subtilisin/kexin type 9 expression. Despite the various pharmacological activities of moracin C, its pharmacokinetic characteristics have yet to be reported. Here, the pharmacokinetic parameters and tissue distribution of moracin C have been investigated in mice, and the plasma concentration of moracin C with multiple dosage regimens was simulated via pharmacokinetic modeling. Our results showed that moracin C was rapidly and well absorbed in the intestinal tract, and was highly distributed in the gastrointestinal tract, liver, kidneys, and lungs. Moracin C was distributed in the ileum, cecum, colon, and liver at a relatively high concentration compared with its plasma concentration. It was extensively metabolized in the liver and intestine, and its glucuronidated metabolites were proposed. In addition, the simulated plasma concentrations of moracin C upon multiple treatments (i.e., every 12 and 24 h) were suggested. We suggest that the pharmacokinetic characteristics of moracin C would be helpful to select a disease model for in vivo evaluation. The simulated moracin C concentrations under various dosage regimens also provide helpful knowledge to support its pharmacological effect.

Risk factors and management for pyloric stenosis occurred after endoscopic submucosal dissection adjacent to pylorus.

Endoscopic submucosal dissection (ESD) has been widely accepted as a curative treatment for gastric neoplasm. Pyloric stenosis is a chronic complication that can be caused by ESD. The aim of this study is to clarify the risk factors and management for pyloric stenosis. From January 2004 to January 2014, a total of 126 patients who underwent ESD adjacent to pylorus were reviewed retrospectively. Pyloric mucosal defect was defined as when any resection margin of ESD was involved in the pyloric ring. Pyloric stenosis was defined as when a conventional endoscope could not be passed to the duodenum. Among the 126 patients, pyloric stenosis was identified in 9. In a univariate analysis, pyloric stenosis was more common in older patients (P < 0.05) and in lesions with resections over 75% of the pyloric ring circumference (P < 0.001). In a multivariate analysis, the factor that was associated with pyloric stenosis was the extent of the pyloric ring dissection (P < 0.001). Four of the 9 patients with pyloric stenosis had mild dyspepsia, and the others had gastric outlet obstruction symptoms. The 5 symptomatic patients underwent endoscopic balloon dilation (EBD), and the frequency of EBD was 1 to 8 times. The asymptomatic patients were treated conservatively. The incidence of pyloric stenosis was higher in lesions with resections over 75% of the pyloric ring circumference. Although EBD was an effective treatment for pyloric stenosis, conservative management was also helpful in patients who had mild symptoms.

Bedside Endoscopic Ultrasound-guided Transgastric Gallbladder Aspiration and Lavage in a High-risk Surgical Case Due to Acute Cholecystitis Accompanied by Multiorgan Failure.

Cholangitis and cholecystitis are intra-abdominal infections that show poor prognosis upon progression to sepsis and multiorgan failure. Administration of antibiotics with high antimicrobial susceptibility and removal of infected bile at the initial treatment are important. After undergoing ERCP for diagnostic purposes, a 58-year-old man developed acute cholangitis and cholecystitis accompanied by rhabdomyolysis, multi-organ failure, and severe sepsis. Broad-spectrum antibiotics with bedside endoscopic nasobiliary drainage were administered, but clinical symptoms did not improve. Therefore, bedside EUS-guided transgastric gallbladder aspiration and lavage was performed, resulting in successful treatment of the patient. We report the above described case along with a discussion of relevant literature.

A case of Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1 with urolithiasis as the initial presentation.

Zollinger-Ellison syndrome (ZES) is characterized by gastrinoma and resultant hypergastrinemia, which leads to recurrent peptic ulcers. Because gastrinoma is the most common pancreatic endocrine tumor seen in multiple endocrine neoplasia type I (MEN 1), the possibility of gastrinoma should be investigated carefully when patients exhibit symptoms associated with hormonal changes. Ureteral stones associated with hyperparathyroidism in the early course of MEN 1 are known to be its most common clinical manifestation; appropriate evaluation and close follow-up of patients with hypercalcemic urolithiasis can lead to an early diagnosis of gastrinoma. We report a patient with ZES associated with MEN 1, and urolithiasis as the presenting entity. A 51-year-old man visited the emergency department with recurrent epigastric pain. He had a history of calcium urinary stone 3 years ago, and 2 years later he had 2 operations for multiple jejunal ulcer perforations; these surgeries were 9 months apart. He was taking intermittent courses of antiulcer medication. Multiple peripancreatic nodular masses, a hepatic metastasis, parathyroid hyperplasia, and a pituitary microadenoma were confirmed by multimodal imaging studies. We diagnosed ZES with MEN 1 and performed sequential surgical excision of the gastrinomas and the parathyroid adenoma. The patient received octreotide injection therapy and close follow-up.

Cronkhite-Canada syndrome associated with serrated adenoma and malignant polyp: a case report and a literature review of 13 cronkhite-Canada syndrome cases in Korea.

Cronkhite-Canada syndrome (CCS) is a rare nonfamilial polyposis syndrome characterized by epithelial disturbances both in the gastrointestinal tract and in the epidermis. The pathologic finding of the polyp is usually a hamartomatous polyp of the juvenile type; however, the possibility of serrated adenoma associated malignant neoplasm was reported in some Japanese cases. Up till now in South Korea, 13 CCS cases have been reported, but there was no case accompanied by the colon cancer. We report the first case of CCS associated with malignant colon polyp and serrated adenoma in Korea. A 72-year-old male patient who complained of diarrhea and weight loss was presented with both hands and feet nail dystrophy, hyperpigmentation, and alopecia. Endoscopic examination showed numerous hamartomatous polyps from the stomach to the colon. The pathologic results confirmed colon cancer and serrated adenoma. Helicobacter pylori eradication and prednisolone was used. Thus, the authors report this case along with a literature review.

A case of peritoneal dialysis-associated peritonitis caused by Sphingomonas paucimobilis.

Sphingomonas paucimobilis is an aerobic Gram-negative bacillus found in soil and water. Knowledge regarding the role of this infectious agent is limited because it is rarely isolated from human material. Furthermore, it is an unusual pathogen in cases of peritoneal dialysis (PD)-associated peritonitis. The clinical courses and outcomes of peritonitis caused by S. paucimobilis are variable. Whereas some patients were cured with appropriate antibiotic therapy, others required catheter removal. Cases of PD-associated peritonitis caused by S. paucimobilis have been reported worldwide, and there was a case report of coinfection with S. paucimobilis and Chryseobacterium indologenes in Korea. However, there has been no case caused by S. paucimobilis as a single pathogen. We report a case of PD-associated peritonitis due to S. paucimobilis in which the patient recovered after catheter removal.

A rare combination of left ventricular noncompaction, patent ductus arteriosus, and persistent left superior vena cava demonstrated by multidetector computed tomography and echocardiography.

Noncompaction of the ventricular myocardium (NCM) is a disorder characterized by numerous prominent ventricular trabeculations and deep intertrabecular recesses. It may present in an isolated form or in association with other cyanotic heart diseases, obstructions of the ventricular outflow tract, and anomalies of coronary arteries. We report on a rare combination of NCM, patent ductus arteriosus, and persistent left superior vena cava in a 27-year-old man examined via echocardiography and multidetector computed tomography.

Annuloaortic ectasia in a 16 year-old boy with Loeys-Dietz syndrome.

Loeys-Dietz syndrome (LDS) is a rare genetic disorder with an autosomal dominant inheritance due to mutations in the transforming growth factor beta-receptor type 1 or type 2. The disease is characterised by the triad of hypertelorism, bifid uvula or cleft palate, arterial tortuosity and aortic aneurysms. These phenotypic characteristics distinguish LDS from other connective tissue disorders related to transforming growth factor beta-receptor. Patients with LDS have a high risk of aortic dissection or rupture at a younger age and smaller aortic diameters. So, clinical suspicion of LDS followed by genotyping is important to prevent aortic dissection, leading cause of death, by surgical treatment.

A case of cryptogenic stroke associated with patent foramen ovale coexisting with pulmonary embolisms, deep vein thromboses, and renal artery infarctions.

A paradoxical embolism is defined as a systemic arterial embolism requiring the passage of a venous thrombus into the arterial circulatory system through a right-to-left shunt, and is commonly related to patent foramen ovale (PFO). However, coexisting pulmonary embolisms, deep vein thromboses (DVT), and multipe systemic arterial embolisms, associated with PFO, are rare. Here, we report a patient who had a cryptogenic ischemic stroke, associated with PFO, which is complicated with a massive pulmonary thromboembolism, DVT, and renal infarctions, and subsequently, the patient was treated using a thrombolytic therapy.