Neuroprotective Effect of Chebulagic Acid via Autophagy Induction in SH-SY5Y Cells

Autophagy is a series of catabolic process mediating the bulk degradation of intracellular proteins and organelles through formation of a double-membrane vesicle, known as an autophagosome, and fusing with lysosome. Autophagy plays an important role of death-survival decisions in neuronal cells, which may influence to several neurodegenerative disorders including Parkinson's disease. Chebulagic acid, the major constituent of Terminalia chebula and Phyllanthus emblica, is a benzopyran tannin compound with various kinds of beneficial effects. This study was performed to investigate the autophagy enhancing effect of chebulagic acid on human neuroblastoma SH-SY5Y cell lines. We determined the effect of chebulagic acid on expression levels of autophagosome marker proteins such as, DOR/TP53INP2, Golgi-associated ATPase Enhancer of 16 kDa (GATE 16) and Light chain 3 II (LC3 II), as well as those of its upstream pathway proteins, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Beclin-1. All of those proteins were modulated by chebulagic acid treatment in a way of enhancing the autophagy. Additionally in our study, chebulagic acid also showed a protective effect against 1-methyl-4-phenylpyridinium (MPP+) - induced cytotoxicity which mimics the pathological symptom of Parkinson's disease. This effect seems partially mediated by enhanced autophagy which increased the degradation of aggregated or misfolded proteins from cells. This study suggests that chebulagic acid is an attractive candidate as an autophagy-enhancing agent and therefore, it may provide a promising strategy to prevent or cure the diseases caused by accumulation of abnormal proteins including Parkinson's disease.

Protective Effects of Geniposide and Genipin against Hepatic Ischemia/Reperfusion Injury in Mice

Geniposide is an active product extracted from the gardenia fruit, and is one of the most widely used herbal preparations for liver disorders. This study examined the cytoprotective properties of geniposide and its metabolite, genipin, against hepatic ischemia/reperfusion (I/R) injury. C57BL/6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion. Geniposide (100 mg/kg) and genipin (50 mg/kg) were administered orally 30 min before ischemia. In the I/R mice, the levels of serum alanine aminotransferase and hepatic lipid peroxidation were elevated, whereas hepatic glutathione/glutathione disulfide ratio was decreased. These changes were attenuated by geniposide and genipin administration. On the other hand, increased hepatic heme oxygenase-1 protein expression was potentiated by geniposide and genipin administration. The increased levels of tBid, cytochrome c protein expression and caspase-3 activity were attenuated by geniposide and genipin. Increased apoptotic cells in the I/R mice were also significantly reduced by geniposide and genipin treatment. Our results suggest that geniposide and genipin offer significant hepatoprotection against I/R injury by reducing oxidative stress and apoptosis.

Distal hereditary motor neuropathy in Korean patients with a small heat shock protein 27 mutation

Distal hereditary motor neuropathy (dHMN) is a heterogeneous disorder characterized by degeneration of motor nerves in the absence of sensory abnormalities. Recently, mutations in the small heat shock protein 27 (HSP27) gene were found to cause dHMN type II or Charcot-Marie-Tooth disease type 2F (CMT2F). The authors studied 151 Korean axonal CMT or dHMN families, and found a large Korean dHMN type II family with the Ser135Phe mutation in HSP27. This mutation was inherited in an autosomal dominant manner, and was well associated with familial members with the dHMN phenotype. This mutation site is located in the ?-crystallin domain and is highly conserved between different species. The frequency of this HSP27 mutation in Koreans was 0.6%. Magnetic resonance imaging analysis revealed that fatty infiltrations tended to progressively extend distal to proximal muscles in lower extremities. In addition, fatty infiltrations in thigh muscles progressed to affect posterior and anterior compartments but to lesser extents in medial compartment, which differs from CMT1A patients presenting with severe involvements of posterior and medial compartments but less involvement of anterior compartment. The authors describe the clinical and neuroimaging findings of the first Korean dHMN patients with the HSP27 Ser135Phe mutation. To our knowledge, this is the first report of the neuroimaging findings of dHMN type II.

A MELAS syndrome family harboring two mutations in mitochondrial genome

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous mitochondrial disorder with variable clinical symptoms. Here, from the sequencing of the entire mitochondrial genome, we report a Korean MELAS family harboring two homoplasmic missense mutations, which were reported 9957T>C (Phe251Leu) transition mutation in the cytochrome c oxidase subunit 3 (COX3) gene and a novel 13849A>C (Asn505His) transversion mutation in the NADH dehydrogenase subunit 5 (ND5) gene. Neither of these mutations was found in 205 normal controls. Both mutations were identified from the proband and his mother, but not his father. The patients showed cataract symptom in addition to MELAS phenotype. We believe that the 9957T>C mutation is pathogenic, however, the 13849A>C mutation is of unclear significance. It is likely that the 13849A>C mutation might function as the secondary mutation which increase the expressivity of overlapping phenotypes of MELAS and cataract. This study also demonstrates the importance of full sequencing of mtDNA for the molecular genetic understanding of mitochondrial disorders.

A Family Harboring CMT1A Duplication and HNPP Deletion

Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with duplication of chromosome 17p11.2-p12, whereas hereditary neuropathy with liability to pressure palsies (HNPP), which is an autosomal dominant neuropathy showing characteristics of recurrent pressure palsies, is associated with 17p11.2-p12 deletion. An altered gene dosage of PMP22 is believed to the main cause underlying the CMT1A and HNPP phenotypes. Although CMT1A and HNPP are associated with the same locus, there has been no report of these two mutations within a single family. We report a rare family harboring CMT1A duplication and HNPP deletion.

Effects of Cognitive-Behavioral Group Therapy for Binge Eating / 신경정신의학

OBJECTIVES: The binge eaters are increasing rapidly since 1990's in Korea. The purpose of this study was to examine the effect of cognitive-behavioral group therapy on improving the frequency of binging and purging, eating attitude, self-esteem, and depression. METHOD: The subjects were 27 women who showed over 17 on the EAT-26 among binge eaters visited at eating disorders clinic "M". 10 sessions of cognitive-behavioral group therapy were provided to each group composed of 8-10 binge eaters. All subjects completed the Eating Disorders Inventory (EDI), Rosenberg Self-Eesteem Scale, Beck Depression Inventory (BDI) pre- and post intervention, and recorded daily food records. Paired t-test was used for the comparison of EDI subscales before and after treatment. RESULTS: Frequency of binging and purging, self-esteem, depression, drive for thinness, bulimia, body dissatisfaction, ineffectiveness, interoceptive awareness subscales of EDI showed significant immprovement but perfectionism, interpersoual distrust, maturity fear subscales of EDI showed no improvement after the cognitive-behavioral group therapy. Frequency of binging and purging per week showed a general trend of decline from the beginning to the end of the treatment and a rapid decrease at the second week was noticed. CONCLUSION: The results of this preliminary study suggest that cognitive-behavioral group therapy may be an effective initial approach for the treatment of binge eating. Future research aimed at replicating these initial results and providing systematic long-term evaluation is needed.

Choledochoscopic Electrohydraulic Lithotripsy for the Retained Bile Duct Stones / 한국간담췌외과학회지

Choledochoscopic lithotomy with the aid of electrohydraulic lithotripsy ( EHL ) was performed in 12 patients at the Department of Surgery, College of Medicine, the Catholic University of Korea, St. Vincent Hospital between January 1996 and March 1998. This retrospective analysis include 4 patients with common bile duct (CBD) stones, 5 patients with intrahepatic duct (IHD) stones, and 3 patients with CBD & IHD stones. The male to female ratio was 1 to 2. The peak incidence of age was the fifty. As a route for the choledochoscopy, a T-tube tract was used in 9 patients, while percutaneous biliary drainage followed by dilatation of the tract was established in 3 patients. The largest stones measured 22mm (by 5mm), the average is 10.3mm. Average number of session which performed for IHD stones was 3.7, while that of CBD stones was 2.7. Complete removal of the stones was achieved in 7 of 12 patients. Retained stones of CBD were removed completely in all cases. We could not removed retained stones completely in cases of multiple, impacted stones in peripheral ducts, associated stricture and acute angulation of IHD & CHD which choledochoscopic manipulation make difficult. Minor complications were bleeding from the bile duct mucosa in 1 patient and postprocedure chills and fever in 1 patient. In conclusion, choledochoscopic lithotomy with electrohydraulic lithotripsy is efficient and will be useful to remove biliary calculi in patients who have poor surgical risks.