Metronidazole-induced encephalopathy in a patient with liver cirrhosis

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis

Protective Effect of Heat Shock Protein 70 Against Oxidative Stresses in Human Corneal Fibroblasts

We evaluated DNA protection effect of heat shock protein (HSP) against cytotoxic effects of exogenous nitric oxide (NO) and reactive oxygen intermediate (ROI). Cultured human corneal fibroblasts were divided into 4 groups. Control (Group I) was not exposed to a sub-lethal heat treatment. Other 3 groups were exposed to 43℃ for 1 hr, then incubated at 37℃ during different duration (1, 6, 24 hr, Group II, III, IV, respectively). Expression pattern of HSP 70 was analyzed by Western blot. Cell viability was measured by MTT assay and the relationship between HSP 70 expression and DNA damage was examined by terminal deoxyribonucleotidyl transferase mediated dUTP-digoxigenin nick and labeling (TUNEL) stain and single cell gel electrophoresis. Expression pattern of HSP 70 was dependent on recovery times. Cell viability following heat treatment was significantly increased and the TUNEL positive cell number was decreased at 6 hr. In single cell gel electrophoresis, tail moments were increased in a dose-dependent manner by SNAP and X/XO. Following heat treatment, tail moments showed decreased significantly at 6 hr. These results suggest that induction of HSP 70 by sub-lethal heat treatment is closely related with cytoprotective effects against oxidative stresses in human corneal fibroblasts

Natural polyphenols antagonize the antimyeloma activity of proteasome inhibitor bortezomib by direct chemical interaction

P>Bortezomib is a therapeutic proteasome inhibitor with antimyeloma activity and polyphenols are well known compounds that exert antiproliferative effects against tumuors. We attempted to co-treat myeloma cells with bortezomib and polyphenols, anticipating a synergistic effect. However, the anticancer activity of bortezomib was blocked by the polyphenols. The structural features of the polyphenols correlated strikingly with their antagonistic effect; in particular, the presence or absence of a vicinal diol moiety was the key element for effective blockage of the anticancer function of bortezomib. We speculated that the vicinal diols in the polyphenols interact with the boronic acid of bortezomib and convert the active triangular boronic acid of bortezomib to an inactive tetrahedral boronate, thus abolishing the antimyeloma activity of bortezomib. We confirmed this hypothesis by (11)B nuclear magnetic resonance spectroscopy and an in vitro assay on multiple myeloma (MM) cell lines and primary myeloma cells from patients. Based on these findings, restriction of the intake of natural polyphenols in foods or vitamin supplements during bortezomib treatment in MM patients should be considered.Liu FT, 2008, BLOOD, V112, P3835, DOI 10.1182/blood-2008-04-150227Chauhan D, 2008, BLOOD, V111, P1654, DOI 10.1182/blood-2006-10-050476Ogawa Y, 2008, CANCER SCI, V99, P140, DOI 10.1111/j.1349-7006.2007.00638.xMiller CP, 2007, BLOOD, V110, P267, DOI 10.1182/blood-2006-03-013128Landis-Piwowar KR, 2006, DRUG RESIST UPDATE, V9, P263, DOI 10.1016/j.drup.2006.11.001Calcabrini A, 2006, CARCINOGENESIS, V27, P1699, DOI 10.1093/carcin/bgl044Alia M, 2006, EUR J NUTR, V45, P19, DOI 10.1007/s00394-005-0558-7Na HK, 2006, MOL NUTR FOOD RES, V50, P152, DOI 10.1002/mnfr.200500154Schroeter H, 2006, P NATL ACAD SCI USA, V103, P1024, DOI 10.1073/pnas.0510168103Fernandez Y, 2006, J BIOL CHEM, V281, P1107, DOI 10.1074/jbc.M511607200Lee KW, 2006, BIOFACTORS, V26, P105Zou W, 2006, CLIN CANCER RES, V12, P273, DOI 10.1158/1078-0432.CCR-05-0503Hideshima T, 2005, P NATL ACAD SCI USA, V102, P8567, DOI 10.1073/pnas.0503221102Park CH, 2005, BIOCHEM BIOPH RES CO, V328, P227, DOI 10.1016/j.bbrc.2004.12.151Afaq F, 2005, INT J CANCER, V113, P423, DOI 10.1002/ijc.20587Kuo PC, 2004, J BIOL CHEM, V279, P55875, DOI 10.1074/jbc.M407985200Bongiorno RA, 2004, SEMIN THROMB HEMOST, V30, P619Hideshima T, 2004, BLOOD, V104, P607, DOI 10.1182/blood-2004-01-0037Dai Y, 2004, BLOOD, V104, P509, DOI 10.1182/blood-2003-12-4121Adams J, 2004, NAT REV CANCER, V4, P349, DOI 10.1038/nrc1361Gao XM, 2003, ORG LETT, V5, P4615, DOI 10.1021/ol035783iSurh YJ, 2003, NAT REV CANCER, V3, P768, DOI 10.1038/nrc1189Beniston RG, 2003, ONCOGENE, V22, P5504, DOI 10.1038/sj.onc.1206848Richardson PG, 2003, NEW ENGL J MED, V348, P2609Russo M, 2003, ONCOGENE, V22, P3330, DOI 10.1038/sj.onc.1206493BARILLENION S, 2003, HEMATOLOGY AM SOC HE, P248LeBlanc R, 2002, CANCER RES, V62, P4996Cusack JC, 2001, CANCER RES, V61, P3535Hideshima T, 2001, CANCER RES, V61, P3071Shahrzad S, 2001, J NUTR, V131, P1207NORRILD JC, 2001, J CHEM SOC PA, V2, P719Ogata S, 2000, BIOSCI BIOTECH BIOCH, V64, P1075, DOI 10.1271/bbb.64.1075Donovan JL, 1999, J NUTR, V129, P1662Cohen HJ, 1998, AM J MED, V104, P439

Role of Dedicated Subspecialized Radiologists in Multidisciplinary Team Discussions on Lower Gastrointestinal Tract Cancers

Objective: To determine the impact of dedicated subspecialized radiologists in multidisciplinary team (MDT) discussions on the management of lower gastrointestinal (GI) tract malignancies. Materials and Methods: We retrospectively analyzed the data of 244 patients (mean age +/- standard deviation, 61.7 +/- 11.9 years) referred to MDT discussions 249 times (i.e., 249 cases, as five patients were discussed twice for different issues) for lower GI tract malignancy including colorectal cancer, small bowel cancer, GI stromal tumor, and GI neuroendocrine tumor between April 2018 and June 2021 in a prospective database. Before the MDT discussions, dedicated GI radiologists reviewed all imaging studies again besides routine clinical reading. The referring clinician's initial diagnosis, initial treatment plan, change in radiologic interpretation compared with the initial radiology report, and the MDT's consensus recommendations for treatment were collected and compared. Factors associated with changes in treatment plans and the implementation of MDT decisions were analyzed. Results: Of the 249 cases, radiologic interpretation was changed in 73 cases (29.3%) after a review by dedicated GI radiologists, with 78.1% (57/73) resulting in changes in the treatment plan. The treatment plan was changed in 92 cases (36.9%), and the rate of change in the treatment plan was significantly higher in cases with changes in radiologic interpretation than in those without (78.1% [57/73] vs. 19.9% [35/176], p < 0.001). Follow-up records of patients showed that 91.2% (227/249) of MDT recommendations for treatment were implemented. Multiple logistic regression analysis revealed that the nonsurgical approach (vs. surgical approach) decided through MDT discussion was a significant factor for patients being managed differently than the MDT recommendations (odds ratio, 4.48; p = 0.017). Conclusion: MDT discussion involving additional review of radiology examinations by dedicated GI radiologists resulted in a change in the treatment plan in 36.9% of cases. Changes in treatment plans were significantly associated with changes in radiologic interpretation.N

Genome sequence of the hot pepper provides insights into the evolution of pungency in Capsicum species

Hot pepper (Capsicum annuum), one of the oldest domesticated crops in the Americas, is the most widely grown spice crop in the world. We report whole-genome sequencing and assembly of the hot pepper (Mexican landrace of Capsicum annuum cv. CM334) at 186.6× coverage. We also report resequencing of two cultivated peppers and de novo sequencing of the wild species Capsicum chinense. The genome size of the hot pepper was approximately fourfold larger than that of its close relative tomato, and the genome showed an accumulation of Gypsy and Caulimoviridae family elements. Integrative genomic and transcriptomic analyses suggested that change in gene expression and neofunctionalization of capsaicin synthase have shaped capsaicinoid biosynthesis. We found differential molecular patterns of ripening regulators and ethylene synthesis in hot pepper and tomato. The reference Hot pepper(Capsicum annuum), one of the oldest domesticated crops in the Americas, is the most widely grown spice crop in the world. We report whole-genome sequencing and assembly of the hot pepper(Mexican landrace of Capsicum annuum cv. CM334) at 186.6×coverage. We also report resequencing of two cultivated peppers and de novo sequencing of the wild species Capsicum chinense. The genome size of the hot pepper was approximately fourfold larger than that of its close relative tomato, and the genome showed an accumulation of Gypsy and Caulimoviridae family elements. Integrative genomic and transcriptomic analyses suggested that change in gene expression and neofunctionalization of capsaicin synthase have shaped capsaicinoid biosynthesis. We found differential molecular patterns of ripening regulators and ethylene synthesis in hot pepper and tomato. The reference genome will serve as a platform for improving the nutritional and medicinal values of Capsicum species.OAIID:oai:osos.snu.ac.kr:snu2014-01/102/0000005113/1SEQ:1PERF_CD:SNU2014-01EVAL_ITEM_CD:102USER_ID:0000005113ADJUST_YN:NEMP_ID:A077085DEPT_CD:517CITE_RATE:35.209FILENAME:pepper-final.pdfDEPT_NM:식물생산과학부EMAIL:[email protected]_YN:YCONFIRM: