Impact of commercial cigarette smoke condensate on brain tissue co-cultured with astrocytes and blood-brain barrier endothelial cells

The purpose of the current study was to investigate the effect of two commercial cigarette smoke condensates (CCSC) on oxidative stress and cell cytotoxicity in human brain (T98G) or astrocytes (U-373 MG) in the presence of human brain microvascular endothelial cells (HBMEC). Cell viability of mono-culture of T98G or U-373 MG was markedly decreased in a concentration-dependent manner, and T98G was more susceptible than U-373 MG to CCSC exposure. Cytotoxicity was less prominent when T98G was co-cultured with HBMEC than when T98G was co-cultured with U-373 MG. Significant reduction in trans-epithelial electric resistance (TEER), a biomarker of cellular integrity was noted in HBMEC co-cultured with T98G (HBMEC-T98G co-culture) and U-373 MG co-cultured with T98G (U-373 MG-T98G co-culture) after 24 or 48 hr CCSC exposure, respectively. TEER value of U-373 MG co-cultured with T98G (79-84%) was higher than HBMEC co-cultured with T98G (62-63%) within 120-hr incubation with CCSC. Reactive oxygen species (ROS) generated by CCSC in mono-culture of T98G and U-373 MG reached highest levels at 4 and 16 mg/ml, respectively. ROS production by T98G fell when co-cultured with HBMEC or U-373MG. These findings suggest that adverse consequences of CCSC treatment on brain cells may be protected by blood-brain barrier or astrocytes, but with chronic exposure toxicity may be worsened due to destruction of cellular integrity.

S6 kinase 1 plays a key role in mitochondrial morphology and cellular energy flow

Mitochondrial morphology, which is associated with changes in metabolism, cell cycle, cell development and cell death, is tightly regulated by the balance between fusion and fission. In this study, we found that S6 kinase 1 (S6K1) contributes to mitochondrial dynamics, homeostasis and function. Mouse embryo fibroblasts lacking S6K1 (S6K1 KO MEFs) exhibited more fragmented mitochondria and a higher level of Dynamin related protein 1 (Drp1) and active Drp1 (pS616) in both whole cell extracts and mitochondria' fraction. In addition, there was no evidence for autophagy and mitophagy induction in S6K1 depleted cells. Glycolysis and mitochondrial respiratory activity was higher in S6K1-KO MEFs, whereas OxPhos ATP production was not altered. However, inhibition of Drp1 by Mdivi1 (Drp1 inhibitor) resulted in higher OxPhos ATP production and lower mitochondrial membrane potential. Taken together the depletion of S6K1 increased Drpl-mediated fission, leading to the enhancement of glycolysis. The fission form of mitochondria resulted in lower yield for OxPhos ATP production as well as in higher mitochondrial membrane potential. Thus, these results have suggested a potential role of S6K1 in energy metabolism by modulating mitochondrial respiratory capacity and mitochondrial morphology.

Fasting Plasma Glucose Cutoff Value for the Prediction of Future Diabetes Development: A Study of Middle-Aged Koreans in a Health Promotion Center

We determined optimal fasting plasma glucose (FPG) cutoff values predictive of future diabetes development in a group of middle-aged Koreans who visited a health promotion center. The medical records of 2,964 subjects, who attended the Health Promotion Center in 1998 and 2003, were examined. Subjects were classified into four groups according to their baseline FPG values (Group 1:FPG <5.0 mM/L; Group 2: 5.0≤FPG <5.6 mM/L; Group 3: 5.6≤FPG <6.1 mM/L; Group 4: 6.1≤FPG <7.0 mM/L). No significant difference was observed between Group 1 and Group 2 in terms of diabetes incidence. However, incidence in Group 3 was significantly higher than that in Group 1 [hazards ratio 4.88 (1.65-14.41), p=0.004] and the hazards ratio in Group 4 for diabetes was 36.91 (13.11-103.61), p<0.001, versus Group 1. Receiver operator characteristics curve analysis showed that an FPG of 5.97 mM/L represents the lower limit and gives the best combination of sensitivity and specificity. Our data shows that the risk of future diabetes development started to increase below an FPG of 6.1 mM/L and suggests the importance of efforts to modify diabetes development risk factors at lower impaired fasting glucose levels

Helicobacter pylori infection combined with DENA revealed altered expression of p53 and 14-3-3 isoforms in Gulo−/− mice

AbstractUnlike most other mammals, human bodies do not have the ability to synthesize vitamin C inside of their own bodies. Therefore, humans must obtain vitamin C through daily diet. Gulo−/− mice strain is known with deficiency, in which vitamin C intake can be controlled by diet like human, and would be valuable for investigating the molecular mechanism of various diseases. In the present study, we established Gulo−/− mice model and investigated the differentially expressed proteins in stomach tissue of Gulo−/− mice after Helicobacter pylori-infected, and followed by DENA, using immunohistochemistry and proteomic approach. The results of immunohistochemistry analysis of stomach tissue showed that the tumor suppressor, p53 protein, expression was significantly decreased (p<0.05) but not messenger RNA (mRNA) transcriptional level, and 14-3-3ε, 14-3-3δ, Ki-67 and cleaved caspase 3 expressions were significantly increased (p<0.05) by H. Pylori infection, and followed by DENA treatment in Gulo−/− mice. Moreover, knockdown of 14-3-3 isoforms (14-3-3ε, 14-3-3σ, 14-3-3ζ and 14-3-3η) were significantly increased sub-G1 phase (characteristics of apoptosis) in AGS cells and, phenotypic changes like cell shrinkage, density and cleaved nuclei were also observed. Proteome analyses showed that 14-3-3σ, 14-3-3η, and tropomyosin alpha-1 chain were down-regulated, and Hspd1 protein and HSC70 were up-regulated after H. Pylori-infection, and followed by DENA. The combined results of immunohistochemistry and proteomic analysis suggest that H. pylori altered the p53 and 14-3-3 isoforms expression and DENA further enhanced the H. pylori effect, which might be involved in carcinogenesis and metastasis of gastric cancer on Gulo−/− mice

Clinical Analysis of Acinic Cell Carcinoma in Parotid Gland

ObjectivesAcinic cell carcinoma (AciCC) is a rarely encountered malignancy in parotid gland. Because AciCC is rare and was recently recognized as the entity of malignancy, AciCC has been difficult to study. We aimed to analyze the diagnosis and treatment experience for this malignancy in our hospital.MethodsWe retrospectively reviewed medical records of the 20 patients with AciCC of parotid gland diagnosed from 1990 to 2009. The preoperative computed tomography scan, preoperative fine needle aspiration cytology (FNAC) and intraoperative frozen section results were compared with the final diagnosis. The survival and recurrence were analyzed with the cancer stages and treatment modalities.ResultsThere were 10 males and 10 females, with a mean age of 44.4 years, ranging 8-77 years. The AJCC tumor stage distributions of the patients were 70%, 15%, and 15% for stages I, II, and IV, respectively. The sensitivity of FNAC and intraoperative frozen section was 26.7% and 50.0% respectively. The 10-year survival rate was 90.9% with a mean follow-up of 111 months, ranging 17-251 months. The 10-year disease free survival rate was 74.2% and the mean duration of recurrence from initial surgery was 92.3 months.ConclusionAciCC of the parotid gland is a rare malignancy that has features of less aggressive behavior, and good prognosis. Intraoperative frozen section examination may be helpful in the diagnosis of AciCC of the parotid gland because of the low sensitivity of preoperative computed tomography scan and FNAC. Surgery with adjuvant postoperative radiotherapy is satisfactory for disease control

Anaphylactic Shock Caused by Ingestion of Polyethylene Glycol

Colonoscopy is the current standard method for evaluation of the colon. The diagnostic accuracy and therapeutic safety of colonoscopy depend on the quality of colonic cleansing and preparation. Generally, all these preparations have been demonstrated to be safe for use in healthy individuals without significant comorbid conditions. Based on safety and efficacy concerns, polyethylene glycol (PEG) is most commonly utilized as a bowel preparation solution for colonoscopy. Adverse events in patients receiving PEG are mostly clinically non-significant. However, fatal adverse events rarely have been shown to occur in the few individuals who experience vomiting or aspiration. Anaphylactic shock associated with ingestion of PEG electrolyte solution is an extremely rare fatal complication, and reported mainly in Western countries. Here, we report the first case of anaphylactic shock following the ingestion of PEG solution in Korea

Practice Pattern of Gastroenterologists for the Management of GERD Under the Minimal Influence of the Insurance Reimbursement Guideline: A Multicenter Prospective Observational Study

The objective of the study was to document practice pattern of gastroenterologists for the management of gastroesophageal reflux disease (GERD) under the minimal influence of the insurance reimbursement guideline. Data on management for 1,197 consecutive patients with typical GERD symptoms were prospectively collected during 16 weeks. In order to minimize the influence of reimbursement guideline on the use of proton pump inhibitors (PPIs), rabeprazole was used for the PPI treatment. A total of 861 patients (72%) underwent endoscopy before the start of treatment. PPIs were most commonly prescribed (87%). At the start of treatment, rabeprazole 20 mg daily was prescribed to 94% of the patients who received PPI treatment and 10 mg daily to the remaining 6%. At the third visits, rabeprazole 20 mg daily was prescribed to 70% of those who were followed and 10 mg daily for the remaining 30%. Continuous PPI treatment during the 16-week period was performed in 63% of the study patients. In conclusion, a full-dose PPI is preferred for the initial and maintenance treatment of GERD under the minimal influence of the insurance reimbursement guideline, which may reflect a high proportion of GERD patients requiring a long-term treatment of a full-dose PPI