Striatal neuroinflammation promotes parkinsonism in rats

The specific role of neuroinflammation in the pathogenesis of Parkinson's disease remains to be fully elucidated. By infusing lipopolysaccharide (LPS) into the striatum, we investigated the effect of neuroinflammation on the dopamine nigrostriatal pathway. Here, we report that LPS-induced neuroinflammation in the striatum causes progressive degeneration of the dopamine nigrostriatal system, which is accompanied by motor impairments resembling parkinsonism. Our results indicate that neurodegeneration is associated with defects in the mitochondrial respiratory chain related to extensive S-nitrosylation/nitration of mitochondrial proteins. Mitochondrial injury was prevented by treatment of L-N^6^-(l-iminoethyl)-lysine, an inducible nitric oxide synthase (iNOS) inhibitor, suggesting that iNOS-derived NO is responsible for mitochondrial dysfunction. Furthermore, the nigral dopamine neurons exhibited intracytoplasmic [alpha]-synuclein and ubiquitin accumulation. These results demonstrate that degeneration of nigral dopamine neurons by neuroinflammation is associated with mitochondrial malfunction induced by NO-mediated S-nitrosylation/nitration of mitochondrial proteins

β-Lapachone Significantly Increases the Effect of Ionizing Radiation to Cause Mitochondrial Apoptosis via JNK Activation in Cancer Cells

β-lapachone (β-lap), has been known to cause NQO1-dependnet death in cancer cells and sensitize cancer cells to ionizing radiation (IR). We investigated the mechanisms underlying the radiosensitization caused by β-lap. cells induced ROS generation, triggered ER stress and stimulated activation of ERK and JNK. Inhibition of ROS generation by NAC effectively attenuated the activation of ERK and JNK, induction of ER stress, and subsequent apoptosis. Importantly, inhibition of ERK abolished ROS generation and ER stress, whereas inhibition of JNK did not, indicating that positive feedback regulation between ERK activation and ROS generation triggers ER stress in response to combined treatment. Furthermore, prevention of ER stress completely blocked combination treatment-induced JNK activation and subsequent apoptotic cell death. In addition, combined treatment efficiently induced the mitochondrial translocation of cleaved Bax, disrupted mitochondrial membrane potential, and the nuclear translocation of AIF, all of which were efficiently blocked by a JNK inhibitor. Caspases 3, 8 and 9 were activated by combined treatment but inhibition of these caspases did not abolish apoptosis indicating caspase activation played a minor role in the induction of apoptosis. cells are treated with combination of IR and β-lap, positive feedback regulation between ERK and ROS leads to ER stress causing JNK activation and mitochondrial translocation of cleaved Bax. The resultant decrease in mitochondrial membrane leads to translocation of AIF and apoptosis

A Structural Equation Modeling on Reproductive Health Promoting Behavior of Unmarried Women: Based on the Theory of Planned Behavior

PURPOSE: The purpose of this study was to construct and test a structural equation modeling on the reproductive health behavior of single women with sexual experiences. This study employed Ajzen's Theory of Planned Behavior (TPB). METHODS: The data were collected after receipt of consent from 250 single women with sexual experiences, and analyzed using SPSS 18.0 and AMOS 18.0. RESULTS: Model fit indices for the hypothetical model were suitable for the recommended level: x²=362.407, RMR=0.065, RMSEA=0.070, GFI=0.867. TLI=0.927, CFI=0.938, IFI=0.939, and x²/dF=2.237. Intention showed direct effect with the biggest effect being on reproductive health behavior. Attitude, subjective norm and perceived behavioral control were found to have a direct effect on intention. Among them, perceived behavioral control revealed the largest influence. CONCLUSION: This study suggests that the TPB is a suitable model in explaining the reproductive health behavior of single women with sexual experience. Strategic plans for educational and intervention programs should be aimed to encourage single women to engage in reproductive health behavior

A Case of Biopsy-proven Early-onset Alzheimer's Disease with Hemiparkinsonism

Patients with dementia and concomitant parkinsonism are frequently encountered in the elderly population. When it comes to young adults, however, coexistence of Alzheimer's disease (AD) and Parkinson's disease (PD) is rare. We described a case of 47-year old man with presenile onset dementia associated with hemiparkinsonism involving the right extremities. Brain biopsy showed neurofibrillary tangles and neuritic plaques, compatible with Alzheimer's disease. Iodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([(123)I]IPT) SPECT, dopamine transporter imaging, revealed a decreased uptake in both basal ganglia, more severe on the left side, particularly the caudal putamen, which is consistent with the finding of idiopathic Parkinson's disease. This case is unique in that damage on the nigrostriatal dopaminergic system in a patient with Alzheimer's disease was demonstrated by a functional neuroimaging study and that early-onset AD and early-onset PD, two rare conditions, coexist in the same individual

Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance

Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan. Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance. Results. The IC50 values of simvastatin alone and irinotecan alone were 115.4±0.14 μM (r=0.98) and 62.5±0.18 μM (r=0.98) in HT-29 cells without resistance to irinotecan. The IC50 values of these two drugs were 221.9±0.22 μM (r=0.98) and 195.9±0.16 μM (r=0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at 2:1 molar ratio showed the best synergistic interaction. Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer

Binge Drinking and Its Relation to Metabolic Syndrome in Korean Adult Men

Background: It is reported that heavy drinking increases the risk of metabolic syndrome. But there have been few studies on the relationship between the intensity of drinking and metabolic syndrome when drinking the same amount of alcohol. This study aimed to assess the relationship between the frequency of binge drinking and metabolic syndrome in Korean adult men.Methods: From the database of the 4th and 5th Korea National Health and Nutrition Examination Survey conducted in 2007?2010, data of 8,305 adult men (≥19 years of age) was included in this analysis. Cross-sectional relationship between the frequency of binge drinking and metabolic syndrome was investigated adjusting for pure alcohol consumed per day.Results: Adjusting for various confounders including pure alcohol consumed per day, the adjusted odds ratio for metabolic syndrome in those in higher frequency (more than 1/wk) binge drinking group was 1.62 (95% confidence interval, 1.30 to 2.03; P for trend = <0.001) compared to those in the non-binge drinking group. Through analysis of the relationship between pure alcohol consumed per day and metabolic syndrome, it was found that pure alcohol consumed per day had a positive relation to metabolic syndrome in the higher frequency binge drinking group (P for trend = 0.041). The relationship was inverse in the non-binge drinking group (P for trend = 0.002).Conclusion: Our study found a positive relationship between frequency of binge drinking and metabolic syndrome in adult men. And the effect of drinking on metabolic syndrome may depend on the frequency of binge drinking. Further studies are required to confirm this association.OAIID:oai:osos.snu.ac.kr:snu2014-01/102/0000052039/10SEQ:10PERF_CD:SNU2014-01EVAL_ITEM_CD:102USER_ID:0000052039ADJUST_YN:YEMP_ID:A079543DEPT_CD:806CITE_RATE:0FILENAME:binge drinking and its relation to metabolic syndrome in korean adult men.pdfDEPT_NM:의과학과SCOPUS_YN:NCONFIRM: