Curcumin protected PC12 cells against beta-amyloid-induced toxicity through the inhibition of oxidative damage and tau hyperphosphorylation

One of the pathological hallmarks of Alzheimer's disease is the progressive accumulation of beta-amyloid (Abeta) in the form of senile plaques, and Abeta insult to neuronal cells has been identified as one of the major causes of the onset of the disease. Curcumin, the major and most active antioxidant of Curcuma longa, protects neuronal cells against Abeta-induced toxicity. Therefore, in this study, we investigated the neuroprotective mechanisms by which curcumin acts against Abeta (25-35)-induced toxicity in PC12 cells. Following the exposure of PC12 cells to 10 microM Abeta (25-35) for 24h, significant increases in the level of antioxidant enzymes, and DNA damage were observed, and these increases were accompanied by a decrease in cell viability, and an increase in intracellular calcium levels and tau hyperphosphorylation. In addition, pretreatment of PC12 cells with 10 microg/ml curcumin for 1h significantly reversed the effect of Abeta, by decreasing the oxidative stress, and DNA damage induced by Abeta, as well as attenuating the elevation of intracellular calcium levels and tau hyperphosphorylation induced by Abeta. Taken together, these data indicate that curucmin protected PC12 cells against Abeta-induced neurotoxicity through the inhibition of oxidative damage, intracellular calcium influx, and tau hyperphosphorylation.     

Benzene increases the ratio of arachidonic acids to docosahexaenoic acids and inhibits the de novo synthesis of ceramide in the rat liver

The present study investigated the effects of inhalation exposure of benzene at 0, 10, 200 and 600 ppm for 1, 2 and 4 weeks on n-6 and n-3 fatty acids and ceramide levels in the rat liver. No significant difference in the ratio of saturated fatty acid to unsaturated fatty acid was found on increasing benzene exposure levels, but the ratio of saturated fatty acid to unsaturated fatty acid decreased with increasing benzene exposure times, with the exception of the phospholipids of rats exposed to 200 and 600 ppm of benzene. A significant increase in the ratio of arachidonic acid to docosahexaenoic acid was found in the phospholipids of rats exposed to 200 and 600 ppm of benzene for 4 weeks. In our study, no change in the relative amounts of sphingomyelin in phospholipids, due to benzene exposure at 600 ppm for 4 weeks resulted in the lack of sphingomyelin turnover. However, ceramide levels in the livers of rats exposed to 600 ppm of benzene for 4 weeks were significantly reduced upon increasing the benzene concentration. This result shows that the de novo synthesis of ceramide was significantly inhibited at higher levels of benzene and that the ratio of arachidonic acid to docosahexaenoic acid in phospholipids is dose-dependently related to benzene exposure.     

Effects of hair dyeing on DNA damage in human lymphocytes

Comet assays were carried out to evaluate DNA damage in human lymphocytes from 20 volunteers before and after hair dyeing. DNA damage in lymphocytes was found to be slightly higher in volunteers after hair dyeing. Tail moments before and after hair dyeing were 1.47 +/- 0.41 and 1.75 +/- 0.29 respectively (p<0.0008). DNA damage in lymphocytes showed significant difference with treatment and heating time. The tail moments after 15 min of treatment time before and after hair dyeing were 1.44 +/- 0.22 and 1.85 +/- 0.36, respectively (p=0.0004) and the corresponding tail moments in 20 min of heating time before and after were 1.37 +/- 0.15 and 1.78 +/- 0.34 (p=0.0002). In conclusion, we found that an acute exposure of hair dyes with heating caused DNA damages in peripheral lymphocytes and that this damage had significant association with treatment and heating time.     

P53 Codon 72 polymorphisms: a case-control study of gastric cancer and potential interactions

P53 codon 72 polymorphisms have been reported to be associated with cancers of the lung, esophagus and cervix. However, there have been no reports on the interaction of select risk factors and p53 codon 72 polymorphisms in gastric cancer susceptibility. 155 gastric cancer cases and 134 cancer-free controls were enrolled at the Memorial Sloan Kettering Cancer Center (MSKCC) from November 1992 to November 1994. The crude odds ratio (OR1) associated with the (Pro/Pro) polymorphism and the risk of gastric cancer was 1.27 (0.70-2.33). Adjusting for age, sex, race and education (OR2) and further adjusting for BMI, calories, sodium, smoking, vitamin C, fiber, alcohol, fat, and H. pylori status (OR3) did not yield significant results. Significant joint effects were associated with high fat consumption (OR1=2.61 (95% CI:1.13-6.06); OR2=2.85 (95% CI:1.14-7.15) for total cancers and for proximal tumors (OR1=2.56 (95%CI:1.00-6.54)). The low vitamin C intake/high-risk polymorphism group (Pro/Pro) had an OR1 of 4.82 (95% CI: 1.72-13.45) and the OR2 was 6.19 (95% CI: 2.08-18.40) for distal tumors. The point estimates were increased for interaction odds ratios but not statistically significant (OR1=4.25 (95% CI: 0.66-27.50); OR2=4.73 (95% CI: 0.67-33.43); OR3=5.55 (95% CI: 0.66-46.47)). Further studies specifically looking at proximal and distal tumors are required to confirm any potential interaction between the p53 codon 72 polymorphisms and environmental risk, in particular low dietary vitamin C and high fat consumption.     

Development of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K): clinical and neuropsychological assessment batteries.

A Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K) was created. The English-American version of CERAD clinical and neuropsychological assessment batteries was translated into Korean, and the psychometrical properties of the cognitive tests in the CERAD-K were established. In the translation, including back-translation, the basic structures of all measures in the original CERAD batteries were maintained. The CERAD-K was administered in a standardized manner to 106 dementia patients (aged 70.4 +/- 8.1 years), including 78 Alzheimer's disease (AD) patients, and 186 controls (aged 68.4 +/- 4.6 years) who were recruited from 3 university hospitals and 2 elderly welfare centers. The cognitive tests in the CERAD-K successfully differentiated controls from the dementia patients and from the AD patients. They also showed substantial interrater reliability and 1-month test-retest reliability. The CERAD-K is an equally reliable and valid equivalent for the English version of the CERAD clinical and neuropsychological assessment batteries.     

Pref-1, a preadipocyte secreted factor that inhibits adipogenesis

Preadipocyte factor 1 (Pref-1) belongs to the Notch/Delta/Serrate family of epidermal growth factor-like repeat-containing proteins. Pref-1 is highly expressed in 3T3-L1 cells but is extinguished during adipocyte differentiation. Pref-1 serves as an excellent marker for preadipocytes. Furthermore, Pref-1 is an inhibitor of adipogenesis. Constitutive expression of Pref-1 inhibits, whereas antisense Pref-1 enhances, 3T3-L1 adipocyte differentiation. We found that Pref-1 is synthesized as a transmembrane protein but processed to generate soluble forms, including a large 50-kDa soluble form and the small soluble forms. Furthermore, only the large soluble form, but not the small soluble or the transmembrane forms of Pref-1, is biologically active to inhibit adipogenesis. We recently elucidated that the 50-kDa soluble form of Pref-1 is released by an ADAM family member, tumor necrosis factor-alpha converting enzyme (ADMA 17). In vivo, mice lacking Pref-1 show accelerated fat deposition; conversely, mice overexpressing soluble Pref-1 in adipose tissue show a decrease in fat mass, reduced expression of adipocyte markers, and lower adipocyte-secreted factors. These findings clearly demonstrate the inhibitory effect of Pref-1 on adipogenesis in vivo.     

Single strand DNA breaks in T- and B-lymphocytes and granulocytes in workers exposed to benzene

Comet assays were carried out to evaluate DNA damage in T- and B-lymphocytes and granulocytes from 41 workers exposed to benzene in a printing company and 41 unexposed donors. In T-lymphocytes, DNA damage was slightly higher in exposed workers than in controls. The tail moments in the two groups were 1.75+/-0.29 and 1.47+/-0.41, respectively (P<0.0006). DNA damage of B-lymphocytes in the two groups showed the most significant difference among the three cell types. The tail moments were 3.86+/-0.71 and 1.51+/-0.39, respectively (P<0.0001). In granulocytes, DNA damage was also different, the tail moments being 3.61+/-0.75 and 2.60+/-0.59, respectively (P<0.0001). The comparison of DNA damage in both groups shows that B-lymphocytes could be a useful target in biomonitoring of human exposure to low levels of benzene.     

Esophageal capsule endoscopy for evaluation of patients with chronic gastroesophageal reflux symptoms: findings and its image quality

Esophageal capsule endoscopy (ECE) may offer an alternative approach to visualize esophageal lesions associated with gastroesophageal reflux (GER) disease. The objective of this study was to report the ECE findings in patients with GER symptoms and validate a new scoring system to assess ECE video quality. Five hundred two ECE were performed in patients with GER symptoms. We devised a new grading scale called ECE Utility score to assess the quality of images using five different parameters: anatomic landmarks visualized, esophageal transit time, image quality, illumination, and artifacts. The ECE cases were independently scored by two interpreters in a randomized, blinded fashion. Reflux esophagitis was diagnosed via ECE in 254 patients (50.5%). We identified 12 cases (2.4%) with suspected Barrett's esophagus and all of them had endoscopic evidence of Barrett's esophagus on esophagogastroduodenoscopy. Histologic confirmation Barrett's esophagus was found in six patients and dysplasia was found in one patient. From the 502 cases, mean ± standard deviation total ECE Utility score was 8.89 ± 0.96 for interpreter 1 and 8.96 ± 0.93 for interpreter 2. The concordance rate between the two interpreters for the ECE Utility score ranged from 75.9–96.8% across the parameters and the Pearson correlation rate of the total score was 0.81. ECE is shown to be a simple noninvasive valuable technique for evaluating esophageal mucosa and producing high quality images in patients with GER symptoms. ECE can help as an alternative screening tool for diagnosing Barrett's esophagus.