Involvement of oxidative stress in bee venom-induced inhibition of Na+/glucose cotransporter in renal proximal tubule cells

1. The present study was conducted to examine the involvement of oxidative stress in bee venom-induced inhibition of the Na+/glucose cotransporter (alpha-methyl-d-glucopyranoside (alpha-MG) uptake), a typical functional marker of proximal tubules, in primary cultured rabbit renal proximal tubule cells (PTC). 2. Bee venom (> or = 1 microg/mL) increased lipid peroxide (LPO) formation over 30 min. The increase in [(3)H]-arachidonic acid (AA) release and LPO formation and the inhibition of alpha-MG uptake induced by bee venom (1 microg/mL) and melittin (a major component of bee venom; 0.5 microg/mL) were blocked by N-acetyl-l-cysteine, vitamin C and vitamin E, anti-oxidants. 3. Bee venom- and melittin-induced increases in LPO formation and inhibition of alpha-MG uptake were significantly prevented by mepacrine and AACOCF(3), phospholipase A(2) inhibitors. In addition, nordihydroguaiareic acid (a lipoxygenase inhibitor) and econazole (a cytochrome P-450 epoxygenase inhibitor), but not indomethacin (a cyclo-oxygenase inhibitor), prevented bee venom- and melittin-induced increases in LPO formation and inhibition of alpha-MG uptake. 4. Nordihydroguaiareic acid prevented bee venom- and melittin-induced increases in Ca(2+) uptake. Moreover, anti- oxidants significantly prevented bee venom- and melittin-induced increases in Ca(2+) uptake. 5. In conclusion, bee venom inhibits alpha-MG uptake via the phospholipase A(2)-oxidative stress-Ca(2+) signalling cascade in primary cultured rabbit renal proximal tubule cells.     

The water-soluble fraction (<10 kD) of bee venom (Apis mellifera) produces inhibitory effect on apical transporters in renal proximal tubule cells

Human envenomation caused by bee stings has been reported to cause acute renal failure and the pathogenetic mechanisms of these renal functional changes are still unclear. Bee venom is also a complex mixture of enzymes and proteins. Thus, this study was conducted to examine the effects of bee venom (BV, Apis mellifera) fractions on apical transporters' activity and its related signal pathways in primary cultured renal proximal tubule cells. Whole BV was extracted into three fractions according to solubility [a water-soluble fraction (BVA), an ethylacetate-soluble fraction (BVE), and a hexane-soluble fraction (BVH)]. BVA fraction was further separated to three portions according to molecular weights: BF1 (>20 kD), BF2 (10-20 kD), and BF3 (<10 kD). Each fraction was treated to the PTCs to the ratio of BV (1 microg/ml). BVA (930 ng/ml) significantly decreased cell viability, but BVH (27 ng/ml) and BVE (43 ng/ml) did not. BF3 (710 ng/ml) among BVA fractions predominantly decreased cell viability and inhibited alpha-methyl-D-glucopyranoside (alpha-MG), phosphate (Pi), and Na(+) uptake. In addition, BF3 increased [(3)H] arachidonic acid release, lipid peroxide formation, and Ca(2+) uptake. These effects of BF3 were blocked by mepacrine and AACOCF(3) (phospholipase A(2) inhibitors) or N-acetylcysteine, vitamin C, and vitamin E (antioxidants). In conclusion, BF3 (<10 kD) among BV fractions is the most effective portion in BV-induced inhibition of alpha-MG, P(i), and Na(+) uptake and these effects of BF3 are associated with phospholipase A(2)-oxidative stress-Ca(2+) signal cascade in the primary cultured rabbit renal proximal tubule cells.     

Dietary factors and gastric cancer in Korea: a case-control study.

To assess gastric cancer (GC) risk in relation to dietary intake in Korea, a case-control study was performed. Trained dietitians interviewed 136 patients diagnosed with GC, and the same number of controls were selected by matching sex, age and hospital. A significant decrease in GC risk was observed with increased intake of Baiechu kimchi (prepared with salted Chinese cabbage and red pepper, etc.), Baiechu kimchi-stew, garlic, mushroom and soybean milk. On the contrary, a significant increase in the risk of GC was observed with increased intake of cooked rice with bean, charcoal grilled beef, pollack soup, Kkakduki (a kind of kimchi prepared with salted radish and red pepper, etc.), Dongchimi (a kind of kimchi prepared with radish and a large quantity of salt water) and cooked spinach. In food groups, increased intake of soybean products was associated with decreased risk of GC. Intake of citrus fruits rather than total fruits was shown to have a protective effect on the risk of GC, but was not significant. In this study, intake of total vegetables was shown to have a protective effect, whereas high nitrate-containing vegetables increased the risk of GC. In conclusion, our study suggests that the risk of GC decreased with high consumption of fresh vegetables and fruits, whereas high consumption of foods rich in nitrate and carcinogenic substances produced during the cooking process increased the risk of GC.     

Kaempferol induced the apoptosis via cell cycle arrest in human breast cancer MDA-MB-453 cells

The aim of present study was to investigate the effects of kaempferol on cellular proliferation and cell cycle arrest and explore the mechanism for these effects in human breast carcinoma MDA-MB-453 cells. Cells were treated with kaempferol at various concentrations (ranging from 1 to 200 µM) for 24 and 48 hrs. Kaempferol significantly inhibited cancer cell growth in cells exposed to 50 and 10 µM of kaempferol and incubated for 24 and 48 hrs, respectively. Exposure to kaempferol resulted in cell cycle arrest at the G2/M phase. Of the G2/M-phase related proteins, kaempferol down-regulated CDK1 and cyclin A and B in cells exposed to kaempferol. In addition, small DNA fragments at the sub-G0 phase were increased by up to 23.12 and 31.90% at 10 and 50 µM incubated for 24 and 48 hrs, respectively. The kaempferol-induced apoptosis was associated with the up-regulation of p53. In addition, the phosphorylation of p53 at the Ser-15 residue was observed with kaempferol. Kaempferol inhibits cell proliferation by disrupting the cell cycle, which is strongly associated with the induction of arrest at G2/M phase and may induce apoptosis via p53 phosphorylation in human breast carcinoma MDA-MB-453 cells.     

Balloon Sheaths for Gastrointestinal Guidance and Access: A Preliminary Phantom Study

Objective

We wanted to evaluate the feasibility and usefulness of a newly designed balloon sheath for gastrointestinal guidance and access by conducting a phantom study.

Materials and Methods

The newly designed balloon sheath consisted of an introducer sheath and a supporting balloon. A coil catheter was advanced over a guide wire into two gastroduodenal phantoms (one was with stricture and one was without stricture); group I was without a balloon sheath, group ll was with a deflated balloon sheath, and groups III and IV were with an inflated balloon and with the balloon in the fundus and body, respectively. Each test was performed for 2 minutes and it was repeated 10 times in each group by two researchers, and the positions reached by the catheter tip were recorded.

Results

Both researchers had better performances with both phantoms in order of group IV, III, II and I. In group IV, both researchers advanced the catheter tip through the fourth duodenal segment in both the phantoms. In group I, however, the catheter tip never reached the third duodenal segment in both the phantoms by both the researchers. The numeric values for the four study groups were significantly different for both the phantoms (p < 0.001). A significant difference was also found between group III and IV for both phantoms (p < 0.001).

Conclusion

The balloon sheath seems to be feasible for clinical use, and it has good clinical potential for gastrointestinal guidance and access, particularly when the inflated balloon is placed in the gastric body.     

Risk factors in predicting a poor response to sildenafil citrate in elderly men with erectile dysfunction

OBJECTIVE: To assess the clinical efficacy of sildenafil and the potential predictors of poor response to sildenafil in elderly patients with erectile dysfunction (ED). PATIENTS AND METHODS: The study included 162 patients (aged > or = 60 years) treated with sildenafil for at least 8 weeks; all patients were evaluated with a history, physical examination, measurement of total testosterone and a pharmacological erection test. Sexual function before and 8 weeks after treatment was assessed using the self-administered International Index of Erectile Function (IIEF). Treatment was considered successful when the patient attained a higher grade on the erectile function (EF) domain score, and an affirmative response to the overall assessment question. Factors influencing treatment outcome were evaluated by univariate and multivariate statistical analysis. RESULTS: The overall efficacy with sildenafil was 47% (76/162). On univariate analysis, uncontrolled diabetes, current smoking, hypogonadism (<3 microg/L testosterone) and low pretreatment EF domain score (<17) were selected as predictors of a poor response. On multivariate logistic regression, a low pretreatment EF domain score was the strongest independent prognostic factor for a poor response (odds ratio 2.25, 95% confidence interval, 1.45-7.33), and this was followed by hypogonadism (1.89, 1.12-3.16) and current smoking (1.34, 1.04-3.52). CONCLUSION: In a real clinical setting, sildenafil was effective for about half of the elderly men. The baseline EF domain score, hypogonadism and current smoking were significantly associated with failure of sildenafil. These results suggest that modifying reversible risk factors, e.g. stopping smoking and replacing testosterone, would be beneficial in augmenting the efficacy of sildenafil in elderly men.     

Inhibitory effect of green tea extract on beta-amyloid-induced PC12 cell death by inhibition of the activation of NF-kappaB and ERK/p38 MAP kinase pathway through antioxidant mechanisms

Beta-amyloid peptide (Abeta) is considered responsible for the pathogenesis of Alzheimer's disease (AD). Several lines of evidence support that Abeta-induced cytotoxicity is mediated through the generation of reactive oxygen species (ROS). Thus, agents that scavenge ROS level may usefully impede the development or progress of AD. Green tea extract has been known to have such antioxidant properties. Our previous studies demonstrate that green tea extract protected ischemia/reperfusion-induced brain cell death by scavenging oxidative damages of macromolecules. In this study, we investigated the effects of green tea extract on Abeta-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with Abeta25-35 (10-50 microM) showed intracellular ROS elevation, the formation of 8-oxodG (an oxidized form of DNA), and underwent apoptotic cell death in a dose-dependent manner. Abeta(25-35) treatment upregulated pro-apoptotic p53 at the gene level, and Bax and caspase-3 at the protein level, but downregulated anti-apoptotic Bcl-2 protein. Interestingly, co-treated green tea extract (10-50 microg/ml) dose-dependently attenuated Abeta(25-35) (50 microM)-induced cell death, intracellular ROS levels, and 8-oxodG formation, in addition to p53, Bax, and caspase-3 expression, but upregulated Bcl-2. Furthermore, green tea extract prevented the Abeta(25-35)-induced activations of the NF-kappaB and ERK and p38 MAP kinase pathways. Our study suggests that green tea extract may usefully prevent or retard the development and progression of AD.