Inhibitory Effects of Quercetin on Muscle-type of Nicotinic Acetylcholine Receptor-Mediated Ion Currents Expressed in Xenopus Oocytes

The flavonoid quercetin is a low molecular weight compound generally found in apple, gingko, tomato, onion and other red-colored fruits and vegetables. Like other flavonoids, quercetin has diverse pharmacological actions. However, relatively little is known about the influence of quercetin effects in the regulation of ligand-gated ion channels. Previously, we reported that quercetin regulates subsets of nicotinic acetylcholine receptors such as α3β4, α7 and α9α10. Presently, we investigated the effects of quercetin on muscle-type of nicotinic acetylcholine receptor channel activity expressed in Xenopus oocytes after injection of cRNA encoding human fetal or adult muscle-type of nicotinic acetylcholine receptor subunits. Acetylcholine treatment elicited an inward peak current (I(ACh)) in oocytes expressing both muscle-type of nicotinic acetylcholine receptors and co-treatment of quercetin with acetylcholine inhibited I(ACh). Pre-treatment of quercetin further inhibited I(ACh) in oocytes expressing adult and fetal muscle-type nicotinic acetylcholine receptors. The inhibition of I(ACh) by quercetin was reversible and concentration-dependent. The IC(50) of quercetin was 18.9±1.2 μM in oocytes expressing adult muscle-type nicotinic acetylcholine receptor. The inhibition of I(ACh) by quercetin was voltage-independent and non-competitive. These results indicate that quercetin might regulate human muscle-type nicotinic acetylcholine receptor channel activity and that quercetin-mediated regulation of muscle-type nicotinic acetylcholine receptor might be coupled to regulation of neuromuscular junction activity.     

Fixed dose rate infusion of gemcitabine with oral doxifluridine and leucovorin for advanced unresectable pancreatic cancer: a phase II study

The standard beneficial chemotherapy proven for patients with advanced pancreatic cancer is a regimen containing gemcitabine. In the pregemcitabine era, 5-fluorouracil (5-FU) was the standard agent. Oral 5-FU can be added to gemcitabine to improve the efficacy of chemotherapy and to provide better patient convenience. The possibility to improve efficacy of gemcitabine by fixed dose rate infusion (FDRI) was proposed in addition to combining it with 5-FU. We tried a new chemotherapy combining FDRI of gemcitabine with doxifluridine and leucovorin. Eligibility criteria were pathologically proven, chemotherapy-na?ve, and metastatic or nonoperable advanced pancreatic cancer. Gemcitabine 1,000 mg/m(2) was infused over 100 min (days 1, 8 and 15). Doxifluridine 200 mg/m(2) t.i.d. and leucovorin 15 mg b.i.d. were given orally (days 1-21). Chemotherapy was repeated every 28 days until a patient had received 6 cycles or progression was found. Twenty-nine patients were enrolled from October 2002 to December 2004. A total of 78 cycles were given at a mean of 2.7 cycles per patient. Response could be evaluated in 26 patients. Responses were partial remission in 4/26 patients (15.4%), stable disease in 8/26 (30.8%) and progression in 14/26 (53.8%). All patients progressed except for 2 in partial remission and 2 in stable disease. Toxicities could be assessed in 23 patients. Maximal hematological toxicities greater than grade 2 were leucopenia in 3 patients (11.5%), neutropenia in 2 (7.7%), anemia in 2 (7.7%), thrombocytopenia in 1 (3.8%) and febrile neutropenia in 3 (11.5%). Maximal nonhematological grade 3 or 4 toxicities were asthenia in 1 patient (3.8%), anorexia in 1 (3.8%), vomiting in 1 (3.8%), diarrhea in 2 (7.7%), allergic reaction in 1 (3.8%), hand-foot syndrome in 1 (3.8%) and hyperbilirubinemia in 1 (3.8%). All 29 patients were dead on last follow-up. Median progression-free survival was 3.91 months in 26 evaluable patients and median overall survival was 5.59 months in all patients. Combination chemotherapy including FDRI of gemcitabine seems minimally active for patients with advanced, nonoperable pancreatic cancer. Further research to improve effectiveness of chemotherapy for advanced pancreatic cancer is mandatory.     

Community level exposure to chemicals and oxidative stress in adult population

Little information is available on the role of environmental chemical exposure in oxidative stress. This study was designed to investigate whether exposure to environmental chemicals, such as polycyclic aromatic hydrocarbons, volatile organic compounds, bisphenol A or phthalates, induces oxidative stress in urban adult populations. A total of 960 adults dwelling in urban areas were evaluated between April and December 2005. To assess environmental chemical exposure, we measured urinary levels of 1-hydroxypyrene, 2-naphthol, hippuric acid, methyl hippuric acid, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-butyl phthalate and bisphenol A. Urinary malondialdehyde and 8-hydroxydeoxyguanosine were also measured to evaluate oxidative stress. Significant dose-responsive relationship was found between urinary concentrations of the chemical exposure biomarkers and oxidative stress levels in simple regression analyses (P < 0.05). Regression coefficients of these exposure biomarkers except bisphenol A remained significantly in the multiple regression models after controlling for age, sex, weight, smoking, and exercise for at least one of the two oxidative stress biomarkers (P < 0.05). The oxidative stress biomarkers significantly affected the indicators of insulin resistance, particularly glucose level. This study indicates that environmental chemical exposure is associated with oxidative stress in urban adult populations and suggests that exposure to certain environmental chemicals might contribute to insulin resistance.     

Development of an improved canine model of percutaneous spinal cord compression injury by balloon catheter

The technique named detrended fluctuation analysis (DFA) has been used to reveal the presence of long-range temporal correlations (LRTC) and scaling behavior (SB) in electroencephalographic (EEG) recordings. The occurrence of these phenomena seems to be a salient characteristic of the healthy human brain and alterations in different pathologies has been described. Here we show how the filtering stages implemented in the systems for digital EEG influence the estimation of the DFA parameters used to characterize the brain signals. In consequence, we conclude that it is important to consider these filtering effects before interpreting the results obtained from digital EEG recordings.     

Identification of ginsenoside interaction sites in 5-HT3A receptors

We previously demonstrated that 20(S)-ginsenoside Rg(3) (Rg(3)), one of the active components of Panax ginseng, non-competitively inhibits 5-HT(3A) receptor channel activity on extracellular side of the cell. Here, we sought to elucidate the molecular mechanisms underlying Rg(3)-induced 5-HT(3A) receptor regulation. We used the two-microelectrode voltage-clamp technique to investigate the effect of Rg(3) on 5-HT-mediated ion currents (I(5-HT)) in Xenopus oocytes expressing wild-type or 5-HT(3A) receptors harboring mutations in the gating pore region of transmembrane domain 2 (TM2). In oocytes expressing wild-type 5-HT(3A) receptors, Rg(3) dose-dependently inhibited peak I(5-HT) with an IC(50) of 27.6+/-4.3microM. Mutations V291A, F292A, and I295A in TM2 greatly attenuated or abolished the Rg(3)-induced inhibition of peak I(5-HT). Mutation V291A but not F292A and I295A induced constitutively active ion currents with decrease of current decay rate. Rg(3) accelerated the rate of current decay with dose-dependent manner in the presence of 5-HT. Rg(3) and TMB-8, an open channel blocker, dose-dependently inhibited constitutively active ion currents. The IC(50) values of constitutively active ion currents in V291A mutant receptor were 72.4+/-23.1 and 6.5+/-0.7microM for Rg(3) and TMB-8, respectively. Diltiazem did not prevent Rg(3)-induced inhibition of constitutively active ion currents in occlusion experiments. These results indicate that Rg(3) inhibits 5-HT(3A) receptor channel activity through interactions with residues V291, F292, and I295 in the channel gating region of TM2 and further demonstrate that Rg(3) regulates 5-HT(3A) receptor channel activity in the open state at different site(s) from those of TMB-8 and diltiazem.     

Nonexudative morphologic changes of neovascularization on optical coherence tomography angiography as predictive factors for exudative recurrence in age-related macular degeneration

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate morphologic changes of choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA) during...     

Effect of pilopool on forced swimming test in mice

Pilopool is composed of high molecular weight water-soluble chitosan, Allium sativum L. extract, mushroom extract, Dioscorea Batatas D., and purple bamboo salt. This study investigated the effect of Pilopool on performance of forced swimming test (FST). First, the immobility time was decreased in Pilopool-fed group in comparison with control group on FST. In blood serum, the contents of creatine kinase and lactic dehydrogenase were decreased and the contents of glucose and total protein were increased. The results predict a potential benefit of Pilopool as an anti-fatigue agent and for improving physical stamina.     

Anti-angiogenic activity of the methanol extract and its fractions of Ulmus davidiana var. japonica

This study aimed to elucidate anti-angiogenic activity of Ulmus davidiana var. japonica that has been widely used in folk medicine. The methanol extract (UDE) of Ulmus davidiana var. japonica concentration-dependently displayed a strong inhibition in the chick chorioallantoic membrane (CAM) angiogenesis. The n-butanol fraction of UDE and subsequent 30% MeOH subfraction were identified to be most responsible for the anti-angiogenic activity.     

Effect of diode-pumped solid state laser on polymerization shrinkage and color change in composite resins

A diode-pumped solid state (DPSS) laser emitting at 473 nm was used to test its influence on the degree of polymerization of composite resins. Eight composite resins were chosen and light cured with three different light-curing systems [a quartz–tungsten–halogen (QTH) lamp-based unit, a light-emitting diode (LED) unit, and a DPSS laser]. Polymerization shrinkage and color change in specimens were measured. According to the statistical analysis, each light-curing system produced a significantly different value of maximum polymerization shrinkage. In most specimens, the DPSS laser induced the least polymerization shrinkage. After being immersed in distilled water for 10 days, specimens light-cured by the DPSS laser had undergone less color change than those cured by the other units. In conclusion, the DPSS laser induced better or similar polymerization in terms of polymerization shrinkage and color change in composite resins compared with those of the QTH lamp-based and LED units.     

Preparation of Various Solid-Lipid Beads for Drug Delivery of Enrofloxacin

Solid-lipid beads were prepared to retard the release rate of enrofloxacin and to mask its bitter taste using carrageenan or sodium alginate as a shell material and either cacao butter or Witepsol W-35 as a solid lipid core. Sodium alginate was a better shell material than carrageenan and the highest loading efficiency was obtained using 2% sodium alginate. The alginate beads had a spherical morphology and a sturdy shell structure. The enrofloxacin release rate at room temperature was greatly reduced. Solid-lipid beads have the potential to mask the bitter taste of enrofloxacin and extend its release rate.