The effects of myricetin on hypothalamic paraventricular nucleus (PVN) neurons in rats were investigated. By whole-cell patch clamp detection in hypothalamic brain slices, we showed that the action potential frequency in type-I PVN neurons dose-dependently decreased after myricetin treatment. Further studies demonstrated that myricetin may enhance potassium currents and shifts the voltage-dependence of activation of potassium currents to more negative potentials by 6.07 mV. Using calcium free/cadmium perfusion solution could reverse myricetin-induced enhancement of potassium currents in PVN neurons. These results suggested that inhibition of hypothalamic PVN neurons by myricetin might be attributed to the enhancement of potassium currents.

The aim of this study was to quantifiably assess left ventricular systolic function by velocity vector imaging (VVI) in fetuses without myocardial hypertrophy born to gestational diabetes mellitus (GDM) mothers. Ventricular images (4-chamber) from 60 normal fetuses and 32 GDM fetuses were selected. Myocardial global and segmental peak strain and systolic strain rates were obtained from VVI offline software. Ejection fraction (EF) was also measured to assess fetal cardiac function. EF of normal fetuses and GDM group were 65.55 ± 4.64% and 65.72 ± 4.92%. No difference was found in EF between the control group and GDM group. Global strain and strain rate of GDM groups were -13.74 ± 3.19% and -1.41 ± 0.54 s(-1), respectively and were found to be lower than the normal group (p < 0.05). Six different segmental peak strains and peak systolic strain rates had identical adjacent segments not only in the control group, but also in GDM fetuses. It was concluded that VVI could reflect fetal cardiac function sensitivity. Global strain and strain rate may be useful parameters for assessing the fetal myocardial systolic function in diabetic mothers.

BACKGROUND:/st>The role of epinephrine combined with lipid emulsion in rescuing cardiovascular collapse induced by local anaesthetic overdose remains unclear. The objective of this study was to explore the effect of epinephrine on delayed lipid-based treatment for bupivacaine-induced cardiac arrest in rats. METHODS:/st>Thirty-two rats were subjected to bupivacaine to induce asystole. Basic life support was performed for 10 min before the rats received saline, epinephrine alone, or 20% lipid emulsion bolus with or without epinephrine pretreatment. ECG and invasive arterial pressure were monitored continuously. Arterial blood gas was analysed at 25 min; the right lungs and hearts of rats were harvested for measurement of dry-to-wet lung weight ratio and myocardial bupivacaine content, respectively. RESULTS:/st>In the rats treated with epinephrine plus lipid emulsion, there was a marked improvement in haemodynamic parameters at 25 min compared with rats treated with lipid alone, P<0.05. The coronary perfusion pressure immediately after lipid rescue was higher in the epinephrine/lipid-treated rats when compared with rats given lipid only (70 and 24 mm Hg, respectively, P<0.05). The myocardial bupivacaine content was lower (8.34 nM g(-1)) in the epinephrine/lipid group relative to other groups (P<0.05). However, the rats treated with lipid alone which survived had higher Po(2), less severe acidosis, and better hypoxaemia relative to surviving rats given epinephrine plus lipid. CONCLUSIONS:/st>Late intervention with epinephrine plus lipid emulsion contributed to sustained improvement in haemodynamic profile, but failed to alleviate deterioration of hypoxaemia and acidaemia in rats.

BACKGROUND:Meta-analysis was performed to evaluate the preventive effects of N-methyl-D-aspartate (NMDA) receptor antagonists on remifentanil-induced increase in postoperative pain and analgesic requirement in patients. METHODS:Pubmed, EMBase, Springer and the Cochrane Controlled Trials Register were searched to identify all randomized controlled trials (RCTs) published to November 2010 which investigated the preventive effects of NMDA receptor antagonists on remifentanil-induced postoperative hyperalgesia and/or tolerance. The studies listed at the end of these articles as reference were also searched. Two authors independently assessed the quality of each study met the inclusion criteria and extracted data. Then Meta-analysis was perfomed using RevMan 5.0 software. The outcomes analyzed were the postoperative analgesic consumption, pain intensity scores, time to first analgesic request, and the incidence of adverse effects. RESULTS: A total of 623 patients (223 in the ketamine group, 87 in the magnesium group and 313 in the control group) from 14 prospective RCTs were included in the Meta-analysis. Administration of NMDA receptor antagonists reduced the pain scores at 4 hr after operation(p<0.05), and the standarded mean differences(SMD) was -0.21 (95% confidence interval was -0.41 to -0.01 ). There were no significant differences in postoperative analgesic consumption, pain scores at other time points, time to first analgesic request and the incidence of adverse effects(p>0.05). Further subgroup analyses based on the type of intervention showed that the results were almost the same. CONCLUSION:These data do not support the use of NMDA receptor antagonists, ketamine and magnesium sulfate to prevent the development of remifentanil-induced postoperative hyperalgesia and tolerance.

An ordered hexagonal closed-packed nanopillar array is fabricated on GaN. A metal coating is then applied to encapsulate the pillars for promoting optical confinement within the cylindrical cavity. Room-temperature lasing at 373 nm is observed under pulsed excitation, at a lasing threshold of 0.42 MW/cm2. With pillar diameters of around 980 nm, the number of modes overlapping the emission spectrum is reduced, giving rise to single-mode whispering gallery stimulated emission. Finite-difference time-domain simulations are carried out for the prediction of resonant frequencies and electric field patterns corresponding to the resonant modes.

A randomized, 2-way crossover study was conducted in healthy Chinese male volunteers to evaluate the bioequivalence of a new generic formulation of entecavir (CAS 142217-69-4) tablets (test) and the available branded formulation (reference) to meet the requirements for marketing the test product in China. Test and reference tablets were administered as a single dose on 2 treatment days separated by a 2-week washout period. Blood samples were collected for a period of 24 h following drug administration. Plasma concentration of entecavir was determined by a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method. Pharmacokinetic parameters were calculated using a noncompartmental model. Bioequivalence was determined by calculating 90% CIs for the ratios of Cmax, AUC0-t and AUC0-∞ values for the test and reference products. Tolerability was assessed by monitoring vital signs, laboratory tests and interviews with the volunteers before administration and every 2 h during the study. The 90% CIs of entecavir for Cmax, AUC0-t and AUC0-∞ were 95.2-106.9%, 98.4-104.6% and 97.3-104.4%, respectively, which fell within the interval of 80-125%. No clinically important adverse effects were reported. These results suggested that the test formulation of entecavir tablets met the regulatory criterion for bioequivalence to the reference formulation.

The mechanisms of iron accumulation in substantia nigra (SN) of Parkinson's diseases remain unclear. The objective of this study was to investigate effects of nifedipine on iron-overload-induced iron accumulation and neurodegeneration in SN of rats. By high performance liquid chromatography-electrochemical detection, tyrosine hydroxylase (TH) immunohistochemistry, and iron content array, we first quantified iron content and the number of dopamine neurons in SN of experimental rats treated with iron dextran. We further assessed effects of treatment with nifedipine. Our results showed that nifedipine treatment prevents iron dextran-induced dopamine depletion in the striatum. Consistently, we found that nifedipine restores the number of TH-positive neurons reduced by iron dextran overload and prevents increase of iron content in the SN. These results suggested that nifedipine may suppress iron toxicity in dopamine neurons and prevent neurodegeneration.

Soluble proteins with amyloidogenic propensity such as the tumor suppressor protein p53 have high proportion of incompletely desolvated backbone H bonds (HB). Such bonds are vulnerable to water attack, thus potentially leading to the misfolding of these proteins. However, it is still not clear how the surrounding solvent influences the protein native states. To address this, systematic surveys by molecular dynamics simulations and entropy analysis were performed on the p53 core domain in this work. We examined seven wild/mutant X-ray structures and observed two types of water-network hydration in three "hot hydration centers"(DNA- or small molecule- binding surfaces of the p53 core domain). The "tight" water, resulting from the local collective hydrogen-bond interactions, is probably fundamental to the protein structural stability. The second type of water is highly "dynamical" and exchanges very fast within the bulk solution, which is unambiguously assisted by the local protein motions. An entropy mapping of the solvent around the protein and a temperature perturbation analysis further present the main features of the p53 hydration network. The particular environment created by different water molecules around the p53 core domain also partly explains the structural vulnerabilities of this protein.

Rab7 plays an important role in regulating endocytic traffic. In view of an emerging role of membrane traffic in signalling and diseases, we have examined the possible role of Rab7 in oncogenesis. The role of Rab7 was investigated using shRNA-mediated knockdown in A431 and MCF7 cancer cells. To our surprise, Rab7 knockdown effectively suppressed anchorage-independent growth of cancer cells in soft agar. Anoikis (matrix-detachment triggered apoptosis) was enhanced, while the level of phosphorylated (active) Akt (which is a key survival factor) was significantly reduced. Also intriguing was the observation that EGFR and Her2 levels were significantly reduced when Rab7 was knocked-down. More robust reduction of EGFR and Her2 levels was observed when knocked-down cells were treated with HSP90 inhibitor geldanamycin (GA). Low concentration of GA (50-100 nm) induced apoptosis of the Rab7 knocked-down cells but not control cells, suggesting that Rab7 and HSP90 together contribute to the optimal stability of EGFR and Her2 as well as to protect cancer cells from apoptosis. Rab7 seems to protect EGFR and Her2 from proteosome-mediated degradation. These results suggest that Rab7 is likely involved in protecting EGFR and Her2 from being degraded by the proteosome and in maintaining optimal Akt survival signal (especially during cell detachment or when HSP90 is inhibited). Rab7 is potentially a novel target for combinatory therapy with Hsp90 inhibitors. J. Cell. Physiol. © 2011 Wiley-Liss, Inc.

Evidence suggested that L-type calcium channels may play a key role in the pathogenesis of dopaminergic neuron degeneration. In the present study, effects of L-type Cav1.2 calcium channel on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity were investigated. By the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) studies, we showed that the expression of L-type Cav1.2 calcium channel α1 subunit mRNA increased in the substantia nigra (SN) of 6-OHDA-lesioned rats. Treatment with nifedipine could improve the apomorphine-induced rotation behavior in 6-OHDA-lesioned rats. Using high-performance liquid chromatography electrochemical detection, we also observed that nifedipine partly restored 6-OHDA-induced dopamine depletion in the striatum of rats. These results suggest that the L-type Cav1.2 calcium channel is associated with the development and progression of dopaminergic neuron degeneration.