The expression of metabolism-related proteins in phyllodes tumors

The purpose of this study was to investigate the association between the expression of hypoxia-inducible factor (HIF)-1α, insulin-like growth factor (IGF)-1, glucose transporter 1 (Glut-1), carbonic anhydrase IX (CAIX), and monocarboxylate transporter (MCT)4, which are metabolism-related proteins in phyllodes tumors (PTs), and clinicopathologic factors and its implication. We used tissue microarrays to analyze 207 PTs and performed immunohistochemical staining against the glycolysis-related molecules HIF-1α, IGF-1, Glut-1, CAIX, and MCT4. We then compared the immunohistochemical results and clinicopathologic parameters. The expressions of HIF-1α, Glut-1, CAIX, and MCT4 in the stromal component of PTs increased (P?=?0.019, P?<?0.001, P?=?0.045, and P?<?0.001, respectively) with increasing tumor grade. According to univariate analysis, factors associated with shorter disease-free survival were Glut-1 expression (P?=?0.001) and MCT4 expression (P?<?0.001) in the stromal component, and the factors associated with shorter overall survival were IGF-1 expression (P?=?0.012), Glut-1 expression (P?<?0.001), CAIX expression (P?=?0.039), and MCT4 expression (P?<?0.001) in the stromal component. Our investigation of stromal expression of the metabolism-related proteins HIF-1α, IGF-1, Glut-1, CAIX, and MCT4 revealed that, as the PT grade increased, the stromal expression of HIF-1α, Glut-1, CAIX, and MCT4 significantly increased. This result suggested that increasing PT grade is associated with increased glycolysis in the stromal component.     

Effect of dissolved oxygen in alcoholic beverages and drinking water on alcohol elimination in humans

Oxygen plays an important role in the metabolism of alcohol. An increased dissolved oxygen level in alcoholic beverages reportedly accelerates the elimination of alcohol. Therefore, we evaluated the effect of dissolved oxygen in alcohol and the supportive effect of oxygenated water on alcohol pharmacokinetics after the excessive consumption of alcohol, i.e., 540 ml of 19.5% alcohol (v/v). Fifteen healthy males were included in this randomized, 3 × 3 crossover study. Three combinations were tested: X, normal alcoholic beverage and normal water; Y, oxygenated alcoholic beverage and normal water; Z, oxygenated alcoholic beverage and oxygenated water. Blood alcohol concentrations (BACs) were determined by conversion of breath alcohol concentrations. Four pharmacokinetic parameters (C_max, T_max, K_el, and AUCall) were obtained using non-compartmental analysis and the times to reach 0.05% and 0.03% BAC (T_0.05% and T_0.03%) were compared using one-way analysis of variance (ANOVA) and Duncan's post hoc test. With combination Z, the BAC decreased to 0.05% significantly faster (p < 0.05) than with combination X. Analyzing the pharmacokinetic parameters, the mean K_el was significantly higher for combination Z than for combinations X and Y (p < 0.05), whereas the mean values of C_max, T_max and AUCall did not differ significantly among the combinations. Dissolved oxygen in drinks accelerates the decrease in BAC after consuming a large amount of alcohol. However, the oxygen dissolved in the alcoholic beverage alone did not have a sufficient effect in this case. We postulate that highly oxygenated water augments the effect of oxygen in the alcoholic beverage in alcohol elimination. Therefore, it is necessary to investigate the supportive effect of ingesting additional oxygenated water after heavy drinking of normal alcoholic beverages.     

The effect of extension of benefit coverage for cancer patients on health care utilization across different income groups in South Korea

To provide financial protection against catastrophic illness, the Korean government expanded the National Health Insurance (NHI) benefit coverage for cancer patients in 2005. This paper examined whether the policy improved the income-related equality in health care utilization. This study analyzed the extent to which the policy improved income-related equality in outpatient visits, inpatient days, and inpatient and outpatient care expenditure based on triple difference estimator. Using nationwide claims data of the NHI from 2002 to 2004 and from 2006 to 2010, we compared cancer patients as a treatment group with liver disease as a control group and low-income group with the highest-income group. The results showed that the extension of NHI benefits coverage led to an increase in the utilization of outpatient services across all income groups, but with a greater increase for the low-income groups, among cancer patients. Moreover, the policy led to a less decrease in the utilization of inpatient services for the low-income group while it decreased across all income groups. Our finding suggests that the extension of NHI benefits coverage improved the income-related equality in health care utilization.     

Binding Mode Characterization of NBD Series CD4-Mimetic HIV-1 Entry Inhibitors by X-Ray Structure and Resistance Study

We previously identified two small-molecule CD4 mimetics—NBD-556 and NBD-557—and synthesized a series of NBD compounds that resulted in improved neutralization activity in a single-cycle HIV-1 infectivity assay. For the current investigation, we selected several of the most active compounds and assessed their antiviral activity on a panel of 53 reference HIV-1 Env pseudoviruses representing diverse clades of clinical isolates. The selected compounds inhibited tested clades with low-micromolar potencies. Mechanism studies indicated that they act as CD4 agonists, a potentially unfavorable therapeutic trait, in that they can bind to the gp120 envelope glycoprotein and initiate a similar physiological response as CD4. However, one of the compounds, NBD-09027, exhibited reduced agonist properties, in both functional and biophysical studies. To understand the binding mode of these inhibitors, we first generated HIV-1-resistant mutants, assessed their behavior with NBD compounds, and determined the X-ray structures of two inhibitors, NBD-09027 and NBD-10007, in complex with the HIV-1 gp120 core at ∼2-Å resolution. Both studies confirmed that the NBD compounds bind similarly to NBD-556 and NBD-557 by inserting their hydrophobic groups into the Phe43 cavity of gp120. The basic nitrogen of the piperidine ring is located in close proximity to D368 of gp120 but it does not form any H-bond or salt bridge, a likely explanation for their nonoptimal antagonist properties. The results reveal the structural and biological character of the NBD series of CD4 mimetics and identify ways to reduce their agonist properties and convert them to antagonists.     

Intraoperative Discography for Detecting Concealed Lumbar Discal Cysts

Lumbar discal cyst is a rare cause of radiculopathy. Their exact pathogenesis and the optimal treatment modality remain unidentified. Depending on their location, discal cysts cannot always be easily identified intraoperatively. We describe 2 patients with discal cysts and introduce an intraoperative discography technique for discal cyst location. Both patients were treated with surgical excision; with intraoperative discography, the cystic lesions could easily be detected and removed.